BK channels regulate spontaneous action potential rhythmicity in the suprachiasmatic nucleus.

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Jack Kent

Full Text Available BACKGROUND: Circadian ( approximately 24 hr rhythms are generated by the central pacemaker localized to the suprachiasmatic nucleus (SCN of the hypothalamus. Although the basis for intrinsic rhythmicity is generally understood to rely on transcription factors encoded by "clock genes", less is known about the daily regulation of SCN neuronal activity patterns that communicate a circadian time signal to downstream behaviors and physiological systems. Action potentials in the SCN are necessary for the circadian timing of behavior, and individual SCN neurons modulate their spontaneous firing rate (SFR over the daily cycle, suggesting that the circadian patterning of neuronal activity is necessary for normal behavioral rhythm expression. The BK K(+ channel plays an important role in suppressing spontaneous firing at night in SCN neurons. Deletion of the Kcnma1 gene, encoding the BK channel, causes degradation of circadian behavioral and physiological rhythms. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that loss of robust behavioral rhythmicity in Kcnma1(-/- mice is due to the disruption of SFR rhythms in the SCN, we used multi-electrode arrays to record extracellular action potentials from acute wild-type (WT and Kcnma1(-/- slices. Patterns of activity in the SCN were tracked simultaneously for up to 3 days, and the phase, period, and synchronization of SFR rhythms were examined. Loss of BK channels increased arrhythmicity but also altered the amplitude and period of rhythmic activity. Unexpectedly, Kcnma1(-/- SCNs showed increased variability in the timing of the daily SFR peak. CONCLUSIONS/SIGNIFICANCE: These results suggest that BK channels regulate multiple aspects of the circadian patterning of neuronal activity in the SCN. In addition, these data illustrate the characteristics of a disrupted SCN rhythm downstream of clock gene-mediated timekeeping and its relationship to behavioral rhythms.

Comparative anatomy of the mammalian hypothalamic suprachiasmatic nucleus.

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Cassone, V M; Speh, J C; Card, J P; Moore, R Y

1988-01-01

A detailed analysis of the cytoarchitecture, retinohypothalamic tract (RHT) projections, and immunohistochemical localization of major cell and fiber types within the hypothalamic suprachiasmatic nuclei (SCN) was conducted in five mammalian species: two species of opossum, the domestic cat, the guinea pig, and the house mouse. Cytoarchitectural and immunohistochemical studies were conducted in three additional species of marsupial mammals and in the domestic pig. The SCN in this diverse transect of mammalian taxonomy bear striking similarities. First, the SCN are similar in location, lying close to the third ventricle (3V) dorsal to the optic chiasm (OC), with a cytoarchitecture characterized by small, tightly packed neurons. Second, in all groups studied, the SCN receive bilateral retinal input. Third, the SCN contain immunohistochemically similar elements. These similarities suggest that the SCN developed characteristic features early in mammalian phylogeny. Some details of SCN organization vary among the species studied. In marsupials, vasopressin-like immunoreactive (VP-LI) and vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) cells codistribute primarily in the dorsomedial aspects of the SCN, while in eutherians, VP-LI and VIP-LI cells are separated into SCN subnuclei. Furthermore, the marsupial RHT projects to the periventricular dorsomedial region, whereas the eutherian RHT projects more ventrally in the SCN into the zone that typically contains VIP-LI perikarya.

The suprachiasmatic nucleus regulates sleep timing and amount in mice

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Easton, Amy; Meerlo, Peter; Bergmann, Bernard; Turek, Fred W.

2004-01-01

Context: Sleep is regulated by circadian and homeostatic processes. The circadian pacemaker, located in the suprachiasmatic nuclei (SCN), regulates the timing and consolidation of the sleep-wake cycle, while a homeostatic mechanism governs the accumulation of sleep debt and sleep, recovery. Recent

The circadian rhythm induced by the heterogeneous network structure of the suprachiasmatic nucleus

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Gu, Changgui; Yang, Huijie

2016-05-01

In mammals, the master clock is located in the suprachiasmatic nucleus (SCN), which is composed of about 20 000 nonidentical neuronal oscillators expressing different intrinsic periods. These neurons are coupled through neurotransmitters to form a network consisting of two subgroups, i.e., a ventrolateral (VL) subgroup and a dorsomedial (DM) subgroup. The VL contains about 25% SCN neurons that receive photic input from the retina, and the DM comprises the remaining 75% SCN neurons which are coupled to the VL. The synapses from the VL to the DM are evidently denser than that from the DM to the VL, in which the VL dominates the DM. Therefore, the SCN is a heterogeneous network where the neurons of the VL are linked with a large number of SCN neurons. In the present study, we mimicked the SCN network based on Goodwin model considering four types of networks including an all-to-all network, a Newman-Watts (NW) small world network, an Erdös-Rényi (ER) random network, and a Barabási-Albert (BA) scale free network. We found that the circadian rhythm was induced in the BA, ER, and NW networks, while the circadian rhythm was absent in the all-to-all network with weak cellular coupling, where the amplitude of the circadian rhythm is largest in the BA network which is most heterogeneous in the network structure. Our finding provides an alternative explanation for the induction or enhancement of circadian rhythm by the heterogeneity of the network structure.

Effects of irradiation on the circadian rhythm in the release of peptides in the suprachiasmatic nucleus culture

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Saito, Kimihiko [Yokohama City Univ. (Japan). School of Medicine

2000-03-01

Mammalian circadian rhythms are regulated by the circadian clock which is located in the hypothalamic suprachiasmatic nucleus (SCN). In the present study, we examined the effect of irradiation on the circadian rhythm in the release of arginine-vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) in slice cultures of the rat SCN. The effect of irradiation on the glial cell proliferation in the SCN culture was also examined by the immunohistochemical method. In SCN cultures which received irradiation, circadian rhythms in the release of AVP and VIP were detected, as observed in the SCN culture not irradiated. However, the AVP and VIP rhythms showed various phase angle differences in some cultures irradiated, which suggested that irradiation caused a looseness of coupling between AVP and VIP oscillators. On the other hand, the number of glial cells was decreased by irradiation. These results suggested that the dissociation of the two peptide rhythms after irradiation might be due to the inhibition of glial cell proliferation. Furthermore, the radiation changed the amplitude of AVP and VIP rhythms, suggesting that couplings within both AVP and VIP oscillators were influenced by irradiation. (author)

Effects of irradiation on the circadian rhythm in the release of peptides in the suprachiasmatic nucleus culture

International Nuclear Information System (INIS)

Saito, Kimihiko

2000-01-01

Mammalian circadian rhythms are regulated by the circadian clock which is located in the hypothalamic suprachiasmatic nucleus (SCN). In the present study, we examined the effect of irradiation on the circadian rhythm in the release of arginine-vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) in slice cultures of the rat SCN. The effect of irradiation on the glial cell proliferation in the SCN culture was also examined by the immunohistochemical method. In SCN cultures which received irradiation, circadian rhythms in the release of AVP and VIP were detected, as observed in the SCN culture not irradiated. However, the AVP and VIP rhythms showed various phase angle differences in some cultures irradiated, which suggested that irradiation caused a looseness of coupling between AVP and VIP oscillators. On the other hand, the number of glial cells was decreased by irradiation. These results suggested that the dissociation of the two peptide rhythms after irradiation might be due to the inhibition of glial cell proliferation. Furthermore, the radiation changed the amplitude of AVP and VIP rhythms, suggesting that couplings within both AVP and VIP oscillators were influenced by irradiation. (author)

Circadian and developmental regulation of N-methyl-d-aspartate-receptor 1 mRNA splice variants and N-methyl-d-aspartate-receptor 3 subunit expression within the rat suprachiasmatic nucleus

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Bendová, Z; Sumová, A; Mikkelsen, Jens D.

2009-01-01

The circadian rhythms of mammals are generated by the circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Its intrinsic period is entrained to a 24 h cycle by external cues, mainly by light. Light impinging on the SCN at night causes either advancing or delaying phase...... shifts of the circadian clock. N-methyl-d-aspartate receptors (NMDAR) are the main glutamate receptors mediating the effect of light on the molecular clockwork in the SCN. They are composed of multiple subunits, each with specific characteristics whose mutual interactions strongly determine properties...

Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus

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Jinmi Koo

2015-09-01

Full Text Available BackgroundIn mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN. Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions.MethodsWe examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2 gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC knock-in mice using a real-time bioluminescence measurement system.ResultsAdministration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms.ConclusionThese findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

Circadian pacemaking in cells and circuits of the suprachiasmatic nucleus.

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Hastings, M H; Brancaccio, M; Maywood, E S

2014-01-01

The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian pacemaker of the brain. It co-ordinates the daily rhythms of sleep and wakefulness, as well as physiology and behaviour, that set the tempo to our lives. Disturbance of this daily pattern, most acutely with jet-lag but more insidiously with rotational shift-work, can have severely deleterious effects for mental function and long-term health. The present review considers recent developments in our understanding of the properties of the SCN that make it a robust circadian time-keeper. It first focuses on the intracellular transcriptional/ translational feedback loops (TTFL) that constitute the cellular clockwork of the SCN neurone. Daily timing by these loops pivots around the negative regulation of the Period (Per) and Cryptochrome (Cry) genes by their protein products. The period of the circadian cycle is set by the relative stability of Per and Cry proteins, and this can be controlled by both genetic and pharmacological interventions. It then considers the function of these feedback loops in the context of cytosolic signalling by cAMP and intracellular calcium ([Ca(2+) ]i ), which are both outputs from, and inputs to, the TTFL, as well as the critical role of vasoactive intestinal peptide (VIP) signalling in synchronising cellular clocks across the SCN. Synchronisation by VIP in the SCN is paracrine, operating over an unconventionally long time frame (i.e. 24 h) and wide spatial domain, mediated via the cytosolic pathways upstream of the TTFL. Finally, we show how intersectional pharmacogenetics can be used to control G-protein-coupled signalling in individual SCN neurones, and how manipulation of Gq/[Ca(2+) ]i -signalling in VIP neurones can re-programme the circuit-level encoding of circadian time. Circadian pacemaking in the SCN therefore provides an unrivalled context in which to understand how a complex, adaptive behaviour can be organised by the dynamic activity of a relatively

Direct projection from the suprachiasmatic nucleus to hypophysiotrophic corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus of the hypothalamus demonstrated...

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Vrang, N.; Larsen, P.J.; Mikkelsen, J.D.

1995-01-01

Suprachiasmatic nucleus, paraventricular nucleus, circadian rhythms, phaseolus vulgaris-leucoagglutinin, corticotropin-releasing factor, dual immunocytochemistry......Suprachiasmatic nucleus, paraventricular nucleus, circadian rhythms, phaseolus vulgaris-leucoagglutinin, corticotropin-releasing factor, dual immunocytochemistry...

Neural Damage in Experimental Trypanosoma brucei gambiense Infection: The Suprachiasmatic Nucleus

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Chiara Tesoriero

2018-02-01

Full Text Available Trypanosoma brucei (T. b. gambiense is the parasite subspecies responsible for most reported cases of human African trypanosomiasis (HAT or sleeping sickness. This severe infection leads to characteristic disruption of the sleep-wake cycle, recalling attention on the circadian timing system. Most animal models of the disease have been hitherto based on infection of laboratory rodents with the T. b. brucei subspecies, which is not infectious to humans. In these animal models, functional, rather than structural, alterations of the master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN, have been reported. Information on the SCN after infection with the human pathogenic T. b. gambiense is instead lacking. The present study was aimed at the examination of the SCN after T. b. gambiense infection of a susceptible rodent, the multimammate mouse, Mastomys natalensis, compared with T. b. brucei infection of the same host species. The animals were examined at 4 and 8 weeks post-infection, when parasites (T. b. gambiense or T. b. brucei were detected in the brain parenchyma, indicating that the disease was in the encephalitic stage. Neuron and astrocyte changes were examined with Nissl staining, immunophenotyping and quantitative analyses. Interestingly, significant neuronal loss (about 30% reduction was documented in the SCN during the progression of T. b. gambiense infection. No significant neuronal density changes were found in the SCN of T. b. brucei-infected animals. Neuronal cell counts in the hippocampal dentate gyrus of T. b. gambiense-infected M. natalensis did not point out significant changes, indicating that no widespread neuron loss had occurred in the brain. Marked activation of astrocytes was detected in the SCN after both T. b. gambiense and T. b. brucei infections. Altogether the findings reveal that neurons of the biological clock are highly susceptible to the infection caused by human pathogenic African trypanosomes

Circadian rhythmicity of active GSK3 isoforms modulates molecular clock gene rhythms in the suprachiasmatic nucleus.

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Besing, Rachel C; Paul, Jodi R; Hablitz, Lauren M; Rogers, Courtney O; Johnson, Russell L; Young, Martin E; Gamble, Karen L

2015-04-01

The suprachiasmatic nucleus (SCN) drives and synchronizes daily rhythms at the cellular level via transcriptional-translational feedback loops comprising clock genes such as Bmal1 and Period (Per). Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, phosphorylates at least 5 core clock proteins and shows diurnal variation in phosphorylation state (inactivation) of the GSK3β isoform. Whether phosphorylation of the other primary isoform (GSK3α) varies across the subjective day-night cycle is unknown. The purpose of this study was to determine if the endogenous rhythm of GSK3 (α and β) phosphorylation is critical for rhythmic BMAL1 expression and normal amplitude and periodicity of the molecular clock in the SCN. Significant circadian rhythmicity of phosphorylated GSK3 (α and β) was observed in the SCN from wild-type mice housed in constant darkness for 2 weeks. Importantly, chronic activation of both GSK3 isoforms impaired rhythmicity of the GSK3 target BMAL1. Furthermore, chronic pharmacological inhibition of GSK3 with 20 µM CHIR-99021 enhanced the amplitude and shortened the period of PER2::luciferase rhythms in organotypic SCN slice cultures. These results support the model that GSK3 activity status is regulated by the circadian clock and that GSK3 feeds back to regulate the molecular clock amplitude in the SCN. © 2015 The Author(s).

The asymmetry of the entrainment range induced by the difference in intrinsic frequencies between two subgroups within the suprachiasmatic nucleus

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Gu, Changgui; Yang, Huijie

2017-06-01

The rhythms of physiological and behavioral activities in mammals, which are regulated by the main clock suprachiasmatic nucleus (SCN) in the brain, can not be only synchronized to the natural 24 h light-dark cycle, but also to cycles with artificial periods. The range of the artificial periods that the animal can be synchronized to is called entrainment range. In the absence of the light-dark cycle, the animal can also maintain the circadian rhythm with an endogenous period close to 24 h. Experiments found that the entrainment range is not symmetrical with respect to the endogenous period. In the present study, an explanation is given for the asymmetry based on a Kuramoto model which describes the neuronal network of the SCN. Our numerical simulations and theoretical analysis show that the asymmetry results from the difference in the intrinsic frequencies between two subgroups of the SCN, as well as the entrainment range is affected by the difference.

Daily changes in synaptic innervation of VIP neurons in the rat suprachiasmatic nucleus: contribution of glutamatergic afferents.

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Girardet, Clémence; Blanchard, Marie-Pierre; Ferracci, Géraldine; Lévêque, Christian; Moreno, Mathias; François-Bellan, Anne-Marie; Becquet, Denis; Bosler, Olivier

2010-01-01

The daily temporal organization of rhythmic functions in mammals, which requires synchronization of the circadian clock to the 24-h light-dark cycle, is believed to involve adjustments of the mutual phasing of the cellular oscillators that comprise the time-keeper within the suprachiasmatic nucleus of the hypothalamus (SCN). Following from a previous study showing that the SCN undergoes day/night rearrangements of its neuronal-glial network that may be crucial for intercellular phasing, we investigated the contribution of glutamatergic synapses, known to play major roles in SCN functioning, to such rhythmic plastic events. Neither expression levels of the vesicular glutamate transporters nor numbers of glutamatergic terminals showed nycthemeral variations in the SCN. However, using quantitative imaging after combined immunolabelling, the density of synapses on neurons expressing vasoactive intestinal peptide, known as targets of the retinal input, increased during the day and both glutamatergic and non-glutamatergic synapses contributed to the increase (+36%). This was not the case for synapses made on vasopressin-containing neurons, the other major source of SCN efferents in the non-retinorecipient region. Together with electron microscope observations showing no differences in the morphometric features of glutamatergic terminals during the day and night, these data show that the light synchronization process in the SCN involves a selective remodelling of synapses at sites of photic integration. They provide a further illustration of how the adult brain may rapidly and reversibly adapt its synaptic architecture to functional needs.

Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice

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Landgraf, Dominic; Long, Jaimie E.; Proulx, Christophe D.; Barandas, Rita; Malinow, Roberto; Welsh, David K.

2016-01-01

Background Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. Methods We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). Results In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Conclusions Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. PMID:27113500

Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice.

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Landgraf, Dominic; Long, Jaimie E; Proulx, Christophe D; Barandas, Rita; Malinow, Roberto; Welsh, David K

2016-12-01

Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

Direct and specific effect of sevoflurane anesthesia on rat Per2 expression in the suprachiasmatic nucleus.

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Megumi Anzai

Full Text Available BACKGROUND: Our previous studies revealed that application of the inhalation anesthetic, sevoflurane, reversibly repressed the expression of Per2 in the mouse suprachiasmatic nucleus (SCN. We aimed to examine whether sevoflurane directly affects the SCN. METHODS: We performed in vivo and in vitro experiments to investigate rat Per2 expression under sevoflurane-treatment. The in vivo effects of sevoflurane on rPer2 expression were examined by quantitative in situ hybridization with a radioactively-labeled cRNA probe. Additionally, we examined the effect of sevoflurane anesthesia on rest/activity rhythms in the rat. In the in vitro experiments, we applied sevoflurane to SCN explant cultures from Per2-dLuc transgenic rats, and monitored luciferase bioluminescence, representing Per2 promoter activity. Bioluminescence from two peripheral organs, the kidney cortex and the anterior pituitary gland, were also analyzed. RESULTS: Application of sevoflurane in rats significantly suppressed Per2 expression in the SCN compared with untreated animals. We observed no sevoflurane-induced phase-shift in the rest/activity rhythms. In the in vitro experiments, the intermittent application of sevoflurane repressed the increase of Per2-dLuc luminescence and led to a phase delay in the Per2-dLuc luminescence rhythm. Sevoflurane treatment did not suppress bioluminescence in the kidney cortex or the anterior pituitary gland. CONCLUSION: The suppression of Per2-dLuc luminescence by sevoflurane in in vitro SCN cultures isolated from peripheral inputs and other nuclei suggest a direct action of sevoflurane on the SCN itself. That sevoflurane has no such effect on peripheral organs suggests that this action might be mediated through a neuron-specific cellular mechanism or a regulation of the signal transduction between neurons.

Pancreatic polypeptide controls energy homeostasis via Npy6r signaling in the suprachiasmatic nucleus in mice.

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Yulyaningsih, Ernie; Loh, Kim; Lin, Shu; Lau, Jackie; Zhang, Lei; Shi, Yanchuan; Berning, Britt A; Enriquez, Ronaldo; Driessler, Frank; Macia, Laurence; Khor, Ee Cheng; Qi, Yue; Baldock, Paul; Sainsbury, Amanda; Herzog, Herbert

2014-01-07

Y-receptors control energy homeostasis, but the role of Npy6 receptors (Npy6r) is largely unknown. Young Npy6r-deficient (Npy6r(-/-)) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r(-/-) mice have low lean mass with increased adiposity. Npy6r(-/-) mice showed reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to WT. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), where we found Npy6r coexpressed in VIP neurons. Peripheral administration of pancreatic polypeptide (PP) increased Fos expression in the SCN, increased energy expenditure, and reduced food intake in WT, but not Npy6r(-/-), mice. Moreover, intraperitoneal (i.p.) PP injection increased hypothalamic Ghrh mRNA expression and serum IGF-1 levels in WT, but not Npy6r(-/-), mice, an effect blocked by intracerebroventricular (i.c.v.) Vasoactive Intestinal Peptide (VPAC) receptors antagonism. Thus, PP-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition. Copyright © 2014 Elsevier Inc. All rights reserved.

Ras Activity Oscillates in the Mouse Suprachiasmatic Nucleus and Modulates Circadian Clock Dynamics.

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Serchov, Tsvetan; Jilg, Antje; Wolf, Christian T; Radtke, Ina; Stehle, Jörg H; Heumann, Rolf

2016-04-01

Circadian rhythms, generated in the mouse suprachiasmatic nucleus (SCN), are synchronized to the environmental day-night changes by photic input. The activation of the extracellular signal-regulated kinases 1 and 2 (ERK1,2) and cAMP response element-binding protein (CREB)-mediated transcription play a critical role in this photoentrainment. The small GTPase Ras is one of the major upstream regulators of the ERK1,2/CREB pathway. In contrast to the well-described role of Ras in structural and functional synaptic plasticity in the adult mouse brain, the physiological regulation of Ras by photic sensory input is yet unknown. Here, we describe for the first time a circadian rhythm of Ras activity in the mouse SCN. Using synRas transgenic mice, expressing constitutively activated V12-Ha-Ras selectively in neurons, we demonstrate that enhanced Ras activation causes shortening of the circadian period length. We found upregulated expression and decreased inhibitory phosphorylation of the circadian period length modulator, glycogen synthase kinase-3 beta (GSK3β), in the SCN of synRas mice. Conversely, downregulation of Ras activity by blocking its function with an antibody in oscillating cell cultures reduced protein levels and increased phosphorylation of GSK3β and lengthened the period of BMAL1 promoter-driven luciferase activity. Furthermore, enhanced Ras activity in synRas mice resulted in a potentiation of light-induced phase delays at early subjective night, and increased photic induction of pERK1,2/pCREB and c-Fos. In contrast, at late subjective night, photic activation of Ras/ERK1,2/CREB in synRas mice was not sufficient to stimulate c-Fos protein expression and phase advance the clock. Taken together, our results demonstrate that Ras activity fine tunes the period length and modulates photoentrainment of the circadian clock.

Dispersion of the intrinsic neuronal periods affects the relationship of the entrainment range to the coupling strength in the suprachiasmatic nucleus

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Gu, Changgui; Yang, Huijie; Wang, Man

2017-11-01

Living beings on the Earth are subjected to and entrained (synchronized) to the natural 24-h light-dark cycle. Interestingly, they can also be entrained to an external artificial cycle of non-24-h periods. The range of these periods is called the entrainment range and it differs among species. In mammals, the entrainment range is regulated by a main clock located in the suprachiasmatic nucleus (SCN) which is composed of 10 000 neurons in the brain. Previous works have found that the entrainment range depends on the cellular coupling strength in the SCN. In particular, the entrainment range decreases with the increase of the cellular coupling strength, provided that all the neuronal oscillators are identical. However, the SCN neurons differ in the intrinsic periods that follow a normal distribution in a range from 22 to 28 h. In the present study, taking the dispersion of the intrinsic neuronal periods into account, we examined the relationship between the entrainment range and the coupling strength. Results from numerical simulations and theoretical analyses both show that the relationship is altered to be paraboliclike if the intrinsic neuronal periods are nonidentical, and the maximal entrainment range is obtained with a suitable coupling strength. Our results shed light on the role of the cellular coupling in the entrainment ability of the SCN network.

Daily fluctuation of hepatic P450 monooxygenase activities in male rats is controlled by the suprachiasmatic nucleus but remains unaffected by adrenal hormones.

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Furukawa, T; Manabe, S; Watanabe, T; Sehata, S; Sharyo, S; Okada, T; Mori, Y

1999-09-01

Hepatic P450 monooxygenase activities, which strongly influence the efficacy and/or toxicity of drugs, are known to fluctuate daily. We also know that the P450 activities assessed by measurement of 7-alkoxycoumarin O-dealkylase (ACD) activities fluctuate daily, with apparently high values during the dark period in male rats. However, there is little knowledge about the factors that regulate daily fluctuation of P450 monooxygenase activities. In the present study using rats, we induced lesions in the suprachiasmatic nucleus (SCN) of the brain, the known site of the body's internal clock, and examined the effects on the daily fluctuation of the ACD activities to clarify the relationship between the SCN and the daily fluctuation of P450 monooxygenase activities. In addition, adrenalectomy was performed to re-evaluate the influence of adrenal hormones on the P450 activities. Our results indicated that daily fluctuations of the hepatic ACD activities were completely eliminated in the SCN-lesioned rats. However, the ACD activities in the adrenalectomized rats showed apparent daily fluctuations with high values during the dark period and low values during the light period. Therefore, this study demonstrated that the daily fluctuation of the hepatic P450 monooxygenase activities in male rats is controlled by the SCN but remains unaffected by the adrenal hormones.

Effects of adrenalectomy on daily gene expression rhythms in the rat suprachiasmatic and paraventricular hypothalamic nuclei and in white adipose tissue

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Su, Yan; van der Spek, Rianne; Foppen, E.; Kwakkel, Joan; Fliers, Eric; Kalsbeek, A.

It is assumed that in mammals the circadian rhythms of peripheral clocks are synchronized to the environment via neural, humoral and/or behavioral outputs of the central pacemaker in the suprachiasmatic nucleus of the hypothalamus (SCN). With regard to the humoral outputs, the daily rhythm of the

Effects of adrenalectomy on daily gene expression rhythms in the rat suprachiasmatic and paraventricular hypothalamic nuclei and in white adipose tissue

NARCIS (Netherlands)

Su, Yan; van der Spek, Rianne; Foppen, Ewout; Kwakkel, Joan; Fliers, Eric; Kalsbeek, Andries

2015-01-01

It is assumed that in mammals the circadian rhythms of peripheral clocks are synchronized to the environment via neural, humoral and/or behavioral outputs of the central pacemaker in the suprachiasmatic nucleus of the hypothalamus (SCN). With regard to the humoral outputs, the daily rhythm of the

Identification of novel light-induced genes in the suprachiasmatic nucleus

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Piontkivska Helen

2007-11-01

Full Text Available Abstract Background The transmission of information about the photic environment to the circadian clock involves a complex array of neurotransmitters, receptors, and second messenger systems. Exposure of an animal to light during the subjective night initiates rapid transcription of a number of immediate-early genes in the suprachiasmatic nucleus of the hypothalamus. Some of these genes have known roles in entraining the circadian clock, while others have unknown functions. Using laser capture microscopy, microarray analysis, and quantitative real-time PCR, we performed a comprehensive screen for changes in gene expression immediately following a 30 minute light pulse in suprachiasmatic nucleus of mice. Results The results of the microarray screen successfully identified previously known light-induced genes as well as several novel genes that may be important in the circadian clock. Newly identified light-induced genes include early growth response 2, proviral integration site 3, growth-arrest and DNA-damage-inducible 45 beta, and TCDD-inducible poly(ADP-ribose polymerase. Comparative analysis of promoter sequences revealed the presence of evolutionarily conserved CRE and associated TATA box elements in most of the light-induced genes, while other core clock genes generally lack this combination of promoter elements. Conclusion The photic signalling cascade in the suprachiasmatic nucleus activates an array of immediate-early genes, most of which have unknown functions in the circadian clock. Detected evolutionary conservation of CRE and TATA box elements in promoters of light-induced genes suggest that the functional role of these elements has likely remained the same over evolutionary time across mammalian orders.

Intracellular Na(+) and metabolic modulation of Na/K pump and excitability in the rat suprachiasmatic nucleus neurons.

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Wang, Yi-Chi; Yang, Jyh-Jeen; Huang, Rong-Chi

2012-10-01

Na/K pump activity and metabolic rate are both higher during the day in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigated the role of intracellular Na(+) and energy metabolism in regulating Na/K pump activity and neuronal excitability. Removal of extracellular K(+) to block the Na/K pump excited SCN neurons to fire at higher rates and return to normal K(+) to reactivate the pump produced rebound hyperpolarization to inhibit firing. In the presence of tetrodotoxin to block the action potentials, both zero K(+)-induced depolarization and rebound hyperpolarization were blocked by the cardiac glycoside strophanthidin. Ratiometric Na(+) imaging with a Na(+)-sensitive fluorescent dye indicated saturating accumulation of intracellular Na(+) in response to pump blockade with zero K(+). The Na(+) ionophore monensin also induced Na(+) loading and hyperpolarized the membrane potential, with the hyperpolarizing effect of monensin abolished in zero Na(+) or by pump blockade. Conversely, Na(+) depletion with Na(+)-free pipette solution depolarized membrane potential but retained residual Na/K pump activity. Cyanide inhibition of oxidative phosphorylation blocked the Na/K pump to depolarize resting potential and increase spontaneous firing in most cells, and to raise intracellular Na(+) levels in all cells. Nonetheless, the Na/K pump was incompletely blocked by cyanide but completely blocked by iodoacetate to inhibit glycolysis, indicating the involvement of both oxidative phosphorylation and glycolysis in fueling the Na/K pump. Together, the results indicate the importance of intracellular Na(+) and energy metabolism in regulating Na/K pump activity as well as neuronal excitability in the SCN neurons.

Functionally Complete Excision of Conditional Alleles in the Mouse Suprachiasmatic Nucleus by Vgat-ires-Cre.

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Weaver, David R; van der Vinne, Vincent; Giannaris, E Lela; Vajtay, Thomas J; Holloway, Kristopher L; Anaclet, Christelle

2018-04-01

Mice with targeted gene disruption have provided important information about the molecular mechanisms of circadian clock function. A full understanding of the roles of circadian-relevant genes requires manipulation of their expression in a tissue-specific manner, ideally including manipulation with high efficiency within the suprachiasmatic nuclei (SCN). To date, conditional manipulation of genes within the SCN has been difficult. In a previously developed mouse line, Cre recombinase was inserted into the vesicular GABA transporter (Vgat) locus. Since virtually all SCN neurons are GABAergic, this Vgat-Cre line seemed likely to have high efficiency at disrupting conditional alleles in SCN. To test this premise, the efficacy of Vgat-Cre in excising conditional (fl, for flanked by LoxP) alleles in the SCN was examined. Vgat-Cre-mediated excision of conditional alleles of Clock or Bmal1 led to loss of immunostaining for products of the targeted genes in the SCN. Vgat-Cre + ; Clock fl/fl ; Npas2 m/m mice and Vgat-Cre + ; Bmal1 fl/fl mice became arrhythmic immediately upon exposure to constant darkness, as expected based on the phenotype of mice in which these genes are disrupted throughout the body. The phenotype of mice with other combinations of Vgat-Cre + , conditional Clock, and mutant Npas2 alleles also resembled the corresponding whole-body knockout mice. These data indicate that the Vgat-Cre line is useful for Cre-mediated recombination within the SCN, making it useful for Cre-enabled technologies including gene disruption, gene replacement, and opto- and chemogenetic manipulation of the SCN circadian clock.

Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording

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Schaap, J.; Bos, N. P.; de Jeu, M. T.; Geurtsen, A. M.; Meijer, J. H.; Pennartz, C. M.

1999-01-01

The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological

Photic induction of Fos in the suprachiasmatic nucleus of African mole-rats: responses to increasing irradiance.

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Oosthuizen, Maria K; Bennett, Nigel C; Cooper, Howard M

2010-09-01

African mole-rats (family Bathyergidae) are strictly subterranean rodent species that are rarely exposed to environmental light. Morphological and physiological adaptations to the underground environment include a severely reduced eye size and regressed visual system. Responses of the circadian system to light, however, appear to be intact, since mole-rats are able to entrain their circadian activity rhythms to the light-dark cycle and light induces Fos expression in the suprachiasmatic nucleus (SCN). Social organization varies from solitary species to highly elaborated eusocial structures, characterized by a distinct division of labor and in which one reproductive female regulates the behavior and reproductive physiology of other individuals in the colony. The authors studied light-induced Fos expression in the SCN to increasing light intensities in four mole-rat species, ranging from strictly solitary to highly social. In the solitary Cape mole-rat, light induces significant Fos expression in the SCN, and the number of Fos-immunopositive cells increases with increasing light intensity. In contrast, Fos induction in the SCN of social species was slightly greater than, but not statistically different from, the dark-control animals as is typical of most rodents. One species showed a trend for an increase in expression with increased light, whereas a second species showed no trend in expression. In the naked mole-rat, Fos expression appeared higher in the dark-controls than in the animals exposed to light, although the differences in Fos expression were not significant. These results suggest a gradient in the sensitivity of the circadian system to light in mole-rats, with a higher percentage of individuals that are unresponsive to light in correlation with the degree of sociality. In highly social species, such as the naked mole-rat that live in a relatively stable subterranean milieu in terms of food availability, temperature, constant darkness, and devoid of 24-h

Time-of-day- and light-dependent expression of ubiquitin protein ligase E3 component N-recognin 4 (UBR4 in the suprachiasmatic nucleus circadian clock.

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Harrod H Ling

Full Text Available Circadian rhythms of behavior and physiology are driven by the biological clock that operates endogenously but can also be entrained to the light-dark cycle of the environment. In mammals, the master circadian pacemaker is located in the suprachiasmatic nucleus (SCN, which is composed of individual cellular oscillators that are driven by a set of core clock genes interacting in transcriptional/translational feedback loops. Light signals can trigger molecular events in the SCN that ultimately impact on the phase of expression of core clock genes to reset the master pacemaker. While transcriptional regulation has received much attention in the field of circadian biology in the past, other mechanisms including targeted protein degradation likely contribute to the clock timing and entrainment process. In the present study, proteome-wide screens of the murine SCN led to the identification of ubiquitin protein ligase E3 component N-recognin 4 (UBR4, a novel E3 ubiquitin ligase component of the N-end rule pathway, as a time-of-day-dependent and light-inducible protein. The spatial and temporal expression pattern of UBR4 in the SCN was subsequently characterized by immunofluorescence microscopy. UBR4 is expressed across the entire rostrocaudal extent of the SCN in a time-of-day-dependent fashion. UBR4 is localized exclusively to arginine vasopressin (AVP-expressing neurons of the SCN shell. Upon photic stimulation in the early subjective night, the number of UBR4-expressing cells within the SCN increases. This study is the first to identify a novel E3 ubiquitin ligase component, UBR4, in the murine SCN and to implicate the N-end rule degradation pathway as a potential player in regulating core clock mechanisms and photic entrainment.

Effects of melatonin on 2-deoxy-[1-14C]glucose uptake within rat suprachiasmatic nucleus

International Nuclear Information System (INIS)

Cassone, V.M.; Roberts, M.H.; Moore, R.Y.

1988-01-01

Previously, we have demonstrated that metabolic activity, shown by autoradiographic determination of 2-deoxy-[1- 14 C]glucose (2-DG) uptake, within the rat hypothalamic suprachiasmatic nuclei (SCN) was inhibited by subcutaneous injection of 1 mg/kg melatonin. To determine whether this effect was specific to a particular time of day, the effects of melatonin on 2-DG uptake were studied in several hypothalamic areas, including the SCN, supraoptic nuclei (SON), lateral hypothalamic area (LHA), and anterior hypothalamic area (AHA) every 4 h throughout the circadian day. In a second experiment, the effects of different melatonin doses were studied at the time of day at which melatonin had its maximal effect to determine the dose-response relationship of melatonin-induced inhibition of SCN 2-DG uptake. The data indicate that melatonin inhibited 2-DG uptake in the SCN alone at one time of day, primarily at circadian time (CT) 6 and CT10, 2-6 h before subjective dusk, and secondarily at CT22, just before subjective dawn. This effect was dose dependent with a 50% effective dose of 1.49 +/- 2.30 micrograms/kg. The temporal and dose-response characteristics of these effects are similar to those characterizing the entraining effects of melatonin on circadian patterns of locomotion and drinking

Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN

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Ono, Daisuke; Honma, Sato; Honma, Ken-ichi

2016-01-01

The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2−/−). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2−/− SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period. PMID:27626074

Multiplexing Visual Signals in the Suprachiasmatic Nuclei

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Adam R. Stinchcombe

2017-11-01

Full Text Available The suprachiasmatic nuclei (SCN, the site of the mammalian circadian (daily pacemaker, contains thousands of interconnected neurons, some of which receive direct retinal input. Here, we study the fast (<1 s responses of SCN neurons to visual stimuli with a large-scale mathematical model tracking the ionic currents and voltage of all SCN neurons. We reconstruct the SCN network connectivity and reject 99.99% of theoretically possible SCN networks by requiring that the model reproduces experimentally determined receptive fields of SCN neurons. The model shows how the SCN neuronal network can enhance circadian entrainment by sensitizing a population of neurons in the ventral SCN to irradiance. This SCN network also increases the spatial acuity of neurons and increases the accuracy of a simulated subconscious spatial visual task. We hypothesize that much of the fast electrical activity within the SCN is related to the processing of spatial information.

Phenobarbital blockade of the preovulatory luteinizing hormone surge: association with phase-advanced circadian clock and altered suprachiasmatic nucleus Period1 gene expression

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Legan, Sandra J.; Donoghue, Kathleen M.; Franklin, Kathleen M.; Duncan, Marilyn J.

2009-01-01

The suprachiasmatic nucleus (SCN) controls the timing of the preovulatory luteinizing hormone (LH) surge in laboratory rodents. Barbiturate administration during a critical period on proestrus delays the surge and prolongs the estrous cycle 1 day. Because a nonphotic timing signal (zeitgeber) during the critical period that phase advances activity rhythms can also induce the latter effect, we hypothesized that barbiturates delay the LH surge by phase-advancing its circadian timing signal beyond the critical period. In experiment 1, locomotor rhythms and estrous cycles were monitored in hamsters for 2–3 wk preinjection and postinjection of vehicle or phenobarbital and after transfer to darkness at zeitgeber time (ZT) 6 on proestrus. Phenobarbital delayed estrous cycles in five of seven hamsters, which exhibited phase shifts that averaged twofold greater than those exhibited by vehicle controls or phenobarbital-injected hamsters with normal cycles. Experiment 2 used a similar protocol, but injections were at ZT 5, and blood samples for LH determination were collected from 1200 to 1800 on proestrus and the next day via jugular cannulae inserted the day before proestrus. Phenobarbital delayed the LH surge 1 day in all six hamsters, but it occurred at an earlier circadian time, supporting the above hypothesis. Experiment 3 investigated whether phenobarbital, like other nonphotic zeitgebers, suppresses SCN Period1 and Period2 transcription. Two hours postinjection, phenobarbital decreased SCN expression of only Period1 mRNA, as determined by in situ hybridization. These results suggest that phenobarbital advances the SCN pacemaker, governing activity rhythms and hormone release in part by decreasing its Period1 gene expression. PMID:19297538

Multiplexing Visual Signals in the Suprachiasmatic Nuclei.

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Stinchcombe, Adam R; Mouland, Joshua W; Wong, Kwoon Y; Lucas, Robert J; Forger, Daniel B

2017-11-07

The suprachiasmatic nuclei (SCN), the site of the mammalian circadian (daily) pacemaker, contains thousands of interconnected neurons, some of which receive direct retinal input. Here, we study the fast (<1 s) responses of SCN neurons to visual stimuli with a large-scale mathematical model tracking the ionic currents and voltage of all SCN neurons. We reconstruct the SCN network connectivity and reject 99.99% of theoretically possible SCN networks by requiring that the model reproduces experimentally determined receptive fields of SCN neurons. The model shows how the SCN neuronal network can enhance circadian entrainment by sensitizing a population of neurons in the ventral SCN to irradiance. This SCN network also increases the spatial acuity of neurons and increases the accuracy of a simulated subconscious spatial visual task. We hypothesize that much of the fast electrical activity within the SCN is related to the processing of spatial information. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Intracellular Physiology of the Rat Suprachiasmatic Nucleus: Electrical Properties, Neurotransmission, and Effects of Neuromodulators

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1992-01-10

Physiology of the Rat Suprachiasmatic Nucleus: Electrical Properties, Neurotransmission, and Effects of Neuromodulators . I-f 12. PERSONAL AUTHOR(S) F...interplay between intrinsic electrophysiological properties, amino-acid-mediated synaptic transmission, and neuromodulation . We have continued to study the

In vivo metabolic activity of hamster suprachiasmatic nuclei: use of anesthesia

International Nuclear Information System (INIS)

Schwartz, W.J.

1987-01-01

In vivo glucose utilization was measured in the suprachiasmatic nuclei (SCN) of Golden hamsters using the 14 C-labeled deoxyglucose technique. A circadian rhythm of SCN metabolic activity could be measured in this species, but only during pentobarbital sodium anesthesia when the surrounding background activity of adjacent hypothalamus was suppressed. Both the SCN's metabolic oscillation and its time-keeping ability are resistant to general anesthesia

Cognitive performance as a zeitgeber: cognitive oscillators and cholinergic modulation of the SCN entrain circadian rhythms.

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Howard J Gritton

Full Text Available The suprachiasmatic nucleus (SCN is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior.

The Neuronal Transition Probability (NTP) Model for the Dynamic Progression of Non-REM Sleep EEG: The Role of the Suprachiasmatic Nucleus

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Merica, H

2011-01-01

Little attention has gone into linking to its neuronal substrates the dynamic structure of non-rapid-eye-movement (NREM) sleep, defined as the pattern of time-course power in all frequency bands across an entire episode. Using the spectral power time-courses in the sleep electroencephalogram (EEG), we showed in the typical first episode, several moves towards-and-away from deep sleep, each having an identical pattern linking the major frequency bands beta, sigma and delta. The neuronal transition probability model (NTP) - in fitting the data well - successfully explained the pattern as resulting from stochastic transitions of the firing-rates of the thalamically-projecting brainstem-activating neurons, alternating between two steady dynamic-states (towards-and-away from deep sleep) each initiated by a so-far unidentified flip-flop. The aims here are to identify this flip-flop and to demonstrate that the model fits well all NREM episodes, not just the first. Using published data on suprachiasmatic nucleus (SCN...

Serotonin regulates the phase of the rat suprachiasmatic circadian pacemaker in vitro only during the subjective day.

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Medanic, M; Gillette, M U

1992-05-01

1. The suprachiasmatic nucleus (SCN) of the hypothalamus is the primary pacemaker for circadian rhythms in mammals. The 24 h pacemaker is endogenous to the SCN and persists for multiple cycles in the suprachiasmatic brain slice. 2. While serotonin is not endogenous to the SCN, a major midbrain hypothalamic afferent pathway is serotonergic. Within this tract the dorsal raphe nucleus sends direct projections to the ventrolateral portions of the SCN. We investigated a possible regulatory role for serotonin in the mammalian circadian system by examining its effect, when applied at projection sites, on the circadian rhythm of neuronal activity in rat SCN in vitro. 3. Eight-week-old male rats from our inbred colony, housed on a 12 h light: 12 h dark schedule, were used. Hypothalamic brain slices containing the paired SCN were prepared in the day and maintained in glucose and bicarbonate-supplemented balanced salt solution for up to 53 h. 4. A 10(-11) ml drop of 10(-6) M-serotonin (5-hydroxytryptamine (5-HT) creatinine sulphate complex) in medium was applied to the ventrolateral portion of one of the SCN for 5 min on the first day in vitro. The effect of the treatment at each of seven time points across the circadian cycle was examined. The rhythm of spontaneous neuronal activity was recorded extracellularly on the second and third days in vitro. Phase shifts were determined by comparing the time-of-peak of neuronal activity in serotonin- vs. media-treated slices. 5. Application of serotonin during the subjective day induced significant advances in the phase of the electrical activity rhythm (n = 11). The most sensitive time of treatment was CT 7 (circadian time 7 is 7 h after 'lights on' in the animal colony), when a 7.0 +/- 0.1 h phase advance was observed (n = 3). This phase advance was perpetuated on day 3 in vitro without decrement. Serotonin treatment during the subjective night had no effect on the timing of the electrical activity rhythm (n = 9). 6. The

External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.

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Fan, Sabrina Mai-Yi; Chang, Yi-Ting; Chen, Chih-Lung; Wang, Wei-Hung; Pan, Ming-Kai; Chen, Wen-Pin; Huang, Wen-Yen; Xu, Zijian; Huang, Hai-En; Chen, Ting; Plikus, Maksim V; Chen, Shih-Kuo; Lin, Sung-Jan

2018-06-29

Changes in external light patterns can alter cell activities in peripheral tissues through slow entrainment of the central clock in suprachiasmatic nucleus (SCN). It remains unclear whether cells in otherwise photo-insensitive tissues can achieve rapid responses to changes in external light. Here we show that light stimulation of animals' eyes results in rapid activation of hair follicle stem cells with prominent hair regeneration. Mechanistically, light signals are interpreted by M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent sympathetic nerves are immediately activated. Increased norepinephrine release in skin promotes hedgehog signaling to activate hair follicle stem cells. Thus, external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic nervous system circuit. Since activation of sympathetic nerves is not limited to skin, this circuit can also facilitate rapid adaptive responses to external light in other homeostatic tissues.

Circadian integration of glutamatergic signals by little SAAS in novel suprachiasmatic circuits.

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Atkins, Norman; Mitchell, Jennifer W; Romanova, Elena V; Morgan, Daniel J; Cominski, Tara P; Ecker, Jennifer L; Pintar, John E; Sweedler, Jonathan V; Gillette, Martha U

2010-09-07

Neuropeptides are critical integrative elements within the central circadian clock in the suprachiasmatic nucleus (SCN), where they mediate both cell-to-cell synchronization and phase adjustments that cause light entrainment. Forward peptidomics identified little SAAS, derived from the proSAAS prohormone, among novel SCN peptides, but its role in the SCN is poorly understood. Little SAAS localization and co-expression with established SCN neuropeptides were evaluated by immunohistochemistry using highly specific antisera and stereological analysis. Functional context was assessed relative to c-FOS induction in light-stimulated animals and on neuronal circadian rhythms in glutamate-stimulated brain slices. We found that little SAAS-expressing neurons comprise the third most abundant neuropeptidergic class (16.4%) with unusual functional circuit contexts. Little SAAS is localized within the densely retinorecipient central SCN of both rat and mouse, but not the retinohypothalamic tract (RHT). Some little SAAS colocalizes with vasoactive intestinal polypeptide (VIP) or gastrin-releasing peptide (GRP), known mediators of light signals, but not arginine vasopressin (AVP). Nearly 50% of little SAAS neurons express c-FOS in response to light exposure in early night. Blockade of signals that relay light information, via NMDA receptors or VIP- and GRP-cognate receptors, has no effect on phase delays of circadian rhythms induced by little SAAS. Little SAAS relays signals downstream of light/glutamatergic signaling from eye to SCN, and independent of VIP and GRP action. These findings suggest that little SAAS forms a third SCN neuropeptidergic system, processing light information and activating phase-shifts within novel circuits of the central circadian clock.

Development of circadian rhythmicity and photoperiodic response in subdivisions of the rat suprachiasmatic nucleus

Czech Academy of Sciences Publication Activity Database

Bendová, Zdeňka; Sumová, Alena; Illnerová, Helena

2004-01-01

Roč. 148, č. 1 (2004), s. 105-112 ISSN 0165-3806 R&D Projects: GA ČR GA309/02/1241; GA ČR GA309/00/1655 Institutional research plan: CEZ:AV0Z5011922 Keywords : suprachiasmatic nucleus * develop ment * photoperiod Subject RIV: ED - Physiology Impact factor: 1.854, year: 2004

Hormones and the autonomic nervous system are involved in suprachiasmatic nucleus modulation of glucose homeostasis.

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Ruiter, Marieke; Buijs, Ruud M; Kalsbeek, Andries

2006-05-01

Glucose is one of the most important energy sources for the body in general, and the brain in particular. It is essential for survival to keep glucose levels within strict boundaries. Acute disturbances of glucose homeostasis are rapidly corrected by hormonal and neuronal mechanisms. Furthermore, changes in energy expenditure associated with the light-dark cycle induce variations in the plasma glucose concentration that are more gradual. Organisms take advantage of adapting their internal physiology to the predictable daily changes in energy expenditure, because it enables them to anticipate these changes and to prevent unnecessary disturbance of homeostasis. The hypothalamic biological clock, located in the suprachiasmatic nucleus (SCN), receives light information from the eyes and transmits this information to the rest of the body to synchronize physiology to the environment. Here we review several studies providing evidence for biological clock control of the daily variation in several aspects of glucose metabolism. Although both hormones and the autonomic nervous system can stimulate glucose uptake or production by organs in the periphery, we have shown that the biological clock control of glucose metabolism mostly occurs through the autonomic nervous system. The critical involvement of the biological clock is also indicated by several studies, indicating that disturbance of the biological clock is often associated with metabolic diseases, such as obesity, diabetes mellitus and hypertension.

Circadian rhythmicity in AVP secretion and GABAergic synaptic transmission in the rat suprachiasmatic nucleus

Czech Academy of Sciences Publication Activity Database

Kretschmannová, Karla; Svobodová, Irena; Balík, Aleš; Mazna, Petr; Zemková, Hana

2005-01-01

Roč. 1048, - (2005), s. 103-115 ISSN 0077-8923 R&D Projects: GA ČR(CZ) GA309/02/1519; GA AV ČR(CZ) IAA5011103; GA AV ČR(CZ) IAA5011408 Institutional research plan: CEZ:AV0Z5011922 Keywords : circadian rhythms * suprachiasmatic nucleus * melatonin Subject RIV: FH - Neuro logy Impact factor: 1.971, year: 2005

Altered energy intake and the amplitude of the body temperature rhythm are associated with changes in phase, but not amplitude, of clock gene expression in the rat suprachiasmatic nucleus in vivo.

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Goh, Grace H; Mark, Peter J; Maloney, Shane K

2016-01-01

Circadian rhythms in mammals are driven by a central clock in the suprachiasmatic nucleus (SCN). In vitro, temperature cycles within the physiological range can act as potent entraining cues for biological clocks. We altered the body temperature (Tc) rhythm in rats by manipulating energy intake (EI) to determine whether EI-induced changes in Tc oscillations are associated with changes in SCN clock gene rhythms in vivo. Male Wistar rats (n = 16 per diet) were maintained on either an ad libitum diet (CON), a high energy cafeteria diet (CAF), or a calorie restricted diet (CR), and Tc was recorded every 30 min for 6-7 weeks. SCN tissue was harvested from rats at zeitgeber time (ZT) 0, ZT6, ZT12, or ZT18. Expression of the clock genes Bmal1, Per2, Cry1, and Rev-erbα, the heat shock transcription factor Hsf1, and the heat shock protein Hsp90aa1, were determined using qPCR. The circadian profile of gene expression for each gene was characterized using cosinor analysis. Compared to the CON rats, the amplitude of Tc was decreased in CAF rats by 0.1 °C (p  0.25). Compared to CON, phase advances of the Tc, Bmal1, and Per2 rhythms were observed with CR feeding (p < 0.05), but CAF feeding elicited no significant changes in phase. The present results indicate that in vivo, the SCN is largely resistant to entrainment by EI-induced changes in the Tc rhythm, although some phase entrainment may occur.

Effects of a free-choice high-fathigh-sugar diet on brain PER2 and BMAL1 protein expression in mice

NARCIS (Netherlands)

Blancas-Velazquez, Aurea; la Fleur, Susanne E.; Mendoza, Jorge

2017-01-01

The suprachiasmatic nucleus (SCN) times the daily rhythms of behavioral processes including feeding. Beyond the SCN, the hypothalamic arcuate nucleus (ARC), involved in feeding regulation and metabolism, and the epithalamic lateral habenula (LHb), implicated in reward processing, show circadian

Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey

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Reppert, S.M.; Perlow, M.J.; Ungerleider, L.G.; Mishkin, M.; Tamarkin, L.; Orloff, D.G.; Hoffman, H.J.; Klein, D.C.

1981-12-01

The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.

Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey

International Nuclear Information System (INIS)

Reppert, S.M.; Perlow, M.J.; Ungerleider, L.G.; Mishkin, M.; Tamarkin, L.; Orloff, D.G.; Hoffman, H.J.; Klein, D.C.

1981-01-01

The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN

Circadian rhythm and photic induction of the C-terminal splice variant of NMDAR1 subunit in the rat suprachiasmatic nucleus

Czech Academy of Sciences Publication Activity Database

Bendová, Zdeňka; Janoušková, Hana; Svobodová, Irena

2014-01-01

Roč. 68, č. 2 (2014), s. 85-88 ISSN 0887-4476 R&D Projects: GA ČR(CZ) GAP303/10/1227 Institutional support: RVO:67985823 Keywords : circadian clock * NMDA receptor * NR1 subunit * rat * suprachiasmatic nucleus Subject RIV: FH - Neurology Impact factor: 2.127, year: 2014

Adrenal-dependent and -independent stress-induced Per1 mRNA in hypothalamic paraventricular nucleus and prefrontal cortex of male and female rats.

Science.gov (United States)

Chun, Lauren E; Christensen, Jenny; Woodruff, Elizabeth R; Morton, Sarah J; Hinds, Laura R; Spencer, Robert L

2018-01-01

Oscillating clock gene expression gives rise to a molecular clock that is present not only in the body's master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), but also in extra-SCN brain regions. These extra-SCN molecular clocks depend on the SCN for entrainment to a light:dark cycle. The SCN has limited neural efferents, so it may entrain extra-SCN molecular clocks through its well-established circadian control of glucocorticoid hormone secretion. Glucocorticoids can regulate the normal rhythmic expression of clock genes in some extra-SCN tissues. Untimely stress-induced glucocorticoid secretion may compromise extra-SCN molecular clock function. We examined whether acute restraint stress during the rat's inactive phase can rapidly (within 30 min) alter clock gene (Per1, Per2, Bmal1) and cFos mRNA (in situ hybridization) in the SCN, hypothalamic paraventricular nucleus (PVN), and prefrontal cortex (PFC) of male and female rats (6 rats per treatment group). Restraint stress increased Per1 and cFos mRNA in the PVN and PFC of both sexes. Stress also increased cFos mRNA in the SCN of male rats, but not when subsequently tested during their active phase. We also examined in male rats whether endogenous glucocorticoids are necessary for stress-induced Per1 mRNA (6-7 rats per treatment group). Adrenalectomy attenuated stress-induced Per1 mRNA in the PVN and ventral orbital cortex, but not in the medial PFC. These data indicate that increased Per1 mRNA may be a means by which extra-SCN molecular clocks adapt to environmental stimuli (e.g. stress), and in the PFC this effect is largely independent of glucocorticoids.

The circadian rhythm of Per1 gene product in the rat suprachiasmatic nucleus and its modulation by seasonal changes in daylength

Czech Academy of Sciences Publication Activity Database

Sumová, Alena; Sládek, Martin; Jáč, Martin; Illnerová, Helena

2002-01-01

Roč. 947, č. 2 (2002), s. 260-270 ISSN 0006-8993 R&D Projects: GA ČR GA309/00/1655 Institutional research plan: CEZ:AV0Z5011922 Keywords : Suprachiasmatic nucleus * PER1 immunoreactivity * circadian rhythm -photoperiod Subject RIV: FH - Neurology Impact factor: 2.409, year: 2002

The Circadian System : A Regulatory Feedback Network of Periphery and Brain

NARCIS (Netherlands)

Buijs, Frederik N; León-Mercado, Luis; Guzmán-Ruiz, Mara; Guerrero-Vargas, Natali N; Romo-Nava, Francisco; Buijs, Ruud M

Circadian rhythms are generated by the autonomous circadian clock, the suprachiasmatic nucleus (SCN), and clock genes that are present in all tissues. The SCN times these peripheral clocks, as well as behavioral and physiological processes. Recent studies show that frequent violations of conditions

Circadian Modulation of the Cl− Equilibrium Potential in the Rat Suprachiasmatic Nuclei

Directory of Open Access Journals (Sweden)

Javier Alamilla

2014-01-01

Full Text Available The suprachiasmatic nuclei (SCN constitute a circadian clock in mammals, where γ-amino-butyric acid (GABA neurotransmission prevails and participates in different aspects of circadian regulation. Evidence suggests that GABA has an excitatory function in the SCN in addition to its typical inhibitory role. To examine this possibility further, we determined the equilibrium potential of GABAergic postsynaptic currents (EGABA at different times of the day and in different regions of the SCN, using either perforated or whole cell patch clamp. Our results indicate that during the day most neurons in the dorsal SCN have an EGABA close to −30 mV while in the ventral SCN they have an EGABA close to −60 mV; this difference reverses during the night, in the dorsal SCN neurons have an EGABA of −60 mV and in the ventral SCN they have an EGABA of −30 mV. The depolarized equilibrium potential can be attributed to the activity of the Na(+-K(+-2Cl(− (NKCC cotransporter since the equilibrium potential becomes more negative following addition of the NKCC blocker bumetanide. Our results suggest an excitatory role for GABA in the SCN and further indicate both time (day versus night and regional (dorsal versus ventral modulation of EGABA in the SCN.

Glutamatergic clock output stimulates melatonin synthesis at night

NARCIS (Netherlands)

Perreau-Lenz, Stéphanie; Kalsbeek, Andries; Pévet, Paul; Buijs, Ruud M.

2004-01-01

The rhythm of melatonin synthesis in the rat pineal gland is under the control of the biological clock, which is located in the suprachiasmatic nucleus of the hypothalamus (SCN). Previous studies demonstrated a daytime inhibitory influence of the SCN on melatonin synthesis, by using

Ultradian feeding in mice not only affects the peripheral clock in the liver, but also the master clock in the brain

NARCIS (Netherlands)

Sen, Satish; Raingard, Hélène; Dumont, Stéphanie; Kalsbeek, A.; Vuillez, Patrick; Challet, Etienne

2017-01-01

Restricted feeding during the resting period causes pronounced shifts in a number of peripheral clocks, but not the central clock in the suprachiasmatic nucleus (SCN). By contrast, daily caloric restriction impacts also the light-entrained SCN clock, as indicated by shifted oscillations of clock

Impact of behavior on central and peripheral circadian clocks in the common vole Microtus arvalis, a mammal with ultradian rhythms

NARCIS (Netherlands)

van der Veen, DR; Le Minh, N; Gos, P; Arneric, M; Gerkema, MP; Schibler, U; Takahashi, Joseph S.

2006-01-01

In most mammals, daily rhythms in physiology are driven by a circadian timing system composed of a master pacemaker in the suprachiasmatic nucleus (SCN) and peripheral oscillators in most body cells. The SCN clock, which is phase-entrained by light-dark cycles, is thought to synchronize subsidiary

Circadian rhythm in Period1 expression within the rat suprachiasmatic nucleus during early ontogenesis and its modulation by photoperiod

Czech Academy of Sciences Publication Activity Database

Laurinová, Kristýna; Kováčiková, Zuzana; Sládek, Martin; Bendová, Zdena; Illnerová, Helena; Sumová, Alena

2005-01-01

Roč. 272, č. S1 (2005), s. 554-555 ISSN 1474-3833. [FEBS Congress /30./ and IUBMB Conference /9./. 02.07.2005-07.07.2005, Budapest] R&D Projects: GA ČR(CZ) GA309/05/0350; GA ČR(CZ) GP309/02/D093 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian rhythm s * Period1 * suprachiasmatic nucleus * development Subject RIV: FH - Neurology

The human pineal gland and melatonin in aging and Alzheimer's disease.

NARCIS (Netherlands)

Wu, Y.-H.; Swaab, D.F.

2005-01-01

The pineal gland is a central structure in the circadian system which produces melatonin under the control of the central clock, the suprachiasmatic nucleus (SCN). The SCN and the output of the pineal gland, i.e. melatonin, are synchronized to the 24-hr day by environmental light, received by the

The human pineal gland and melatonin in aging and Alzheimer's disease

NARCIS (Netherlands)

Wu, Ying-Hui; Swaab, Dick F.

2005-01-01

The pineal gland is a central structure in the circadian system which produces melatonin under the control of the central clock, the suprachiasmatic nucleus (SCN). The SCN and the output of the pineal gland, i.e. melatonin, are synchronized to the 24-hr day by environmental light, received by the

Morphometric analysis of the suprachiasmatic and paraventricular nuclei in the human brain: sex differences and age-dependent changes

NARCIS (Netherlands)

Hofman, M. A.; Fliers, E.; Goudsmit, E.; Swaab, D. F.

1988-01-01

The size, shape and cellular morphology of the suprachiasmatic (SCN) and paraventricular nuclei (PVN) in the human hypothalamus were examined in relation to sex and age. In both nuclear regions the following parameters were determined: length of the rostrocaudal axis, maximum cross sectional area,

Suprachiasmatic nuclei of the fetal rat: characterization of a functional circadian clock using 14C-labeled deoxyglucose

International Nuclear Information System (INIS)

Reppert, S.M.; Schwartz, W.J.

1984-01-01

The circadian clock located in the suprachiasmatic nuclei (SCN) was characterized in the fetal rat by using 14 C-labeled deoxyglucose to monitor glucose utilization (metabolic activity) of the nuclei. A clear day-night oscillation of metabolic activity was detectable in the fetal SCN from the 19th through the 21st days of gestation; the nuclei were metabolically active during the subjective day and metabolically inactive during the subjective night. During the subjective day on gestational day 21, the fetal SCN were found to manifest high metabolic activity for most of the subjective day. The authors were able to acutely dissociate SCN metabolic activity in the mother rat from that in the fetus by exposing the pregnant animals to light during the normal dark period of diurnal lighting on gestational day 20. The results show the utility of the deoxyglucose method for directly investigating prenatally the function of the biological clock located in the SCN

The role of feeding rhythm, adrenal hormones and neuronal inputs in synchronizing daily clock gene rhythms in the liver

NARCIS (Netherlands)

Su, Yan; Cailotto, Cathy; Foppen, Ewout; Jansen, Remi; Zhang, Zhi; Buijs, Ruud; Fliers, Eric; Kalsbeek, Andries

2016-01-01

The master clock in the hypothalamic suprachiasmatic nucleus (SCN) is assumed to distribute rhythmic information to the periphery via neural, humoral and/or behavioral connections. Until now, feeding, corticosterone and neural inputs are considered important signals for synchronizing daily rhythms

Effects of 6-meals-a-day feeding and 6-meals-a-day feeding combined with adrenalectomy on daily gene expression rhythms in rat epididymal white adipose tissue

NARCIS (Netherlands)

Su, Yan; Foppen, Ewout; Zhang, Zhi; Fliers, Eric; Kalsbeek, A.

The master clock in the hypothalamic suprachiasmatic nucleus (SCN) is assumed to synchronize the tissue-specific rhythms of the peripheral clocks with the environmental day/night changes via neural, humoral and/or behavioral connections. The feeding rhythm is considered an important Zeitgeber for

Effects of 6-meals-a-day feeding and 6-meals-a-day feeding combined with adrenalectomy on daily gene expression rhythms in rat epididymal white adipose tissue

NARCIS (Netherlands)

Su, Yan; Foppen, Ewout; Zhang, Zhi; Fliers, Eric; Kalsbeek, Andries

2016-01-01

The master clock in the hypothalamic suprachiasmatic nucleus (SCN) is assumed to synchronize the tissue-specific rhythms of the peripheral clocks with the environmental day/night changes via neural, humoral and/or behavioral connections. The feeding rhythm is considered an important Zeitgeber for

Bright light in elderly subjects with nonseasonal major depression: a double blind, randomised clinical trial using early morning bright blue light comparing dim red light treatment

NARCIS (Netherlands)

Lieverse, Ritsaert; Nielen, Marjan M. A.; Veltman, Dick J.; Uitdehaag, Bernard; van Someren, Eus J. W.; Smit, Jan H.; Hoogendijk, Witte J. G.

2008-01-01

ABSTRACT: BACKGROUND: Depression frequently occurs in the elderly. Its cause is largely unknown, but several studies point to disturbances of biological rhythmicity. In both normal aging, and depression, the functioning of the suprachiasmatic nucleus (SCN) is impaired, as evidenced by an increased

Influence of photoperiod duration and light–dark transitions on entrainment of Per1 and Per2 gene and protein expression in subdivisions of the mouse suprachiasmatic nucleus

Czech Academy of Sciences Publication Activity Database

Sosniyenko, Serhiy; Hut, R.A.; Daan, S.; Sumová, Alena

2009-01-01

Roč. 30, č. 9 (2009), s. 1802-1814 ISSN 0953-816X R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA309/08/0503 Grant - others:EC(XE) LSH-2004115-4-018741 Institutional research plan: CEZ:AV0Z50110509 Keywords : clock gene * suprachiasmatic nucleus * photoperiod Subject RIV: FH - Neuro logy Impact factor: 3.418, year: 2009

Dynamics of the Adjustment of Clock Gene Expression in the Rat Suprachiasmatic Nucleus to an Asymmetrical Change from a Long to a Short Photoperiod

Czech Academy of Sciences Publication Activity Database

Sumová, Alena; Kováčiková, Zuzana; Illnerová, Helena

2007-01-01

Roč. 22, č. 3 (2007), s. 259-267 ISSN 0748-7304 R&D Projects: GA AV ČR IAA5011304; GA ČR GA309/05/0350; GA MŠk(CZ) LC554 Grant - others:EUCLOCK(XE) LSH-2004-115-4-018741 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK Keywords : circadian rhythm s * photoperiod * suprachiasmatic nucleus Subject RIV: FH - Neurology Impact factor: 3.868, year: 2007

Hypothalamic control of liver and white adipose tissue metabolism

NARCIS (Netherlands)

Su, Yan

2016-01-01

Living organisms have to adjust their physiological processes and behavior to the changes in the environment, and therefore they developed, amongst others, a well conserved circadian timing system. The central clock of the circadian timing system is located in the suprachiasmatic nucleus (SCN) of

Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer's disease

NARCIS (Netherlands)

Wu, Y.-H.; Swaab, D.F.

2007-01-01

Circadian rhythm disturbances, such as sleep disorders, are frequently seen in aging and are even more pronounced in Alzheimer's disease (AD). Alterations in the biological clock, the suprachiasmatic nucleus (SCN), and the pineal gland during aging and AD are considered to be the biological basis

Melatonin reduces neuronal loss and cytoskeletal deterioration: implications for Psychiatry

OpenAIRE

Reiter, Russel J.; Benitez-King, Gloria

2009-01-01

This review article summarizes the potential role of circadian rhythmicity and melatonin in psychiatric disorders. The melatonin rhythm, with high blood levels at night and low values during the day, is a reflection of the biological clock, i.e., the suprachiasmatic nucleus (SCN). The SCN receive information about the prevailing light: dark conditions from specialized ganglion cells (only 1-2% of the total ganglion cells) in the retina. These unique cells contain a newly-discovered photopigme...

Genetic Disruption of the Core Circadian Clock Impairs Hippocampus-Dependent Memory

Science.gov (United States)

Wardlaw, Sarah M.; Phan, Trongha X.; Saraf, Amit; Chen, Xuanmao; Storm, Daniel R.

2014-01-01

Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1[superscript -/-] mice, which are arrhythmic…

Dim light at night disturbs the daily sleep-wake cycle in the rat

NARCIS (Netherlands)

Stenvers, Dirk Jan; van Dorp, Rick; Foppen, Ewout; Mendoza, Jorge; Opperhuizen, Anne-Loes; Fliers, Eric; Bisschop, Peter H; Meijer, Johanna H; Kalsbeek, A.; Deboer, Tom

2016-01-01

Exposure to light at night (LAN) is associated with insomnia in humans. Light provides the main input to the master clock in the hypothalamic suprachiasmatic nucleus (SCN) that coordinates the sleep-wake cycle. We aimed to develop a rodent model for the effects of LAN on sleep. Therefore, we exposed

Circadian ATP Release in Organotypic Cultures of the Rat Suprachiasmatic Nucleus Is Dependent on P2X7 and P2Y Receptors

Czech Academy of Sciences Publication Activity Database

Svobodová, Irena; Bhattacharya, Anirban; Ivetic, Milorad; Bendová, Z.; Zemková, Hana

2018-01-01

Roč. 9, Mar 6 (2018), č. článku 192. ISSN 1663-9812 R&D Projects: GA ČR(CZ) GA16-12695S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : suprachiasmatic nucleus * organotypic cultures * astrocytes * P2X7 receptor * P2Y1 receptor * P2Y2 receptor * pannexin-1 hemichannel * ATP release Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.400, year: 2016

Circadian control of kisspeptin and a gated GnRH response mediate the preovulatory luteinizing hormone surge

DEFF Research Database (Denmark)

Williams, Wilbur P; Jarjisian, Stephan G; Mikkelsen, Jens D

2011-01-01

In spontaneously ovulating rodents, the preovulatory LH surge is initiated on the day of proestrus by a timed, stimulatory signal originating from the circadian clock in the suprachiasmatic nucleus (SCN). The present studies explored whether kisspeptin is part of the essential neural circuit...... linking the SCN to the GnRH system to stimulate ovulation in Syrian hamsters (Mesocricetus auratus). Kisspeptin neurons exhibit an estrogen-dependent, daily pattern of cellular activity consistent with a role in the circadian control of the LH surge. The SCN targets kisspeptin neurons via vasopressinergic...... of ovulatory control with interactions among the circadian system, kisspeptin signaling, and a GnRH gating mechanism of control....

Vitamin A is a necessary factor for sympathetic-independent rhythmic activation of mitogen-activated protein kinase in the rat pineal gland.

Science.gov (United States)

Guillaumond, F; Giraudet, F; Becquet, D; Sage, D; Laforge-Anglade, G; Bosler, O; François-Bellan, A M

2005-02-01

The circadian clock in the suprachiasmatic nucleus (SCN) controls day-to-day physiology and behavior by sending timing messages to multiple peripheral oscillators. In the pineal gland, a major SCN target, circadian events are believed to be driven exclusively by the rhythmic release of norepinephrine from superior cervical ganglia (SCG) neurons relaying clock messages through a polysynaptic pathway. Here we show in rat an SCN-driven daily rhythm of pineal MAPK activation that is not dependent on the SCG and whose maintenance requires vitamin A as a blood-borne factor. This finding challenges the dogma that SCG-released norepinephrine is an exclusive mediator of SCN-pineal communication and allows the assumption that humoral mechanisms are involved in pineal integration of temporal messages.

Effects of Photoperiod Extension on Clock Gene and Neuropeptide RNA Expression in the SCN of the Soay Sheep.

Directory of Open Access Journals (Sweden)

Hugues Dardente

Full Text Available In mammals, changing daylength (photoperiod is the main synchronizer of seasonal functions. The photoperiodic information is transmitted through the retino-hypothalamic tract to the suprachiasmatic nuclei (SCN, site of the master circadian clock. To investigate effects of day length change on the sheep SCN, we used in-situ hybridization to assess the daily temporal organization of expression of circadian clock genes (Per1, Per2, Bmal1 and Fbxl21 and neuropeptides (Vip, Grp and Avp in animals acclimated to a short photoperiod (SP; 8h of light and at 3 or 15 days following transfer to a long photoperiod (LP3, LP15, respectively; 16h of light, achieved by an acute 8-h delay of lights off. We found that waveforms of SCN gene expression conformed to those previously seen in LP acclimated animals within 3 days of transfer to LP. Mean levels of expression for Per1-2 and Fbxl21 were nearly 2-fold higher in the LP15 than in the SP group. The expression of Vip was arrhythmic and unaffected by photoperiod, while, in contrast to rodents, Grp expression was not detectable within the sheep SCN. Expression of the circadian output gene Avp cycled robustly in all photoperiod groups with no detectable change in phasing. Overall these data suggest that synchronizing effects of light on SCN circadian organisation proceed similarly in ungulates and in rodents, despite differences in neuropeptide gene expression.

Circadian oscillations of molecular clock components in the cerebellar cortex of the rat

DEFF Research Database (Denmark)

Rath, Martin Fredensborg; Rohde, Kristian; Møller, Morten

2012-01-01

these genes, Per1, Per2, Per3, Cry1, Arntl, Nr1d1, and Dbp were found to exhibit circadian rhythms in a sequential temporal manner similar to that of the SCN, but with several hours of delay. The results of lesion studies indicate that the molecular oscillatory profiles of Per1, Per2, and Cry1......The central circadian clock of the mammalian brain resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. At the molecular level, the circadian clockwork of the SCN constitutes a self-sustained autoregulatory feedback mechanism reflected by the rhythmic expression of clock genes. However...... in the cerebellum are controlled, though possibly indirectly, by the central clock of the SCN. These data support the presence of a circadian oscillator in the cortex of the rat cerebellum....

Potentiation of Inhibitory Synaptic Transmission by Extracellular ATP in Rat Suprachiasmatic Nuclei

Czech Academy of Sciences Publication Activity Database

Bhattacharya, Anirban; Vávra, Vojtěch; Svobodová, Irena; Bendová, Z.; Vereb, G.; Zemková, Hana

2013-01-01

Roč. 33, č. 18 (2013), s. 8035-8044 ISSN 0270-6474 R&D Projects: GA AV ČR(CZ) IAA500110910; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : suprachiasmatic nucleus * P2X receptors * P2Y receptors * ATP * GABA * spontaneous inhibitory synaptic currents Subject RIV: ED - Physiology Impact factor: 6.747, year: 2013

Effect of photic stimuli disturbing overt circadian rhythms on the dorsomedial and ventrolateral SCN rhythmicity

Czech Academy of Sciences Publication Activity Database

Sumová, Alena; Illnerová, Helena

2005-01-01

Roč. 1048, č. 1-2 (2005), s. 161-169 ISSN 0006-8993 R&D Projects: GA AV ČR(CZ) IAA5011304 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian clock * suprachiasmatic nucleus * photic entrainment Subject RIV: ED - Physiology Impact factor: 2.296, year: 2005

Temporal phasing of locomotor activity, heart rate rhythmicity, and core body temperature is disrupted in VIP receptor 2-deficient mice

DEFF Research Database (Denmark)

Hannibal, Jens; Hsiung, Hansen M; Fahrenkrug, Jan

2011-01-01

Neurons of the brain's biological clock located in the hypothalamic suprachiasmatic nucleus (SCN) generate circadian rhythms of physiology (core body temperature, hormone secretion, locomotor activity, sleep/wake, and heart rate) with distinct temporal phasing when entrained by the light/dark (LD......) cycle. The neuropeptide vasoactive intestinal polypetide (VIP) and its receptor (VPAC2) are highly expressed in the SCN. Recent studies indicate that VIPergic signaling plays an essential role in the maintenance of ongoing circadian rhythmicity by synchronizing SCN cells and by maintaining rhythmicity...... within individual neurons. To further increase the understanding of the role of VPAC2 signaling in circadian regulation, we implanted telemetric devices and simultaneously measured core body temperature, spontaneous activity, and heart rate in a strain of VPAC2-deficient mice and compared...

Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

OpenAIRE

Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

2017-01-01

Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Droso...

NPAS2 Compensates for Loss of CLOCK in Peripheral Circadian Oscillators.

Directory of Open Access Journals (Sweden)

Dominic Landgraf

2016-02-01

Full Text Available Heterodimers of CLOCK and BMAL1 are the major transcriptional activators of the mammalian circadian clock. Because the paralog NPAS2 can substitute for CLOCK in the suprachiasmatic nucleus (SCN, the master circadian pacemaker, CLOCK-deficient mice maintain circadian rhythms in behavior and in tissues in vivo. However, when isolated from the SCN, CLOCK-deficient peripheral tissues are reportedly arrhythmic, suggesting a fundamental difference in circadian clock function between SCN and peripheral tissues. Surprisingly, however, using luminometry and single-cell bioluminescence imaging of PER2 expression, we now find that CLOCK-deficient dispersed SCN neurons and peripheral cells exhibit similarly stable, autonomous circadian rhythms in vitro. In CLOCK-deficient fibroblasts, knockdown of Npas2 leads to arrhythmicity, suggesting that NPAS2 can compensate for loss of CLOCK in peripheral cells as well as in SCN. Our data overturn the notion of an SCN-specific role for NPAS2 in the molecular circadian clock, and instead indicate that, at the cellular level, the core loops of SCN neuron and peripheral cell circadian clocks are fundamentally similar.

Maternal feeding controls fetal biological clock.

Directory of Open Access Journals (Sweden)

Hidenobu Ohta

Full Text Available BACKGROUND: It is widely accepted that circadian physiological rhythms of the fetus are affected by oscillators in the maternal brain that are coupled to the environmental light-dark (LD cycle. METHODOLOGY/PRINCIPAL FINDINGS: To study the link between fetal and maternal biological clocks, we investigated the effects of cycles of maternal food availability on the rhythms of Per1 gene expression in the fetal suprachiasmatic nucleus (SCN and liver using a transgenic rat model whose tissues express luciferase in vitro. Although the maternal SCN remained phase-locked to the LD cycle, maternal restricted feeding phase-advanced the fetal SCN and liver by 5 and 7 hours respectively within the 22-day pregnancy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that maternal feeding entrains the fetal SCN and liver independently of both the maternal SCN and the LD cycle. This indicates that maternal-feeding signals can be more influential for the fetal SCN and particular organ oscillators than hormonal signals controlled by the maternal SCN, suggesting the importance of a regular maternal feeding schedule for appropriate fetal molecular clockwork during pregnancy.

Bilateral lesions of suprachiasmatic nuclei affect circadian rhythms in [3H]-thymidine incorporation into deoxyribonucleic acid in mouse intestinal tract, mitotic index of corneal epithelium, and serum corticosterone

International Nuclear Information System (INIS)

Scheving, L.E.; Tsai, T.H.; Powell, E.W.; Pasley, J.N.; Halberg, F.; Dunn, J.

1983-01-01

Investigations into the role of the suprachiasmatic nuclei (SCN) in the coordination of circadian rhythms have presented differing results. Several reports have shown that ablation of the suprachiasmatic nuclei (SCNA) alters the phase and amplitude of rhythms but does not abolish them. The present study investigates the effect of SCNA on the rhythms in cell proliferation in various regions of the intestinal tract as measured by the incorporation of [ 3 H]-thymidine into deoxyribonucleic acid, in the mitotic activity of the corneal epithelium, and in serum corticosterone levels. The study involved mice with verified lesions of the SCN (six to 13 mice per time point) and control groups of both sham-operated and unoperated mice (seven of each per time point). The mice were killed in groups that represented seven time points over a single 24 hr span (3 hr intervals with the 0800 hr sampled both at start and end of the series). The tissues examined were the tongue, esophagus, gastric stomach, and colon for DNA synthesis, the corneal epithelium for mitotic index, and blood serum for corticosterone level. The most consistent result of SCNA was a phase advance in the rhythms in cell proliferation in the tongue, esophagus, gastric stomach, colon, and corneal epithelium. A reduction in rhythm amplitude occurred in the tongue, esophagus, and corneal epithelium; however, there was an amplitude increase for the stomach, colon, and serum corticosterone. The mesor (rhythm-adjusted mean) was increased by SCNA in all tissues except the corneal epithelium. These findings further support the role of the suprachiasmatic nuclear area in the control of rhythms in cell proliferation and corticosterone production, by acting as a ''phase-resetter'' and as a modulator of rhythm amplitude

Day-night variations in zinc sensitivity of GABA(A) receptor-channels in rat suprachiasmatic nucleus

Czech Academy of Sciences Publication Activity Database

Kretschmannová, Karla; Svobodová, Irena; Zemková, Hana

2003-01-01

Roč. 120, č. 1 (2003), s. 46-51 ISSN 0169-328X R&D Projects: GA ČR GA309/02/1519; GA AV ČR IAA5011103; GA AV ČR IAA5011105 Institutional research plan: CEZ:AV0Z5011922 Keywords : GABA * circadian rhythm * suprachiasmatic nuclei Subject RIV: ED - Physiology Impact factor: 2.107, year: 2003

Genetic disruption of the core circadian clock impairs hippocampus-dependent memory

OpenAIRE

2014-01-01

Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1−/− mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippoca...

The Development of the circadian heart rate rhytm (CDR) in Asian infants

OpenAIRE

Stanislaus Sandarupa, Drs., M.A., Ph.D.

2011-01-01

Although the human fetus can follow the maternal circadian thythm, the enterained expression of the circadian clock, based in the suprachiasmatic nucleus (SCN) of the hypothalamus awaits postnatal maturation of the retinal hypothalamic tract, and melatonin neurotransmission. Objective: To test the hypothesis that term-born Asian Infants, at reduced risk to die of Sudden Infant Death Syndrome (SIDS) exhibit a circadian heat rate thythm (CHR) at a later age than non-Asian term infants.

Emergence of noise-induced oscillations in the central circadian pacemaker.

Directory of Open Access Journals (Sweden)

Caroline H Ko

2010-10-01

Full Text Available Bmal1 is an essential transcriptional activator within the mammalian circadian clock. We report here that the suprachiasmatic nucleus (SCN of Bmal1-null mutant mice, unexpectedly, generates stochastic oscillations with periods that overlap the circadian range. Dissociated SCN neurons expressed fluctuating levels of PER2 detected by bioluminescence imaging but could not generate circadian oscillations intrinsically. Inhibition of intercellular communication or cyclic-AMP signaling in SCN slices, which provide a positive feed-forward signal to drive the intracellular negative feedback loop, abolished the stochastic oscillations. Propagation of this feed-forward signal between SCN neurons then promotes quasi-circadian oscillations that arise as an emergent property of the SCN network. Experimental analysis and mathematical modeling argue that both intercellular coupling and molecular noise are required for the stochastic rhythms, providing a novel biological example of noise-induced oscillations. The emergence of stochastic circadian oscillations from the SCN network in the absence of cell-autonomous circadian oscillatory function highlights a previously unrecognized level of circadian organization.

In Vivo Imaging of the Central and Peripheral Effects of Sleep Deprivation and Suprachiasmatic Nuclei Lesion on PERIOD-2 Protein in Mice.

Science.gov (United States)

Curie, Thomas; Maret, Stephanie; Emmenegger, Yann; Franken, Paul

2015-09-01

That sleep deprivation increases the brain expression of various clock genes has been well documented. Based on these and other findings we hypothesized that clock genes not only underlie circadian rhythm generation but are also implicated in sleep homeostasis. However, long time lags have been reported between the changes in the clock gene messenger RNA levels and their encoded proteins. It is therefore crucial to establish whether also protein levels increase within the time frame known to activate a homeostatic sleep response. We report on the central and peripheral effects of sleep deprivation on PERIOD-2 (PER2) protein both in intact and suprachiasmatic nuclei-lesioned mice. In vivo and in situ PER2 imaging during baseline, sleep deprivation, and recovery. Mouse sleep-recording facility. Per2::Luciferase knock-in mice. N/A. Six-hour sleep deprivation increased PER2 not only in the brain but also in liver and kidney. Remarkably, the effects in the liver outlasted those observed in the brain. Within the brain the increase in PER2 concerned the cerebral cortex mainly, while leaving suprachiasmatic nuclei (SCN) levels unaffected. Against expectation, sleep deprivation did not increase PER2 in the brain of arrhythmic SCN-lesioned mice because of higher PER2 levels in baseline. In contrast, liver PER2 levels did increase in these mice similar to the sham and partially lesioned controls. Our results stress the importance of considering both sleep-wake dependent and circadian processes when quantifying clock-gene levels. Because sleep deprivation alters PERIOD-2 in the brain as well as in the periphery, it is tempting to speculate that clock genes constitute a common pathway mediating the shared and well-known adverse effects of both chronic sleep loss and disrupted circadian rhythmicity on metabolic health. © 2015 Associated Professional Sleep Societies, LLC.

A new sodium channel {alpha}-subunit gene (Scn9a) from Schwann cells maps to the Scn1a, Scn2a, Scn3a cluster of mouse chromosome 2

Energy Technology Data Exchange (ETDEWEB)

Beckers, M.C.; Ernst, E.; Gros, P. [McGill Univ., Montreal (Canada)

1996-08-15

We have used a total of 27 AXB/BXA recombinant inbred mouse strains to determine the chromosomal location of a newly identified gene encoding an {alpha}-subunit isoform of the sodium channel from Schwann cells, Scn9a. Linkage analysis established that Scn9a mapped to the proximal segment of mouse chromosome 2. The segregation of restriction fragment length polymorphisms in 145 progeny from a Mus spretus x C57BL/6J backcross indicates that Scn9a is very tightly linked to Scn1a (gene encoding the type I sodium channel {alpha}-subunit of the brain) and forms part of a cluster of four Scna genes located on mouse chromosome 2. 17 refs., 1 fig., 3 tabs.

Neuroanatomical circuitry between kidney and rostral elements of brain: a virally mediated transsynaptic tracing study in mice.

Science.gov (United States)

Zhou, Ye-Ting; He, Zhi-Gang; Liu, Tao-Tao; Feng, Mao-Hui; Zhang, Ding-Yu; Xiang, Hong-Bing

2017-02-01

The identity of higher-order neurons and circuits playing an associative role to control renal function is not well understood. We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3-6 days after injecting a retrograde tracer pseudorabies virus (PRV)-614 into kidney of 13 adult male C57BL/6J strain mice. PRV-614 infected neurons were detected in a number of mesencephalic (e.g. central amygdala nucleus), telencephalic regions and motor cortex. These divisions included the preoptic area (POA), dorsomedial hypothalamus (DMH), lateral hypothalamus, arcuate nucleus (Arc), suprachiasmatic nucleus (SCN), periventricular hypothalamus (PeH), and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus (PVN). PRV-614/Tyrosine hydroxylase (TH) double-labeled cells were found within DMH, Arc, SCN, PeH, PVN, the anterodorsal and medial POA. A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic. PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin. These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.

Vibrational Analysis of (SCN)2 and the Transient (SCN)2

DEFF Research Database (Denmark)

Jensen, N. H.; Wilbrandt, Robert Walter; Pagsberg, Palle Bjørn

1979-01-01

The vibrational spectra of thiocyanogen and the transient radical anion (SCN)2− are interpreted in detail through molecular orbital and normal coordinate calculations. The results support the assignment of (SCN)2− to the anion of thiocyanogen and indicate a substantial weakening of the S–S and C......≡N bonds in going from the parent molecule to its radical anion....

Melatonin administered during the fetal stage affects circadian clock in the suprachiasmatic nucleus but not in the liver

Czech Academy of Sciences Publication Activity Database

Houdek, Pavel; Polidarová, Lenka; Nováková, Marta; Matějů, Kristýna; Kubík, Štěpán; Sumová, Alena

2015-01-01

Roč. 75, č. 2 (2015), s. 131-144 ISSN 1932-8451 R&D Projects: GA ČR(CZ) GAP303/12/1108 Institutional support: RVO:67985823 Keywords : ontogenesis * circadian system * suprachiasmatic nuclei * clock gene * melatonin Subject RIV: FH - Neurology Impact factor: 2.529, year: 2015

Fos expression in the suprachiasmatic nucleus in response to light stimulation in a solitary and social species of African mole-rat (family Bathyergidae).

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Oosthuizen, M K; Bennett, N C; Cooper, H M

2005-01-01

Mole-rats are strictly subterranean rodents that are rarely exposed to environmental light. They are well adapted to their environment and have reduced eyes and a severely regressed visual system. It has been shown, however, that mole-rats do exhibit endogenous circadian rhythms that can be entrained, suggesting an intact and functional circadian system. To determine whether light is the entraining agent in these animals, Fos expression in response to light pulses at different circadian times was investigated to obtain phase response curves. Light is integrated effectively in the suprachiasmatic nucleus of the Cape mole-rat (Georychus capensis), and Fos expression is gated according to the phase of the circadian clock. The Fos response in the Cape mole-rat was comparable to that of aboveground rodents. In contrast, the highveld mole-rat (Cryptomys hottentotus pretoriae) was less sensitive to light and did not show a selective Fos response according to the phase of the circadian cycle. Social species appear to be less sensitive to light than their solitary counterparts, which compares well with results from locomotor activity studies.

Signals from the brainstem sleep/wake centers regulate behavioral timing via the circadian clock.

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Sabra M Abbott

Full Text Available Sleep-wake cycling is controlled by the complex interplay between two brain systems, one which controls vigilance state, regulating the transition between sleep and wake, and the other circadian, which communicates time-of-day. Together, they align sleep appropriately with energetic need and the day-night cycle. Neural circuits connect brain stem sites that regulate vigilance state with the suprachiasmatic nucleus (SCN, the master circadian clock, but the function of these connections has been unknown. Coupling discrete stimulation of pontine nuclei controlling vigilance state with analytical chemical measurements of intra-SCN microdialysates in mouse, we found significant neurotransmitter release at the SCN and, concomitantly, resetting of behavioral circadian rhythms. Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or glutamate levels were augmented and generated shifts of behavioral rhythms. These results establish modes of neurochemical communication from brain regions controlling vigilance state to the central circadian clock, with behavioral consequences. They suggest a basis for dynamic integration across brain systems that regulate vigilance states, and a potential vulnerability to altered communication in sleep disorders.

Signals from the brainstem sleep/wake centers regulate behavioral timing via the circadian clock.

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Abbott, Sabra M; Arnold, Jennifer M; Chang, Qing; Miao, Hai; Ota, Nobutoshi; Cecala, Christine; Gold, Paul E; Sweedler, Jonathan V; Gillette, Martha U

2013-01-01

Sleep-wake cycling is controlled by the complex interplay between two brain systems, one which controls vigilance state, regulating the transition between sleep and wake, and the other circadian, which communicates time-of-day. Together, they align sleep appropriately with energetic need and the day-night cycle. Neural circuits connect brain stem sites that regulate vigilance state with the suprachiasmatic nucleus (SCN), the master circadian clock, but the function of these connections has been unknown. Coupling discrete stimulation of pontine nuclei controlling vigilance state with analytical chemical measurements of intra-SCN microdialysates in mouse, we found significant neurotransmitter release at the SCN and, concomitantly, resetting of behavioral circadian rhythms. Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or glutamate levels were augmented and generated shifts of behavioral rhythms. These results establish modes of neurochemical communication from brain regions controlling vigilance state to the central circadian clock, with behavioral consequences. They suggest a basis for dynamic integration across brain systems that regulate vigilance states, and a potential vulnerability to altered communication in sleep disorders.

Differential effect of lithium on the circadian oscillator in young and old hamsters

International Nuclear Information System (INIS)

Iwahana, Eiko; Hamada, Toshiyuki; Uchida, Ayumi; Shibata, Shigenobu

2007-01-01

Lithium is one of the most commonly used drugs in the prophylaxis and treatment of bipolar disorder. It is also known to lengthen circadian period in several organisms. Previously, we reported that there was the association between lengthening circadian period by lithium and GSK-3 protein and its enzyme activity in the mouse suprachiasmatic nucleus (SCN). In this study, we show that lithium affects the circadian oscillator in young and old hamster SCN, in an age-dependent manner. We found that basal levels of phosphorylated GSK-3 (pGSK-3) protein expression in old hamsters are much lower than that in young hamsters. Furthermore, in the old hamsters, lithium did not affect the period of the locomotor activity rhythm or pGSK-3 expression, while changing period and pGSK-3 in the younger animals. These results indicate that the content of pGSK-3 in the SCN has an important role in age-dependent effects of lithium on the circadian oscillator

GAPDH-mediated posttranscriptional regulations of sodium channel Scn1a and Scn3a genes under seizure and ketogenic diet conditions.

Science.gov (United States)

Lin, Guo-Wang; Lu, Ping; Zeng, Tao; Tang, Hui-Ling; Chen, Yong-Hong; Liu, Shu-Jing; Gao, Mei-Mei; Zhao, Qi-Hua; Yi, Yong-Hong; Long, Yue-Sheng

2017-02-01

Abnormal expressions of sodium channel SCN1A and SCN3A genes alter neural excitability that are believed to contribute to the pathogenesis of epilepsy, a long-term risk of recurrent seizures. Ketogenic diet (KD), a high-fat and low-carbohydrate treatment for difficult-to-control (refractory) epilepsy in children, has been suggested to reverse gene expression patterns. Here, we reveal a novel role of GAPDH on the posttranscriptional regulation of mouse Scn1a and Scn3a expressions under seizure and KD conditions. We show that GAPDH binds to a conserved region in the 3' UTRs of human and mouse SCN1A and SCN3A genes, which decreases and increases genes' expressions by affecting mRNA stability through SCN1A 3' UTR and SCN3A 3' UTR, respectively. In seizure mice, the upregulation and phosphorylation of GAPDH enhance its binding to the 3' UTR, which lead to downregulation of Scn1a and upregulation of Scn3a. Furthermore, administration of KD generates β-hydroxybutyric acid which rescues the abnormal expressions of Scn1a and Scn3a by weakening the GAPDH's binding to the element. Taken together, these data suggest that GAPDH-mediated expression regulation of sodium channel genes may be associated with epilepsy and the anticonvulsant action of KD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Projections from the raphe nuclei to the suprachiasmatic nucleus of the rat

DEFF Research Database (Denmark)

Hay-Schmidt, Anders; Vrang, N.; Larsen, P.J.

2003-01-01

Hypothalamus, Circadian rhythm, Serotonin, Nucleus, Neuronal connections, Phaseolus vulgaris-leucoagglutinin (PHA-L), Cholera toxin (ChB)......Hypothalamus, Circadian rhythm, Serotonin, Nucleus, Neuronal connections, Phaseolus vulgaris-leucoagglutinin (PHA-L), Cholera toxin (ChB)...

Glutamatergic induction of CREB phosphorylation and Fos expression in primary cultures of the suprachiasmatic hypothalamus in vitro is mediated by co-ordinate activity of NMDA and non-NMDA receptors.

Science.gov (United States)

Schurov, I L; McNulty, S; Best, J D; Sloper, P J; Hastings, M H

1999-01-01

Exposure of Syrian hamsters to light 1 h after lights-off rapidly (10 min) induced nuclear immunoreactivity (-ir) to the phospho-Ser133 form of the Ca2+/cAMP response element (CRE) binding protein (pCREB) in the retinorecipient zone of the suprachiasmatic nuclei (SCN). Light also induced nuclear Fos-ir in the same region of the SCN after 1 h. The glutamatergic N-methyl-D-aspartate (NMDA) receptor blocker MK801 attenuated the photic induction of both factors. To investigate glutamatergic regulation of pCREB and Fos further, tissue blocks and primary cultures of neonatal hamster SCN were examined by Western blotting and immunocytochemistry in vitro. On Western blots of SCN tissue, the pCREB-ir signal at 45 kDa was enhanced by glutamate or a mixture of glutamatergic agonists (NMDA, amino-methyl proprionic acid (AMPA), and Kainate (KA)), whereas total CREB did not change. Glutamate or the mixture of agonists also induced a 56 kDa band identified as Fos protein in SCN tissue. In dissociated cultures of SCN, glutamate caused a rapid (15 min) induction of nuclear pCREB-ir and Fos-ir (after 60 min) exclusively in neurones, both GABA-ir and others. Treatment with NMDA alone had no effect on pCREB-ir. AMPA alone caused a slight increase in pCREB-ir. However, kainate alone or in combination with NMDA and AMPA induced nuclear pCREB-ir equal to that induced by glutamate. The effects of glutamate on pCREB-ir and Fos-ir were blocked by antagonists of both NMDA (MK801) and AMPA/KA (NBQX) receptors. In the absence of extracellular Mg2+, MK801 blocked glutamatergic induction of Fos-ir. However, the AMPA/KA receptor antagonist was no longer effective at blocking glutamatergic induction of either Fos-ir or pCREB-ir, consistent with the model that glutamate regulates gene expression in the SCN by a co-ordinate action through both NMDA and AMPA/KA receptors. Glutamatergic induction of nuclear pCREB-ir in GABA-ir neurones was blocked by KN-62 an inhibitor of Ca2+/Calmodulin (Ca

Compensation of native donor doping in ScN: Carrier concentration control and p-type ScN

Science.gov (United States)

Saha, Bivas; Garbrecht, Magnus; Perez-Taborda, Jaime A.; Fawey, Mohammed H.; Koh, Yee Rui; Shakouri, Ali; Martin-Gonzalez, Marisol; Hultman, Lars; Sands, Timothy D.

2017-06-01

Scandium nitride (ScN) is an emerging indirect bandgap rocksalt semiconductor that has attracted significant attention in recent years for its potential applications in thermoelectric energy conversion devices, as a semiconducting component in epitaxial metal/semiconductor superlattices and as a substrate material for high quality GaN growth. Due to the presence of oxygen impurities and native defects such as nitrogen vacancies, sputter-deposited ScN thin-films are highly degenerate n-type semiconductors with carrier concentrations in the (1-6) × 1020 cm-3 range. In this letter, we show that magnesium nitride (MgxNy) acts as an efficient hole dopant in ScN and reduces the n-type carrier concentration, turning ScN into a p-type semiconductor at high doping levels. Employing a combination of high-resolution X-ray diffraction, transmission electron microscopy, and room temperature optical and temperature dependent electrical measurements, we demonstrate that p-type Sc1-xMgxN thin-film alloys (a) are substitutional solid solutions without MgxNy precipitation, phase segregation, or secondary phase formation within the studied compositional region, (b) exhibit a maximum hole-concentration of 2.2 × 1020 cm-3 and a hole mobility of 21 cm2/Vs, (c) do not show any defect states inside the direct gap of ScN, thus retaining their basic electronic structure, and (d) exhibit alloy scattering dominating hole conduction at high temperatures. These results demonstrate MgxNy doped p-type ScN and compare well with our previous reports on p-type ScN with manganese nitride (MnxNy) doping.

Ab initio study of structural, electronic and optical properties of MnHg(SCN)4 and FeHg(SCN)4

International Nuclear Information System (INIS)

He, K.H.; Zheng, G.; Chen, G.; Lue, T.; Wan, M.; Ji, G.F.

2007-01-01

The structural, electronic and optical properties of MnHg(SCN) 4 and FeHg(SCN) 4 were studied by means of quantum-mechanical calculations based on the density-functional theory and pseudopotential method. The lattice constants can be compared with the experimental values when the effects of temperature are considered. The peaks of partial density of states of S, C, N and Hg of FeHg(SCN) 4 have a tendency of shifting to the higher energy levels relative to those of MnHg(SCN) 4 . The distributions of the 3d electronic states in the transition metal atoms show quite large difference and decide different optical properties. We found that absorptional peaks of FeHg(SCN) 4 lag behind those of MnHg(SCN) 4 and the peak in the infrared range has a higher absorptional intensity, which are in accord with the experimental results. By analyzing the distributions and transitions of the 3d electronic states, we explained the different absorption phenomena

Altered Rhythm of Adrenal Clock Genes, StAR and Serum Corticosterone in VIP Receptor 2-Deficient Mice

DEFF Research Database (Denmark)

Fahrenkrug, Jan; Georg, Birgitte; Hannibal, Jens

2012-01-01

oscillator based on a group of clock genes and their protein products. Mice lacking the VPAC2 receptor display disrupted circadian rhythm of physiology and behaviour, and therefore, we using real-time RT-PCR quantified (1) the mRNAs for the clock genes Per1 and Bmal1 in the adrenal gland and SCN, (2......RNA expression and serum corticosterone concentration. Double immunohistochemistry showed that the PER1 protein and StAR were co-localised in the same steroidogenic cells. Circulating corticosterone plays a role in the circadian timing system and the misaligned corticosterone rhythm in the VPAC2 receptor......The circadian time-keeping system consists of clocks in the suprachiasmatic nucleus (SCN) and in peripheral organs including an adrenal clock linked to the rhythmic corticosteroid production by regulating steroidogenic acute regulatory protein (StAR). Clock cells contain an autonomous molecular...

Interaction between circadian rhythms and stress

Directory of Open Access Journals (Sweden)

C.E. Koch

2017-02-01

Full Text Available Life on earth has adapted to the day-night cycle by evolution of internal, so-called circadian clocks that adjust behavior and physiology to the recurring changes in environmental conditions. In mammals, a master pacemaker located in the suprachiasmatic nucleus (SCN of the hypothalamus receives environmental light information and synchronizes peripheral tissues and central non-SCN clocks to geophysical time. Regulatory systems such as the hypothalamus-pituitary-adrenal (HPA axis and the autonomic nervous system (ANS, both being important for the regulation of stress responses, receive strong circadian input. In this review, we summarize the interaction of circadian and stress systems and the resulting physiological and pathophysiological consequences. Finally, we critically discuss the relevance of rodent stress studies for humans, addressing complications of translational approaches and offering strategies to optimize animal studies from a chronobiological perspective.

The Circadian Timing System: Making Sense of day/night gene expression

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HANS G RICHTER

2004-01-01

Full Text Available The circadian time-keeping system ensures predictive adaptation of individuals to the reproducible 24-h day/night alternations of our planet by generating the 24-h (circadian rhythms found in hormone release and cardiovascular, biophysical and behavioral functions, and others. In mammals, the master clock resides in the suprachiasmatic nucleus (SCN of the hypothalamus. The molecular events determining the functional oscillation of the SCN neurons with a period of 24-h involve recurrent expression of several clock proteins that interact in complex transcription/translation feedback loops. In mammals, a glutamatergic monosynaptic pathway originating from the retina regulates the clock gene expression pattern in the SCN neurons, synchronizing them to the light:dark cycle. The emerging concept is that neural/humoral output signals from the SCN impinge upon peripheral clocks located in other areas of the brain, heart, lung, gastrointestinal tract, liver, kidney, fibroblasts, and most of the cell phenotypes, resulting in overt circadian rhythms in integrated physiological functions. Here we review the impact of day/night alternation on integrated physiology; the molecular mechanisms and input/output signaling pathways involved in SCN circadian function; the current concept of peripheral clocks; and the potential role of melatonin as a circadian neuroendocrine transducer

Stress affects expression of the clock gene Bmal1 in the suprachiasmatic nucleus of neonatal rats via glucocorticoid‐dependent mechanism

Czech Academy of Sciences Publication Activity Database

Olejníková, Lucie; Polidarová, Lenka; Sumová, Alena

2018-01-01

Roč. 223, č. 1 (2018), č. článku e13020. ISSN 1748-1708 R&D Projects: GA ČR(CZ) GA16-03932S Institutional support: RVO:67985823 Keywords : clock genes * development * glucocorticoids * mifepristone * restricted feeding * stress * suprachiasmatic nuclei Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 4.867, year: 2016

Adrenal clocks and the role of adrenal hormones in the regulation of circadian physiology.

Science.gov (United States)

Leliavski, Alexei; Dumbell, Rebecca; Ott, Volker; Oster, Henrik

2015-02-01

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders. © 2014 The Author(s).

SCN8A encephalopathy: Research progress and prospects.

Science.gov (United States)

Meisler, Miriam H; Helman, Guy; Hammer, Michael F; Fureman, Brandy E; Gaillard, William D; Goldin, Alan L; Hirose, Shinichi; Ishii, Atsushi; Kroner, Barbara L; Lossin, Christoph; Mefford, Heather C; Parent, Jack M; Patel, Manoj; Schreiber, John; Stewart, Randall; Whittemore, Vicky; Wilcox, Karen; Wagnon, Jacy L; Pearl, Phillip L; Vanderver, Adeline; Scheffer, Ingrid E

2016-07-01

On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav 1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav 1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

The phenotypic spectrum of SCN8A> encephalopathy

DEFF Research Database (Denmark)

Larsen, Jan; Carvill, Gemma L; Gardella, Elena

2015-01-01

OBJECTIVE: SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate the phenotype associated with SCN8A mutations. METHODS: We used high-throughput sequence analysis of t...

Circadian Rhythm Control: Neurophysiological Investigations

Science.gov (United States)

Glotzbach, S. F.

1985-01-01

The suprachiasmatic nucleus (SCN) was implicated as a primary component in central nervous system mechanisms governing circadian rhythms. Disruption of the normal synchronization of temperature, activity, and other rhythms is detrimental to health. Sleep wake disorders, decreases in vigilance and performance, and certain affective disorders may result from or be exacerbated by such desynchronization. To study the basic neurophysiological mechanisms involved in entrainment of circadian systems by the environment, Parylene-coated, etched microwire electrode bundles were used to record extracellular action potentials from the small somata of the SCN and neighboring hypothalamic nuclei in unanesthetized, behaving animals. Male Wistar rats were anesthetized and chronically prepared with EEG ane EMG electrodes in addition to a moveable microdrive assembly. The majority of cells had firing rates 10 Hz and distinct populations of cells which had either the highest firing rate or lowest firing rate during sleep were seen.

Hericium erinaceus extracts alter behavioral rhythm in mice.

Science.gov (United States)

Furuta, Shoko; Kuwahara, Rika; Hiraki, Eri; Ohnuki, Koichiro; Yasuo, Shinobu; Shimizu, Kuniyoshi

2016-01-01

Hericium erinaceus (HE), an edible mushroom, has been used as a herbal medicine in several Asian countries since ancient times. HE has potential as a medicine for the treatment and prevention of dementia, a disorder closely linked with circadian rhythm. This study investigated the effects of the intake of HE extracts on behavioral rhythm, photosensitivity of the circadian clock, and clock gene mRNA expression in the suprachiasmatic nucleus (SCN), a central clock, in mice. Although the HE ethanol extract only affected the offset time of activity, the HE water extract advanced the sleep-wake cycle without affecting the free-running period, photosensitivity, or the clock gene mRNA expression in SCN. In addition, both extracts decreased wakefulness around end of active phase. The findings of the present study suggest that HE may serve as a functional food in the prevention and treatment of Alzheimer's disease and delayed sleep phase syndrome.

Ab initio study of structural, electronic and optical properties of MnHg(SCN){sub 4} and FeHg(SCN){sub 4}

Energy Technology Data Exchange (ETDEWEB)

He, K.H. [College of Maths and Physics, China University of Geosciences, Wuhan 430074 (China)]. E-mail: he23981006@126.com; Zheng, G. [College of Maths and Physics, China University of Geosciences, Wuhan 430074 (China)]. E-mail: gzheng25@yahoo.com; Chen, G. [College of Maths and Physics, China University of Geosciences, Wuhan 430074 (China); Lue, T. [College of Maths and Physics, China University of Geosciences, Wuhan 430074 (China); Wan, M. [College of Maths and Physics, China University of Geosciences, Wuhan 430074 (China); Ji, G.F. [Laboratory for Shock Wave and Detonation Physics, China Academy of Engineering Physics, Mianyang 621900 (China)

2007-03-01

The structural, electronic and optical properties of MnHg(SCN){sub 4} and FeHg(SCN){sub 4} were studied by means of quantum-mechanical calculations based on the density-functional theory and pseudopotential method. The lattice constants can be compared with the experimental values when the effects of temperature are considered. The peaks of partial density of states of S, C, N and Hg of FeHg(SCN){sub 4} have a tendency of shifting to the higher energy levels relative to those of MnHg(SCN){sub 4}. The distributions of the 3d electronic states in the transition metal atoms show quite large difference and decide different optical properties. We found that absorptional peaks of FeHg(SCN){sub 4} lag behind those of MnHg(SCN){sub 4} and the peak in the infrared range has a higher absorptional intensity, which are in accord with the experimental results. By analyzing the distributions and transitions of the 3d electronic states, we explained the different absorption phenomena.

Single-cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes and Interaction Networks involved In the Central Circadian Clock

Directory of Open Access Journals (Sweden)

James Park

2016-10-01

Full Text Available Single-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN. Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular phenotypes, we characterized the transcriptional, spatial, and functional organization of 352 SCN neurons from mice experiencing phase-shifts in their circadian cycle. Using the community structure detection method and multivariate analytical techniques, we identified previously undescribed neuronal phenotypes that are likely to participate in regulatory networks with known SCN cell types. Based on the newly discovered neuronal phenotypes, we developed a data-driven neuronal network structure in which multiple cell types interact through known synaptic and paracrine signaling mechanisms. These results provide a basis from which to interpret the functional variability of SCN neurons and describe methodologies towards understanding how a population of heterogeneous single cells organizes into cellular networks that underlie tissue-level function.

Impact of dispersed coupling strength on the free running periods of circadian rhythms

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Gu, Changgui; Rohling, Jos H. T.; Liang, Xiaoming; Yang, Huijie

2016-03-01

The dominant endogenous clock, named the suprachiasmatic nucleus (SCN), regulates circadian rhythms of behavioral and physiological activity in mammals. One of the main characteristics of the SCN is that the animal maintains a circadian rhythm with a period close to 24 h in the absence of a daily light-dark cycle (called the free running period). The free running period varies among species due to heterogeneity of the SCN network. Previous studies have shown that the heterogeneity in cellular coupling as well as in intrinsic neuronal periods shortens the free running period. Furthermore, as derived from experiments, one neuron's coupling strength is negatively associated with its period. It is unknown what the effects of this association between coupling strength and period are on the free running period and how the heterogeneity in coupling strength influences this free running period. In the present study we found that in the presence of a negative relationship between one neuron's coupling strength and its period, surprisingly, the dispersion of coupling strengths increases the free running period. Our present finding may shed new light on the understanding of the heterogeneous SCN network and provides an alternative explanation for the diversity of free running periods between species.

Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.

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Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

2016-09-26

As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of feeding rhythm, adrenal hormones and neuronal inputs in synchronizing daily clock gene rhythms in the liver.

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Su, Yan; Cailotto, Cathy; Foppen, Ewout; Jansen, Remi; Zhang, Zhi; Buijs, Ruud; Fliers, Eric; Kalsbeek, Andries

2016-02-15

The master clock in the hypothalamic suprachiasmatic nucleus (SCN) is assumed to distribute rhythmic information to the periphery via neural, humoral and/or behavioral connections. Until now, feeding, corticosterone and neural inputs are considered important signals for synchronizing daily rhythms in the liver. In this study, we investigated the necessity of neural inputs as well as of the feeding and adrenal hormone rhythms for maintaining daily hepatic clock gene rhythms. Clock genes kept their daily rhythm when only one of these three signals was disrupted, or when we disrupted hepatic neuronal inputs together with the adrenal hormone rhythm or with the daily feeding rhythm. However, all clock genes studied lost their daily expression rhythm after simultaneous disruption of the feeding and adrenal hormone rhythm. These data indicate that either a daily rhythm of feeding or adrenal hormones should be present to synchronize clock gene rhythms in the liver with the SCN. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Exposure of Pregnant Rats to Restricted Feeding Schedule Synchronizes the SCN Clocks of Their Fetuses under Constant Light but Not under a Light-Dark Regime

Czech Academy of Sciences Publication Activity Database

Nováková, Marta; Sládek, Martin; Sumová, Alena

2010-01-01

Roč. 25, č. 5 (2010), s. 350-360 ISSN 0748-7304 R&D Projects: GA ČR(CZ) GA309/08/0503; GA MŠk(CZ) LC554 Grant - others:GA ČR(CZ) GD309/08/H079; EC(XE) LSH-2004-115-4-018741 Institutional research plan: CEZ:AV0Z50110509 Keywords : suprachiasmatic nucleus * restricted food * ontogenesis Subject RIV: FH - Neurology Impact factor: 3.309, year: 2010

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

In mammals, the mechanism for the generation of circadian rhythms and entrainment by light–dark (LD) cycles resides in the hypothalamic suprachiasmatic nuclei (SCN), and the principal signal that adjusts this biological clock with environmental timing is the light:dark cycle. Within the SCN, rhythms are generated by a ...

Improvement of a patient's circadian rhythm sleep disorders by aripiprazole was associated with stabilization of his bipolar illness.

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Tashiro, Tetsuo

2017-04-01

Splitting of the behavioural activity phase has been found in nocturnal rodents with suprachiasmatic nucleus (SCN) coupling disorder. A similar phenomenon was observed in the sleep phase in the diurnal human discussed here, suggesting that there are so-called evening and morning oscillators in the SCN of humans. The present case suffered from bipolar disorder refractory to various treatments, and various circadian rhythm sleep disorders, such as delayed sleep phase, polyphasic sleep, separation of the sleep bout resembling splitting and circabidian rhythm (48 h), were found during prolonged depressive episodes with hypersomnia. Separation of sleep into evening and morning components and delayed sleep-offset (24.69-h cycle) developed when lowering and stopping the dose of aripiprazole (APZ). However, resumption of APZ improved these symptoms in 2 weeks, accompanied by improvement in the patient's depressive state. Administration of APZ may improve various circadian rhythm sleep disorders, as well as improve and prevent manic-depressive episodes, via augmentation of coupling in the SCN network. © 2017 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

Causes and consequences of hyperexcitation in central clock neurons.

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Casey O Diekman

Full Text Available Hyperexcited states, including depolarization block and depolarized low amplitude membrane oscillations (DLAMOs, have been observed in neurons of the suprachiasmatic nuclei (SCN, the site of the central mammalian circadian (~24-hour clock. The causes and consequences of this hyperexcitation have not yet been determined. Here, we explore how individual ionic currents contribute to these hyperexcited states, and how hyperexcitation can then influence molecular circadian timekeeping within SCN neurons. We developed a mathematical model of the electrical activity of SCN neurons, and experimentally verified its prediction that DLAMOs depend on post-synaptic L-type calcium current. The model predicts that hyperexcited states cause high intracellular calcium concentrations, which could trigger transcription of clock genes. The model also predicts that circadian control of certain ionic currents can induce hyperexcited states. Putting it all together into an integrative model, we show how membrane potential and calcium concentration provide a fast feedback that can enhance rhythmicity of the intracellular circadian clock. This work puts forward a novel role for electrical activity in circadian timekeeping, and suggests that hyperexcited states provide a general mechanism for linking membrane electrical dynamics to transcription activation in the nucleus.

Multidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: correlation among phenotype, genotype, and mRNA expression.

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Kwan, Patrick; Poon, Wai Sang; Ng, Ho-Keung; Kang, David E; Wong, Virginia; Ng, Ping Wing; Lui, Colin H T; Sin, Ngai Chuen; Wong, Ka S; Baum, Larry

2008-11-01

Many antiepileptic drugs (AEDs) prevent seizures by blocking voltage-gated brain sodium channels. However, treatment is ineffective in 30% of epilepsy patients, which might, at least in part, result from polymorphisms of the sodium channel genes. We investigated the association of AED responsiveness with genetic polymorphisms and correlated any association with mRNA expression of the neuronal sodium channels. We performed genotyping of tagging and candidate single nucleotide polymorphisms (SNPs) of SCN1A, 2A, and 3A in 471 Chinese epilepsy patients (272 drug responsive and 199 drug resistant). A total of 27 SNPs were selected based on the HapMap database. Genotype distributions in drug-responsive and drug-resistant patients were compared. SCN2A mRNA was quantified by real-time PCR in 24 brain and 57 blood samples. Its level was compared between patients with different genotypes of an SCN2A SNP found to be associated with drug responsiveness. SCN2A IVS7-32A>G (rs2304016) A alleles were associated with drug resistance (odds ratio = 2.1, 95% confidence interval: 1.2-3.7, P=0.007). Haplotypes containing the IVS7-32A>G allele A were also associated with drug resistance. IVS7-32A>G is located within the putative splicing branch site for splicing exons 7 and 9. PCR of reverse-transcribed RNA from blood or brain of patients with different IVS7-32A>G genotypes using primers in exons 7 and 9 showed no skipping of exon 8, and real-time PCR showed no difference in SCN2A mRNA levels among genotypes. Results of this study suggest an association between SCN2A IVS7-32A>G and AED responsiveness, without evidence of an effect on splicing or mRNA expression.

The circadian system and the balance of the autonomic nervous system.

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Buijs, Ruud M; Escobar, Carolina; Swaab, Dick F

2013-01-01

Our biological clock, the suprachiasmatic nucleus (SCN), sets the pace of our life: it provides a rhythmic function to our sleep-wake cycle. In order to do so properly the SCN synchronizes our physiology to behavioral patterns by directing the autonomic and hormonal output of the hypothalamus to the different organs of the body that require a different setting - activity or inactivity - during particular phases of the day or night. In this chapter we show that this delicate balance requires that the SCN should not only provide an output to these organs but also be informed about the physiological state of the organs in order to adapt its output. This occurs via a hypothalamic neuronal network that provides the necessary input to the SCN. We argue that the feedback that the SCN receives from its hypothalamic target structures is essential to maintain a balance in our physiological functions, which fluctuate during the sleep-wake cycle. We propose that this crucial role of the hypothalamus in the homeostatic response is the reason why, e.g., in aging or depression, changes in the functioning of the biological clock, the SCN, lead to the development of pathology. In addition, if this balance is not adequately organized, for example, if the signals of the biological clock are violated by being active and eating during the night, as in shift work, one will be more susceptible to diseases such as hypertension, obesity, diabetes, and metabolic syndrome. © 2013, Elsevier B.V. All rights reserved.

Simulated shift work in rats perturbs multiscale regulation of locomotor activity

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Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana; Lo, Men-Tzung; Pittman-Polletta, Benjamin; Salgado-Delgado, Roberto; Scheer, Frank A. J. L.; Shea, Steven A.; Buijs, Ruud M.; Hu, Kun

2014-01-01

Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation. PMID:24829282

Collective behaviors of suprachiasm nucleus neurons under different light—dark cycles

International Nuclear Information System (INIS)

Gu Chang-Gui; Liu Zong-Hua; Zhang Xin-Hua

2014-01-01

The principal circadian clock in the suprachiasm nucleus (SCN) regulates the circadian rhythm of physiological and behavioral activities of mammals. Except for the normal function of the circadian rhythm, the ensemble of SCN neurons may show two collective behaviors, i.e., a free running period in the absence of a light—dark cycle and an entrainment ability to an external T cycle. Experiments show that both the free running periods and the entrainment ranges may vary from one species to another and can be seriously influenced by the coupling among the SCN neurons. We here review the recent progress on how the heterogeneous couplings influence these two collective behaviors. We will show that in the case of homogeneous coupling, the free running period increases monotonically while the entrainment range decreases monotonically with the increase of the coupling strength. While in the case of heterogenous coupling, the dispersion of the coupling strength plays a crucial role. It has been found that the free running period decreases with the increase of the dispersion while the entrainment ability is enhanced by the dispersion. These findings provide new insights into the mechanism of the circadian clock in the SCN. (topical review - statistical physics and complex systems)

Cholecystokinin (CCK)-expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK-deficient mice

DEFF Research Database (Denmark)

Hannibal, Jens; Hundahl, Christian; Fahrenkrug, Jan

2010-01-01

FOS, and did not express the core clock protein PER1. Accordingly, CCK-deficient mice showed normal entrainment and had similar t, light-induced phase shift and negative masking behaviour as wild-type animals. In conclusion, CCK signalling seems not to be involved directly in light-induced resetting......, CCK-containing processes make synaptic contacts with both groups of neurons and some CCK cell bodies were innervated by VIPergic neurons. The CCK neurons received no direct input from the three major pathways to the SCN, and the CCK neurons were not light-responsive as evaluated by induction of c...

Cholecystokinin (CCK)-expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK-deficient mice

DEFF Research Database (Denmark)

Hannibal, Jens; Hundahl, Christian; Fahrenkrug, Jan

2010-01-01

FOS, and did not express the core clock protein PER1. Accordingly, CCK-deficient mice showed normal entrainment and had similar τ, light-induced phase shift and negative masking behaviour as wild-type animals. In conclusion, CCK signalling seems not to be involved directly in light-induced resetting......, CCK-containing processes make synaptic contacts with both groups of neurons and some CCK cell bodies were innervated by VIPergic neurons. The CCK neurons received no direct input from the three major pathways to the SCN, and the CCK neurons were not light-responsive as evaluated by induction of c...

Afferent projections to the hamster intergeniculate leaflet demonstrated by retrograde and anterograde tracing

DEFF Research Database (Denmark)

Vrang, Niels; Mrosovsky, N.; Mikkelsen, Jens D.

2003-01-01

Circadian rhythms, Suprachiasmatic nucleus, Cholera toxin B, Phaseolus vulgaris-leucoagglutinin, Nonphotic......Circadian rhythms, Suprachiasmatic nucleus, Cholera toxin B, Phaseolus vulgaris-leucoagglutinin, Nonphotic...

Effects of a free-choice high-fat high-sugar diet on brain PER2 and BMAL1 protein expression in mice.

Science.gov (United States)

Blancas-Velazquez, Aurea; la Fleur, Susanne E; Mendoza, Jorge

2017-10-01

The suprachiasmatic nucleus (SCN) times the daily rhythms of behavioral processes including feeding. Beyond the SCN, the hypothalamic arcuate nucleus (ARC), involved in feeding regulation and metabolism, and the epithalamic lateral habenula (LHb), implicated in reward processing, show circadian rhythmic activity. These brain oscillators are functionally coupled to coordinate the daily rhythm of food intake. In rats, a free choice high-fat high-sugar (fcHFHS) diet leads to a rapid increase of calorie intake and body weight gain. Interestingly, under a fcHFHS condition, rats ingest a similar amount of sugar during day time (rest phase) as during night time (active phase), but keep the rhythmic intake of regular chow-food. The out of phase between feeding patterns of regular (chow) and highly rewarding food (sugar) may involve alterations of brain circadian oscillators regulating feeding. Here, we report that the fcHFHS diet is a successful model to induce calorie intake, body weight gain and fat tissue accumulation in mice, extending its effectiveness as previously reported in rats. Moreover, we observed that whereas in the SCN the day-night difference in the PER2 clock protein expression was similar between chow-fed and fcHFHS-fed animals, in the LHb, this day-night difference was altered in fcHFHS-exposed animals compared to control chow mice. These findings confirm previous observations in rats showing disrupted daily patterns of feeding behavior under a fcHFHS diet exposure, and extend our insights on the effects of the diet on circadian gene expression in brain clocks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

International Nuclear Information System (INIS)

Weiland, N.G.; Wise, P.M.

1987-01-01

Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with [ 3 H]prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland

Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

Energy Technology Data Exchange (ETDEWEB)

Weiland, N.G.; Wise, P.M.

1987-11-01

Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with (/sup 3/H)prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland.

PPARα is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders

International Nuclear Information System (INIS)

Shirai, Hidenori; Oishi, Katsutaka; Kudo, Takashi; Shibata, Shigenobu; Ishida, Norio

2007-01-01

Recent progress at the molecular level has revealed that nuclear receptors play an important role in the generation of mammalian circadian rhythms. To examine whether peroxisome proliferator-activated receptor alpha (PPARα) is involved in the regulation of circadian behavioral rhythms in mammals, we evaluated the locomotor activity of mice administered with the hypolipidemic PPARα ligand, bezafibrate. Circadian locomotor activity was phase-advanced about 3 h in mice given bezafibrate under light-dark (LD) conditions. Transfer from LD to constant darkness did not change the onset of activity in these mice, suggesting that bezafibrate advanced the phase of the endogenous clock. Surprisingly, bezafibrate also advanced the phase in mice with lesions of the suprachiasmatic nucleus (SCN; the central clock in mammals). The circadian expression of clock genes such as period2, BMAL1, and Rev-erbα was also phase-advanced in various tissues (cortex, liver, and fat) without affecting the SCN. Bezafibrate also phase-advanced the activity phase that is delayed in model mice with delayed sleep phase syndrome (DSPS) due to a Clock gene mutation. Our results indicated that PPARα is involved in circadian clock control independently of the SCN and that PPARα could be a potent target of drugs to treat circadian rhythm sleep disorders including DSPS

The effect of lens aging and cataract surgery on circadian rhythm.

Science.gov (United States)

Yan, Shen-Shen; Wang, Wei

2016-01-01

Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment. Suprachiasmatic nucleus (SCN) is the central pacemaker of circadian rhythm, and its activity is entrained to the external light-dark cycle. The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway. Light, especially short-wavelength blue light, is the most potent environmental time cue in circadian photoentrainment. Recently, the discovery of a novel type of retinal photoreceptors, intrinsically photosensitive retinal ganglion cells, sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system. With age, light transmittance is significantly decreased due to the aging of crystalline lens, thus possibly resulting in progressive loss of circadian photoreception. In the current review, we summarize the circadian physiology, highlight the important role of light in circadian rhythm regulation, discuss about the correlation between age-related cataract and sleep disorders, and compare the effect of blue light- filtering intraocular lenses (IOLs) and ultraviolet only filtering IOLs on circadian rhythm.

Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention.

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David E Blask

Full Text Available The central circadian clock within the suprachiasmatic nucleus (SCN plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.

Central control of circadian phase in arousal-promoting neurons.

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Carrie E Mahoney

Full Text Available Cells of the dorsomedial/lateral hypothalamus (DMH/LH that produce hypocretin (HCRT promote arousal in part by activation of cells of the locus coeruleus (LC which express tyrosine hydroxylase (TH. The suprachiasmatic nucleus (SCN drives endogenous daily rhythms, including those of sleep and wakefulness. These circadian oscillations are generated by a transcriptional-translational feedback loop in which the Period (Per genes constitute critical components. This cell-autonomous molecular clock operates not only within the SCN but also in neurons of other brain regions. However, the phenotype of such neurons and the nature of the phase controlling signal from the pacemaker are largely unknown. We used dual fluorescent in situ hybridization to assess clock function in vasopressin, HCRT and TH cells of the SCN, DMH/LH and LC, respectively, of male Syrian hamsters. In the first experiment, we found that Per1 expression in HCRT and TH oscillated in animals held in constant darkness with a peak phase that lagged that in AVP cells of the SCN by several hours. In the second experiment, hamsters induced to split their locomotor rhythms by exposure to constant light had asymmetric Per1 expression within cells of the middle SCN at 6 h before activity onset (AO and in HCRT cells 9 h before and at AO. We did not observe evidence of lateralization of Per1 expression in the LC. We conclude that the SCN communicates circadian phase to HCRT cells via lateralized neural projections, and suggests that Per1 expression in the LC may be regulated by signals of a global or bilateral nature.

Photoperiod Modulates Fast Delayed Rectifier Potassium Currents in the Mammalian Circadian Clock.

Science.gov (United States)

Farajnia, Sahar; Meijer, Johanna H; Michel, Stephan

2016-10-01

One feature of the mammalian circadian clock, situated in the suprachiasmatic nucleus (SCN), is its ability to measure day length and thereby contribute to the seasonal adaptation of physiology and behavior. The timing signal from the SCN, namely the 24 hr pattern of electrical activity, is adjusted according to the photoperiod being broader in long days and narrower in short days. Vasoactive intestinal peptide and gamma-aminobutyric acid play a crucial role in intercellular communication within the SCN and contribute to the seasonal changes in phase distribution. However, little is known about the underlying ionic mechanisms of synchronization. The present study was aimed to identify cellular mechanisms involved in seasonal encoding by the SCN. Mice were adapted to long-day (light-dark 16:8) and short-day (light-dark 8:16) photoperiods and membrane properties as well as K + currents activity of SCN neurons were measured using patch-clamp recordings in acute slices. Remarkably, we found evidence for a photoperiodic effect on the fast delayed rectifier K + current, that is, the circadian modulation of this ion channel's activation reversed in long days resulting in 50% higher peak values during the night compared with the unaltered day values. Consistent with fast delayed rectifier enhancement, duration of action potentials during the night was shortened and afterhyperpolarization potentials increased in amplitude and duration. The slow delayed rectifier, transient K + currents, and membrane excitability were not affected by photoperiod. We conclude that photoperiod can change intrinsic ion channel properties of the SCN neurons, which may influence cellular communication and contribute to photoperiodic phase adjustment. © The Author(s) 2016.

Photoperiod Modulates Fast Delayed Rectifier Potassium Currents in the Mammalian Circadian Clock

Directory of Open Access Journals (Sweden)

Sahar Farajnia

2016-09-01

Full Text Available One feature of the mammalian circadian clock, situated in the suprachiasmatic nucleus (SCN, is its ability to measure day length and thereby contribute to the seasonal adaptation of physiology and behavior. The timing signal from the SCN, namely the 24 hr pattern of electrical activity, is adjusted according to the photoperiod being broader in long days and narrower in short days. Vasoactive intestinal peptide and gamma-aminobutyric acid play a crucial role in intercellular communication within the SCN and contribute to the seasonal changes in phase distribution. However, little is known about the underlying ionic mechanisms of synchronization. The present study was aimed to identify cellular mechanisms involved in seasonal encoding by the SCN. Mice were adapted to long-day (light–dark 16:8 and short-day (light–dark 8:16 photoperiods and membrane properties as well as K+ currents activity of SCN neurons were measured using patch-clamp recordings in acute slices. Remarkably, we found evidence for a photoperiodic effect on the fast delayed rectifier K+ current, that is, the circadian modulation of this ion channel’s activation reversed in long days resulting in 50% higher peak values during the night compared with the unaltered day values. Consistent with fast delayed rectifier enhancement, duration of action potentials during the night was shortened and afterhyperpolarization potentials increased in amplitude and duration. The slow delayed rectifier, transient K+ currents, and membrane excitability were not affected by photoperiod. We conclude that photoperiod can change intrinsic ion channel properties of the SCN neurons, which may influence cellular communication and contribute to photoperiodic phase adjustment.

Synthesis and characterizations of AgSCN nanospheres using AgCl as the precursor

International Nuclear Information System (INIS)

Yang Ming; Ma Jing

2009-01-01

Nanospheres of AgSCN with an average radius of 30-80 nm have been prepared by a simple reaction between AgCl suspension and KSCN in the presence of gelatin. Gelatin played a decisive role as an inhibitor of the direct attack of SCN - ions to AgCl surfaces and coagulation of the growing AgSCN in producing the spherical AgSCN nanoparticles. The products were characterized by X-ray powder diffraction, transmission electron microscopy and X-ray photoelectron spectra techniques. The electrical conductivity of thin films of as-prepared AgSCN nanoparticles and polyethylene oxide (PEO) at room temperature was measured. The maximum value of electrical conductivity of as-prepared AgSCN-PEO was 1.53 x 10 -5 S cm -1 .

Progress in Understanding and Treating SCN2A-Mediated Disorders

DEFF Research Database (Denmark)

Sanders, Stephan J.; Campbell, Arthur J.; Cottrell, Jeffrey R.

2018-01-01

Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel NaV1.2. Functional assays demonstrate strong correlation between...... of neurodevelopmental disorders more generally. Here, we discuss the progress made, through the concerted efforts of a diverse group of academic and industry scientists as well as policy advocates, in understanding and treating SCN2A-related disorders....

Pseudohalide (SCN(-))-Doped MAPbI3 Perovskites: A Few Surprises.

Science.gov (United States)

Halder, Ansuman; Chulliyil, Ramya; Subbiah, Anand S; Khan, Tuhin; Chattoraj, Shyamtanu; Chowdhury, Arindam; Sarkar, Shaibal K

2015-09-03

Pseudohalide thiocyanate anion (SCN(-)) has been used as a dopant in a methylammonium lead tri-iodide (MAPbI3) framework, aiming for its use as an absorber layer for photovoltaic applications. The substitution of SCN(-) pseudohalide anion, as verified using Fourier transform infrared (FT-IR) spectroscopy, results in a comprehensive effect on the optical properties of the original material. Photoluminescence measurements at room temperature reveal a significant enhancement in the emission quantum yield of MAPbI3-x(SCN)x as compared to MAPbI3, suggestive of suppression of nonradiative channels. This increased intensity is attributed to a highly edge specific emission from MAPbI3-x(SCN)x microcrystals as revealed by photoluminescence microscopy. Fluoresence lifetime imaging measurements further established contrasting carrier recombination dynamics for grain boundaries and the bulk of the doped material. Spatially resolved emission spectroscopy on individual microcrystals of MAPbI3-x(SCN)x reveals that the optical bandgap and density of states at various (local) nanodomains are also nonuniform. Surprisingly, several (local) emissive regions within MAPbI3-x(SCN)x microcrystals are found to be optically unstable under photoirradiation, and display unambiguous temporal intermittency in emission (blinking), which is extremely unusual and intriguing. We find diverse blinking behaviors for the undoped MAPbI3 crystals as well, which leads us to speculate that blinking may be a common phenomenon for most hybrid perovskite materials.

Food-Anticipatory Behavior in Neonatal Rabbits and Rodents: An Update on the Role of Clock Genes

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Mario Caba

2018-05-01

Full Text Available In mammals, the suprachiasmatic nucleus (SCN, the master circadian clock, is mainly synchronized to the environmental light/dark cycle. SCN oscillations are maintained by a molecular clockwork in which certain genes, Period 1–2, Cry1–2, Bmal1, and Clock, are rhythmically expressed. Disruption of these genes leads to a malfunctioning clockwork and behavioral and physiological rhythms are altered. In addition to synchronization of circadian rhythms by light, when subjects are exposed to food for a few hours daily, behavioral and physiological rhythms are entrained to anticipate mealtime, even in the absence of the SCN. The presence of anticipatory rhythms synchronized by food suggests the existence of an SCN-independent circadian pacemaker that might be dependent on clock genes. Interestingly, rabbit pups, unable to perceive light, suckle milk once a day, which entrains behavioral rhythms to anticipate nursing time. Mutations of clock genes, singly or in combination, affect diverse rhythms in brain activity and physiological processes, but anticipatory behavior and physiology to feeding time remains attenuated or unaffected. It had been suggested that compensatory upregulation of paralogs or subtypes genes, or even non-transcriptional mechanisms, are able to maintain circadian oscillations entrained to mealtime. In the present mini-review, we evaluate the current state of the role played by clock genes in meal anticipation and provide evidence for rabbit pups as a natural model of food-anticipatory circadian behavior.

A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse

DEFF Research Database (Denmark)

Rovsing, Louise; Rath, Martin F; Lund-Andersen, Casper

2010-01-01

The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx(-)(/)(-)), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx(-/-) mouse exhibit...... melanopsin neurons or the SCN may be necessary for a normal function of the non-image forming system of the mouse. However, a change in the SCN of the Crx(-/-) mouse might also explain the observed circadian differences between the knock out mouse and wild type mouse....

Re-determination of succinonitrile (SCN) camphor phase diagram

Science.gov (United States)

Teng, Jing; Liu, Shan

2006-04-01

Low-melting temperature transparent organic materials have been extensively used to study the pattern formation and microstructure evolution. It proves to be very challenging to accurately determine the phase diagram since there is no viable way to measure the composition microscopically. In this paper, we presented the detailed experimental characterization of the phase diagram of succinonitrile (SCN)-camphor binary system. Differential scanning calorimetry, a ring-heater, and the directional solidification technique have been combined to determine the details of the phase diagram by using the purified materials. The advantages and disadvantages have been discussed for the different experimental techniques. SCN and camphor constitute a simple binary eutectic system with the eutectic composition at 23.6 wt% camphor and eutectic temperature at 37.65 °C. The solidus and the solubility of the SCN base solid solution have been precisely determined for the first time in this binary system.

Pitfalls in genetic testing: the story of missed SCN1A mutations.

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Djémié, Tania; Weckhuysen, Sarah; von Spiczak, Sarah; Carvill, Gemma L; Jaehn, Johanna; Anttonen, Anna-Kaisa; Brilstra, Eva; Caglayan, Hande S; de Kovel, Carolien G; Depienne, Christel; Gaily, Eija; Gennaro, Elena; Giraldez, Beatriz G; Gormley, Padhraig; Guerrero-López, Rosa; Guerrini, Renzo; Hämäläinen, Eija; Hartmann, Corinna; Hernandez-Hernandez, Laura; Hjalgrim, Helle; Koeleman, Bobby P C; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes R; Leu, Costin; Marini, Carla; McMahon, Jacinta M; Mei, Davide; Møller, Rikke S; Muhle, Hiltrud; Myers, Candace T; Nava, Caroline; Serratosa, Jose M; Sisodiya, Sanjay M; Stephani, Ulrich; Striano, Pasquale; van Kempen, Marjan J A; Verbeek, Nienke E; Usluer, Sunay; Zara, Federico; Palotie, Aarno; Mefford, Heather C; Scheffer, Ingrid E; De Jonghe, Peter; Helbig, Ingo; Suls, Arvid

2016-07-01

Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome (DS) patients, we focused on missed SCN1A mutations. We sent out a survey to 16 genetic centers performing SCN1A testing. We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation-negative, both due to technical limitations and human errors. We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated.

Development of diabetes does not alter behavioral and molecular circadian rhythms in a transgenic rat model of type 2 diabetes mellitus.

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Qian, Jingyi; Thomas, Anthony P; Schroeder, Analyne M; Rakshit, Kuntol; Colwell, Christopher S; Matveyenko, Aleksey V

2017-08-01

Metabolic state and circadian clock function exhibit a complex bidirectional relationship. Circadian disruption increases propensity for metabolic dysfunction, whereas common metabolic disorders such as obesity and type 2 diabetes (T2DM) are associated with impaired circadian rhythms. Specifically, alterations in glucose availability and glucose metabolism have been shown to modulate clock gene expression and function in vitro; however, to date, it is unknown whether development of diabetes imparts deleterious effects on the suprachiasmatic nucleus (SCN) circadian clock and SCN-driven outputs in vivo. To address this question, we undertook studies in aged diabetic rats transgenic for human islet amyloid polypeptide, an established nonobese model of T2DM (HIP rat), which develops metabolic defects closely recapitulating those present in patients with T2DM. HIP rats were also cross-bred with a clock gene reporter rat model (Per1:luciferase transgenic rat) to permit assessment of the SCN and the peripheral molecular clock function ex vivo. Utilizing these animal models, we examined effects of diabetes on 1 ) behavioral circadian rhythms, 2 ) photic entrainment of circadian activity, 3 ) SCN and peripheral tissue molecular clock function, and 4 ) melatonin secretion. We report that circadian activity, light-induced entrainment, molecular clockwork, as well as melatonin secretion are preserved in the HIP rat model of T2DM. These results suggest that despite the well-characterized ability of glucose to modulate circadian clock gene expression acutely in vitro, SCN clock function and key behavioral and physiological outputs appear to be preserved under chronic diabetic conditions characteristic of nonobese T2DM. Copyright © 2017 the American Physiological Society.

Mice Lacking EGR1 Have Impaired Clock Gene (BMAL1) Oscillation, Locomotor Activity, and Body Temperature.

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Riedel, Casper Schwartz; Georg, Birgitte; Jørgensen, Henrik L; Hannibal, Jens; Fahrenkrug, Jan

2018-01-01

Early growth response transcription factor 1 (EGR1) is expressed in the suprachiasmatic nucleus (SCN) after light stimulation. We used EGR1-deficient mice to address the role of EGR1 in the clock function and light-induced resetting of the clock. The diurnal rhythms of expression of the clock genes BMAL1 and PER1 in the SCN were evaluated by semi-quantitative in situ hybridization. We found no difference in the expression of PER1 mRNA between wildtype and EGR1-deficient mice; however, the daily rhythm of BMAL1 mRNA was completely abolished in the EGR1-deficient mice. In addition, we evaluated the circadian running wheel activity, telemetric locomotor activity, and core body temperature of the mice. Loss of EGR1 neither altered light-induced phase shifts at subjective night nor affected negative masking. Overall, circadian light entrainment was found in EGR1-deficient mice but they displayed a reduced locomotor activity and an altered temperature regulation compared to wild type mice. When placed in running wheels, a subpopulation of EGR1-deficient mice displayed a more disrupted activity rhythm with no measurable endogenous period length (tau). In conclusion, the present study provides the first evidence that the circadian clock in the SCN is disturbed in mice deficient of EGR1.

Contrast between the mechanisms for dissociative electron attachment to CH3SCN and CH3NCS

Science.gov (United States)

Miller, Thomas M.; Viggiano, Albert A.; Shuman, Nicholas S.

2018-05-01

The kinetics of thermal electron attachment to methyl thiocyanate (CH3SCN), methyl isothiocyanate (CH3NCS), and ethyl thiocyanate (C2H5SCN) were measured using flowing afterglow-Langmuir probe apparatuses at temperatures between 300 and 1000 K. CH3SCN and C2H5SCN undergo inefficient dissociative attachment to yield primarily SCN- at 300 K (k = 2 × 10-10 cm3 s-1), with increasing efficiency as temperature increases. The increase is well described by activation energies of 0.17 eV (CH3SCN) and 0.14 eV (C2H5SCN). CN- product is formed at product but at a rate at 300 K that is below our detection threshold (k differentiating the two mechanisms. The kinetic modeling reproduces the CH3NCS data only if dissociation through the transient anion is considered.

Atom-transfer radical polymerization of methyl methacrylate (MMA) using CuSCN as the catalyst

NARCIS (Netherlands)

Singha, N.K.; Klumperman, B.

2000-01-01

The effect of CuSCN as a catalyst in atom-transfer radical polymerization (ATRP) was investigated. CuSCN can successfully be used for the ATRP of MMA. Substituted bipyridines as well as imines can be used to stabilize the copper complex in solution. CuSCN induces faster polymerization compared to

Reduction of the thermal conductivity of the thermoelectric material ScN by Nb alloying

DEFF Research Database (Denmark)

Tureson, Nina; Van Nong, Ngo; Fournier, Daniele

2017-01-01

) orientation. The crystal structure, morphology, thermal conductivity, and thermoelectric and electrical properties were investigated. The ScN reference film exhibited a Seebeck coefficient of −45 μV/K and a power factor of 6 × 10−4 W/m K2 at 750 K. Estimated from room temperature Hall measurements, all...... samples exhibit a high carrier density of the order of 1021 cm−3. Inclusion of heavy transition metals into ScN enables the reduction in thermal conductivity by an increase in phonon scattering. The Nb inserted ScN thin films exhibited a thermal conductivity lower than the value of the ScN reference (10.......5 W m−1 K−1) down to a minimum value of 2.2 Wm−1 K−1. Insertion of Nb into ScN thus resulted in a reduction in thermal conductivity by a factor of ∼5 due to the mass contrast in ScN, which increases the phonon scattering in the material....

Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death

DEFF Research Database (Denmark)

Bezzina, Connie; Barc, Julien; Mizusawa, Yuka

2013-01-01

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) a...

Common and rare variants in SCN10A modulate the risk of atrial fibrillation

DEFF Research Database (Denmark)

Jabbari, Javad; Olesen, Morten S; Yuan, Lei

2015-01-01

BACKGROUND: Genome-wide association studies have shown that the common single nucleotide polymorphism rs6800541 located in SCN10A, encoding the voltage-gated Nav1.8 sodium channel, is associated with PR-interval prolongation and atrial fibrillation (AF). Single nucleotide polymorphism rs6800541...... is in high linkage disequilibrium with the nonsynonymous variant in SCN10A, rs6795970 (V1073A, r(2)=0.933). We therefore sought to determine whether common and rare SCN10A variants are associated with early onset AF. METHODS AND RESULTS: SCN10A was sequenced in 225 AF patients in whom there was no evidence...... of other cardiovascular disease or dysfunction (lone AF). In an association study of the rs6795970 single nucleotide polymorphism variant, we included 515 AF patients and 2 control cohorts of 730 individuals free of AF and 6161 randomly sampled individuals. Functional characterization of SCN10A variants...

Autosomal dominant SCN8A mutation with an unusually mild phenotype.

Science.gov (United States)

Anand, G; Collett-White, F; Orsini, A; Thomas, S; Jayapal, S; Trump, N; Zaiwalla, Z; Jayawant, S

2016-09-01

Mutations in SCN8A, coding for the voltage-gated sodium channel Nav 1.6, have been described in relation to infantile onset epilepsy with developmental delay and cognitive impairment, in particular early onset epileptic encephalopathy (EIEE) type 13. Here we report an infant and his father with early onset focal epileptic seizures but without cognitive or neurological impairment in whom next generation sequence analysis identified a heterozygous mutation (c.5630A > G, p. (Asn1877Ser)) in the SCN8A gene. This mutation, confirmed by Sanger sequence analysis, affects a highly conserved amino acid and in silico tools predicts that it may be pathogenic. The reported infant has a normal developmental profile at 16-month follow-up. His father also had normal development and has no cognitive impairment at 42 years. This is the second known SCN8A mutation associated with a phenotype of benign familial infantile epilepsy. Good seizure control was achieved in our patients with sodium channel blockers. Based on our proband and a recently described group of families with benign familial infantile epilepsy and SCN8A variant we suggest expanding testing to patients with infantile epilepsy and no cognitive impairment. In addition, the same SCN8A variant (c.5630A > G, p. (Asn1877Ser)) is also found in patients with epilepsy and developmental delay highlighting the phenotypic variability and the possible role of other protective genetic factors. Copyright © 2016. Published by Elsevier Ltd.

Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals

NARCIS (Netherlands)

Kumar Jha, Pawan; Challet, Etienne; Kalsbeek, Andries

2015-01-01

Most aspects of energy metabolism display clear variations during day and night. This daily rhythmicity of metabolic functions, including hormone release, is governed by a circadian system that consists of the master clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and many secondary

Facile synthesis of silver/silver thiocyanate (Ag@AgSCN plasmonic nanostructures with enhanced photocatalytic performance

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Xinfu Zhao

2017-12-01

Full Text Available A nanostructured plasmonic photocatalyst, silver/silver thiocyanate (Ag@AgSCN, has been prepared by a simple precipitation method followed by UV-light-induced reduction. The ratio of Ag to silver thiocyanate (AgSCN can be controlled by simply adjusting the photo-induced reduction time. The formation mechanism of the product was investigated based on the time-dependent experiments. Further experiments indicated that the prepared Ag@AgSCN nanostructures with an atomic ratio of Ag/AgSCN = 0.0463 exhibited high photocatalytic activity and long-term stability for the degradation of oxytetracycline (84% under visible-light irradiation. In addition to the microstructure and high specific surface area, the enhanced photocatalytic activity was mainly caused by the surface plasmon resonance of Ag nanoparticles, and the high stability of AgSCN resulted in the long-term stability of the photocatalyst product.

The Regulatory Factor ZFHX3 Modifies Circadian Function in SCN via an AT Motif-Driven Axis

Science.gov (United States)

Parsons, Michael J.; Brancaccio, Marco; Sethi, Siddharth; Maywood, Elizabeth S.; Satija, Rahul; Edwards, Jessica K.; Jagannath, Aarti; Couch, Yvonne; Finelli, Mattéa J.; Smyllie, Nicola J.; Esapa, Christopher; Butler, Rachel; Barnard, Alun R.; Chesham, Johanna E.; Saito, Shoko; Joynson, Greg; Wells, Sara; Foster, Russell G.; Oliver, Peter L.; Simon, Michelle M.; Mallon, Ann-Marie; Hastings, Michael H.; Nolan, Patrick M.

2015-01-01

Summary We identified a dominant missense mutation in the SCN transcription factor Zfhx3, termed short circuit (Zfhx3Sci), which accelerates circadian locomotor rhythms in mice. ZFHX3 regulates transcription via direct interaction with predicted AT motifs in target genes. The mutant protein has a decreased ability to activate consensus AT motifs in vitro. Using RNA sequencing, we found minimal effects on core clock genes in Zfhx3Sci/+ SCN, whereas the expression of neuropeptides critical for SCN intercellular signaling was significantly disturbed. Moreover, mutant ZFHX3 had a decreased ability to activate AT motifs in the promoters of these neuropeptide genes. Lentiviral transduction of SCN slices showed that the ZFHX3-mediated activation of AT motifs is circadian, with decreased amplitude and robustness of these oscillations in Zfhx3Sci/+ SCN slices. In conclusion, by cloning Zfhx3Sci, we have uncovered a circadian transcriptional axis that determines the period and robustness of behavioral and SCN molecular rhythms. PMID:26232227

Experience-independent development of the hamster circadian visual system.

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August Kampf-Lassin

2011-04-01

Full Text Available Experience-dependent functional plasticity is a hallmark of the primary visual system, but it is not known if analogous mechanisms govern development of the circadian visual system. Here we investigated molecular, anatomical, and behavioral consequences of complete monocular light deprivation during extended intervals of postnatal development in Syrian hamsters. Hamsters were raised in constant darkness and opaque contact lenses were applied shortly after eye opening and prior to the introduction of a light-dark cycle. In adulthood, previously-occluded eyes were challenged with visual stimuli. Whereas image-formation and motion-detection were markedly impaired by monocular occlusion, neither entrainment to a light-dark cycle, nor phase-resetting responses to shifts in the light-dark cycle were affected by prior monocular deprivation. Cholera toxin-b subunit fluorescent tract-tracing revealed that in monocularly-deprived hamsters the density of fibers projecting from the retina to the suprachiasmatic nucleus (SCN was comparable regardless of whether such fibers originated from occluded or exposed eyes. In addition, long-term monocular deprivation did not attenuate light-induced c-Fos expression in the SCN. Thus, in contrast to the thalamocortical projections of the primary visual system, retinohypothalamic projections terminating in the SCN develop into normal adult patterns and mediate circadian responses to light largely independent of light experience during development. The data identify a categorical difference in the requirement for light input during postnatal development between circadian and non-circadian visual systems.

A network of (autonomic) clock outputs

NARCIS (Netherlands)

Kalsbeek, A.; Perreau-Lenz, S.; Buijs, R. M.

2006-01-01

The circadian clock in the suprachiasmatic nuclei (SCN) is composed of thousands of oscillator neurons, each dependent on the cell-autonomous action of a defined set of circadian clock genes. A major question is still how these individual oscillators are organized into a biological clock that

Modulation of learning and memory by the targeted deletion of the circadian clock gene Bmal1 in forebrain circuits.

Science.gov (United States)

Snider, Kaitlin H; Dziema, Heather; Aten, Sydney; Loeser, Jacob; Norona, Frances E; Hoyt, Kari; Obrietan, Karl

2016-07-15

A large body of literature has shown that the disruption of circadian clock timing has profound effects on mood, memory and complex thinking. Central to this time keeping process is the master circadian pacemaker located within the suprachiasmatic nucleus (SCN). Of note, within the central nervous system, clock timing is not exclusive to the SCN, but rather, ancillary oscillatory capacity has been detected in a wide range of cell types and brain regions, including forebrain circuits that underlie complex cognitive processes. These observations raise questions about the hierarchical and functional relationship between the SCN and forebrain oscillators, and, relatedly, about the underlying clock-gated synaptic circuitry that modulates cognition. Here, we utilized a clock knockout strategy in which the essential circadian timing gene Bmal1 was selectively deleted from excitatory forebrain neurons, whilst the SCN clock remained intact, to test the role of forebrain clock timing in learning, memory, anxiety, and behavioral despair. With this model system, we observed numerous effects on hippocampus-dependent measures of cognition. Mice lacking forebrain Bmal1 exhibited deficits in both acquisition and recall on the Barnes maze. Notably, loss of forebrain Bmal1 abrogated time-of-day dependent novel object location memory. However, the loss of Bmal1 did not alter performance on the elevated plus maze, open field assay, and tail suspension test, indicating that this phenotype specifically impairs cognition but not affect. Together, these data suggest that forebrain clock timing plays a critical role in shaping the efficiency of learning and memory retrieval over the circadian day. Copyright © 2016 Elsevier B.V. All rights reserved.

Perovskite solar cells with CuSCN hole extraction layers yield stabilized efficiencies greater than 20%

Science.gov (United States)

Arora, Neha; Dar, M. Ibrahim; Hinderhofer, Alexander; Pellet, Norman; Schreiber, Frank; Zakeeruddin, Shaik Mohammed; Grätzel, Michael

2017-11-01

Perovskite solar cells (PSCs) with efficiencies greater than 20% have been realized only with expensive organic hole-transporting materials. We demonstrate PSCs that achieve stabilized efficiencies exceeding 20% with copper(I) thiocyanate (CuSCN) as the hole extraction layer. A fast solvent removal method enabled the creation of compact, highly conformal CuSCN layers that facilitate rapid carrier extraction and collection. The PSCs showed high thermal stability under long-term heating, although their operational stability was poor. This instability originated from potential-induced degradation of the CuSCN/Au contact. The addition of a conductive reduced graphene oxide spacer layer between CuSCN and gold allowed PSCs to retain >95% of their initial efficiency after aging at a maximum power point for 1000 hours under full solar intensity at 60°C. Under both continuous full-sun illumination and thermal stress, CuSCN-based devices surpassed the stability of spiro-OMeTAD-based PSCs.

Cloning and expression of a zebrafish SCN1B ortholog and identification of a species-specific splice variant

Directory of Open Access Journals (Sweden)

Slat Emily A

2007-07-01

Full Text Available Abstract Background Voltage-gated Na+ channel β1 (Scn1b subunits are multi-functional proteins that play roles in current modulation, channel cell surface expression, cell adhesion, cell migration, and neurite outgrowth. We have shown previously that β1 modulates electrical excitability in vivo using a mouse model. Scn1b null mice exhibit spontaneous seizures and ataxia, slowed action potential conduction, decreased numbers of nodes of Ranvier in myelinated axons, alterations in nodal architecture, and differences in Na+ channel α subunit localization. The early death of these mice at postnatal day 19, however, make them a challenging model system to study. As a first step toward development of an alternative model to investigate the physiological roles of β1 subunits in vivo we cloned two β1-like subunit cDNAs from D. rerio. Results Two β1-like subunit mRNAs from zebrafish, scn1ba_tv1 and scn1ba_tv2, arise from alternative splicing of scn1ba. The deduced amino acid sequences of Scn1ba_tv1 and Scn1ba_tv2 are identical except for their C-terminal domains. The C-terminus of Scn1ba_tv1 contains a tyrosine residue similar to that found to be critical for ankyrin association and Na+ channel modulation in mammalian β1. In contrast, Scn1ba_tv2 contains a unique, species-specific C-terminal domain that does not contain a tyrosine. Immunohistochemical analysis shows that, while the expression patterns of Scn1ba_tv1 and Scn1ba_tv2 overlap in some areas of the brain, retina, spinal cord, and skeletal muscle, only Scn1ba_tv1 is expressed in optic nerve where its staining pattern suggests nodal expression. Both scn1ba splice forms modulate Na+ currents expressed by zebrafish scn8aa, resulting in shifts in channel gating mode, increased current amplitude, negative shifts in the voltage dependence of current activation and inactivation, and increases in the rate of recovery from inactivation, similar to the function of mammalian β1 subunits. In

Large-scale structural alteration of brain in epileptic children with SCN1A mutation.

Science.gov (United States)

Lee, Yun-Jeong; Yum, Mi-Sun; Kim, Min-Jee; Shim, Woo-Hyun; Yoon, Hee Mang; Yoo, Il Han; Lee, Jiwon; Lim, Byung Chan; Kim, Ki Joong; Ko, Tae-Sung

2017-01-01

Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS +) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic children with SCN1A mutation compared to healthy control subjects. We obtained cortical morphology (thickness, and surface area) and brain volume (global, subcortical, and regional) measurements using FreeSurfer (version 5.3.0, https://surfer.nmr.mgh.harvard.edu) and compared measurements of children with epilepsy and SCN1A gene mutation ( n  = 21) with those of age and gender matched healthy controls ( n  = 42). Compared to the healthy control group, children with epilepsy and SCN1A gene mutation exhibited smaller total brain, total gray matter and white matter, cerebellar white matter, and subcortical volumes, as well as mean surface area and mean cortical thickness. A regional analysis revealed significantly reduced gray matter volume in the patient group in the bilateral inferior parietal, left lateral orbitofrontal, left precentral, right postcentral, right isthmus cingulate, right middle temporal area with smaller surface area and white matter volume in some of these areas. However, the regional cortical thickness was not significantly different in two groups. This study showed large-scale developmental brain changes in patients with epilepsy and SCN1A gene mutation, which may be associated with the core symptoms of the patients. Further longitudinal MRI studies with larger cohorts are required to confirm the effect of SCN1A gene mutation on structural brain development.

A network of (autonomic) clock outputs

NARCIS (Netherlands)

Kalsbeek, A.; Perreau-Lenz, S.; Buijs, R. M.

2006-01-01

The circadian clock in the suprachiasmatic nuclei (SCN) is composed of thousands of oscillator neurons, each of which is dependent on the cell-autonomous action of a defined set of circadian clock genes. A major question is still how these individual oscillators are organized into a biological clock

Neural substrates for sexual and thermoregulatory behavior in the male leopard gecko, Eublepharis macularius.

Science.gov (United States)

Edwards, Nora; Kriegsfeld, Lance; Crews, David

2004-12-10

The preoptic area-anterior hypothalamus (POAH) continuum is critical for the integration of environmental, physiological, and behavioral cues associated with reproduction in vertebrates. In the present study, radiofrequency lesions in the POAH abolished sexual behavior in the leopard gecko (Eublepharis macularius). Furthermore, results suggest a differential effect of POAH lesions on those behaviors regarded as appetitive (tail vibration and grip) and those regarded as consummatory (mounting and copulation), with consummatory behaviors being affected to a greater extent. E. macularius is an ectothermic vertebrate that modulates body temperature behaviorally relative to ambient temperature. In vertebrates, the POAH is also an important integrator of thermoregulation. Thus, the present study investigated whether lesions that disrupt reproductive behavior also disrupt body temperature regulation. While virtually all males displayed diurnal rhythms in thermoregulatory behavior prior to surgery, this pattern was abolished in a small proportion of animals bearing POAH lesions. Lesions that abolished thermoregulatory rhythms involved the suprachiasmatic nucleus (SCN), whereas lesions confined to the POAH, while dramatically influencing sexual behavior, did not affect thermoregulatory rhythms or temperature set point. Together, these findings identify the POAH as an important neural locus regulating sexual behavior but not thermoregulation and suggest that the SCN acts as a pacemaker controlling daily behavioral temperature regulation in this species.

Distribution of vasopressin in the brain of the eusocial naked mole-rat.

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Rosen, Greta J; De Vries, Geert J; Goldman, Sharry L; Goldman, Bruce D; Forger, Nancy G

2007-02-20

Naked mole-rats are eusocial rodents that live in large subterranean colonies in which one queen breeds with one to three males. All other animals are nonbreeding subordinates. The external features of male and female subordinates, including their genitalia, are remarkably monomorphic, as is their behavior. Because vasopressin (VP) is associated with social behaviors and sex differences in other species, its distribution in naked mole-rats was of interest. We used immunohistochemistry to examine VP in the brains of subordinate and breeding naked mole-rats of both sexes. As in other mammals, VP-immunoreactive (-ir) somata were found in the paraventricular (PVN) and supraoptic nuclei (SON) and VP-ir projections from these nuclei ran through the internal and external zone of the median eminence. However, naked mole-rats had very few VP-ir cells in the bed nucleus of the stria terminalis (BST) and none in the suprachiasmatic nucleus (SCN); the extensive network of fine-caliber VP-ir fibers usually seen in projection sites of the BST and SCN were also absent. Equally unexpected was the abundance of large-caliber VP-ir fibers in the dorsomedial septum. VP immunoreactivity was generally similar in all groups, with the exception of VP-ir cell number in the dorsomedial hypothalamus (DMH). Breeders had a population of labeled cells in the DMH that was absent, or nearly absent, in subordinates. Future studies on the function of VP in these areas are needed to determine how the atypical distribution of VP immunoreactivity relates to eusociality and the unusual physiology of naked mole-rats.

Decrease in scale invariance of activity fluctuations with aging and in patients with suprasellar tumors

DEFF Research Database (Denmark)

Joustra, S. D.; Gu, C.; Rohling, J. H.T.

2018-01-01

-matched healthy controls (age range 21.0–70.6 years). Spontaneous wrist locomotor activity was measured for 7 days with actigraphy, and detrended fluctuation analysis was applied to assess correlations over a range of time scales from minutes to 24 h. For all the subjects, complex scale-invariant correlations...... scale invariance. Conversely, activity patterns at time scales between 10 and 24 h were significantly more regular than all other time scales, and this was mostly associated with age. In conclusion, scale invariance is degraded in healthy subjects at the ages of >33 year as characterized by attenuation......Motor activity in healthy young humans displays intrinsic fluctuations that are scale-invariant over a wide range of time scales (from minutes to hours). Human postmortem and animal lesion studies showed that the intact function of the suprachiasmatic nucleus (SCN) is required to maintain...

Physiological links of circadian clock and biological clock of aging.

Science.gov (United States)

Liu, Fang; Chang, Hung-Chun

2017-07-01

Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self-sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurodegenerative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resembled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.

Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain

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Goldstein-Kral Lauren

2011-01-01

Full Text Available Abstract Background The mammalian suprachiasmatic nucleus (SCN, located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish cyclops (cyc mutants lack ventral brain, including the region that gives rise to the SCN. We have used cyc embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression. Results We find that pineal rhythms are present in cyc mutants despite the absence of an SCN. The arginine vasopressin-like protein (Avpl, formerly called Vasotocin is a peptide hormone expressed in and around the SCN. We find avpl mRNA is absent in cyc mutants, supporting previous work suggesting the SCN is missing. In contrast, expression of the putative circadian clock genes, cryptochrome 1b (cry1b and cryptochrome 3 (cry3, in the brain of the developing fish is unaltered. Expression of two pineal rhythmic genes, exo-rhodopsin (exorh and serotonin-N-acetyltransferase (aanat2, involved in photoreception and melatonin synthesis, respectively, is also similar between cyc embryos and their wildtype (WT siblings. The timing of the peaks and troughs of expression are the same, although the amplitude of expression is slightly decreased in the mutants. Cyclic gene expression persists for two days in cyc embryos transferred to constant light or constant dark, suggesting a circadian clock is driving the rhythms. However, the amplitude of rhythms in cyc mutants kept in constant conditions decreased more quickly than in their

Mutations in sodium channel {beta}-subunit SCN3B are associated with early-onset lone atrial fibrillation

DEFF Research Database (Denmark)

Olesen, Morten Salling; Jespersen, Thomas; Nielsen, Jonas Bille

2011-01-01

AIMS: Atrial fibrillation (AF) is the most frequent arrhythmia. Screening of SCN5A-the gene encoding the a-subunit of the cardiac sodium channel-has indicated that disturbances of the sodium current may play a central role in the mechanism of lone AF. We tested the hypothesis that lone AF in young...... across species. Electrophysiological studies on the SCN3B mutation were carried out and all three SCN3B mutations caused a functionally reduced sodium channel current. One synonymous variant was found in SCN4B. CONCLUSION: In 192 young lone AF patients, we found three patients with suspected disease...

Electronic structure and physical properties of ScN in pressure: density-functional theory calculations

International Nuclear Information System (INIS)

Guan Pengfei; Wang Chongyu; Yu Tao

2008-01-01

Local density functional is investigated by using the full-potential linearized augmented plane wave (FP-LAPW) method for ScN in the hexagonal structure and the rocksalt structure and for hexagonal structures linking a layered hexagonal phase with wurtzite structure along a homogeneous strain transition path. It is found that the wurtzite ScN is unstable and the layered hexagonal phase, labelled as h o , in which atoms are approximately fivefold coordinated, is metastable, and the rocksalt ScN is stable. The electronic structure, the physical properties of the intermediate structures and the energy band structure along the transition are presented. It is found that the band gaps change from 4.0 to 1.0 eV continuously when c/a value varies from 1.68 to 1.26. It is noticeable that the study of ScN provides an opportunity to apply this kind of material (in wurtzite[h]-derived phase). (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Resonance Raman Spectrum of the Transient (SCN)2 Free Radical Anion

DEFF Research Database (Denmark)

Wilbrandt, Robert Walter; Jensen, N. H.; Pagsberg, Palle Bjørn

1979-01-01

The resonance Raman spectrum of the transient species (λmax = 475 nm, τ½ = 1.6 μs) formed by pulse radiolysis of aqueous solutions of thiocyanate, SCN2−, is reported. The spectrum is discussed in terms of the previous assignment of this transient to the radical anion, (SCN)−2. The observed...... vibrational frequencies of the radical anion are consistent with substantial weakening of the S---S and the Ctriple bond; length as m-dashN bonds are compared with neutral thiocyanogen....

A case of recurrent encephalopathy with SCN2A missense mutation.

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Fukasawa, Tatsuya; Kubota, Tetsuo; Negoro, Tamiko; Saitoh, Makiko; Mizuguchi, Masashi; Ihara, Yukiko; Ishii, Atsushi; Hirose, Shinichi

2015-06-01

Voltage-gated sodium channels regulate neuronal excitability, as well as survival and the patterning of neuronal connectivity during development. Mutations in SCN2A, which encodes the Na(+) channel Nav1.2, cause epilepsy syndromes and predispose children to acute encephalopathy. Here, we report the case of a young male with recurrent acute encephalopathy who carried a novel missense mutation in the SCN2A gene. He was born by normal delivery and developed repetitive apneic episodes at 2days of age. Diffusion-weighted imaging revealed high-intensity areas in diffuse subcortical white matter, bilateral thalami, and basal nuclei. His symptoms improved gradually without any specific treatment, but he exhibited a motor milestone delay after the episode. At the age of 10months, he developed acute cerebellopathy associated with a respiratory syncytial viral infection. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy and seemed to have no obvious sequelae after the episode. He then developed severe diffuse encephalopathy associated with gastroenteritis at the age of 14months. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy but was left with severe neurological sequelae. PCR-based analysis revealed a novel de novo missense mutation, c.4979T>G (p.Leu1660Trp), in the SCN2A gene. This case suggests that SCN2A mutations might predispose children to repetitive encephalopathy with variable clinical and imaging findings. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Differential contribution of Ca2+ sources to day and night BK current activation in the circadian clock.

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Whitt, Joshua P; McNally, Beth A; Meredith, Andrea L

2018-02-05

Large conductance K + (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca 2+ (Ca 2+ i ). To enable this regulation, BK channels functionally couple to both voltage-gated Ca 2+ channels (VGCCs) and channels mediating Ca 2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca 2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca 2+ i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca 2+ i are reduced. Here, to determine whether diurnal regulation of Ca 2+ is relevant for BK channel activation, we combine pharmacology with day and night patch-clamp recordings in acute slices of SCN. We find that activation of BK current depends primarily on three types of channels but that the relative contribution changes between day and night. BK current can be abrogated with nimodipine during the day but not at night, establishing that L-type Ca 2+ channels (LTCCs) are the primary daytime Ca 2+ source for BK activation. In contrast, dantrolene causes a significant decrease in BK current at night, suggesting that nighttime BK activation is driven by ryanodine receptor (RyR)-mediated Ca 2+ i release. The N- and P/Q-type Ca 2+ channel blocker ω-conotoxin MVIIC causes a smaller reduction of BK current that does not differ between day and night. Finally, inhibition of LTCCs, but not RyRs, eliminates BK inactivation, but the BK β2 subunit was not required for activation of BK current by LTCCs. These data reveal a dynamic coupling strategy between BK channels and their Ca 2+ sources in the SCN, contributing to diurnal regulation of SCN excitability. © 2018 Whitt et al.

Circadian and Metabolic Effects of Light: Implications in Weight Homeostasis and Health

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Santiago A. Plano

2017-10-01

Full Text Available Daily interactions between the hypothalamic circadian clock at the suprachiasmatic nucleus (SCN and peripheral circadian oscillators regulate physiology and metabolism to set temporal variations in homeostatic regulation. Phase coherence of these circadian oscillators is achieved by the entrainment of the SCN to the environmental 24-h light:dark (LD cycle, coupled through downstream neural, neuroendocrine, and autonomic outputs. The SCN coordinate activity and feeding rhythms, thus setting the timing of food intake, energy expenditure, thermogenesis, and active and basal metabolism. In this work, we will discuss evidences exploring the impact of different photic entrainment conditions on energy metabolism. The steady-state interaction between the LD cycle and the SCN is essential for health and wellbeing, as its chronic misalignment disrupts the circadian organization at different levels. For instance, in nocturnal rodents, non-24 h protocols (i.e., LD cycles of different durations, or chronic jet-lag simulations might generate forced desynchronization of oscillators from the behavioral to the metabolic level. Even seemingly subtle photic manipulations, as the exposure to a “dim light” scotophase, might lead to similar alterations. The daily amount of light integrated by the clock (i.e., the photophase duration strongly regulates energy metabolism in photoperiodic species. Removing LD cycles under either constant light or darkness, which are routine protocols in chronobiology, can also affect metabolism, and the same happens with disrupted LD cycles (like shiftwork of jetlag and artificial light at night in humans. A profound knowledge of the photic and metabolic inputs to the clock, as well as its endocrine and autonomic outputs to peripheral oscillators driving energy metabolism, will help us to understand and alleviate circadian health alterations including cardiometabolic diseases, diabetes, and obesity.

Large-scale structural alteration of brain in epileptic children with SCN1A mutation

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Yun-Jeong Lee

2017-01-01

Significance: This study showed large-scale developmental brain changes in patients with epilepsy and SCN1A gene mutation, which may be associated with the core symptoms of the patients. Further longitudinal MRI studies with larger cohorts are required to confirm the effect of SCN1A gene mutation on structural brain development.

Regulation of reproduction by the circadian rhythms.

Science.gov (United States)

Zhang, Wen-Xiang; Chen, Si-Yu; Liu, Chang

2016-12-25

Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. Circadian rhythm is controlled by the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and the peripheral clocks in various tissues. More importantly, the central clock can integrate photic/nonphotic signals to generate rhythmic outputs, and then drive the slave oscillators in peripheral tissues through neuroendocrine and behavioral signals. Human reproductive activities, as some other physiological functions, are controlled by the biological clocks. Accumulating lines of epidemiological and genetic evidence indicate that disruption of circadian clock can be directly involved in multiple pathological processes, including infertility. In this review, we mainly discuss the presence of a circadian clock in reproductive tissues and its roles in follicles development, ovulation, spermatogenesis, fertilization and embryo implantation, etc. As the increased shift work and assisted reproductive technologies possibly disrupt circadian rhythmicity to impact reproduction, the importance of circadian rhythms should be highlighted in the regulation of reproductive process.

Development of Field-Controlled Smart Optic Materials (ScN, AlN) with Rare Earth Dopants

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Kim, Hyun-Jung; Park, Yeonjoon; King, Glen C.; Choi, Sang H.

2012-01-01

The purpose of this investigation is to develop the fundamental materials and fabrication technology for field-controlled spectrally active optics that are essential for industry, NASA, and DOD applications such as: membrane optics, filters for LIDARs, windows for sensors, telescopes, spectroscopes, cameras, flat-panel displays, etc. ScN and AlN thin films were fabricated on c-axis Sapphire (0001) or quartz substrate with the RF and DC magnetron sputtering. The crystal structure of AlN in fcc (rocksalt) and hcp (wurtzite) were controlled. Advanced electrical characterizations were performed, including I-V and Hall Effect Measurement. ScN film has a free carrier density of 5.8 x 10(exp 20)/per cubic centimeter and a conductivity of 1.1 x 10(exp 3) per centimeter. The background ntype conductivity of as-grown ScN has enough free electrons that can readily interact with the photons. The high density of free electrons and relatively low mobility indicate that these films contain a high level of shallow donors as well as deep levels. Also, the UV-Vis spectrum of ScN and AlN thin films with rare earth elements (Er or Ho) were measured at room temperature. Their optical band gaps were estimated to be about 2.33eV and 2.24eV, respectively, which are obviously smaller than that of undoped thin film ScN (2.4eV). The red-shifted absorption onset gives direct evidence for the decrease of band gap (Eg) and the energy broadening of valence band states are attributable to the doping. As the doped elements enter the ScN crystal lattices, the localized band edge states form at the doped sites with a reduction of Eg. Using a variable angle spectroscopic ellipsometer, the decrease in refractive index with applied field is observed with a smaller shift in absorption coefficient.

A colourful clock.

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Hester C van Diepen

2015-05-01

Full Text Available Circadian rhythms are an essential property of life on Earth. In mammals, these rhythms are coordinated by a small set of neurons, located in the suprachiasmatic nuclei (SCN. The environmental light/dark cycle synchronizes (entrains the SCN via a distinct pathway, originating in a subset of photosensitive retinal ganglion cells (pRGCs that utilize the photopigment melanopsin (OPN4. The pRGCs are also innervated by rods and cones and, so, are both endogenously and exogenously light sensitive. Accumulating evidence has shown that the circadian system is sensitive to ultraviolet (UV, blue, and green wavelengths of light. However, it was unclear whether colour perception itself can help entrain the SCN. By utilizing both behavioural and electrophysiological recording techniques, Walmsley and colleagues show that multiple photic channels interact and enhance the capacity of the SCN to synchronize to the environmental cycle. Thus, entrainment of the circadian system combines both environmental irradiance and colour information to ensure that internal and external time are appropriately aligned.

Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.

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Anna Ka-Yee Kwong

Full Text Available BACKGROUND: Dravet syndrome is a severe form of epilepsy. Majority of patients have a mutation in SCN1A gene, which encodes a voltage-gated sodium channel. A recent study has demonstrated that 16% of SCN1A-negative patients have a mutation in PCDH19, the gene encoding protocadherin-19. Mutations in other genes account for only a very small proportion of families. TSPYL4 is a novel candidate gene within the locus 6q16.3-q22.31 identified by linkage study. OBJECTIVE: The present study examined the mutations in epileptic Chinese children with emphasis on Dravet syndrome. METHODS: A hundred children with severe epilepsy were divided into Dravet syndrome and non-Dravet syndrome groups and screened for SCN1A mutations by direct sequencing. SCN1A-negative Dravet syndrome patients and patients with phenotypes resembling Dravet syndrome were checked for PCDH19 and TSPYL4 mutations. RESULTS: Eighteen patients (9 males, 9 females were diagnosed to have Dravet syndrome. Among them, 83% (15/18 had SCN1A mutations including truncating (7, splice site (2 and missense mutations (6. The truncating/splice site mutations were associated with moderate to severe degree of intellectual disability (p<0.05. During the progression of disease, 73% (11/15 had features fitting into the diagnostic criteria of autism spectrum disorder and 53% (8/15 had history of vaccination-induced seizures. A novel PCDH19 p.D377N mutation was identified in one SCN1A-negative female patient with Dravet syndrome and a known PCDH19 p.N340S mutation in a female non-Dravet syndrome patient. The former also inherited a TSPYL4 p.G60R variant. CONCLUSION: A high percentage of SCN1A mutations was identified in our Chinese cohort of Dravet syndrome patients but none in the rest of patients. We demonstrated that truncating/splice site mutations were linked to moderate to severe intellectual disability in these patients. A de novo PCDH19 missense mutation together with an inherited TSPYL4 missense

Implications of Circadian Rhythm in Dopamine and Mood Regulation.

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Kim, Jeongah; Jang, Sangwon; Choe, Han Kyoung; Chung, Sooyoung; Son, Gi Hoon; Kim, Kyungjin

2017-07-31

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-erbα induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

Dim light at night disturbs the daily sleep-wake cycle in the rat.

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Stenvers, Dirk Jan; van Dorp, Rick; Foppen, Ewout; Mendoza, Jorge; Opperhuizen, Anne-Loes; Fliers, Eric; Bisschop, Peter H; Meijer, Johanna H; Kalsbeek, Andries; Deboer, Tom

2016-10-20

Exposure to light at night (LAN) is associated with insomnia in humans. Light provides the main input to the master clock in the hypothalamic suprachiasmatic nucleus (SCN) that coordinates the sleep-wake cycle. We aimed to develop a rodent model for the effects of LAN on sleep. Therefore, we exposed male Wistar rats to either a 12 h light (150-200lux):12 h dark (LD) schedule or a 12 h light (150-200 lux):12 h dim white light (5 lux) (LDim) schedule. LDim acutely decreased the amplitude of daily rhythms of REM and NREM sleep, with a further decrease over the following days. LDim diminished the rhythms of 1) the circadian 16-19 Hz frequency domain within the NREM sleep EEG, and 2) SCN clock gene expression. LDim also induced internal desynchronization in locomotor activity by introducing a free running rhythm with a period of ~25 h next to the entrained 24 h rhythm. LDim did not affect body weight or glucose tolerance. In conclusion, we introduce the first rodent model for disturbed circadian control of sleep due to LAN. We show that internal desynchronization is possible in a 24 h L:D cycle which suggests that a similar desynchronization may explain the association between LAN and human insomnia.

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes

DEFF Research Database (Denmark)

Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav

2016-01-01

OBJECTIVE: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are...

Development of 68Ga-SCN-DOTA-Capsaicin as an Imaging Agent Targeting Apoptosis and Cell Cycle Arrest in Breast Cancer.

Science.gov (United States)

Lee, Jun Young; Lee, Sang-Yeun; Kim, Gun Gyun; Hur, Min Goo; Yang, Seung Dae; Park, Jeong-Hoon; Kim, Sang Wook

2017-06-01

68 Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [ 68 Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, 69 Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of 68 Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes). 68 Ga-SCN-Bn-DOTA-capsaicin showed a cellular uptake of 0.93% Injected Dose (ID) after 30 minutes of incubation, whereas 68 Ga-SCN-Bn-DOTA showed a lower uptake of 0.25% ID. The tumor-to-blood ID/g% ratios increased and were found to be 0.49, 0.22, and 0.77 for 15, 30, and 60 minutes, respectively. The small-animal PET study showed that the uptake of 68 Ga-SCN-Bn-DOTA-capsaicin was higher in the tumor regions even at 30 minutes after injection. These results suggest that 68 Ga-SCN-Bn-DOTA-capsaicin is a potential targeting agent for PET imaging of MCF-7.

Circadian Clock Protein Content and Daily Rhythm of Locomotor Activity Are Altered after Chronic Exposure to Lead in Rat

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Sabbar, Mariam; Dkhissi-Benyahya, Ouria; Benazzouz, Abdelhamid; Lakhdar-Ghazal, Nouria

2017-01-01

Lead exposure has been reported to produce many clinical features, including parkinsonism. However, its consequences on the circadian rhythms are still unknown. Here we aimed to examine the circadian rhythms of locomotor activity following lead intoxication and investigate the mechanisms by which lead may induce alterations of circadian rhythms in rats. Male Wistar rats were injected with lead or sodium acetate (10 mg/kg/day, i.p.) during 4 weeks. Both groups were tested in the “open field” to quantify the exploratory activity and in the rotarod to evaluate motor coordination. Then, animals were submitted to continuous 24 h recordings of locomotor activity under 14/10 Light/dark (14/10 LD) cycle and in complete darkness (DD). At the end of experiments, the clock proteins BMAL1, PER1-2, and CRY1-2 were assayed in the suprachiasmatic nucleus (SCN) using immunohistochemistry. We showed that lead significantly reduced the number of crossing in the open field, impaired motor coordination and altered the daily locomotor activity rhythm. When the LD cycle was advanced by 6 h, both groups adjusted their daily locomotor activity to the new LD cycle with high onset variability in lead-intoxicated rats compared to controls. Lead also led to a decrease in the number of immunoreactive cells (ir-) of BMAL1, PER1, and PER2 without affecting the number of ir-CRY1 and ir-CRY2 cells in the SCN. Our data provide strong evidence that lead intoxication disturbs the rhythm of locomotor activity and alters clock proteins expression in the SCN. They contribute to the understanding of the mechanism by which lead induce circadian rhythms disturbances. PMID:28970786

Shift work or food intake during the rest phase promotes metabolic disruption and desynchrony of liver genes in male rats.

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Salgado-Delgado, Roberto C; Saderi, Nadia; Basualdo, María del Carmen; Guerrero-Vargas, Natali N; Escobar, Carolina; Buijs, Ruud M

2013-01-01

In the liver, clock genes are proposed to drive metabolic rhythms. These gene rhythms are driven by the suprachiasmatic nucleus (SCN) mainly by food intake and via autonomic and hormonal pathways. Forced activity during the normal rest phase, induces also food intake, thus neglecting the signals of the SCN, leading to conflicting time signals to target tissues of the SCN. The present study explored in a rodent model of night-work the influence of food during the normal sleep period on the synchrony of gene expression between clock genes and metabolic genes in the liver. Male Wistar rats were exposed to forced activity for 8 h either during the rest phase (day) or during the active phase (night) by using a slow rotating wheel. In this shift work model food intake shifts spontaneously to the forced activity period, therefore the influence of food alone without induced activity was tested in other groups of animals that were fed ad libitum, or fed during their rest or active phase. Rats forced to be active and/or eating during their rest phase, inverted their daily peak of Per1, Bmal1 and Clock and lost the rhythm of Per2 in the liver, moreover NAMPT and metabolic genes such as Pparα lost their rhythm and thus their synchrony with clock genes. We conclude that shift work or food intake in the rest phase leads to desynchronization within the liver, characterized by misaligned temporal patterns of clock genes and metabolic genes. This may be the cause of the development of the metabolic syndrome and obesity in individuals engaged in shift work.

Intracerebroventricular Infusion of Vasoactive Intestinal Peptide (VIP Rescues the Luteinizing Hormone Surge in Middle-Aged Female Rats

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Yan eSun

2012-02-01

Full Text Available Reproductive aging is characterized by delayed and attenuated luteinizing hormone (LH surges apparent in middle-aged rats. The suprachiasmatic nucleus (SCN contains the circadian clock that is responsible for the timing of diverse neuroendocrine rhythms. Electrophysiological studies suggest vasoactive intestinal peptide (VIP originating from the SCN excites gonadotropin-releasing hormone (GnRH neurons and affects daily patterns of GnRH-LH release. Age-related LH surge dysfunction correlates with reduced VIP mRNA expression in the SCN and fewer GnRH neurons with VIP contacts expressing c-fos, a marker of neuronal activation, on the day of the LH surge. To determine if age-related LH surge dysfunction reflects reduced VIP availability or altered VIP responsiveness under estradiol positive feedback conditions, we assessed the effect of intracerebroventricular (icv VIP infusion on c-fos expression in GnRH neurons and on LH release in ovariohysterectomized, hormone-primed young and middle-aged rats. Icv infusion of VIP between 1300 and 1600 h significantly advanced the time of peak LH release, increased total and peak LH release, and increased the number of GnRH neurons expressing c-fos on the day of the LH surge in middle-aged rats. Surprisingly, icv infusion of VIP in young females significantly reduced the number of GnRH neurons expressing c-fos and delayed and reduced the LH surge. These observations suggest that a critical balance of VIP signaling is required to activate GnRH neurons for an appropriately timed and robust LH surge in young and middle-aged females. Age-related LH surge changes may, in part, result from decreased availability and reduced VIP-mediated neurotransmission under estradiol positive feedback conditions.

Formation of scandium nitride (ScN) layer on gallium arsenide (GaAs) substrate using a combined technique of e-beam evaporator and ammonia annealing treatment

Energy Technology Data Exchange (ETDEWEB)

Yong Shee Meng, Alvin [Institute of Nano Optoelectronics Research and Technology (INOR), sains@usm, Persiaran Bukit Jambul, 11900 Bayan Lepas, Penang (Malaysia); Zainal, Norzaini, E-mail: norzaini@usm.my [Nano Optoelectronics Research and Laboratory, Universiti Sains Malaysia, sains@usm, Persiaran Bukit Jambul, 11900, Bayan Lepas, Penang (Malaysia); Hassan, Zainuriah; Ibrahim, Kamarulazizi [Institute of Nano Optoelectronics Research and Technology (INOR), sains@usm, Persiaran Bukit Jambul, 11900 Bayan Lepas, Penang (Malaysia)

2015-12-30

Graphical abstract: - Highlights: • Forming ScN layer using electron e-beam evaporator with successive NH{sub 3} annealing thermal has been successfully demonstrated. • NH{sub 3} annealing played the role in changing the grain structure of the ScN layer. • The existence of Sc−N bonds was confirmed by XPS measurement. • The 900 °C annealed ScN layer showed the best structural and optical characteristics. • ScN layer annealed at 980 °C exhibited poor structural and optical characteristics. - Abstract: A demonstration on a new technique of growing ScN using electron beam (e-beam) evaporator, coupled with successive ammonia (NH{sub 3}) annealing treatment is presented in this paper. The annealing temperature was varied at 750, 800, 850, 900 and 980 °C in order to obtain the best ScN layer. It was found that as the annealing temperature increased, the surface morphology of the ScN layer changed and ScN grains formed abundantly on the surface. The best surface of ScN layer was found in the 900 °C annealed sample. However, the roughness of the ScN increased with temperature. The photoluminescence (PL) peak of the near-to-band-edge (NBE) of ScN was observable in all samples and its intensity was the highest in the 900 °C annealed sample. Note that when the annealing treatment was conducted at 980 °C, the GaN PL peak is observable. Raman peaks of TO(X) of ScN were much evident at the annealing temperature above 900 °C. The formation of Sc−N bonds was confirmed by X-ray spectroscopy (XPS) measurement. In the end of this work, we propose that the formation of ScN using the above techniques was successful, with thermal annealing at the temperature of 900 °C.

Formation of scandium nitride (ScN) layer on gallium arsenide (GaAs) substrate using a combined technique of e-beam evaporator and ammonia annealing treatment

International Nuclear Information System (INIS)

Yong Shee Meng, Alvin; Zainal, Norzaini; Hassan, Zainuriah; Ibrahim, Kamarulazizi

2015-01-01

Graphical abstract: - Highlights: • Forming ScN layer using electron e-beam evaporator with successive NH_3 annealing thermal has been successfully demonstrated. • NH_3 annealing played the role in changing the grain structure of the ScN layer. • The existence of Sc−N bonds was confirmed by XPS measurement. • The 900 °C annealed ScN layer showed the best structural and optical characteristics. • ScN layer annealed at 980 °C exhibited poor structural and optical characteristics. - Abstract: A demonstration on a new technique of growing ScN using electron beam (e-beam) evaporator, coupled with successive ammonia (NH_3) annealing treatment is presented in this paper. The annealing temperature was varied at 750, 800, 850, 900 and 980 °C in order to obtain the best ScN layer. It was found that as the annealing temperature increased, the surface morphology of the ScN layer changed and ScN grains formed abundantly on the surface. The best surface of ScN layer was found in the 900 °C annealed sample. However, the roughness of the ScN increased with temperature. The photoluminescence (PL) peak of the near-to-band-edge (NBE) of ScN was observable in all samples and its intensity was the highest in the 900 °C annealed sample. Note that when the annealing treatment was conducted at 980 °C, the GaN PL peak is observable. Raman peaks of TO(X) of ScN were much evident at the annealing temperature above 900 °C. The formation of Sc−N bonds was confirmed by X-ray spectroscopy (XPS) measurement. In the end of this work, we propose that the formation of ScN using the above techniques was successful, with thermal annealing at the temperature of 900 °C.

Large-scale structural alteration of brain in epileptic children with SCN1A mutation

OpenAIRE

Lee, Yun-Jeong; Yum, Mi-Sun; Kim, Min-Jee; Shim, Woo-Hyun; Yoon, Hee Mang; Yoo, Il Han; Lee, Jiwon; Lim, Byung Chan; Kim, Ki Joong; Ko, Tae-Sung

2017-01-01

Objective: Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic chil...

SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy.

Science.gov (United States)

Ma, Chun-Lai; Wu, Xun-Yi; Jiao, Zheng; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang

2015-01-01

Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated. Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method. Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p GA > AA. SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

Measurement and correlation of vapour pressures of pyridine and thiophene with [EMIM][SCN] ionic liquid

International Nuclear Information System (INIS)

Khelassi-Sefaoui, Asma; Mutelet, Fabrice; Mokbel, Ilham; Jose, Jacques; Negadi, Latifa

2014-01-01

Highlights: • VLE of (pyridine + [EMIM][SCN]), or (thiophene + [EMIM][SCN]) binary mixtures were measured. • The investigated temperatures are 273 K to 363 K. • The PC-SAFT equation of state has been used to correlate the vapour pressures of the binary systems. - Abstract: In this work (vapour + liquid) equilibrium (VLE) measurements were performed on binary systems of the ionic liquid 1-ethyl-3-methylimidazolium thiocynate [EMIM][SCN] with thiophene or pyridine at pressures close to the atmospheric pressure using a static device at temperatures between 273 K and 363 K. Experimental data were correlated by the PC-SAFT EoS. The binary interaction parameters k ij were optimised on experimental VLE data. The results obtained for the two binary mixtures studied in this paper indicate that the PC-SAFT EoS can be used to represent systems containing ionic liquids

Thermoelectric properties of epitaxial ScN films deposited by reactive magnetron sputtering onto MgO(001) substrates

Science.gov (United States)

Burmistrova, Polina V.; Maassen, Jesse; Favaloro, Tela; Saha, Bivas; Salamat, Shuaib; Rui Koh, Yee; Lundstrom, Mark S.; Shakouri, Ali; Sands, Timothy D.

2013-04-01

Epitaxial ScN(001) thin films were grown on MgO(001) substrates by dc reactive magnetron sputtering. The deposition was performed in an Ar/N2 atmosphere at 2 × 10-3 Torr at a substrate temperature of 850 °C in a high vacuum chamber with a base pressure of 10-8 Torr. In spite of oxygen contamination of 1.6 ± 1 at. %, the electrical resistivity, electron mobility, and carrier concentration obtained from a typical film grown under these conditions by room temperature Hall measurements are 0.22 mΩ cm, 106 cm2 V-1 s-1, and 2.5 × 1020 cm-3, respectively. These films exhibit remarkable thermoelectric power factors of 3.3-3.5 × 10-3 W/mK2 in the temperature range of 600 K to 840 K. The cross-plane thermal conductivity is 8.3 W/mK at 800 K yielding an estimated ZT of 0.3. Theoretical modeling of the thermoelectric properties of ScN calculated using a mean-free-path of 23 nm at 300 K is in very good agreement with the experiment. These results also demonstrate that further optimization of the power factor of ScN is possible. First-principles density functional theory combined with the site occupancy disorder technique was used to investigate the effect of oxygen contamination on the electronic structure and thermoelectric properties of ScN. The computational results suggest that oxygen atoms in ScN mix uniformly on the N site forming a homogeneous solid solution alloy. Behaving as an n-type donor, oxygen causes a shift of the Fermi level in ScN into the conduction band without altering the band structure and the density of states.

Hereditary sensory and autonomic neuropathy type IID caused by an SCN9A mutation.

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Yuan, Junhui; Matsuura, Eiji; Higuchi, Yujiro; Hashiguchi, Akihiro; Nakamura, Tomonori; Nozuma, Satoshi; Sakiyama, Yusuke; Yoshimura, Akiko; Izumo, Shuji; Takashima, Hiroshi

2013-04-30

To identify the clinical features of Japanese patients with suspected hereditary sensory and autonomic neuropathy (HSAN) on the basis of genetic diagnoses. On the basis of clinical, in vivo electrophysiologic, and pathologic findings, 9 Japanese patients with sensory and autonomic nervous dysfunctions were selected. Eleven known HSAN disease-causing genes and 5 related genes were screened using a next-generation sequencer. A homozygous mutation, c.3993delGinsTT, was identified in exon 22 of SCN9A from 2 patients/families. The clinical phenotype was characterized by adolescent or congenital onset with loss of pain and temperature sensation, autonomic nervous dysfunctions, hearing loss, and hyposmia. Subsequently, this mutation was discovered in one of patient 1's sisters, who also exhibited sensory and autonomic nervous system dysfunctions, with recurrent fractures being the most predominant feature. Nerve conduction studies revealed definite asymmetric sensory nerve involvement in patient 1. In addition, sural nerve pathologic findings showed loss of large myelinated fibers in patient 1, whereas the younger patient showed normal sural nerve pathology. We identified a novel homozygous mutation in SCN9A from 2 Japanese families with autosomal recessive HSAN. This loss-of-function SCN9A mutation results in disturbances in the sensory, olfactory, and autonomic nervous systems. We propose that SCN9A mutation results in the new entity of HSAN type IID, with additional symptoms including hyposmia, hearing loss, bone dysplasia, and hypogeusia.

A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy.

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Atkin, Talia A; Maher, Chani M; Gerlach, Aaron C; Gay, Bryant C; Antonio, Brett M; Santos, Sonia C; Padilla, Karen M; Rader, JulieAnn; Krafte, Douglas S; Fox, Matthew A; Stewart, Gregory R; Petrovski, Slavé; Devinsky, Orrin; Might, Matthew; Petrou, Steven; Goldstein, David B

2018-04-01

Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high-throughput screening to identify inhibitors of a gain-of-function mutation in the SCN8A gene associated with severe pediatric epilepsy. We developed cellular models expressing wild-type or an R1872Q mutation in the Na v 1.6 sodium channel encoded by SCN8A. Voltage clamp experiments in HEK-293 cells expressing the SCN8A R1872Q mutation demonstrated a leftward shift in sodium channel activation as well as delayed inactivation; both changes are consistent with a gain-of-function mutation. We next developed a fluorescence-based, sodium flux assay and used it to assess an extensive library of approved drugs, including a panel of antiepileptic drugs, for inhibitory activity in the mutated cell line. Lead candidates were evaluated in follow-on studies to generate concentration-response curves for inhibiting sodium influx. Select compounds of clinical interest were evaluated by electrophysiology to further characterize drug effects on wild-type and mutant sodium channel functions. The screen identified 90 drugs that significantly inhibited sodium influx in the R1872Q cell line. Four drugs of potential clinical interest-amitriptyline, carvedilol, nilvadipine, and carbamazepine-were further investigated and demonstrated concentration-dependent inhibition of sodium channel currents. A comprehensive drug repurposing screen identified potential new candidates for the treatment of epilepsy caused by the R1872Q mutation in the SCN8A gene. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Circadian control of the daily plasma glucose rhythm: an interplay of GABA and glutamate.

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Kalsbeek, Andries; Foppen, Ewout; Schalij, Ingrid; Van Heijningen, Caroline; van der Vliet, Jan; Fliers, Eric; Buijs, Ruud M

2008-09-15

The mammalian biological clock, located in the hypothalamic suprachiasmatic nuclei (SCN), imposes its temporal structure on the organism via neural and endocrine outputs. To further investigate SCN control of the autonomic nervous system we focused in the present study on the daily rhythm in plasma glucose concentrations. The hypothalamic paraventricular nucleus (PVN) is an important target area of biological clock output and harbors the pre-autonomic neurons that control peripheral sympathetic and parasympathetic activity. Using local administration of GABA and glutamate receptor (ant)agonists in the PVN at different times of the light/dark-cycle we investigated whether daily changes in the activity of autonomic nervous system contribute to the control of plasma glucose and plasma insulin concentrations. Activation of neuronal activity in the PVN of non-feeding animals, either by administering a glutamatergic agonist or a GABAergic antagonist, induced hyperglycemia. The effect of the GABA-antagonist was time dependent, causing increased plasma glucose concentrations only when administered during the light period. The absence of a hyperglycemic effect of the GABA-antagonist in SCN-ablated animals provided further evidence for a daily change in GABAergic input from the SCN to the PVN. On the other hand, feeding-induced plasma glucose and insulin responses were suppressed by inhibition of PVN neuronal activity only during the dark period. These results indicate that the pre-autonomic neurons in the PVN are controlled by an interplay of inhibitory and excitatory inputs. Liver-dedicated sympathetic pre-autonomic neurons (responsible for hepatic glucose production) and pancreas-dedicated pre-autonomic parasympathetic neurons (responsible for insulin release) are controlled by inhibitory GABAergic contacts that are mainly active during the light period. Both sympathetic and parasympathetic pre-autonomic PVN neurons also receive excitatory inputs, either from the

Functional Na(V)1.8 Channels in Intracardiac Neurons The Link Between SCN10A and Cardiac Electrophysiology

NARCIS (Netherlands)

Verkerk, Arie O.; Remme, Carol Ann; Schumacher, Cees A.; Scicluna, Brendon P.; Wolswinkel, Rianne; de Jonge, Berend; Bezzina, Connie R.; Veldkamp, Marieke W.

2012-01-01

Rationale: The SCN10A gene encodes the neuronal sodium channel isoform Na(V)1.8. Several recent genome-wide association studies have linked SCN10A to PR interval and QRS duration, strongly suggesting an as-yet unknown role for Na(V)1.8 in cardiac electrophysiology. Objective: To demonstrate the

Pitfalls in genetic testing: the story of missed SCN1A mutations

OpenAIRE

Jennings, Lawrence J.; Kirschmann, Dawn

2016-01-01

Investigators from the EuroEPINOMICS rare epilepsy syndromes Dravet working group performed whole-exome sequencing on 31 trios that had been reported negative for SCN1A mutations by Sanger sequencing.

Circadian behaviour in neuroglobin deficient mice.

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Christian A Hundahl

Full Text Available Neuroglobin (Ngb, a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN. The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1 and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night.

The Zfhx3-Mediated Axis Regulates Sleep and Interval Timing in Mice

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Edoardo Balzani

2016-07-01

Full Text Available An AT motif-dependent axis, modulated by the transcription factor Zfhx3, influences the circadian clock in mice. In particular, gain of function of Zfhx3 significantly shortens circadian rhythms and alters the transcriptional activity of an important class of neuropeptides that controls intercellular signaling in the suprachiasmatic nucleus (SCN of the hypothalamus. The ZFHX3/AT axis revealed an important, largely cell-nonautonomous control of the circadian clock. Here, by studying the recently identified circadian mouse mutant Zfhx3Sci/+, we identify significant effects on sleep homeostasis, a phenomenon that is outside the canonical circadian clock system and that is modulated by the activity of those neuropeptides at a circuit level. We show that the Zfhx3Sci/+ mutation accelerates the circadian clock at both the hourly scale (i.e., advancing circadian rhythms and the seconds-to-minutes scale (i.e., anticipating behavioral responses in mice. The in vivo results are accompanied by a significant presence of sleep targets among protein-protein interactions of the Zfhx3Sci/+-dependent network.

Daily chronomics of proteomic profile in aging and rotenone-induced Parkinson's disease model in male Wistar rat and its modulation by melatonin.

Science.gov (United States)

Jagota, Anita; Mattam, Ushodaya

2017-08-01

Aging is associated with changes in several basic parameters of circadian timing system (CTS) in mammals leading to circadian dysfunction. We had reported earlier that upon aging and in rotenone induced Parkinson's disease (RIPD) rat model there were significant alterations in the core clock genes expression levels and daily pulses. To identify biomarkers of aging and PD chronomics of proteomic day-night profiles in suprachiasmatic nucleus (SCN), pineal and substantia nigra (SN) in 3 month (m), 12, 24 m and RIPD rat model were studied at two time points i.e. Zeitgeber Time (ZT)-6 (mid-day) and ZT-18 (mid-night). Proteome analysis was done by using two dimensional (2-D) electrophoresis and the spots showing robust day-night variations were identified by using MALDI TOF/TOF analysis. In 3 m rats the number of proteins showing day-night variations were relatively more than 12, 24 m and RIPD rat model in SCN and SN. But in pineal there was increase in number of protein spots showing day-night variations in 24 m. Mass spectroscopy of the protein spots showing robust day night variation in aging and RIPD rats were identified. As melatonin, a multitasking molecule, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging, the effects of melatonin administration on differential alterations in chronomics of 2-D protein profiles in aging and RIPD male Wistar rats were studied. We report here that the melatonin could be playing an important role in modulating the chronomics of 2-D protein profiles. Additionally, various proteins were identified for the first time in this study showing significant day night variation in SCN, pineal and SN may prove useful towards targeting novel treatments for circadian dysfunction, good health and longevity.

The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers

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Makoto eBannai

2012-04-01

Full Text Available Approximately 30% of the general population suffers from insomnia. Given that insomnia causes many problems, amelioration of the symptoms is crucial. Recently, we found that a nonessential amino acid, glycine subjectively and objectively improves sleep quality in humans who have difficulty sleeping. We evaluated the effects of glycine on daytime sleepiness, fatigue and performances in sleep-restricted healthy subjects. Sleep was restricted to 25% less than the usual sleep time for three consecutive nights. Before bedtime, 3 g of glycine or placebo were ingested, sleepiness and fatigue were evaluated using the visual analogue scale (VAS and a questionnaire, and performance were estimated by personal computer (PC performance test program on the following day. In subjects given glycine, the VAS data showed a significant reduction in fatigue and a tendency toward reduced sleepiness. These observations were also found via the questionnaire, indicating that glycine improves daytime sleepiness and fatigue induced by acute sleep restriction. PC performance test revealed significant improvement in psychomotor vigilance test. We also measured plasma melatonin and the expression of circadian-modulated genes expression in the rat suprachiasmatic nucleus (SCN to evaluate the effects of glycine on circadian rhythms. Glycine did not show significant effects on plasma melatonin concentrations during either the dark or light period. Moreover, the expression levels of clock genes such as Bmal1 and Per2 remained unchanged. However, we observed a glycine-induced increase in the neuropeptides arginine vasopressin and vasoactive intestinal polypeptide in the light period. Although no alterations in the circadian clock itself were observed, our results indicate that glycine modulated SCN function. Thus, glycine modulates certain neuropeptides in the SCN and this phenomenon may indirectly contribute to improving the occasional sleepiness and fatigue induced by sleep

Linkage between increased nociception and olfaction via a SCN9A haplotype.

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Dirk Heimann

Full Text Available BACKGROUND AND AIMS: Mutations reducing the function of Nav1.7 sodium channels entail diminished pain perception and olfactory acuity, suggesting a link between nociception and olfaction at ion channel level. We hypothesized that if such link exists, it should work in both directions and gain-of-function Nav1.7 mutations known to be associated with increased pain perception should also increase olfactory acuity. METHODS: SCN9A variants were assessed known to enhance pain perception and found more frequently in the average population. Specifically, carriers of SCN9A variants rs41268673C>A (P610T; n = 14 or rs6746030C>T (R1150W; n = 21 were compared with non-carriers (n = 40. Olfactory function was quantified by assessing odor threshold, odor discrimination and odor identification using an established olfactory test. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (punctate and blunt mechanical pressure, heat and electrical stimuli. RESULTS: The number of carried alleles of the non-mutated SCN9A haplotype rs41268673C/rs6746030C was significantly associated with the comparatively highest olfactory threshold (0 alleles: threshold at phenylethylethanol dilution step 12 of 16 (n = 1, 1 allele: 10.6±2.6 (n = 34, 2 alleles: 9.5±2.1 (n = 40. The same SCN9A haplotype determined the pain threshold to blunt pressure stimuli (0 alleles: 21.1 N/m(2, 1 allele: 29.8±10.4 N/m(2, 2 alleles: 33.5±10.2 N/m(2. CONCLUSIONS: The findings established a working link between nociception and olfaction via Nav1.7 in the gain-of-function direction. Hence, together with the known reduced olfaction and pain in loss-of-function mutations, a bidirectional genetic functional association between nociception and olfaction exists at Nav1.7 level.

Epidural Analgesia with Ropivacaine during Labour in a Patient with a SCN5A Gene Mutation

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A. L. M. J. van der Knijff-van Dortmont

2016-01-01

Full Text Available SCN5A gene mutations can lead to ion channel defects which can cause cardiac conduction disturbances. In the presence of specific ECG characteristics, this mutation is called Brugada syndrome. Many drugs are associated with adverse events, making anesthesia in patients with SCN5A gene mutations or Brugada syndrome challenging. In this case report, we describe a pregnant patient with this mutation who received epidural analgesia using low dose ropivacaine and sufentanil during labour.

Solution-processed inorganic copper(I) thiocyanate (CuSCN) hole transporting layers for efficient p–i–n perovskite solar cells

KAUST Repository

Zhao, Kui

2015-08-27

CuSCN is a highly transparent, highly stable, low cost and easy to solution process HTL that is proposed as a low cost replacement to existing organic and inorganic metal oxide hole transporting materials. Here, we demonstrate hybrid organic-inorganic perovskite-based p-i-n planar heterojunction solar cells using a solution-processed copper(I) thiocyanate (CuSCN) bottom hole transporting layer (HTL). CuSCN, with its high workfunction, increases the open circuit voltage (Voc) by 0.23 V to 1.06 V as compared with devices based on the well-known poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) (0.83 V), resulting in a superior power conversion efficiency (PCE) of 10.8% without any notable hysteresis. Photoluminescence measurements suggest a similar efficiency of charge transfer at HTL/perovskite interface as PEDOT:PSS. However, we observe more efficient light harvesting in the presence of CuSCN at shorter wavelengths despite PEDOT:PSS being more transparent. Further investigation of the microstructure and morphology reveals differences in the crystallographic texture of the polycrystalline perovskite film, suggesting somewhat modified perovskite growth on the surface of CuSCN. The successful demonstration of the solution-processed inorganic HTL using simple and low temperature processing routes bodes well for the development of reliable and efficient flexible p-i-n perovskite modules or for integration as a front cell in hybrid tandem solar cells.

(1-Butyl-4-methyl-pyridinium)[Cu(SCN)2]: a coordination polymer and ionic liquid.

Science.gov (United States)

Spielberg, Eike T; Edengeiser, Eugen; Mallick, Bert; Havenith, Martina; Mudring, Anja-Verena

2014-04-25

The compound (C4C1py)[Cu(SCN)2], (C4C1py = 1-Butyl-4-methyl-pyridinium), which can be obtained from CuSCN and the ionic liquid (C4C1py)(SCN), turns out to be a new organic-inorganic hybrid material as it qualifies both, as a coordination polymer and an ionic liquid. It features linked [Cu(SCN)2](-) units, in which the thiocyanates bridge the copper ions in a μ1,3-fashion. The resulting one-dimensional chains run along the a axis, separated by the C4C1py counterions. Powder X-ray diffraction not only confirms the single-crystal X-ray structure solution but proves the reformation of the coordination polymer from an isotropic melt. However, the materials shows a complex thermal behavior often encountered for ionic liquids such as a strong tendency to form a supercooled melt. At a relatively high cooling rate, glass formation is observed. When heating this melt in differential scanning calorimetry (DSC) and temperature-dependent polarizing optical microscopy (POM), investigations reveal the existence of a less thermodynamically stable crystalline polymorph. Raman measurements conducted at 10 and 100 °C point towards the formation of polyanionic chain fragments in the melt. Solid-state UV/Vis spectroscopy shows a broad absorption band around 18,870 cm(-1) (530 nm) and another strong one below 20,000 cm(-1) (<500 nm). The latter is attributed to the d(Cu(I))→π*(SCN)-MLCT (metal-to-ligand charge transfer) transition within the coordination polymer yielding an energy gap of 2.4 eV. At room temperature and upon irradiation with UV light, the material shows a weak fluorescence band at 15,870 cm(-1) (630 nm) with a quantum efficiency of 0.90(2) % and a lifetime of 131(2) ns. Upon lowering the temperature, the luminescence intensity strongly increases. Simultaneously, the band around 450 nm in the excitation spectrum decreases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polysialic acid enters the cell nucleus attached to a fragment of the neural cell adhesion molecule NCAM to regulate the circadian rhythm in mouse brain.

Science.gov (United States)

Westphal, Nina; Kleene, Ralf; Lutz, David; Theis, Thomas; Schachner, Melitta

2016-07-01

In the mammalian nervous system, the neural cell adhesion molecule NCAM is the major carrier of the glycan polymer polysialic acid (PSA) which confers important functions to NCAM's protein backbone. PSA attached to NCAM contributes not only to cell migration, neuritogenesis, synaptic plasticity, and behavior, but also to regulation of the circadian rhythm by yet unknown molecular mechanisms. Here, we show that a PSA-carrying transmembrane NCAM fragment enters the nucleus after stimulation of cultured neurons with surrogate NCAM ligands, a phenomenon that depends on the circadian rhythm. Enhanced nuclear import of the PSA-carrying NCAM fragment is associated with altered expression of clock-related genes, as shown by analysis of cultured neuronal cells deprived of PSA by specific enzymatic removal. In vivo, levels of nuclear PSA in different mouse brain regions depend on the circadian rhythm and clock-related gene expression in suprachiasmatic nucleus and cerebellum is affected by the presence of PSA-carrying NCAM in the cell nucleus. Our conceptually novel observations reveal that PSA attached to a transmembrane proteolytic NCAM fragment containing part of the extracellular domain enters the cell nucleus, where PSA-carrying NCAM contributes to the regulation of clock-related gene expression and of the circadian rhythm. Copyright © 2016 Elsevier Inc. All rights reserved.

Contrasting oxygen-effects in the inactivation of ribonuclease A by N3, (SCN)-2 and OH radicals

International Nuclear Information System (INIS)

Pruetz, W.A.

1979-01-01

N 3 exhibits higher efficiency than OH in the inactivation of RNase in de-acerated (neutral) aqueous solution. In O 2 -saturated solution the OH-induced inactivation is enhanced, but N 3 and (SCN) - 2 become remarkably inefficient. Our results suggest that semi-oxidized tyrosine, the predominant initial defect induced by N 3 and (SCN) - 2 but not by OH, can be re-reduced upon reaction with O - 2 or cysteine. (orig.) [de

Zero lattice mismatch and twin-free single crystalline ScN buffer layers for GaN growth on silicon

Energy Technology Data Exchange (ETDEWEB)

Lupina, L.; Zoellner, M. H.; Dietrich, B.; Capellini, G. [IHP, Im Technologiepark 25, 15236 Frankfurt, Oder (Germany); Niermann, T.; Lehmann, M. [Technische Universität Berlin, Institut für Optik und Atomare Physik, Straße des 17. Juni 135, 10623 Berlin (Germany); Thapa, S. B.; Haeberlen, M.; Storck, P. [SILTRONIC AG, Hanns-Seidel-Platz 4, 81737 München (Germany); Schroeder, T. [IHP, Im Technologiepark 25, 15236 Frankfurt, Oder (Germany); BTU Cottbus, Konrad-Zuse-Str. 1, 03046 Cottbus (Germany)

2015-11-16

We report the growth of thin ScN layers deposited by plasma-assisted molecular beam epitaxy on Sc{sub 2}O{sub 3}/Y{sub 2}O{sub 3}/Si(111) substrates. Using x-ray diffraction, Raman spectroscopy, and transmission electron microscopy, we find that ScN films grown at 600 °C are single crystalline, twin-free with rock-salt crystal structure, and exhibit a direct optical band gap of 2.2 eV. A high degree of crystalline perfection and a very good lattice matching between ScN and GaN (misfit < 0.1%) makes the ScN/Sc{sub 2}O{sub 3}/Y{sub 2}O{sub 3} buffer system a very promising template for the growth of high quality GaN layers on silicon.

Sick sinus syndrome, progressive cardiac conduction disease, atrial flutter and ventricular tachycardia caused by a novel SCN5A mutation

DEFF Research Database (Denmark)

Holst, Anders G; Liang, Bo; Jespersen, Thomas

2010-01-01

father carried the same mutation, but had a milder phenotype, presenting with progressive cardiac conduction later in life. The mutation was found to result in a loss-of-function in the sodium current. In conclusion, the same SCN5A mutation can result in a wide array of clinical phenotypes and perhaps......Mutations in the cardiac sodium channel encoded by the gene SCN5A can result in a wide array of phenotypes. We report a case of a young male with a novel SCN5A mutation (R121W) afflicted by sick sinus syndrome, progressive cardiac conduction disorder, atrial flutter and ventricular tachycardia. His...

Particle correlations in proton-nucleus and nucleus-nucleus collisions

International Nuclear Information System (INIS)

Nagamiya, Sh.

1981-01-01

Particle correlations in proton-nucleus and nucleus-nucleus collisions at energies of 1-2 GeV/nucleon are investigated. The problems of measurement of the mean free path lambda of protons inside the nucleus and the interaction radius of nucleus-nucleus collisions is considered. The value of lambda has been determined in two-proton coincidence experiment in proton-nucleus interaction at 800 MeV. The observed value of lambda is slightly longer than the expected from free nucleon-nucleon collisions. Some preliminary results on proton emission beyond free nucleon-nucleon kinemaics are given

Ab-initio studies of the Sc adsorption and the ScN thin film formation on the GaN(000-1)-(2 × 2) surface

International Nuclear Information System (INIS)

Guerrero-Sánchez, J.; Sánchez-Ochoa, F.; Cocoletzi, Gregorio H.; Rivas-Silva, J.F.; Takeuchi, Noboru

2013-01-01

First principles total energy calculations have been performed to investigate the initial stages of the Sc adsorption and ScN thin film formation on the GaN(000-1)-(2 × 2) surface. Studies are done within the periodic density functional theory as implemented in the PWscf code of the Quantum ESPRESSO package. The Sc adsorption at high symmetry sites results in the bridge site as the most stable structure. When a Sc monolayer is deposited above the surface the T4 site results as the most stable geometry. The Sc migration into the first Ga monolayer induces the Ga displaced ad-atom to be adsorbed at the T4-2 site. A ScN bilayer may be obtained under the Ga monolayer. Finally a ScN bilayer may be formed in the wurtzite phase above the surface. The formation energy plots show that in the moderate Ga-rich conditions we obtain the formation of a ScN bilayer under the gallium monolayer. However at N-rich conditions the formation of ScN bilayer above the surface is the most favorable structure. We report the density of states to explain the electronic structure of the most favorable geometries. - Highlights: • Studies of the initial stages in the formation of Sc and ScN structures on GaN • In the adsorption of Sc on the GaN the Br site is the most favorable geometry. • When a Sc replaces a Ga of the first monolayer the displaced Ga occupies a T4-2 site. • For Ga-rich conditions there is formation of ScN under the Ga monolayer. • In N-rich conditions there is formation of ScN in the wurtzite phase

A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

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Vargas-Alarcon Gilberto

2012-02-01

Full Text Available Abstract Background A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM; and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7 act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms. Methods We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ. Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637. Results The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036 mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88 than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002 and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001. Conclusion In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that

Hole-transporting transistors and circuits based on the transparent inorganic semiconductor copper(I) thiocyanate (CuSCN) processed from solution at room temperature

KAUST Repository

Pattanasattayavong, Pichaya

2012-12-27

The wide bandgap and highly transparent inorganic compound copper(I) thiocyanate (CuSCN) is used for the first time to fabricate p-type thin-film transistors processed from solution at room temperature. By combining CuSCN with the high-k relaxor ferroelectric polymeric dielectric P(VDF-TrFE-CFE), we demonstrate low-voltage transistors with hole mobilities on the order of 0.1 cm2 V-1 s-1. By integrating two CuSCN transistors, unipolar logic NOT gates are also demonstrated. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SCN5A mutations and polymorphisms in patients with ventricular fibrillation during acute myocardial infarction.

Science.gov (United States)

Boehringer, Tim; Bugert, Peter; Borggrefe, Martin; Elmas, Elif

2014-10-01

Mutations in the SCN5A gene encoding the Nav1.5 channel α-subunit are known to be risk factors of arrhythmia, including Brugada Syndrome and Long QT syndrome subtype 3. The present study focused on the role of SCN5A variants in the development of ventricular fibrillation (VF) during acute myocardial infarction (AMI). Since VF during AMI is the major cause of sudden death in the Western world, SCN5A mutations represent genetic risk factors for sudden death. By exon re-sequencing, the entire coding region and flanking intron regions were sequenced in 46 AMI/VF+ patients. In total, nine single nucleotide variants were identified of which four represented common single nucleotide polymorphisms (SNPs; 87G>A, 1673A>G, IVS16‑6C>T and 5457T>A). Only five rare variants were identified, each in only one patient. Only two of the rare variants represented missense mutations (3578G>A and 4786T>A). The common SNPs and the missense mutations were also genotyped using polymerase chain reaction methods in 79 AMI/VF‑ patients and 480 healthy controls. The SNPs did not demonstrate significant differences in allele and genotype frequencies between the study groups. The 3578G>A mutation was identified in one out of the 480 controls, whereas the 4786T>A mutation was not present in AMI/VF- patients and controls. In conclusion, the majority of AMI/VF+ patients demonstrated a wild type sequence or common SNPs in SCN5A. Only two out of 46 (4.3%) AMI/VF+ patients revealed mutations that may be involved in Nav1.5 dysfunction and VF. However, this requires further functional validation.

Constant Light Desynchronizes Olfactory versus Object and Visuospatial Recognition Memory Performance.

Science.gov (United States)

Tam, Shu K E; Hasan, Sibah; Choi, Harry M C; Brown, Laurence A; Jagannath, Aarti; Hughes, Steven; Hankins, Mark W; Foster, Russell G; Vyazovskiy, Vladyslav V; Bannerman, David M; Peirson, Stuart N

2017-03-29

Circadian rhythms optimize physiology and behavior to the varying demands of the 24 h day. The master circadian clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and it regulates circadian oscillators in tissues throughout the body to prevent internal desynchrony. Here, we demonstrate for the first time that, under standard 12 h:12 h light/dark (LD) cycles, object, visuospatial, and olfactory recognition performance in C57BL/6J mice is consistently better at midday relative to midnight. However, under repeated exposure to constant light ( r LL), recognition performance becomes desynchronized, with object and visuospatial performance better at subjective midday and olfactory performance better at subjective midnight. This desynchrony in behavioral performance is mirrored by changes in expression of the canonical clock genes Period1 and Period2 ( Per1 and Per2 ), as well as the immediate-early gene Fos in the SCN, dorsal hippocampus, and olfactory bulb. Under r LL, rhythmic Per1 and Fos expression is attenuated in the SCN. In contrast, hippocampal gene expression remains rhythmic, mirroring object and visuospatial performance. Strikingly, Per1 and Fos expression in the olfactory bulb is reversed, mirroring the inverted olfactory performance. Temporal desynchrony among these regions does not result in arrhythmicity because core body temperature and exploratory activity rhythms persist under r LL. Our data provide the first demonstration that abnormal lighting conditions can give rise to temporal desynchrony between autonomous circadian oscillators in different regions, with different consequences for performance across different sensory domains. Such a dispersed network of dissociable circadian oscillators may provide greater flexibility when faced with conflicting environmental signals. SIGNIFICANCE STATEMENT A master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus regulates physiology and behavior across the 24 h day by

Constant Light Desynchronizes Olfactory versus Object and Visuospatial Recognition Memory Performance

Science.gov (United States)

Tam, Shu K.E.; Hasan, Sibah; Brown, Laurence A.; Jagannath, Aarti; Hankins, Mark W.; Foster, Russell G.; Vyazovskiy, Vladyslav V.

2017-01-01

Circadian rhythms optimize physiology and behavior to the varying demands of the 24 h day. The master circadian clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and it regulates circadian oscillators in tissues throughout the body to prevent internal desynchrony. Here, we demonstrate for the first time that, under standard 12 h:12 h light/dark (LD) cycles, object, visuospatial, and olfactory recognition performance in C57BL/6J mice is consistently better at midday relative to midnight. However, under repeated exposure to constant light (rLL), recognition performance becomes desynchronized, with object and visuospatial performance better at subjective midday and olfactory performance better at subjective midnight. This desynchrony in behavioral performance is mirrored by changes in expression of the canonical clock genes Period1 and Period2 (Per1 and Per2), as well as the immediate-early gene Fos in the SCN, dorsal hippocampus, and olfactory bulb. Under rLL, rhythmic Per1 and Fos expression is attenuated in the SCN. In contrast, hippocampal gene expression remains rhythmic, mirroring object and visuospatial performance. Strikingly, Per1 and Fos expression in the olfactory bulb is reversed, mirroring the inverted olfactory performance. Temporal desynchrony among these regions does not result in arrhythmicity because core body temperature and exploratory activity rhythms persist under rLL. Our data provide the first demonstration that abnormal lighting conditions can give rise to temporal desynchrony between autonomous circadian oscillators in different regions, with different consequences for performance across different sensory domains. Such a dispersed network of dissociable circadian oscillators may provide greater flexibility when faced with conflicting environmental signals. SIGNIFICANCE STATEMENT A master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus regulates physiology and behavior across the 24 h day by

Pathophysiological mechanisms of sino-atrial dysfunction and ventricular conduction disease associated with SCN5A deficiency: insights from mouse models

Directory of Open Access Journals (Sweden)

Christopher L-H Huang

2012-07-01

Full Text Available Genetically modified mice provide a number of models for studying cardiac channelopathies related to cardiac Na+ channel (SCN5A abnormalities. We review key pathophysiological features in these murine models that may underlie clinical features observed in sinus node dysfunction and progressive cardiac conduction disease, thereby providing insights into their pathophysiological mechanisms. We describe loss of Na+ channel function and fibrotic changes associated with both loss and gain-of-function Na+ channel mutations. Recent reports further relate the progressive fibrotic changes to upregulation of TGF-β1 production and the transcription factors, Atf3, a stress-inducible gene, and Egr1, to the presence of heterozygous Scn5a inactivation. Both changes are thus directly implicated in the clinically observed disruptions in sino-atrial node pacemaker function, and sino-atrial and ventricular conduction, and their progression with age. Murine systems with genetic modifications in Scn5a thus prove a useful tool to address questions concerning roles of genetic and environmental modifiers on human SCN5A disease phenotypes.

β1-C121W Is Down But Not Out: Epilepsy-Associated Scn1b-C121W Results in a Deleterious Gain-of-Function

Science.gov (United States)

Kruger, Larisa C.; O'Malley, Heather A.; Hull, Jacob M.; Kleeman, Amanda; Patino, Gustavo A.

2016-01-01

Voltage-gated sodium channel (VGSC) β subunits signal through multiple pathways on multiple time scales. In addition to modulating sodium and potassium currents, β subunits play nonconducting roles as cell adhesion molecules, which allow them to function in cell–cell communication, neuronal migration, neurite outgrowth, neuronal pathfinding, and axonal fasciculation. Mutations in SCN1B, encoding VGSC β1 and β1B, are associated with epilepsy. Autosomal-dominant SCN1B-C121W, the first epilepsy-associated VGSC mutation identified, results in genetic epilepsy with febrile seizures plus (GEFS+). This mutation has been shown to disrupt both the sodium-current-modulatory and cell-adhesive functions of β1 subunits expressed in heterologous systems. The goal of this study was to compare mice heterozygous for Scn1b-C121W (Scn1b+/W) with mice heterozygous for the Scn1b-null allele (Scn1b+/−) to determine whether the C121W mutation results in loss-of-function in vivo. We found that Scn1b+/W mice were more susceptible than Scn1b+/− and Scn1b+/+ mice to hyperthermia-induced convulsions, a model of pediatric febrile seizures. β1-C121W subunits are expressed at the neuronal cell surface in vivo. However, despite this, β1-C121W polypeptides are incompletely glycosylated and do not associate with VGSC α subunits in the brain. β1-C121W subcellular localization is restricted to neuronal cell bodies and is not detected at axon initial segments in the cortex or cerebellum or at optic nerve nodes of Ranvier of Scn1bW/W mice. These data, together with our previous results showing that β1-C121W cannot participate in trans-homophilic cell adhesion, lead to the hypothesis that SCN1B-C121W confers a deleterious gain-of-function in human GEFS+ patients. SIGNIFICANCE STATEMENT The mechanisms underlying genetic epilepsy syndromes are poorly understood. Closing this gap in knowledge is essential to the development of new medicines to treat epilepsy. We have used mouse models to

Nucleus-nucleus potential with repulsive core and elastic scattering. Part 1. Nucleus-nucleus interaction potential

International Nuclear Information System (INIS)

Davidovs'ka, O.Yi.; Denisov, V.Yu.; Nesterov, V.O.

2010-01-01

Various approaches for nucleus-nucleus interaction potential evaluation are discussed in details. It is shown that the antisymmetrization of nucleons belonging to different nuclei and the Pauli principle give the essential contribution into the nucleus-nucleus potential at distances, when nuclei are strongly overlapping, and lead to appearance of the repulsive core of nucleus nucleus interaction at small distances between nuclei.

In a rat model of night work, activity during the normal resting phase produces desynchrony in the hypothalamus.

Science.gov (United States)

Salgado-Delgado, Roberto; Nadia, Saderi; Angeles-Castellanos, M; Buijs, Ruud M; Escobar, Carolina

2010-12-01

Internal synchrony among external cycles and internal oscillators allows adaptation of physiology to cyclic demands for homeostasis. Night work and shift work lead to a disrupted phase relationship between external time cues and internal rhythms, also losing internal coherence among oscillations. This process results in internal desynchrony (ID) in which behavioral, hormonal, and metabolic variables cycle out of phase. It is still not clear whether ID originates at a peripheral or at a central level. In order to determine the possible role of hypothalamic oscillators in ID, we explored with a rat model of "night work" daily rhythms of activity and clock gene expression in the hypothalamus. This study provides evidence that wakefulness and activity during the normal resting phase lead to a shift in the diurnal rhythms of c-Fos and induce a rhythm of PER1 in the arcuate and dorsomedial nucleus of the hypothalamus, both associated with metabolism and regulation of the sleep/wake cycle. Moreover, the number of orexin (ORX)-positive neurons and c-Fos in the perifornical area increased during the working period, suggesting a relevant switch of activity in this brain region induced by the scheduled activity; however, the colocalization of c-Fos in ORX-positive cells was not increased. In contrast, the suprachiasmatic nucleus and the paraventricular nucleus remained locked to the light/dark cycle, resulting in ID in the hypothalamus. Present data suggest that ID occurs already at the level of the first output projections from the SCN, relaying nuclei that transmit temporal signals to other brain areas and to the periphery.

Shift Work in Rats Results in Increased Inflammatory Response after Lipopolysaccharide Administration: A Role for Food Consumption.

Science.gov (United States)

Guerrero-Vargas, Natalí N; Guzmán-Ruiz, Mara; Fuentes, Rebeca; García, Joselyn; Salgado-Delgado, Roberto; Basualdo, María del Carmen; Escobar, Carolina; Markus, Regina P; Buijs, Ruud M

2015-08-01

The suprachiasmatic nucleus (SCN) drives circadian rhythms in behavioral and physiological variables, including the inflammatory response. Shift work is known to disturb circadian rhythms and is associated with increased susceptibility to develop disease. In rodents, circadian disruption due to shifted light schedules (jet lag) induced increased innate immune responses. To gain more insight into the influence of circadian disruption on the immune response, we characterized the inflammatory response in a model of rodent shift work and demonstrated that circadian disruption affected the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. Since food consumption is a main disturbing element in the shift work schedule, we also evaluated the inflammatory response to LPS in a group of rats that had no access to food during their working hours. Our results demonstrated that the shift work schedule decreased basal TNF-α levels in the liver but not in the circulation. Despite this, we observed that shift work induced increased cytokine response after LPS stimulation in comparison to control rats. Also, Kupffer cells (liver macrophages) isolated from shift work rats produced more TNF-α in response to in vitro LPS stimulation, suggesting important effects of circadian desynchronization on the functionality of this cell type. Importantly, the effects of shift work on the inflammatory response to LPS were prevented when food was not available during the working schedule. Together, these results show that dissociating behavior and food intake from the synchronizing drive of the SCN severely disturbs the immune response. © 2015 The Author(s).

Effects of simulated microgravity on circadian rhythm of caudal arterial pressure and heart rate in rats and their underlying mechanism

Directory of Open Access Journals (Sweden)

Li CHEN

2016-04-01

Full Text Available Objective 　To explore the effects of simulated microgravity on the circadian rhythm of rats' caudal arterial pressure and heart rate, and their underlying mechanism. Methods 　Eighteen male SD rats (aged 8 weeks were randomly assigned to control (CON and tail suspension (SUS group (9 each. Rats with tail suspension for 28 days were adopted as the animal model to simulate microgravity. Caudal arterial pressure and heart rate of rats were measured every 3 hours. The circadian difference of abdominal aorta contraction was measured by aortic ring test. Western blotting was performed to determine and compare the protein expression level of clock genes such as Per2 (Period2, Bmal1 (Aryl hydrocarbon receptor nuclear translocatorlike and dbp (D element binding protein in suprachiasmatic nucleus (SCN and abdominal aorta of rats in CON and SUS group at different time points. Results 　Compared with CON group, the caudal arterial pressure, both systolic and diastolic pressure, decreased significantly and the diurnal variability disappeared, meanwhile the heart rate increased obviously and also the diurnal variability disappeared in rats of SUS group. Compared with CON group, the contraction reactivity of abdominal aorta decreased with disappearence of the diurnal variability, and also the clock genes expression in SCN and abdominal aorta showed no diurnal variability in rats of SUS group. Conclusion 　Simulated microgravity may lead to circadian rhythm disorders in rats' cardiovascular system, which may be associated with the changes of the clock genes expression. DOI: 10.11855/j.issn.0577-7402.2016.04.06

Role of common and rare variants in SCN10A

DEFF Research Database (Denmark)

Behr, Elijah R.; Savio-Galimberti, Eleonora; Barc, Julien

2015-01-01

AIMS: Brugada syndrome (BrS) remains genetically heterogeneous and is associated with slowed cardiac conduction. We aimed to identify genetic variation in BrS cases at loci associated with QRS duration. METHODS AND RESULTS: A multi-centre study sequenced seven candidate genes (SCN10A, HAND1, PLN,...

Red light emission from ZnO:Eu"3"+|CuSCN hetero-junction under cathodic polarization

International Nuclear Information System (INIS)

Sirimanne, P.M.; Minoura, H.

2015-01-01

Eu"3"+ ions were bonded to ZnO ceramic via organic ligand. Surface bonded Eu"3"+ ions were exhibited specific luminescence bands due to electron transitions between f–f intra-configurationally transitions. Further enhancement of luminescence bands was observed by attaching selected oligomers to Eu"3"+ ions. A hetero-junction was prepared by depositing copper-thiocyanate on Eu"3"+ ions bonded ZnO ceramic. Red light emission was observed from surface bonded Eu"3"+ ions in ZnO:Eu"3"+|CuSCN hetero-junction under reverse bias. - Highlights: • Europium doped ZnO ceramic exhibits photo-luminescence. • Semiconductor hetro-junction was prepared. • ZnO:Eu"3"+|CuSCN hetero-junction emits red light under reverse bias.

Momentum loss in proton-nucleus and nucleus-nucleus collisions

International Nuclear Information System (INIS)

Khan, F.; Townsend, L.W.

1993-12-01

An optical model description, based on multiple scattering theory, of longitudinal momentum loss in proton-nucleus and nucleus-nucleus collisions is presented. The crucial role of the imaginary component of the nucleon-nucleon transition matrix in accounting for longitudinal momentum transfer is demonstrated. Results obtained with this model are compared with Intranuclear Cascade (INC) calculations, as well as with predictions from Vlasov-Uehling-Uhlenbeck (VUU) and quantum molecular dynamics (QMD) simulations. Comparisons are also made with experimental data where available. These indicate that the present model is adequate to account for longitudinal momentum transfer in both proton-nucleus and nucleus-nucleus collisions over a wide range of energies

Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission.

Science.gov (United States)

Han, Sung; Tai, Chao; Westenbroek, Ruth E; Yu, Frank H; Cheah, Christine S; Potter, Gregory B; Rubenstein, John L; Scheuer, Todd; de la Iglesia, Horacio O; Catterall, William A

2012-09-20

Haploinsufficiency of the SCN1A gene encoding voltage-gated sodium channel Na(V)1.1 causes Dravet's syndrome, a childhood neuropsychiatric disorder including recurrent intractable seizures, cognitive deficit and autism-spectrum behaviours. The neural mechanisms responsible for cognitive deficit and autism-spectrum behaviours in Dravet's syndrome are poorly understood. Here we report that mice with Scn1a haploinsufficiency exhibit hyperactivity, stereotyped behaviours, social interaction deficits and impaired context-dependent spatial memory. Olfactory sensitivity is retained, but novel food odours and social odours are aversive to Scn1a(+/-) mice. GABAergic neurotransmission is specifically impaired by this mutation, and selective deletion of Na(V)1.1 channels in forebrain interneurons is sufficient to cause these behavioural and cognitive impairments. Remarkably, treatment with low-dose clonazepam, a positive allosteric modulator of GABA(A) receptors, completely rescued the abnormal social behaviours and deficits in fear memory in the mouse model of Dravet's syndrome, demonstrating that they are caused by impaired GABAergic neurotransmission and not by neuronal damage from recurrent seizures. These results demonstrate a critical role for Na(V)1.1 channels in neuropsychiatric functions and provide a potential therapeutic strategy for cognitive deficit and autism-spectrum behaviours in Dravet's syndrome.

Electric field-induced hole transport in copper(i) thiocyanate (CuSCN) thin-films processed from solution at room temperature

KAUST Repository

Pattanasattayavong, Pichaya; Ndjawa, Guy Olivier Ngongang; Zhao, Kui; Chou, Kang Wei; Yaacobi-Gross, Nir; O'Regan, Brian C.; Amassian, Aram; Anthopoulos, Thomas D.

2013-01-01

The optical, structural and charge transport properties of solution-processed films of copper(i) thiocyanate (CuSCN) are investigated in this work. As-processed CuSCN films of ∼20 nm in thickness are found to be nano-crystalline, highly transparent and exhibit intrinsic hole transporting characteristics with a maximum field-effect mobility in the range of 0.01-0.1 cm2 V-1 s-1. © 2013 The Royal Society of Chemistry.

Mechanisms of High Energy Hadron-Nucleus and Nucleus-Nucleus Collision Processes

International Nuclear Information System (INIS)

Strugalski, Z.

1994-01-01

Mechanisms of high energy hadron-nucleus and nucleus-nucleus collision processes are depicted qualitatively, as prompted experimentally. In hadron-nucleus collisions the interaction of the incident hadron in intranuclear matter is localized in small cylindrical volume, with the radius as large as the strong interaction range is, centered on the hadron course in the nucleus. The nucleon emission is induced by the hadron in its passing through the nucleus; particles are produced via intermediate objects produced in 2 → 2 endoergic reactions of the hadron and its successors with downstream nucleons. In nucleus-nucleus collisions, the outcome of the reaction appears as the composition of statistically independent hadron-nucleus collision outcomes at various impact parameters. Observable effects supporting such mechanisms are discussed. 51 refs

Terminal distribution of retinal fibers in the tegu lizard (Tupinambis nigropunctatus).

Science.gov (United States)

Ebbesson, S O; Karten, H J

1981-01-01

The retinal projections in the tegu lizard were traced using degeneration-silver methods. Bilateral projections were found to the dorsolateral geniculate and the posterodorsal nuclei. Unilateral, crossed projections were traced to the suprachiasmatic nucleus, the ventrolateral geniculate nucleus, the mesencephalic lentiform nucleus, nucleus geniculatus praetectalis, the ectomammillary nucleus, and the optic tectum. Some of these connections are distinctly different from those reported in other reptiles and suggest that important interspecific variations occur among reptiles.

Efficient and stable CH3NH3PbI3-x(SCN)x planar perovskite solar cells fabricated in ambient air with low-temperature process

Science.gov (United States)

Zhang, Zongbao; Zhou, Yang; Cai, Yangyang; Liu, Hui; Qin, Qiqi; Lu, Xubing; Gao, Xingsen; Shui, Lingling; Wu, Sujuan; Liu, Jun-Ming

2018-02-01

Planar perovskite solar cells (PSCs) based on CH3NH3PbI3-x(SCN)x (SCN: thiocyanate) active layer and low-temperature processed TiO2 films are fabricated by a sequential two-step method in ambient air. Here, alkali thiocyanates (NaSCN, KSCN) are added into Pb(SCN)2 precursor to improve the microstructure of CH3NH3PbI3-x(SCN)x perovskite layers and performance of the as-prepared PSCs. At the optimum concentrations of alkali thiocyanates as additives, the as-prepared NaSCN-modified and KSCN-modified PSCs demonstrate the efficiencies of 16.59% and 15.63% respectively, being much higher than 12.73% of the reference PSCs without additives. This improvement is primarily ascribed to the enhanced electron transport, reduced recombination rates and much improved microstructures with large grain size and low defect density at grain boundaries. Importantly, it is revealed that the modified PSCs at the optimized concentrations of alkali thiocyanates additives exhibit remarkably improved stability than the reference PSCs against humid circumstance, and a continuous exposure to humid air without encapsulation over 45 days only records about 5% degradation of the efficiency. These findings provide a facile approach to fabricate efficient and stable PSCs by low processing temperature in ambient air, both of which are highly preferred for future practical applications of PSCs.

Antiproton production in nucleon-nucleus and nucleus-nucleus collisions at the CERN-SPS

International Nuclear Information System (INIS)

Kadija, K.; Schmitz, N.; Seyboth, P.

1996-01-01

A model for antiproton production in nucleon-nucleus and nucleus-nucleus collisions at 200 GeV per nucleon, based on the wounded nucleon model is developed. The predictions are compared to published nucleon-nucleus and sulphur-nucleus data. The results suggest the presence of similar antiproton production processes in nucleon-nucleus and nucleus-nucleus collisions near midrapidity. (orig.)

Nucleus-nucleus total reaction cross sections

International Nuclear Information System (INIS)

DeVries, R.M.; Peng, J.C.

1980-01-01

We compare sigma/sub R/(E) for nucleus-nucleus systems (obtained from existing direct measurements and derived from elastic scattering data) with nucleon-nucleon and nucleon-nucleus data. The energy dependence of sigma/sub R/(E) for nucleus-nucleus systems is found to be quite rapid; there appears to be no evidence for an energy independent, geometric sigma/sub R/. Simple parameter free microscopic calculations are able to quantitatively reproduce the data and thus, emphasize the dominance of nucleon-nucleon interactions in medium energy nucleus-nucleus collisions

Nucleus-Nucleus Collision as Superposition of Nucleon-Nucleus Collisions

International Nuclear Information System (INIS)

Orlova, G.I.; Adamovich, M.I.; Aggarwal, M.M.; Alexandrov, Y.A.; Andreeva, N.P.; Badyal, S.K.; Basova, E.S.; Bhalla, K.B.; Bhasin, A.; Bhatia, V.S.; Bradnova, V.; Bubnov, V.I.; Cai, X.; Chasnikov, I.Y.; Chen, G.M.; Chernova, L.P.; Chernyavsky, M.M.; Dhamija, S.; Chenawi, K.El; Felea, D.; Feng, S.Q.; Gaitinov, A.S.; Ganssauge, E.R.; Garpman, S.; Gerassimov, S.G.; Gheata, A.; Gheata, M.; Grote, J.; Gulamov, K.G.; Gupta, S.K.; Gupta, V.K.; Henjes, U.; Jakobsson, B.; Kanygina, E.K.; Karabova, M.; Kharlamov, S.P.; Kovalenko, A.D.; Krasnov, S.A.; Kumar, V.; Larionova, V.G.; Li, Y.X.; Liu, L.S.; Lokanathan, S.; Lord, J.J.; Lukicheva, N.S.; Lu, Y.; Luo, S.B.; Mangotra, L.K.; Manhas, I.; Mittra, I.S.; Musaeva, A.K.; Nasyrov, S.Z.; Navotny, V.S.; Nystrand, J.; Otterlund, I.; Peresadko, N.G.; Qian, W.Y.; Qin, Y.M.; Raniwala, R.; Rao, N.K.; Roeper, M.; Rusakova, V.V.; Saidkhanov, N.; Salmanova, N.A.; Seitimbetov, A.M.; Sethi, R.; Singh, B.; Skelding, D.; Soderstrem, K.; Stenlund, E.; Svechnikova, L.N.; Svensson, T.; Tawfik, A.M.; Tothova, M.; Tretyakova, M.I.; Trofimova, T.P.; Tuleeva, U.I.; Vashisht, Vani; Vokal, S.; Vrlakova, J.; Wang, H.Q.; Wang, X.R.; Weng, Z.Q.; Wilkes, R.J.; Yang, C.B.; Yin, Z.B.; Yu, L.Z.; Zhang, D.H.; Zheng, P.Y.; Zhokhova, S.I.; Zhou, D.C.

1999-01-01

Angular distributions of charged particles produced in 16 O and 32 S collisions with nuclear track emulsion were studied at momenta 4.5 and 200 A GeV/c. Comparison with the angular distributions of charged particles produced in proton-nucleus collisions at the same momentum allows to draw the conclusion, that the angular distributions in nucleus-nucleus collisions can be seen as superposition of the angular distributions in nucleon-nucleus collisions taken at the same impact parameter b NA , that is mean impact parameter between the participating projectile nucleons and the center of the target nucleus

Nucleus-Nucleus Collision as Superposition of Nucleon-Nucleus Collisions

Energy Technology Data Exchange (ETDEWEB)

Orlova, G I; Adamovich, M I; Aggarwal, M M; Alexandrov, Y A; Andreeva, N P; Badyal, S K; Basova, E S; Bhalla, K B; Bhasin, A; Bhatia, V S; Bradnova, V; Bubnov, V I; Cai, X; Chasnikov, I Y; Chen, G M; Chernova, L P; Chernyavsky, M M; Dhamija, S; Chenawi, K El; Felea, D; Feng, S Q; Gaitinov, A S; Ganssauge, E R; Garpman, S; Gerassimov, S G; Gheata, A; Gheata, M; Grote, J; Gulamov, K G; Gupta, S K; Gupta, V K; Henjes, U; Jakobsson, B; Kanygina, E K; Karabova, M; Kharlamov, S P; Kovalenko, A D; Krasnov, S A; Kumar, V; Larionova, V G; Li, Y X; Liu, L S; Lokanathan, S; Lord, J J; Lukicheva, N S; Lu, Y; Luo, S B; Mangotra, L K; Manhas, I; Mittra, I S; Musaeva, A K; Nasyrov, S Z; Navotny, V S; Nystrand, J; Otterlund, I; Peresadko, N G; Qian, W Y; Qin, Y M; Raniwala, R; Rao, N K; Roeper, M; Rusakova, V V; Saidkhanov, N; Salmanova, N A; Seitimbetov, A M; Sethi, R; Singh, B; Skelding, D; Soderstrem, K; Stenlund, E; Svechnikova, L N; Svensson, T; Tawfik, A M; Tothova, M; Tretyakova, M I; Trofimova, T P; Tuleeva, U I; Vashisht, Vani; Vokal, S; Vrlakova, J; Wang, H Q; Wang, X R; Weng, Z Q; Wilkes, R J; Yang, C B; Yin, Z B; Yu, L Z; Zhang, D H; Zheng, P Y; Zhokhova, S I; Zhou, D C

1999-03-01

Angular distributions of charged particles produced in {sup 16}O and {sup 32}S collisions with nuclear track emulsion were studied at momenta 4.5 and 200 A GeV/c. Comparison with the angular distributions of charged particles produced in proton-nucleus collisions at the same momentum allows to draw the conclusion, that the angular distributions in nucleus-nucleus collisions can be seen as superposition of the angular distributions in nucleon-nucleus collisions taken at the same impact parameter b{sub NA}, that is mean impact parameter between the participating projectile nucleons and the center of the target nucleus.

Nucleus-nucleus collision as superposition of nucleon-nucleus collisions

International Nuclear Information System (INIS)

Orlova, G.I.; Adamovich, M.I.; Aggarwal, M.M.

1999-01-01

Angular distributions of charged particles produced in 16 O and 32 S collisions with nuclear track emulsion were studied at momenta 4.5 and 200 A GeV/c. Comparison with the angular distributions of charged particles produced in proton-nucleus collisions at the same momentum allows to draw the conclusion, that the angular distributions in nucleus-nucleus collisions can be seen as superposition of the angular distributions in nucleon-nucleus collisions taken at the same impact parameter b NA , that is mean impact parameter between the participating projectile nucleons and the center of the target nucleus. (orig.)

ipRGCs: possible causation accounts for the higher prevalence of sleep disorders in glaucoma patients

Directory of Open Access Journals (Sweden)

Zhen-Zhen Guo

2017-07-01

Full Text Available Sleep accounts for a third of one’s lifetime, partial or complete deprivation of sleep could elicit sever disorders of body function. Previous studies have reported the higher prevalence of sleep disorders in glaucoma patients, but the definite mechanism for this phenomenon is unknown. On the other hand, it is well known by us that the intrinsically photosensitive retinal ganglion cells (ipRGCs serve additional ocular functions, called non-image-forming (NIF functions, in the regulation of circadian rhythm, melatonin secretion, sleep, mood and others. Specifically, ipRGCs can directly or indirectly innervate the central areas such as suprachiasmatic nucleus (SCN, downstream pineal gland (the origin of melatonin, sleep and wake-inducing centers and mood regulation areas, making NIF functions of ipRGCs relate to sleep. The more interesting thing is that previous research showed glaucoma not only affected visual functions such as the degeneration of classical retinal ganglion cells (RGCs, but also affected ipRGCs. Therefore, we hypothesize that higher prevalence of sleep disorders in glaucoma patients maybe result from the underlying glaucomatous injuries of ipRGCs leading to the abnormalities of diverse NIF functions corresponding to sleep.

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

NARCIS (Netherlands)

Wolff, Markus; Johannesen, Katrine M; Hedrich, Ulrike B S; Masnada, Silvia; Rubboli, Guido; Gardella, Elena; Lesca, Gaetan; Ville, Dorothée; Milh, Mathieu; Villard, Laurent; Afenjar, Alexandra; Chantot-Bastaraud, Sandra; Mignot, Cyril; Lardennois, Caroline; Nava, Caroline; Schwarz, Niklas; Gérard, Marion; Perrin, Laurence; Doummar, Diane; Auvin, Stéphane; Miranda, Maria J; Hempel, Maja; Brilstra, Eva; Knoers, Nine; Verbeek, Nienke; van Kempen, Marjan; Braun, Kees P; Mancini, Grazia; Biskup, Saskia; Hörtnagel, Konstanze; Döcker, Miriam; Bast, Thomas; Loddenkemper, Tobias; Wong-Kisiel, Lily; Baumeister, Friedrich M; Fazeli, Walid; Striano, Pasquale; Dilena, Robertino; Fontana, Elena; Zara, Federico; Kurlemann, Gerhard; Klepper, Joerg; Thoene, Jess G; Arndt, Daniel H; Deconinck, Nicolas; Schmitt-Mechelke, Thomas; Maier, Oliver; Muhle, Hiltrud; Wical, Beverly; Finetti, Claudio; Brückner, Reinhard; Pietz, Joachim; Golla, Günther; Jillella, Dinesh; Linnet, Karen M; Charles, Perrine; Moog, Ute; Õiglane-Shlik, Eve; Mantovani, John F; Park, Kristen; Deprez, Marie; Lederer, Damien; Mary, Sandrine; Scalais, Emmanuel; Selim, Laila; Van Coster, Rudy; Lagae, Lieven; Nikanorova, Marina; Hjalgrim, Helle; Korenke, G Christoph; Trivisano, Marina; Specchio, Nicola; Ceulemans, Berten; Dorn, Thomas; Helbig, Katherine L; Hardies, Katia; Stamberger, Hannah; de Jonghe, Peter; Weckhuysen, Sarah; Lemke, Johannes R; Krägeloh-Mann, Ingeborg; Helbig, Ingo; Kluger, Gerhard; Lerche, Holger; Møller, Rikke S

2017-01-01

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with

Efficient modeling of chiral media using SCN-TLM method

Directory of Open Access Journals (Sweden)

Yaich M.I.

2004-01-01

Full Text Available An efficient approach allowing to include linear bi-isotropic chiral materials in time-domain transmission line matrix (TLM calculations by employing recursive evaluation of the convolution of the electric and magnetic fields and susceptibility functions is presented. The new technique consists to add both voltage and current sources in supplementary stubs of the symmetrical condensed node (SCN of the TLM method. In this article, the details and the complete description of this approach are given. A comparison of the obtained numerical results with those of the literature reflects its validity and efficiency.

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

Science.gov (United States)

Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav; May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M Arfan; van Duijn, Cornelia M; Uitterlinden, Andre G; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G; Cilio, Maria Roberta; Kunz, Wolfram S; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A

2016-01-01

The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

High-Efficiency Fullerene Solar Cells Enabled by a Spontaneously Formed Mesostructured CuSCN-Nanowire Heterointerface

KAUST Repository

Sit, Wai-Yu

2018-02-02

Fullerenes and their derivatives are widely used as electron acceptors in bulk-heterojunction organic solar cells as they combine high electron mobility with good solubility and miscibility with relevant semiconducting polymers. However, studies on the use of fullerenes as the sole photogeneration and charge-carrier material are scarce. Here, a new type of solution-processed small-molecule solar cell based on the two most commonly used methanofullerenes, namely [6,6]-phenyl-C61-butyric acid methyl ester (PC60BM) and [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM), as the light absorbing materials, is reported. First, it is shown that both fullerene derivatives exhibit excellent ambipolar charge transport with balanced hole and electron mobilities. When the two derivatives are spin-coated over the wide bandgap p-type semiconductor copper (I) thiocyanate (CuSCN), cells with power conversion efficiency (PCE) of ≈1%, are obtained. Blending the CuSCN with PC70BM is shown to increase the performance further yielding cells with an open-circuit voltage of ≈0.93 V and a PCE of 5.4%. Microstructural analysis reveals that the key to this success is the spontaneous formation of a unique mesostructured p–n-like heterointerface between CuSCN and PC70BM. The findings pave the way to an exciting new class of single photoactive material based solar cells.

Some experimental results of the investigation of hadron-nucleus and nucleus-nucleus interactions

International Nuclear Information System (INIS)

Azimov, S.A.; Gulamov, K.G.; Chernov, G.M.

1978-01-01

Recent experimental data on the hadron-nucleus and nucleus-nucleus inelastic interactions are analyzed. A particular attention is paid to the description of the leading hadron spectra and of the spectra of nucleon recoils in hadron-nucleus interactions. Some of the results of the experimental studies of correlations between secondary particles are discussed. This discussion demonstrates that an analysis of the multiparticle phenomena is very promising regarding the discrimination between the different models for the hadron-nucleus and nucleus-nucleus interactions. It is pointed out that the actual mechanism of the hadron-nucleus and nucleus-nucleus interactions is a rather complex one and can be described comprehensively by none of the existing models

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

DEFF Research Database (Denmark)

Wolff, Markus; Johannesen, Katrine M.; Hedrich, Ulrike B. S.

2017-01-01

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infa...

Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor-null mice.

Science.gov (United States)

Sheward, W John; Maywood, Elizabeth S; French, Karen L; Horn, Jacqueline M; Hastings, Michael H; Seckl, Jonathan R; Holmes, Megan C; Harmar, Anthony J

2007-04-18

The master clock driving mammalian circadian rhythms is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and entrained by daily light/dark cycles. SCN lesions abolish circadian rhythms of behavior and result in a loss of synchronized circadian rhythms of clock gene expression in peripheral organs (e.g., the liver) and of hormone secretion (e.g., corticosterone). We examined rhythms of behavior, hepatic clock gene expression, and corticosterone secretion in VPAC2 receptor-null (Vipr2-/-) mice, which lack a functional SCN clock. Unexpectedly, although Vipr2-/- mice lacked robust circadian rhythms of wheel-running activity and corticosterone secretion, hepatic clock gene expression was strongly rhythmic, but advanced in phase compared with that in wild-type mice. The timing of food availability is thought to be an important entrainment signal for circadian clocks outside the SCN. Vipr2-/- mice consumed food significantly earlier in the 24 h cycle than wild-type mice, consistent with the observed timing of peripheral rhythms of circadian gene expression. When restricted to feeding only during the daytime (RF), mice develop rhythms of activity and of corticosterone secretion in anticipation of feeding time, thought to be driven by a food-entrainable circadian oscillator, located outside the SCN. Under RF, mice of both genotypes developed food-anticipatory rhythms of activity and corticosterone secretion, and hepatic gene expression rhythms also became synchronized to the RF stimulus. Thus, food intake is an effective zeitgeber capable of coordinating circadian rhythms of behavior, peripheral clock gene expression, and hormone secretion, even in the absence of a functional SCN clock.

A clinical case of epilepsy in a female patient with double mutations in the SCN2A and PCDH19 genes

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M. B. Mironov

2017-01-01

Full Text Available The paper describes a 6-year-old female patient with epilepsy caused by mutations in the SCN2A and PCDH19 genes, which clinically appears as epileptic seizures, drug-resistant epilepsy, secondary microcephaly, mental retardation, and autism. It reviews the literature regarding both mutations. World literature lacks publications on a combination of two SCN2A and PCDH19 mutations in one female patient with epileptic encephalopathies.

Distinct functions of Period2 and Period3 in the mouse circadian system revealed by in vitro analysis.

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Julie S Pendergast

2010-01-01

Full Text Available The mammalian circadian system, which is composed of a master pacemaker in the suprachiasmatic nuclei (SCN as well as other oscillators in the brain and peripheral tissues, controls daily rhythms of behavior and physiology. Lesions of the SCN abolish circadian rhythms of locomotor activity and transplants of fetal SCN tissue restore rhythmic behavior with the periodicity of the donor's genotype, suggesting that the SCN determines the period of the circadian behavioral rhythm. According to the model of timekeeping in the SCN, the Period (Per genes are important elements of the transcriptional/translational feedback loops that generate the endogenous circadian rhythm. Previous studies have investigated the functions of the Per genes by examining locomotor activity in mice lacking functional PERIOD proteins. Variable behavioral phenotypes were observed depending on the line and genetic background of the mice. In the current study we assessed both wheel-running activity and Per1-promoter-driven luciferase expression (Per1-luc in cultured SCN, pituitary, and lung explants from Per2(-/- and Per3(-/- mice congenic with the C57BL/6J strain. We found that the Per2(-/- phenotype is enhanced in vitro compared to in vivo, such that the period of Per1-luc expression in Per2(-/- SCN explants is 1.5 hours shorter than in Per2+/+ SCN, while the free-running period of wheel-running activity is only 11 minutes shorter in Per2(-/- compared to Per2+/+ mice. In contrast, circadian rhythms in SCN explants from Per3(-/- mice do not differ from Per3+/+ mice. Instead, the period and phase of Per1-luc expression are significantly altered in Per3(-/- pituitary and lung explants compared to Per3+/+ mice. Taken together these data suggest that the function of each Per gene may differ between tissues. Per2 appears to be important for period determination in the SCN, while Per3 participates in timekeeping in the pituitary and lung.

Nighttime dim light exposure alters the responses of the circadian system.

Science.gov (United States)

Shuboni, D; Yan, L

2010-11-10

The daily light dark cycle is the most salient entraining factor for the circadian system. However, in modern society, darkness at night is vanishing as light pollution steadily increases. The impact of brighter nights on wild life ecology and human physiology is just now being recognized. In the present study, we tested the possible detrimental effects of dim light exposure on the regulation of circadian rhythms, using CD1 mice housed in light/dim light (LdimL, 300 lux:20 lux) or light/dark (LD, 300 lux:1 lux) conditions. We first examined the expression of clock genes in the suprachiasmatic nucleus (SCN), the locus of the principal brain clock, in the animals of the LD and LdimL groups. Under the entrained condition, there was no difference in PER1 peak expression between the two groups, but at the trough of the PER 1 rhythm, there was an increase in PER1 in the LdimL group, indicating a decrease in the amplitude of the PER1 rhythm. After a brief light exposure (30 min, 300 lux) at night, the light-induced expression of mPer1 and mPer2 genes was attenuated in the SCN of LdimL group. Next, we examined the behavioral rhythms by monitoring wheel-running activity to determine whether the altered responses in the SCN of LdimL group have behavioral consequence. Compared to the LD controls, the LdimL group showed increased daytime activity. After being released into constant darkness, the LdimL group displayed shorter free-running periods. Furthermore, following the light exposure, the phase shifting responses were smaller in the LdimL group. The results indicate that nighttime dim light exposure can cause functional changes of the circadian system, and suggest that altered circadian function could be one of the mechanisms underlying the adverse effects of light pollution on wild life ecology and human physiology. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

A Switchable Molecular Dielectric with Two Sequential Reversible Phase Transitions: [(CH3)4P]4[Mn(SCN)6].

Science.gov (United States)

Li, Qiang; Shi, Ping-Ping; Ye, Qiong; Wang, Hui-Ting; Wu, De-Hong; Ye, Heng-Yun; Fu, Da-Wei; Zhang, Yi

2015-11-16

A new organic-inorganic hybrid switchable and tunable dielectric compound, [(CH3)4P]4[Mn(SCN)6] (1), exhibits three distinct dielectric states above room temperature and undergoes two reversible solid-state phase transitions, including a structural phase transition at 330 K and a ferroelastic phase transition with the Aizu notation of mmmF2/m at 352 K. The variable-temperature structural analyses disclose that the origin of the phase transitions and dielectric anomalies can be ascribed to the reorientation or motion of both the [(CH3)4P](+) cations and [Mn(SCN)6](4-) anions in solid-state crystals.

The Novel SCN''- Ion-selective Electrode Based on the 1-Benzyl-3-(4-nitrophenyl) thio-urea Ionophore

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyung Mi; Kang, Dong Hyeon; Choe, Ju Eun; You, Jung Min; Go, Min Jeong; Lee, Jung Seong; Jeon, Seung Won [Chungnam National University, Daejeon (Korea, Republic of)

2014-09-15

A potentiometric sensor based on the 1-benzyl-3-(4-nitrophenyl) thio-urea was synthesized and tested as an ionophore in PVC based membrane sensor towards SCN - ions. This membrane exhibits a linear stable response over a wide concentration range (1.0 × 10''-5 to 1.0 × 10''-2 M) with a slope of -59.2 mV/dec., a detection limit of log[SCN''- ] = -5.05, and a selectivity coefficient for thiocyanate against perchlorate anion of logK{sub s}cn''pot = -0.133. The selectivity series of the membrane is as follows: SCN''- > ClO{sub 4}''- > I''- >NO{sub 3}''- >HSO{sub 3}''- > Cl''-HSO{sub '}'-''4 > F''- > CH{sub 3}COO''- > HCO''-''3 > Br''- > H{sub 2}PO{sub 4}''- > SO{sub 3}''-''2 > SO{sub 4}''-''2 > CO{sub 3}''-''2. The proposed electrode showed good selectivity and a good response for the SCN''- ion over a wide variety of other anions in pH 6.0 buffer solutions and has a fast response time of about < 5s.. The influences of the membrane by pH, ionophore, and plasticizer were studied.

High energy nucleus-nucleus scattering and matter radius of unstable nucleus

International Nuclear Information System (INIS)

Sato, H.; Okuhara, Y.

1985-07-01

The interaction cross sections of high energy nucleus-nucleus scattering have been studied with the Glauber Model and Hartree-Fock like variational calculation for the nuclear structure. It is found that the experimental interaction cross sections of the light unstable nucleus-stable nucleus scatterings measured by INS-LBL collaboration are well reproduceable. (author)

Copper(I) Thiocyanate (CuSCN) Hole-Transport Layers Processed from Aqueous Precursor Solutions and Their Application in Thin-Film Transistors and Highly Efficient Organic and Organometal Halide Perovskite Solar Cells

KAUST Repository

Wijeyasinghe, Nilushi

2017-07-28

This study reports the development of copper(I) thiocyanate (CuSCN) hole-transport layers (HTLs) processed from aqueous ammonia as a novel alternative to conventional n-alkyl sulfide solvents. Wide bandgap (3.4–3.9 eV) and ultrathin (3–5 nm) layers of CuSCN are formed when the aqueous CuSCN–ammine complex solution is spin-cast in air and annealed at 100 °C. X-ray photoelectron spectroscopy confirms the high compositional purity of the formed CuSCN layers, while the high-resolution valence band spectra agree with first-principles calculations. Study of the hole-transport properties using field-effect transistor measurements reveals that the aqueous-processed CuSCN layers exhibit a fivefold higher hole mobility than films processed from diethyl sulfide solutions with the maximum values approaching 0.1 cm2 V−1 s−1. A further interesting characteristic is the low surface roughness of the resulting CuSCN layers, which in the case of solar cells helps to planarize the indium tin oxide anode. Organic bulk heterojunction and planar organometal halide perovskite solar cells based on aqueous-processed CuSCN HTLs yield power conversion efficiency of 10.7% and 17.5%, respectively. Importantly, aqueous-processed CuSCN-based cells consistently outperform devices based on poly(3,4-ethylenedioxythiophene) polystyrene sulfonate HTLs. This is the first report on CuSCN films and devices processed via an aqueous-based synthetic route that is compatible with high-throughput manufacturing and paves the way for further developments.

Aging does not compromise in vitro oscillation of the suprachiasmatic nuclei but makes it more vulnerable to constant light

Czech Academy of Sciences Publication Activity Database

Polidarová, Lenka; Sládek, Martin; Novosadová, Zuzana; Sumová, Alena

2017-01-01

Roč. 34, č. 1 (2017), s. 105-117 ISSN 0742-0528 R&D Projects: GA ČR(CZ) GA14-07711S Institutional support: RVO:67985823 Keywords : aging * circadian clock * constant light * suprachiasmatic nuclei * mPer2Luc mice Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 2.562, year: 2016

High energy nucleus-nucleus collisions

International Nuclear Information System (INIS)

Bhalla, K.B.

1980-01-01

An attempt is made to explain nucleus-nucleus collisions based on nuclear emulsion experiments. Peripheral and central collisions are described in detail. Assuming the fireball model, the concepts of geometry, kinematics and thermodynamics in this model are discussed. Projectile and target fragmentations are studied. The advantages of using nuclear emulsions as detectors, are mentioned. Proton-nucleus collisions and nucleus-nucleus collisions are compared. Interactions, of projectiles such as Ca, B and C on targets such as Pb, Ag, Br etc. at very high energies (approximately 300 to 1700 Gev) are listed. A comparison of the near multiplicities in these interactions is given. A generalized explanation is given on the processes involved in these interactions. (A.K.)

Common and rare variants in SCN10A> modulate the risk of atrial fibrillation

DEFF Research Database (Denmark)

Jabbari, Javad; Olesen, Morten S.; Yuan, Lei

2015-01-01

Background: Genome-wide assocn. studies have shown that the common single nucleotide polymorphism rs6800541 located in SCN10A, encoding the voltage-gated Nav1.8 sodium channel, is assocd. with PR-interval prolongation and atrial fibrillation (AF). Single nucleotide polymorphism rs6800541 is in hi...

Reduced Penetrance and Variable Expression of SCN5A Mutations and the Importance of Co-inherited Genetic Variants: Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

T. Robyns, MD.

2014-05-01

Full Text Available Mutations in the SCN5A gene are responsible for multiple phenotypical presentations including Brugada syndrome, long QT syndrome, progressive familial heart block, sick sinus syndrome, dilated cardiomyopathy, lone atrial fibrillation and multiple overlap syndromes. These different phenotypic expressions of a mutation in a single gene can be explained by variable expression and reduced penetrance. One of the possible explanations of these phenomena is the co-inheritance of genetic variants. We describe a family where the individuals exhibit a compound heterozygosity in the SCN5A gene including a mutation (R1632H and a new variant (M858L. Individuals with both the mutation and new variant present with a more severe phenotype including spontaneous atrial tachyarrhythmia at young age. We give an overview of the different phenotypes of "SCN5A disease" and discuss the importance of co-inherited genetic variants in the expression of SCN5A disease.

Melatonin modulates monochromatic light-induced melatonin receptor expression in the hypothalamus of chicks.

Science.gov (United States)

Zhang, Liwei; Chen, Funing; Cao, Jing; Dong, Yulan; Wang, Zixu; Chen, Yaoxing

2017-09-01

To study the mechanism of the effect of monochromatic light on physiological function in chicken, a total of 192 newly hatched chicks were randomly divided into intact, sham-operated and pinealectomy groups then exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) using a light-emitting diode (LED) system for two weeks. At P14, the hypothalami were immediately collected for immunohistochemical staining of melatonin receptor subtypes (Mel1a and Mel1b) and detection of Mel1a and Mel1b expressions using RT-PCR and western blot. Immunohistochemical staining of the hypothalamus showed that the Mel1a-ir cells were distributed in the preoptic area (POA), nucleus preopticus periventricularis (POP) and suprachiasmatic nuclei (SCN), and the Mel1b-ir cells were presented in the POA and SCN. Analysis of RT-PCR and western blot showed that the mRNA and protein levels of Mel1a and Mel1b in the hypothalamus of chick exposed to GL were increased by 10.7-29.3%, 9.18-35.9% and 8.97-27.3% compared to those in the chicks exposed to WL (P=0.029-0.002), RL (P=0.027-0.001) and BL (P=0.038-0.007) in the intact group, respectively. After pinealectomy, however, these parameters decreased and there were no significant differences among the WL, RL, GL and BL groups. These findings suggested that melatonin plays a critical role in GL illumination-enhanced Mel1a and Mel1b expressions in the hypothalamus of chicks. Copyright © 2017 Elsevier GmbH. All rights reserved.

Sleep Deprivation and Caffeine Treatment Potentiate Photic Resetting of the Master Circadian Clock in a Diurnal Rodent.

Science.gov (United States)

Jha, Pawan Kumar; Bouâouda, Hanan; Gourmelen, Sylviane; Dumont, Stephanie; Fuchs, Fanny; Goumon, Yannick; Bourgin, Patrice; Kalsbeek, Andries; Challet, Etienne

2017-04-19

Circadian rhythms in nocturnal and diurnal mammals are primarily synchronized to local time by the light/dark cycle. However, nonphotic factors, such as behavioral arousal and metabolic cues, can also phase shift the master clock in the suprachiasmatic nuclei (SCNs) and/or reduce the synchronizing effects of light in nocturnal rodents. In diurnal rodents, the role of arousal or insufficient sleep in these functions is still poorly understood. In the present study, diurnal Sudanian grass rats, Arvicanthis ansorgei , were aroused at night by sleep deprivation (gentle handling) or caffeine treatment that both prevented sleep. Phase shifts of locomotor activity were analyzed in grass rats transferred from a light/dark cycle to constant darkness and aroused in early night or late night. Early night, but not late night, sleep deprivation induced a significant phase shift. Caffeine on its own induced no phase shifts. Both sleep deprivation and caffeine treatment potentiated light-induced phase delays and phase advances in response to a 30 min light pulse, respectively. Sleep deprivation in early night, but not late night, potentiated light-induced c-Fos expression in the ventral SCN. Caffeine treatment in midnight triggered c-Fos expression in dorsal SCN. Both sleep deprivation and caffeine treatment potentiated light-induced c-Fos expression in calbindin-containing cells of the ventral SCN in early and late night. These findings indicate that, in contrast to nocturnal rodents, behavioral arousal induced either by sleep deprivation or caffeine during the sleeping period potentiates light resetting of the master circadian clock in diurnal rodents, and activation of calbindin-containing suprachiasmatic cells may be involved in this effect. SIGNIFICANCE STATEMENT Arousing stimuli have the ability to regulate circadian rhythms in mammals. Behavioral arousal in the sleeping period phase shifts the master clock in the suprachiasmatic nuclei and/or slows down the photic

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

Directory of Open Access Journals (Sweden)

Dennis Lal

Full Text Available The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic.We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients.We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%. Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1 are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test, previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

Interacting gluon model for hadron-nucleus and nucleus-nucleus collisions in the central rapidity region

International Nuclear Information System (INIS)

Fowler, G.N.; Navarra, F.S.; Plumer, M.; Lawrence Berkeley Laboratory, Nuclear Science Division, Berkeley, California 94720); Vourdas, A.; Weiner, R.M.

1989-01-01

The interacting gluon model developed to describe the inelasticity distribution in hadron-nucleon collisions has been generalized and applied to hadron-nucleus and nucleus-nucleus interactions. Leading particle spectra and energy distributions in hadron-nucleus and nucleus-nucleus collisions are calculated

Sodium channel SCN8A (Nav1.6: properties and de novo mutations in epileptic encephalopathy and intellectual disability

Directory of Open Access Journals (Sweden)

Janelle Elizabeth O'Brien

2013-10-01

Full Text Available The sodium channel Nav1.6, encoded by the gene SCN8A, is one of the major voltage-gated channels in human brain. The sequences of sodium channels have been highly conserved during evolution, and minor changes in biophysical properties can have a major impact in vivo. Insight into the role of Nav1.6 has come from analysis of spontaneous and induced mutations of mouse Scn8a during the past 18 years. Only within the past year has the role of SCN8A in human disease become apparent from whole exome and genome sequences of patients with sporadic disease. Unique features of Nav1.6 include its contribution to persistent current, resurgent current, repetitive neuronal firing, and subcellular localization at the axon initial segment and nodes of Ranvier. Loss of Nav1.6 activity results in reduced neuronal excitability, while gain-of-function mutations can increase neuronal excitability. Mouse Scn8a (med mutants exhibit movement disorders including ataxia, tremor and dystonia. Thus far, more than ten human de novo mutations have been identified in patients with two types of disorders, epileptic encephalopathy and intellectual disability. We review these human mutations as well as the unique features of Nav1.6 that contribute to its role in determining neuronal excitability in vivo. A supplemental figure illustrating the positions of amino acid residues within the 4 domains and 24 transmembrane segments of Nav1.6 is provided to facilitate the location of novel mutations within the channel protein.

Pitfalls in genetic testing: the story of missed SCN1A mutations

OpenAIRE

Djémié, T.; Weckhuysen, S.; von Spiczak, S.; Carvill, G. L.; Jaehn, J.; Anttonen, A-K; Brilstra, E.; Caglayan, H. S.; de Kovel, C. G.; Depienne, C.; Gaily, E.; Gennaro, E.; Giraldez, B. G.; Gormley, P.; Guerrero-López, R.

2016-01-01

BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated ...

Pitfalls in genetic testing : the story of missed SCN1A mutations

OpenAIRE

Djémié, Tania; Weckhuysen, Sarah; von Spiczak, Sarah; Carvill, Gemma L; Jaehn, Johanna; Anttonen, Anna-Kaisa; Brilstra, Eva; Caglayan, Hande S; de Kovel, Carolien G; Depienne, Christel; Gaily, Eija; Gennaro, Elena; Giraldez, Beatriz G; Gormley, Padhraig; Guerrero-López, Rosa

2016-01-01

BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated ...

Prevalence of SCN1A-related dravet syndrome among children reported with seizures following vaccination: a population-based ten-year cohort study.

Directory of Open Access Journals (Sweden)

Nienke E Verbeek

Full Text Available OBJECTIVES: To determine the prevalence of Dravet syndrome, an epileptic encephalopathy caused by SCN1A-mutations, often with seizure onset after vaccination, among infants reported with seizures following vaccination. To determine differences in characteristics of reported seizures after vaccination in children with and without SCN1A-related Dravet syndrome. METHODS: Data were reviewed of 1,269 children with seizures following immunization in the first two years of life, reported to the safety surveillance system of the Dutch national immunization program between 1 January 1997 and 31 December 2006. Selective, prospective follow-up was performed of children with clinical characteristics compatible with a diagnosis of Dravet syndrome. RESULTS: In 21.9% (n = 279 of children, a diagnosis of Dravet syndrome could not be excluded based on available clinical data (median age at follow-up 16 months. Additional follow-up data were obtained in 83.9% (n = 234 of these children (median age 8.5 years. 15 (1.2% of 1,269; 95%CI:0.6 to 1.8% children were diagnosed with SCN1A-related Dravet syndrome. Of all reported seizures following vaccinations in the first year of life, 2.5% (95%CI:1.3 to 3.6% were due to SCN1A-related Dravet syndrome, as were 5.9% of reported seizures (95%CI:3.1 to 8.7% after 2(nd or 3(rd DTP-IPV-Hib vaccination. Seizures in children with SCN1A-related Dravet syndrome occurred more often with a body temperature below 38.5°C (57.9% vs. 32.6%, p = 0.020 and reoccurred more often after following vaccinations (26.7% vs. 4.0%, p = 0.003, than in children without a diagnosis of SCN1A-related Dravet Syndrome. CONCLUSIONS: Although Dravet syndrome is a rare genetic epilepsy syndrome, 2.5% of reported seizures following vaccinations in the first year of life in our cohort occurred in children with this disorder. Knowledge on the specific characteristics of vaccination-related seizures in this syndrome might promote early diagnosis

Kinetics of photocurrent generation and an efficient charge separation of a dye-sensitized n-Cu2O/p-CuSCN junction photoelectrode in a solid-state photovoltaic cell

International Nuclear Information System (INIS)

Fernando, C A N; Kumara, N T R N; Gamage, T N

2010-01-01

A Cu/n-Cu 2 O/dye/p-CuSCN junction photoelectrode is fabricated to produce a solid-state dye-sensitized photovoltaic cell. Samples are characterized by XRD, SEM and surface resistivity measurements. Photocurrent generation is found due to light absorption of n-Cu 2 O thin film and dye sensitization between p-CuSCN and the dye. Kinetics of the photocurrent generation of the dye sensitization is studied solving the rate equations by the iteration method obtaining a relationship for the photocurrent quantum efficiency (Φ) depending on the surface concentration (D o ) of the dye and the rate constants of the reactions with connection to the dye sensitization process. The solution obtained in the steady state by iteration is found to be of the form Φ = AD o −BD o 2 (A and B are constants related to the reaction rates of the photocurrent generation process and the concentration of the n-Cu 2 O film). The variation of the n-Cu 2 O concentration with photocurrent is presented. A photocurrent enhancement is observed for the Cu/n-Cu 2 O/dye/p-CuSCN photovoltaic cell compared to that of Cu/n-Cu 2 O, Cu/p-CuSCN/dye and Cu/n-Cu 2 O/p-CuSCN photovoltaic cells. Good rectification characteristics are observed for the Cu/n-Cu 2 O/p-CuSCN photoelectrode compared to that of Cu/n-Cu 2 O and Cu/p-CuSCN photoelectrodes. Photocurrent enhancement is found due to the efficient charge separation process at the n–p junction. Energy band structures of the n–p junction are proposed according to the onset potentials which are used to discuss the mechanism of the efficient charge separation suppressing the recombination process

Diffractive ''semioptical'' model for nucleus-nucleus collisions

International Nuclear Information System (INIS)

Barashenkov, V.S.; Musulmanbekov, Zh.Zh.

1979-01-01

Diffraction Glauber theory for nucleus-nucleus collisions is considered in approximation when the initial nucleus interacts as a whole with nucleons of the target nucleus. Such an approach, being intermediate between precise Glauber theory and its optical limit, essentially simplifies numerical calculations and gives a good agreement with experiments as well. (author)

Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome

DEFF Research Database (Denmark)

Petitprez, Séverine; Jespersen, Thomas; Pruvot, Etienne

2008-01-01

S SCN5A mutation. METHODS AND RESULTS: SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in HEK293 cells. Sodium currents (I(Na)) were analysed using the whole-cell patch-clamp technique at 37 degrees C......AIMS: Brugada syndrome (BrS) is characterized by arrhythmias leading to sudden cardiac death. BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Na(v)1.5. Here, we aimed to characterize the biophysical properties and consequences of a novel Br....... The electrophysiological effects of the mutation were simulated using the Luo-Rudy model, into which the transient outward current (I(to)) was incorporated. A new mutation (C1850S) was identified in the Na(v)1.5 C-terminal domain. In HEK293 cells, mutant I(Na) density was decreased by 62% at -20 mV. Inactivation of mutant...

The first pseudo-ternary thiocyanate containing two alkali metals. Synthesis and single-crystal structure of LiK{sub 2}[SCN]{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Reckeweg, Olaf; DiSalvo, Francis J. [Cornell Univ., Ithaca, NY (United States). Baker Lab.

2016-04-01

A procedure was empirically developed to prepare the compound LiK{sub 2}[SCN]{sub 3}, which forms colorless, transparent, very fragile, and extremely hygroscopic thin rectangular plates. Its unique crystal structure was determined by single-crystal X-ray diffraction. LiK{sub 2}[SCN]{sub 3} adopts the orthorhombic space group Pna2{sub 1} (no. 33, Z = 4) with the cell parameters a = 1209.32(9), b = 950.85(9), and c = 849.95(6) pm.

Association Between IL1B and SCN1A Polymorphism and Febrile Seizures in Children in Siberia

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Maria A. Stroganova

2017-06-01

Full Text Available Background: Febrile seizures (FS are a benign, age-dependent, genetically determined state, in which the child’s brain is susceptible to epileptic seizures occurring in response to hyperthermia. We assessed whether polymorphisms of IL1B and SCN1A genes, encoding the proinflammatory cytokine IL1B and SCN1A, respectively, could help to predict FS development and find a new way to treat FS. Methods: We examined 121 children with FS and 30 children with HTS aged from 3 to 36 months. SNPs rs1143634 and rs16944 of IL1B gene, and rs3812718 and rs16851603 of SCN1A gene were determined by quantitative real-time PCR. Results: The analysis for rs1143634 revealed an association between the CC genotype and increased risk of FS development (OR 6.56; P=0.0008 against the background of acute respiratory viral infection. The same result was obtained for rs16944 (OR 3.13; P=0.04 and an association of two homozygous genotypes CC/CC. For rs3812718, the carriage of heterozygous genotype CT demonstrated a direct relationship with FS development (OR 44.95; P=0.000. Conclusion: Children with high FS risk need preventive treatment and joint observation of a pediatrician, pediatric infectionist, and a neurologist-epileptologist.

COLOCALIZATION OF MUSCARINIC AND NICOTINIC RECEPTORS IN CHOLINOCEPTIVE NEURONS OF THE SUPRACHIASMATIC REGION IN YOUNG AND AGED RATS

NARCIS (Netherlands)

VANDERZEE, EA; STREEFLAND, C; STROSBERG, AD; SCHRODER, H; LUITEN, PGM; Schröder, H.

1991-01-01

In the present study muscarinic and nicotinic cholinergic receptors in the SCN region were demonstrated and analyzed, employing monoclonal antibodies to purified muscarinic and nicotinic cholinergic receptor proteins. A near-total colocalization of the two acetylcholine receptor subclasses in

Ovarian steroid regulation of monoamine oxidase-A and -B mRNAs in the macaque dorsal raphe and hypothalamic nuclei.

Science.gov (United States)

Gundlah, Chrisana; Lu, Nick Z; Bethea, Cynthia L

2002-03-01

The serotonin neural system plays a pivotal role in mood, affective regulation and integrative cognition, as well as numerous autonomic functions. We have shown that ovarian steroids alter the expression of several genes in the dorsal raphe of macaques, which may increase serotonin synthesis and decrease serotonin autoinhibition. Another control point in aminergic neurotransmission involves degradation by MAO. This enzyme occurs in two isoforms, A and B, which have different substrate preferences. We questioned the effect of ovarian steroid hormones on MAO-A and MAO-B mRNA expression in the dorsal raphe nucleus and hypothalamus using in situ hybridization in non-human primates. Rhesus monkeys ( Macaca mulatta; n=5/group) were spayed and either placebo treated (controls), estrogen (E) treated (28 days), progesterone (P) treated (14 days placebo+14 days P), or E+P treated (14 days E+14 days E+P). Perfusion-fixed sections (25 microm) were hybridized with a 233 bp MAO-A, or a 373 bp MAO-B, radiolabeled-antisense monkey specific probes. Autoradiographic films were analyzed by densitometry, which was performed with NIH Image Software. MAO-A and -B mRNAs were detected in the dorsal raphe nucleus (DRN) and in the hypothalamic suprachiasmatic nucleus (SCN), preoptic area (POA), paraventricular nucleus (PVN), supraoptic nucleus (SON), lateral hypothalamus (LH) and ventromedial nucleus (VMN). MAO-A mRNA optical density was significantly decreased by E, P, and E+P in the DRN and in the hypothalamic PVN, LH and VMN. Ovarian hormones had no effect on MAO-B mRNA expression in the DRN. However, there was a significant decrease in MAO-B optical density in the hypothalamic POA, LH and VMN with E, P or E+P treatment. Pixel area generally reflected optical density. Ovarian steroids decreased MAO-A, but not B, in the raphe nucleus. However, both MAO-A and B were decreased in discrete hypothalamic nuclei by hormone replacement. These data suggest that the transcriptional regulation of

The incidence of SCN1A-related Dravet syndrome in Denmark is 1:22,000

DEFF Research Database (Denmark)

Bayat, Allan; Hjalgrim, Helle; Møller, Rikke S.

2015-01-01

Dravet syndrome is a severe infantile-onset epileptic encephalopathy associated with mutations in the sodium channel alpha-1 subunit gene SCN1A. We aimed to describe the incidence of Dravet syndrome in the Danish population. Based on a 6-year birth cohort from 2004 to 2009, we propose an incidenc...

Photoproduction of lepton pairs in proton-nucleus and nucleus-nucleus collisions at RHIC and LHC energies

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Moreira, B. D.; Goncalves, V. P.; De Santana Amaral, J. T. [Universidade Federal de Pelotas, Instituto de Fisica e Matematica (Brazil)

2013-03-25

In this contribution we study coherent interactions as a probe of the nonlinear effects in the Quantum Electrodynamics (QED). In particular, we study the multiphoton effects in the production of leptons pairs for proton-nucleus and nucleus-nucleus collisions for heavy nuclei. In the proton-nucleus we assume the ultrarelativistic proton as a source of photons and estimate the photoproduction of lepton pairs on nuclei at RHIC and LHC energies considering the multiphoton effects associated to multiple rescattering of the projectile photon on the proton of the nucleus. In nucleus - nucleus colllisions we consider the two nuclei as a source of photons. As each scattering contributes with a factor {alpha}Z to the cross section, this contribution must be taken into account for heavy nuclei. We consider the Coulomb corrections to calculate themultiple scatterings and estimate the total cross section for muon and tau pair production in proton-nucleus and nucleus-nucleus collisions at RHIC and LHC energies.

Sleep, Rhythms, and the Endocrine Brain: Influence of Sex and Gonadal Hormones

Science.gov (United States)

Mong, Jessica A.; Baker, Fiona C.; Mahoney, Megan M.; Paul, Ketema N.; Schwartz, Michael D.; Semba, Kazue; Silver, Rae

2011-01-01

While much is known about the mechanisms that underlie sleep and circadian rhythms, the investigation into sex differences and gonadal steroid modulation of sleep and biological rhythms is in its infancy. There is a growing recognition of sex disparities in sleep and rhythm disorders. Understanding how neuroendocrine mediators and sex differences influence sleep and biological rhythms is central to advancing our understanding of sleep-related disorders. While it is known that ovarian steroids affect circadian rhythms in rodents, the role of androgen is less understood. Surprising findings that androgens, acting via androgen receptors in the master “circadian clock” within the suprachiasmatic nucleus (SCN), modulate photic effects on activity in males points to novel mechanisms of circadian control. Work in aromatase deficient (ArKO) mice suggests that some sex differences in photic responsiveness are independent of gonadal hormone effects during development. In parallel, aspects of sex differences in sleep are also reported to be independent of gonadal steroids and may involve sex chromosome complement. This a summary of recent work illustrating how sex differences and gonadal hormones influence sleep and circadian rhythms that was presented at a mini-symposium at the 2011 annual meeting of the Society for Neuroscience. PMID:22072663

Circadian rhythm and its role in malignancy

Directory of Open Access Journals (Sweden)

Mahmood Saqib

2010-03-01

Full Text Available Abstract Circadian rhythms are daily oscillations of multiple biological processes directed by endogenous clocks. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN of the hypothalamus. Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs including various cell cycle genes. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. This may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder. The genetic or functional disruption of the molecular circadian clock has been found in various cancers including breast, ovarian, endometrial, prostate and hematological cancers. The acquisition of current data in circadian clock mechanism may help chronotherapy, which takes into consideration the biological time to improve treatments by devising new therapeutic approaches for treating circadian-related disorders, especially cancer.

Model for nucleus-nucleus, hadron-nucleus and hadron-proton multiplicity distributions

International Nuclear Information System (INIS)

Singh, C.P.; Shyam, M.; Tuli, S.K.

1986-07-01

A model relating hadron-proton, hadron-nucleus and nucleus-nucleus multiplicity distributions is proposed and some interesting consequences are derived. The values of the parameters are the same for all the processes and are given by the QCD hypothesis of ''universal'' hadronic multiplicities which are found to be asymptotically independent of target and beam in hadronic and current induced reactions in particle physics. (author)

Hydride vapor phase epitaxy growth of GaN, InGaN, ScN, and ScAIN

NARCIS (Netherlands)

Bohnen, T.

2010-01-01

Chemical vapor deposition (CVD); hydride vapor phase epitaxy (HVPE); gallium nitride (GaN); indium gallium nitride (InGaN); scandium nitride (ScN); scandium aluminum nitride (ScAlN); semiconductors; thin films; nanowires; III nitrides; crystal growth - We studied the HVPE growth of different III

Higgs-boson production in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Anon.

1992-01-01

Cross section calculations are presented for the production of intermediate-mass Higgs bosons produced in ultrarelativistic nucleus-nucleus collisions via two photon fusion. The calculations are performed in position space using Baur's method for folding together the Weizsacker-Williams virtual-photon spectra of the two colliding nuclei. It is found that two photon fusion in nucleus-nucleus collisions is a plausible way of finding intermediate-mass Higgs bosons at the Superconducting Super Collider or the CERN Large Hadron Collider

Higgs-Boson Production in Nucleus-Nucleus Collisions

Science.gov (United States)

Norbury, John W.

1992-01-01

Cross section calculations are presented for the production of intermediate-mass Higgs bosons produced in ultrarelativistic nucleus-nucleus collisions via two photon fusion. The calculations are performed in position space using Baur's method for folding together the Weizsacker-Williams virtual-photon spectra of the two colliding nuclei. It is found that two photon fusion in nucleus-nucleus collisions is a plausible way of finding intermediate-mass Higgs bosons at the Superconducting Super Collider or the CERN Large Hadron Collider.

Angular momentum and incident-energy dependence of nucleus-nucleus interaction

International Nuclear Information System (INIS)

Yamaguchi, S.

1991-01-01

The purpose of this paper is to understand intuitively the origin of the angular momentum and incident-energy dependence of the nucleus-nucleus interaction on the basis of the totally- antisymmetrized many-body theory. With the aim of understanding the structure of the nucleus-nucleus interaction, we show first that the nucleus-nucleus interaction can be written by the use of the density-distribution function and the phase-space distribution function instead of using the many-body wave function itself. And we show that the structure change of the density-distribution function with the increase of the angular momentum causes the angular momentum dependence of the nucleus-nucleus interaction and that the incident-energy dependence of the nucleus-nucleus interaction originates from the structure change of the phase-space distribution function

New results on nuclear multifragmentation in nucleon-nucleus and nucleus-nucleus collisions at relativistic energies

International Nuclear Information System (INIS)

Besliu, Calin; Jipa, Alexandru; Iliescu, Bogdan; Felea, Daniel

2002-01-01

Some new aspects on the multifragmentation processes in nucleus-nucleus and nucleon-nucleus collisions at high energies are discussed in this work. Experimental data obtained in international collaborations (for example, MULTI Collaboration with KEK Tsukuba (Japan) and SKM 200 Collaboration with JINR Dubna (Russia)) are used to discuss new mechanisms in the target nucleus fragmentation. Correlations with stopping power, participant region size and energy density are included. Comparisons of the experimental results with the predictions of a phenomenological geometric model of intermediate mass fragment multiplicity, caloric curves and angular distributions are also presented. These results are used for global description of the multifragmentation processes in nucleon-nucleus and nucleus-nucleus collisions at relativistic energies. The size of the participant region and the average intermediate mass fragments multiplicity are taken into consideration using the free space probability. A few correlations between the deposited energy in the participant region and stability state of the intermediate mass fragments are presented in this work. The importance of the collision geometry in the multifragmentation processes is stressed. The results suggest different time moments for the incident nucleus fragmentation and for the target nucleus fragmentation. The associated entropies are distinct. (authors)

Prevention of depression and sleep disturbances in elderly with memory-problems by activation of the biological clock with light--a randomized clinical trial.

Science.gov (United States)

Most, Els I S; Scheltens, Philip; Van Someren, Eus J W

2010-02-23

Depression frequently occurs in the elderly and in patients suffering from dementia. Its cause is largely unknown, but several studies point to a possible contribution of circadian rhythm disturbances. Post-mortem studies on aging, dementia and depression show impaired functioning of the suprachiasmatic nucleus (SCN) which is thought to be involved in the increased prevalence of day-night rhythm perturbations in these conditions. Bright light enhances neuronal activity in the SCN. Bright light therapy has beneficial effects on rhythms and mood in institutionalized moderate to advanced demented elderly. In spite of the fact that this is a potentially safe and inexpensive treatment option, no previous clinical trial evaluated the use of long-term daily light therapy to prevent worsening of sleep-wake rhythms and depressive symptoms in early to moderately demented home-dwelling elderly. This study investigates whether long-term daily bright light prevents worsening of sleep-wake rhythms and depressive symptoms in elderly people with memory complaints. Patients with early Alzheimer's Disease (AD), Mild Cognitive Impairment (MCI) and Subjective Memory Complaints (SMC), between the ages of 50 and 75, are included in a randomized double-blind placebo-controlled trial. For the duration of two years, patients are exposed to approximately 10,000 lux in the active condition or approximately 300 lux in the placebo condition, daily, for two half-hour sessions at fixed times in the morning and evening. Neuropsychological, behavioral, physiological and endocrine measures are assessed at baseline and follow-up every five to six months. If bright light therapy attenuates the worsening of sleep-wake rhythms and depressive symptoms, it will provide a measure that is easy to implement in the homes of elderly people with memory complaints, to complement treatments with cholinesterase inhibitors, sleep medication or anti-depressants or as a stand-alone treatment. ISRCTN29863753.

Prevention of depression and sleep disturbances in elderly with memory-problems by activation of the biological clock with light - a randomized clinical trial

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Scheltens Philip

2010-02-01

Full Text Available Abstract Background Depression frequently occurs in the elderly and in patients suffering from dementia. Its cause is largely unknown, but several studies point to a possible contribution of circadian rhythm disturbances. Post-mortem studies on aging, dementia and depression show impaired functioning of the suprachiasmatic nucleus (SCN which is thought to be involved in the increased prevalence of day-night rhythm perturbations in these conditions. Bright light enhances neuronal activity in the SCN. Bright light therapy has beneficial effects on rhythms and mood in institutionalized moderate to advanced demented elderly. In spite of the fact that this is a potentially safe and inexpensive treatment option, no previous clinical trial evaluated the use of long-term daily light therapy to prevent worsening of sleep-wake rhythms and depressive symptoms in early to moderately demented home-dwelling elderly. Methods/Design This study investigates whether long-term daily bright light prevents worsening of sleep-wake rhythms and depressive symptoms in elderly people with memory complaints. Patients with early Alzheimer's Disease (AD, Mild Cognitive Impairment (MCI and Subjective Memory Complaints (SMC, between the ages of 50 and 75, are included in a randomized double-blind placebo-controlled trial. For the duration of two years, patients are exposed to ~10,000 lux in the active condition or ~300 lux in the placebo condition, daily, for two half-hour sessions at fixed times in the morning and evening. Neuropsychological, behavioral, physiological and endocrine measures are assessed at baseline and follow-up every five to six months. Discussion If bright light therapy attenuates the worsening of sleep-wake rhythms and depressive symptoms, it will provide a measure that is easy to implement in the homes of elderly people with memory complaints, to complement treatments with cholinesterase inhibitors, sleep medication or anti-depressants or as a stand

Effects of caffeine on circadian phase, amplitude and period evaluated in cells in vitro and peripheral organs in vivo in PER2::LUCIFERASE mice

Science.gov (United States)

Narishige, Seira; Kuwahara, Mari; Shinozaki, Ayako; Okada, Satoshi; Ikeda, Yuko; Kamagata, Mayo; Tahara, Yu; Shibata, Shigenobu

2014-01-01

Background and Purpose Caffeine is one of the most commonly used psychoactive substances. Circadian rhythms consist of the main suprachiasmatic nucleus (SCN) clocks and peripheral clocks. Although caffeine lengthens circadian rhythms and modifies phase changes in SCN-operated rhythms, the effects on caffeine on the phase, period and amplitude of peripheral organ clocks are not known. In addition, the role of cAMP/Ca2+ signalling in effects of caffeine on rhythm has not been fully elucidated. Experimental Approach We examined whether chronic or transient application of caffeine affects circadian period/amplitude and phase by evaluating bioluminescence rhythm in PER2::LUCIFERASE knock-in mice. Circadian rhythms were monitored in vitro using fibroblasts and ex vivo and in vivo for monitoring of peripheral clocks. Key Results Chronic application of caffeine (0.1–10 mM) increased period and amplitude in vitro. Transient application of caffeine (10 mM) near the bottom of the decreasing phase of bioluminescence rhythm caused phase advance in vitro. Caffeine (0.1%) intake caused a phase delay under light–dark or constant dark conditions, suggesting a period-lengthening effect in vivo. Caffeine (20 mg·kg−1) at daytime or at late night-time caused phase advance or delay in bioluminescence rhythm in the liver and kidney respectively. The complicated roles of cAMP/Ca2+ signalling may be involved in the caffeine-induced increase of period and amplitude in vitro. Conclusions and Implications Caffeine affects circadian rhythm in mice by lengthening the period and causing a phase shift of peripheral clocks. These results suggest that caffeine intake with food/drink may help with food-induced resetting of peripheral circadian clocks. PMID:25160990

Molecular Mechanisms of Circadian Regulation During Spaceflight

Science.gov (United States)

Zanello, S. B.; Boyle, R.

2012-01-01

The physiology of both vertebrates and invertebrates follows internal rhythms coordinated in phase with the 24-hour daily light cycle. This circadian clock is governed by a central pacemaker, the suprachiasmatic nucleus (SCN) in the brain. However, peripheral circadian clocks or oscillators have been identified in most tissues. How the central and peripheral oscillators are synchronized is still being elucidated. Light is the main environmental cue that entrains the circadian clock. Under the absence of a light stimulus, the clock continues its oscillation in a free-running condition. In general, three functional compartments of the circadian clock are defined. The vertebrate retina contains endogenous clocks that control many aspects of retinal physiology, including retinal sensitivity to light, neurohormone synthesis (melatonin and dopamine), rod disk shedding, signalling pathways and gene expression. Neurons with putative local circadian rhythm generation are found among all the major neuron populations in the mammalian retina. In the mouse, clock genes and function are more localized to the inner retinal and ganglion cell layers. The photoreceptor, however, secrete melatonin which may still serve a an important circadian signal. The reception and transmission of the non-visual photic stimulus resides in a small subpopulation (1-3%) or retinal ganglion cells (RGC) that express the pigment melanopsin (Opn4) and are called intrisically photoreceptive RGC (ipRGC). Melanopsin peak absorption is at 420 nm and all the axons of the ipRGC reach the SCN. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate the risk of fatigue and health and performance decrement due to circadian rhythm disruption. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. We hypothesize that spaceflight may affect ip

Electrophysiological characteristics of a SCN5A voltage sensors mutation R1629Q associated with Brugada syndrome.

Directory of Open Access Journals (Sweden)

Zhipeng Zeng

Full Text Available Brugada syndrome (BrS is an inherited arrhythmogenic syndrome leading to sudden cardiac death, partially associated with autosomal dominant mutations in SCN5A, which encodes the cardiac sodium channel alpha-subunit (Nav1.5. To date some SCN5A mutations related with BrS have been identified in voltage sensor of Nav1.5. Here, we describe a dominant missense mutation (R1629Q localized in the fourth segment of domain IV region (DIV-S4 in a Chinese Han family. The mutation was identified by direct sequencing of SCN5A from the proband's DNA. Co-expression of Wild-type (WT or R1629Q Nav1.5 channel and hβ1 subunit were achieved in human embryonic kidney cells by transient transfection. Sodium currents were recorded using whole cell patch-clamp protocols. No significant changes between WT and R1629Q currents were observed in current density or steady-state activation. However, hyperpolarized shift of steady-state inactivation curve was identified in cells expressing R1629Q channel (WT: V1/2 = -81.1 ± 1.3 mV, n = 13; R1629Q: V1/2 = -101.7 ± 1.2 mV, n = 18. Moreover, R1629Q channel showed enhanced intermediate inactivation and prolonged recovery time from inactivation. In summary, this study reveals that R1629Q mutation causes a distinct loss-of-function of the channel due to alter its electrophysiological characteristics, and facilitates our understanding of biophysical mechanisms of BrS.

Deconfinement of quarks and gluons in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Gorenstein, M.I.

2011-01-01

The energy dependence of hadron production in relativistic nucleus-nucleus collisions reveals the anomalies. They were predicted as the signals of the deconfinement phase transition and observed by NA49 collaboration in Pb+Pb collisions at the CERN SPS. This indicates the onset of the deconfinement in central nucleus-nucleus collisions at about 30 AGeV.

Analytical approximations for thermophysical properties of supercritical nitrogen (SCN) to be used in futuristic high temperature superconducting (HTS) cables

Energy Technology Data Exchange (ETDEWEB)

Dondapati, Raja Sekhar, E-mail: drsekhar@ieee.org [School of Mechanical Engineering, Lovely Professional University, Phagwara, Punjab 144401 (India); Ravula, Jeswanth [School of Mechanical Engineering, Lovely Professional University, Phagwara, Punjab 144401 (India); Thadela, S. [Department of Mechanical Engineering, Andhra University, Visakhapatnam, Andhra Pradesh (India); Usurumarti, Preeti Rao [Department of Mechanical Engineering, P.V.K. Institute of Technology, Anantapur, Andhra Pradesh (India)

2015-12-15

Future power transmission applications demand higher efficiency due to the limited resources of energy. In order to meet such demand, a novel method of transmission is being developed using High Temperature Superconducting (HTS) cables. However, these HTS cables need to be cooled below the critical temperature of superconductors used in constructing the cable to retain the superconductivity. With the advent of new superconductors whose critical temperatures having reached up to 134 K (Hg based), a need arises to find a suitable coolant which can accommodate the heating loads on the superconductors. The present work proposes, Supercritical Nitrogen (SCN) to be a feasible coolant to achieve the required cooling. Further, the feasibility of proposed coolant to be used in futuristic HTS cables is investigated by studying the thermophysical properties such as density, viscosity, specific heat and thermal conductivity with respect to temperature (T{sub C} + 10 K) and pressure (P{sub C} + 10 bar). In addition, few temperature dependent analytical functions are developed for thermophysical properties of SCN which are useful in predicting thermohydraulic performance (pressure drop, pumping power and cooling capacity) using numerical or computational techniques. Also, the developed analytical functions are used to calculate the pumping power and the temperature difference between inlet and outlet of HTS cable. These results are compared with those of liquid nitrogen (LN2) and found that the circulating pumping power required to pump SCN is significantly smaller than that to pump LN2. Further, it is found that the temperature difference between the inlet and outlet is smaller as compared to that when LN2 is used, SCN can be preferred to cool long length Hg based HTS cables. - Highlights: • Analytical functions are developed for thermophysical properties of Supercritical Nitrogen. • Error analysis shows extremely low errors in the developed analytical functions. �

Analytical approximations for thermophysical properties of supercritical nitrogen (SCN) to be used in futuristic high temperature superconducting (HTS) cables

International Nuclear Information System (INIS)

Dondapati, Raja Sekhar; Ravula, Jeswanth; Thadela, S.; Usurumarti, Preeti Rao

2015-01-01

Future power transmission applications demand higher efficiency due to the limited resources of energy. In order to meet such demand, a novel method of transmission is being developed using High Temperature Superconducting (HTS) cables. However, these HTS cables need to be cooled below the critical temperature of superconductors used in constructing the cable to retain the superconductivity. With the advent of new superconductors whose critical temperatures having reached up to 134 K (Hg based), a need arises to find a suitable coolant which can accommodate the heating loads on the superconductors. The present work proposes, Supercritical Nitrogen (SCN) to be a feasible coolant to achieve the required cooling. Further, the feasibility of proposed coolant to be used in futuristic HTS cables is investigated by studying the thermophysical properties such as density, viscosity, specific heat and thermal conductivity with respect to temperature (T_C + 10 K) and pressure (P_C + 10 bar). In addition, few temperature dependent analytical functions are developed for thermophysical properties of SCN which are useful in predicting thermohydraulic performance (pressure drop, pumping power and cooling capacity) using numerical or computational techniques. Also, the developed analytical functions are used to calculate the pumping power and the temperature difference between inlet and outlet of HTS cable. These results are compared with those of liquid nitrogen (LN2) and found that the circulating pumping power required to pump SCN is significantly smaller than that to pump LN2. Further, it is found that the temperature difference between the inlet and outlet is smaller as compared to that when LN2 is used, SCN can be preferred to cool long length Hg based HTS cables. - Highlights: • Analytical functions are developed for thermophysical properties of Supercritical Nitrogen. • Error analysis shows extremely low errors in the developed analytical functions. �

Stress-induced changes in the expression of the clock protein PERIOD1 in the rat limbic forebrain and hypothalamus: role of stress type, time of day, and predictability.

Directory of Open Access Journals (Sweden)

Sherin Al-Safadi

Full Text Available Stressful events can disrupt circadian rhythms in mammals but mechanisms underlying this disruption remain largely unknown. One hypothesis is that stress alters circadian protein expression in the forebrain, leading to functional dysregulation of the brain circadian network and consequent disruption of circadian physiological and behavioral rhythms. Here we characterized the effects of several different stressors on the expression of the core clock protein, PER1 and the activity marker, FOS in select forebrain and hypothalamic nuclei in rats. We found that acute exposure to processive stressors, restraint and forced swim, elevated PER1 and FOS expression in the paraventricular and dorsomedial hypothalamic nuclei and piriform cortex but suppressed PER1 and FOS levels exclusively in the central nucleus of the amygdala (CEAl and oval nucleus of the bed nucleus of the stria terminalis (BNSTov. Conversely, systemic stressors, interleukin-1β and 2-Deoxy-D-glucose, increased PER1 and FOS levels in all regions studied, including the CEAl and BNSTov. PER1 levels in the suprachiasmatic nucleus (SCN, the master pacemaker, were unaffected by any of the stress manipulations. The effect of stress on PER1 and FOS was modulated by time of day and, in the case of daily restraint, by predictability. These results demonstrate that the expression of PER1 in the forebrain is modulated by stress, consistent with the hypothesis that PER1 serves as a link between stress and the brain circadian network. Furthermore, the results show that the mechanisms that control PER1 and FOS expression in CEAl and BNSTov are uniquely sensitive to differences in the type of stressor. Finally, the finding that the effect of stress on PER1 parallels its effect on FOS supports the idea that Per1 functions as an immediate-early gene. Our observations point to a novel role for PER1 as a key player in the interface between stress and circadian rhythms.

Circadian and dark-pulse activation of orexin/hypocretin neurons

Directory of Open Access Journals (Sweden)

Marston Oliver J

2008-12-01

Full Text Available Temporal control of brain and behavioral states emerges as a consequence of the interaction between circadian and homeostatic neural circuits. This interaction permits the daily rhythm of sleep and wake, regulated in parallel by circadian cues originating from the suprachiasmatic nuclei (SCN and arousal-promoting signals arising from the orexin-containing neurons in the tuberal hypothalamus (TH. Intriguingly, the SCN circadian clock can be reset by arousal-promoting stimuli while activation of orexin/hypocretin neurons is believed to be under circadian control, suggesting the existence of a reciprocal relationship. Unfortunately, since orexin neurons are themselves activated by locomotor promoting cues, it is unclear how these two systems interact to regulate behavioral rhythms. Here mice were placed in conditions of constant light, which suppressed locomotor activity, but also revealed a highly pronounced circadian pattern in orexin neuronal activation. Significantly, activation of orexin neurons in the medial and lateral TH occurred prior to the onset of sustained wheel-running activity. Moreover, exposure to a 6 h dark pulse during the subjective day, a stimulus that promotes arousal and phase advances behavioral rhythms, activated neurons in the medial and lateral TH including those containing orexin. Concurrently, this stimulus suppressed SCN activity while activating cells in the median raphe. In contrast, dark pulse exposure during the subjective night did not reset SCN-controlled behavioral rhythms and caused a transient suppression of neuronal activation in the TH. Collectively these results demonstrate, for the first time, pronounced circadian control of orexin neuron activation and implicate recruitment of orexin cells in dark pulse resetting of the SCN circadian clock.

Visible light induced changes in the immune response through an eye-brain mechanism (photoneuroimmunology).

Science.gov (United States)

Roberts, J E

1995-07-01

The immune system is susceptible to a variety of stresses. Recent work in neuroimmunology has begun to define how mood alteration, stress, the seasons, and daily rhythms can have a profound effect on immune response through hormonal modifications. Central to these factors may be light through an eye-brain hormonal modulation. In adult primates, only visible light (400-700 nm) is received by the retina. This photic energy is then transduced and delivered to the visual cortex and by an alternative pathway to the suprachiasmatic nucleus (SCN). The SCN is a part of the hypothalamic region in the brain believed to direct circadian rhythm. Visible light exposure also modulates the pituitary and pineal gland which leads to neuroendocrine changes. Melatonin, norepinephrine and acetylcholine decrease with light activation, while cortisol, serotonin, gaba and dopamine levels increase. The synthesis of vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP) and neuropeptide Y (NPY) in rat SCN has been shown to be modified by light. These induced neuroendocrine changes can lead to alterations in mood and circadian rhythm. All of these neuroendocrine changes can lead to immune modulation. An alternative pathway for immune modulation by light is through the skin. Visible light (400-700 nm) can penetrate epidermal and dermal layers of the skin and may directly interact with circulating lymphocytes to modulate immune function. However, even in the presence of phototoxic agents such as eosin and rose bengal, visible light did not produce suppression of contact hypersensitivity with suppresser cells. In contrast to visible light, in vivo exposure to UV-B (280-320 nm) and UV-A (320-400 nm) radiation can only alter normal human immune function by a skin mediated response. Each UV subgroup (B, A) induces an immunosuppressive response but by differing mechanisms involving the regulation of differing interleukins and growth factors. Some effects observed in humans are

Bright light in elderly subjects with nonseasonal major depressive disorder: a double blind randomised clinical trial using early morning bright blue light comparing dim red light treatment

Directory of Open Access Journals (Sweden)

van Someren Eus JW

2008-07-01

Full Text Available Abstract Background Depression frequently occurs in the elderly. Its cause is largely unknown, but several studies point to disturbances of biological rhythmicity. In both normal aging, and depression, the functioning of the suprachiasmatic nucleus (SCN is impaired, as evidenced by an increased prevalence of day-night rhythm perturbations, such as sleeping disorders. Moreover, the inhibitory SCN neurons on the hypothalamus-pituitary adrenocortical axis (HPA-axis have decreased activity and HPA-activity is enhanced, when compared to non-depressed elderly. Using bright light therapy (BLT the SCN can be stimulated. In addition, the beneficial effects of BLT on seasonal depression are well accepted. BLT is a potentially safe, nonexpensive and well accepted treatment option. But the current literature on BLT for depression is inconclusive. Methods/Design This study aims to show whether BLT can reduce non-seasonal major depression in elderly patients. Randomized double blind placebo controlled trial in 126 subjects of 60 years and older with a diagnosis of major depressive disorder (MDD, DSM-IV/SCID-I. Subjects are recruited through referrals of psychiatric outpatient clinics and from case finding from databases of general practitioners and old-people homes in the Amsterdam region. After inclusion subjects are randomly allocated to the active (bright blue light vs. placebo (dim red light condition using two Philips Bright Light Energy boxes type HF 3304 per subject, from which the light bulbs have been covered with bright blue- or dim red light- permitting filters. Patients will be stratified by use of antidepressants. Prior to treatment a one-week period without light treatment will be used. At three time points several endocrinological, psychophysiological, psychometrically, neuropsychological measures are performed: just before the start of light therapy, after completion of three weeks therapy period, and three weeks thereafter. Discussion If BLT

Deep Ultraviolet Copper(I) Thiocyanate (CuSCN) Photodetectors Based on Coplanar Nanogap Electrodes Fabricated via Adhesion Lithography

KAUST Repository

Wyatt-Moon, Gwenhivir

2017-11-28

Adhesion lithography (a-Lith) is a versatile fabrication technique used to produce asymmetric coplanar electrodes separated by a <15 nm nanogap. Here, we use a-Lith to fabricate deep ultraviolet (DUV) photodetectors by combining coplanar asymmetric nanogap electrode architectures (Au/Al) with solution-processable wide-band-gap (3.5–3.9 eV) p-type semiconductor copper(I) thiocyanate (CuSCN). Because of the device’s unique architecture, the detectors exhibit high responsivity (≈79 A W–1) and photosensitivity (≈720) when illuminated with a DUV-range (λpeak = 280 nm) light-emitting diode at 220 μW cm–2. Interestingly, the photosensitivity of the photodetectors remains fairly high (≈7) even at illuminating intensities down to 0.2 μW cm–2. The scalability of the a-Lith process combined with the unique properties of CuSCN paves the way to new forms of inexpensive, yet high-performance, photodetectors that can be manufactured on arbitrary substrate materials including plastic.

Deep Ultraviolet Copper(I) Thiocyanate (CuSCN) Photodetectors Based on Coplanar Nanogap Electrodes Fabricated via Adhesion Lithography

KAUST Repository

Wyatt-Moon, Gwenhivir; Georgiadou, Dimitra G; Semple, James; Anthopoulos, Thomas D.

2017-01-01

Adhesion lithography (a-Lith) is a versatile fabrication technique used to produce asymmetric coplanar electrodes separated by a <15 nm nanogap. Here, we use a-Lith to fabricate deep ultraviolet (DUV) photodetectors by combining coplanar asymmetric nanogap electrode architectures (Au/Al) with solution-processable wide-band-gap (3.5–3.9 eV) p-type semiconductor copper(I) thiocyanate (CuSCN). Because of the device’s unique architecture, the detectors exhibit high responsivity (≈79 A W–1) and photosensitivity (≈720) when illuminated with a DUV-range (λpeak = 280 nm) light-emitting diode at 220 μW cm–2. Interestingly, the photosensitivity of the photodetectors remains fairly high (≈7) even at illuminating intensities down to 0.2 μW cm–2. The scalability of the a-Lith process combined with the unique properties of CuSCN paves the way to new forms of inexpensive, yet high-performance, photodetectors that can be manufactured on arbitrary substrate materials including plastic.

Bright Light Treatment in Elderly Patients With Nonseasonal Major Depressive Disorder A Randomized Placebo-Controlled Trial

NARCIS (Netherlands)

Lieverse, R.; van Someren, E.J.W.; Nielen, M.M.A.; Uitdehaag, B.M.; Smit, J.H.; Hoogendijk, W.J.G.

2011-01-01

Context: Major depressive disorder (MDD) in elderly individuals is prevalent and debilitating. It is accompanied by circadian rhythm disturbances associated with impaired functioning of the suprachiasmatic nucleus, the biological clock of the brain. Circadian rhythm disturbances are common in the

Light induces Fos expression via extracellular signal-regulated kinases 1/2 in melanopsin-expressing PC12 cells

DEFF Research Database (Denmark)

Moldrup, Marie-Louise Bülow; Georg, Birgitte; Falktoft, Birgitte

2010-01-01

The photopigment melanopsin is expressed in a subtype of mammalian ganglion cells in the retina that project to the circadian clock in the hypothalamic suprachiasmatic nucleus to mediate non-visual light information. Melanopsin renders these retinal ganglion cells intrinsically photosensitive...

Adult siblings with homozygous G6PC3 mutations expand our understanding of the severe congenital neutropenia type 4 (SCN4 phenotype

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Fernandez Bridget A

2012-11-01

Full Text Available Abstract Background Severe congenital neutropenia type 4 (SCN4 is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3. Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4 is caused by autosomal recessive mutations in SLC45A2. Methods We report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane et al., 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature. Results The siblings’ phenotype is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their ages are 38 and 37 years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in SLC45A2, which explains her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2 mutation and was diagnosed with “partial OCA” in childhood. Conclusions This family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.

Solution-processed inorganic copper(I) thiocyanate (CuSCN) hole transporting layers for efficient p–i–n perovskite solar cells

KAUST Repository

Zhao, Kui; Munir, Rahim; Yan, Buyi; Yang, Yang; Kim, Taesoo; Amassian, Aram

2015-01-01

CuSCN is a highly transparent, highly stable, low cost and easy to solution process HTL that is proposed as a low cost replacement to existing organic and inorganic metal oxide hole transporting materials. Here, we demonstrate hybrid organic

Study of Hadron Production in Hadron-Nucleus and Nucleus-Nucleus Collisions at the CERN SPS

CERN Multimedia

Klochkov, V; Herve, A E; Kowalski, S; Kaptur, E A; Kowalik, K L; Dominik, W M; Matulewicz, T N; Krasnoperov, A; Feofilov, G; Vinogradov, L; Kovalenko, V; Johnson, S R; Planeta, R J; Rubbia, A; Marton, K; Messerly, B A; Puzovic, J; Bogomilov, M V; Bravar, A; Renfordt, R A E; Deveaux, M; Engel, R R; Grzeszczuk, A; Davis, N; Kuich, M; Lyubushkin, V; Kondratev, V; Kadija, K; Diakonos, F; Slodkowski, M A; Rauch, W H; Pistillo, C; Laszlo, A; Nakadaira, T; Hasegawa, T; Sadovskiy, A; Morozov, S; Petukhov, O; Mathes, H; Roehrich, D; Marcinek, A J; Marino, A D; Grebieszkow, K; Di luise, S; Wlodarczyk, Z; Rybczynski, M A; Wojtaszek-szwarc, A; Nirkko, M C; Sakashita, K; Golubeva, M; Kurepin, A; Manic, D; Kolev, D I; Kisiel, J E; Koziel, M E; Rondio, E; Larsen, D T; Czopowicz, T R; Seyboth, P; Turko, L; Guber, F; Marin, V; Busygina, O; Strikhanov, M; Taranenko, A; Cirkovic, M; Roth, M A; Pulawski, S M; Aduszkiewicz, A M; Bunyatov, S; Vechernin, V; Nagai, Y; Anticic, T; Dynowski, K M; Mackowiak-pawlowska, M K; Stefanek, G; Pavin, M; Fodor, Z P; Nishikawa, K; Tada, M; Blondel, A P P; Stroebele, H W; Posiadala, M Z; Kolesnikov, V; Andronov, E; Zimmerman, E D; Antoniou, N; Majka, Z; Dumarchez, J; Naskret, M; Ivashkin, A; Tsenov, R V; Koziel, M G; Schmidt, K J; Melkumov, G; Popov, B; Panagiotou, A; Richter-was, E M; Morgala, S J; Paolone, V; Damyanova, A; Gazdzicki, M; Unger, M T; Wilczek, A G; Stepaniak, J M; Seryakov, A; Susa, T; Staszel, P P; Brzychczyk, J; Maksiak, B; Tefelski, D B

2007-01-01

The NA61/SHINE (SHINE = SPS Heavy Ion and Neutrino Experiment) experiment is a large acceptance hadron spectrometer at the CERN SPS for the study of the hadronic final states produced in interactions of various beam particles (pions, protons, C, S and In) with a variety of fixed targets at the SPS energies. The main components of the current detector were constructed and used by the NA49 experiment. The physics program of NA61/SHINE consists of three main subjects. In the first stage of data taking (2007-2009) measurements of hadron production in hadron-nucleus interactions needed for neutrino (T2K) and cosmic-ray (Pierre Auger and KASCADE) experiments will be performed. In the second stage (2009-2011) hadron production in proton-proton and proton-nucleus interactions needed as reference data for a better understanding of nucleus-nucleus reactions will be studied. In the third stage (2009-2013) energy dependence of hadron production properties will be measured in nucleus-nucleus collisions as well as in p+p a...

Pion production in nucleus--nucleus collisions

International Nuclear Information System (INIS)

Schroeder, L.S.

1975-06-01

Current work on pion production in high-energy nucleus-nucleus collisions is reviewed. The majority of existing data are of the inclusive variety in which a single final state pion is detected. Experimental data are compared and their possible contributions to obtaining new information on nuclear structure is discussed. Various models which attempt to explain the observed single-inclusive-pion spectra either on the basis of a nucleon-nucleus interaction in which Fermi motion is included or on some type of cooperative model are examined. Other areas of interest involving pion production include tests of charge symmetry and pion multiplicities. (9 figures, 1 table) (U.S.)

[14C]2-deoxyglucose uptake in ground squirrel brain during hibernation

International Nuclear Information System (INIS)

Kilduff, T.S.; Sharp, F.R.; Heller, H.C.

1982-01-01

Autoradiographic patterns of [14C]2-deoxyglucose uptake are described throughout the brains of hibernating and euthermic ground squirrels. Autoradiographs of the brains of hibernating animals are generally homogeneous in comparison to euthermic animals; hence, the relative 2-deoxyglucose uptake (R2DGU) of gray to white matter for the majority of the 85 neural structures examined decreases during hibernation. Two categories of structures are identified as potentially important in hibernation: (1) structures that have the highest R2DGU during hibernation (cochlear nucleus, paratrigeminal nucleus, and superior colliculus) and (2) structures that undergo the least reduction in R2DGU in the transition from euthermia to hibernation (suprachiasmatic nucleus and lateral septal nucleus). The percentage of reduction in R2DGU that a structure undergoes in the transition from euthermia to hibernation is proportional to the R2DGU of that structure during euthermia. The suprachiasmatic, paratrigeminal, and cochlear nuclei undergo less of a reduction than would be predicted from this relationship and may be particularly important during hibernation. Sensory nuclei that receive primary afferent projections are among the structures with the highest R2DGU during hibernation. These metabolically active structures may be responsible for the sensitivity of the hibernator to environmental stimuli

Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy.

Science.gov (United States)

Dilena, Robertino; Striano, Pasquale; Gennaro, Elena; Bassi, Laura; Olivotto, Sara; Tadini, Laura; Mosca, Fabio; Barbieri, Sergio; Zara, Federico; Fumagalli, Monica

2017-04-01

Recent clinical evidence supports a targeted therapeutic approach for genetic epileptic encephalopathies based on the molecular dysfunction. A 2-day-old male infant presented with epileptic encephalopathy characterized by burst-suppression EEG background and tonic-clonic migrating partial seizures. The condition was refractory to phenobarbital, pyridoxine, pyridoxal phosphate and levetiracetam, but a dramatic response to an intravenous loading dose of phenytoin was documented by video-EEG monitoring. Over weeks phenytoin was successfully switched to carbamazepine to prevent seizure relapses associated with difficulty in maintaining proper blood levels of phenytoin. Genetic analysis identified a novel de novo heterozygous mutation (c.[4633A>G]p.[Met1545Val]) in SCN2A. At two years and three months of age the patient is still seizure-free on carbamazepine, although a developmental delay is evident. Sodium channel blockers represent the first-line treatment for confirmed or suspected SCN2A-related epileptic encephalopathies. In severe cases with compatible electro-clinical features we propose a treatment algorithm based on a test trial with high dose intravenous phenytoin followed in case of a positive response by carbamazepine, more suitable for long-term maintenance treatment. Because of their rarity, collaborative studies are needed to delineate shared therapeutic protocols for EIEE based on the electro-clinical features and the presumed underlying genetic substrate. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Perspective of ultrarelativistic nucleus-nucleus collisions

International Nuclear Information System (INIS)

Specht, H.J.

1985-01-01

The paper concerns the lectures given at the International School of nuclear physics, Erice, 1985, which survey the expectations for the field of ultrarelativistic nucleus-nucleus collisions. The primary motivation for the field, the organization of the lectures, and a description of the NA 34 experiment, are all briefly given. (U.K.)

Generación de un modelo knock-out del gen SCN1A en Drosophila melanogaster para el estudio del síndrome de Dravet.

OpenAIRE

PLANELLS CÁRCEL, ANDRÉS

2017-01-01

[ES] El Síndrome de Dravet (SD) es una enfermedad rara infantil que se manifiesta en crisis epilépticas a temprana edad y provoca un deterioro cognitivo y conductual. Esta enfermedad es causada por mutaciones dominantes en el gen SCN1A. Este trabajo se centra en la generación de un modelo knock-out (KO) del gen paralytic en Drosophila melanogaster, homólogo al gen SCN1A en humanos, para su aplicación en el estudio del SD. A la vez se ha estudiado la conducta de cepas sensibles ...

Altered Light Conditions Contribute to Abnormalities in Emotion and Cognition Through HINT1 Dysfunction in C57BL/6 Mice

Directory of Open Access Journals (Sweden)

Yuan Zhou

2018-06-01

Full Text Available In recent years, the environmental impact of artificial light at night has been a rapidly growing global problem, affecting 99% of the population in the US and Europe, and 62% of the world population. The present study utilized a mouse model exposed to long-term artificial light and light deprivation to explore the impact of these conditions on emotion and cognition. Based on the potential links between histidine triad nucleotide binding protein 1 (HINT1 and mood disorders, we also examined the expression of HINT1 and related apoptosis factors in the suprachiasmatic nucleus (SCN, prefrontal cortex (PFC, nucleus accumbens (NAc and hippocampus (Hip. Mice exposed to constant light (CL exhibited depressive- and anxiety-like behaviors, as well as impaired spatial memory, as demonstrated by an increased immobility time in the tail suspension and forced swimming tests, less entries and time spent in the open arms of elevated plus-maze, and less platform site crossings and time spent in the target quadrant in the Morris water maze (MWM. The effects of constant darkness (CD partially coincided with long-term illumination, except that mice in the CD group failed to show anxiety-like behaviors. Furthermore, HINT1 was upregulated in four encephalic regions, indicating that HINT1 may be involved in mood disorders and cognitive impairments due to altered light exposure. The apoptosis-related proteins, BAX and BCL-2, showed the opposite expression pattern, reflecting an activated apoptotic pathway. These findings suggest that exposure to CL and/or darkness can induce significant changes in affective and cognitive responses, possibly through HINT1-induced activation of apoptotic pathways.

Central melanopsin projections in the diurnal rodent, Arvicanthis niloticus

DEFF Research Database (Denmark)

Langel, Jennifer L; Smale, Laura; Esquiva, Gema

2015-01-01

projections of ipRGCs by examining the distribution of immunoreactive PACAP fibers in intact and enucleated animals. This revealed evidence that these cells project to the suprachiasmatic nucleus, lateral geniculate nucleus (LGN), pretectum, and superior colliculus. This distribution was confirmed...... with injections of cholera toxin subunit β coupled with Alexa Fluor 488 in one eye and Alexa Fluor 594 in the other, combined with IHC staining of PACAP. These studies also revealed that the ventral and dorsal LGN and the caudal olivary pretectal nucleus receive less innervation from ipRGCs than that reported...

Formation of light particles in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Zagrebaev, V.; Penionzhkevich, Yu.

1993-01-01

The principal experimental results on the yield of the light charged particles in nucleus-nucleus collisions at the low and intermediate energies are reviewed. Inclusive spectra of light particles and their coincidences with the characteristic KX-rays, γ-rays, neutrons, projectile-like fragments, other light particles, fission fragments, and evaporation residues are analyzed. The main theoretical models used for the description of the light particle formation are briefly outlined together with their merits and shortcomings. The unsolved problems of fast light particle formation, in particular, and of nucleus-nucleus interaction dynamics, on the whole, are discussed with the outlooks of new experiments able to clear up some of these problems. (author) 144 refs., 40 figs., 2 tabs

Global features of nucleus-nucleus collisions in ultrarelativistic domain

International Nuclear Information System (INIS)

Savina, M.V.; Shmatov, S.V.; Slavin, N.V.; Zarubin, P.I.

1998-01-01

HIJING generator simulation of nucleus-nucleus collisions at ultrarelativistic energies is presented. It is shown that the global characteristics of nucleus-nucleus collisions, such as distribution of a charged multiplicity, total and electromagnetic transverse energy over pseudorapidity are rather sensitive to some predictions of models of high-exited nuclear medium formation, namely parton energy losses in dense nuclear matter. These losses result in appearance of a broad maximum in global variable distributions over pseudorapidity. The most profound of this effect occurs at central heavy ion collisions at LHC energy

Scaling phenomenon in relativistic nucleus-nucleus collisions

International Nuclear Information System (INIS)

Wong, C.Y.; Blankenbecler, R.

1980-01-01

New scaling variables for proton and pion production in relativistic nucleus-nucleus collisions are introduced which are the generalizations of the Feynmann scaling variable. They allow a simple description of the cross sections at forward and backward angles. 2 figures

Nucleus--nucleus potential

International Nuclear Information System (INIS)

Jaqaman, H.R.

1977-01-01

The nucleus--nucleus interaction is studied within the framework of the generator coordinate method that permits an easy incorporation of the full effects of antisymmetrization. It is found that the interaction, as far as the elastic scattering problem is concerned, can be described by a simple effective potential that is equivalent to the original many-body (and hence non-local) problem. The potential is obtained by dividing the wavefunction into a long-range part and a short-range part and requiring the former to satisfy a Schroedinger equation. This enables avoiding dealing with the troublesome short-range part of the wavefunction and provides a direct link with the optical model so that the potential obtained here is equivalent to the real part of the optical potential (the imaginary part is not investigated). The effective potential is found to consist of three parts: an interaction term between the nucleons belonging to different nuclei, a kinetic energy term due to the change in the intrinsic kinetic energy of the system as a result of the antisymmetrization, and finally an l-dependent part. The kinetic energy term is found to be very repulsive and effectively gives a hard core, and is calculated for the α--α and 16 O-- 16 O cases. The full potential is calculated for the α--α case for the S, D, and G partial waves and then used to calculate the corresponding phase shifts that are then compared with experimental results and other microscopic calculations. Finally, some recent results and analyses of fusion and deep inelastic reactions are reviewed that seem to indicate the presence of a hard core in the nucleus--nucleus potential. Such a hard core is present in the potential obtained in the sudden approximation

Hadron-nucleus collisions

International Nuclear Information System (INIS)

Strugalski, Z.

1981-01-01

Qualitative picture of high energy hadron-nucleus collision process, emerging from the analysis of experimental data, is presented. Appropriate description procedure giving a possibility of reproducing various characteristics of this process in terms of the data on elementary hadron-nucleon interaction is proposed. Formula reproducing hadron-nucleus collision cross sections is derived. Inelastic collision cross sections for pion-nucleus and proton-nucleus reactions at wide energy interval are calculated for Pb, Ag, and Al targets. A-dependence of cross sections for pion-nucleus and proton-nucleus collisions at nearly 50 GeV/c momentum were calculated and compared with existing experimental data. Energy dependence of cross sections for hadron-nucleus collisions is determined simply by energy dependence of corresponding cross sections for hadron-nucleon collisions; A-dependence is determined simply by nuclear sizes and nucleon density distributions in nuclei

Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion

Science.gov (United States)

House, Carrie D.; Vaske, Charles J.; Schwartz, Arnold M.; Obias, Vincent; Frank, Bryan; Luu, Truong; Sarvazyan, Narine; Irby, Rosalyn; Strausberg, Robert L.; Hales, Tim G.; Stuart, Joshua M.; Lee, Norman H.

2010-01-01

Voltage-gated Na+ channels (VGSCs) have been implicated in the metastatic potential of human breast, prostate and lung cancer cells. Specifically, the SCN5A gene encoding the VGSC isotype Nav1.5 has been defined as a key driver of human cancer cell invasion. In this study, we examined the expression and function of VGSCs in a panel of colon cancer cell lines by electrophysiological recordings. Na+ channel activity and invasive potential were inhibited pharmacologically by tetrodotoxin or genetically by siRNAs specifically targeting SCN5A. Clinical relevance was established by immunohistochemistry of patient biopsies, where there was strong Nav1.5 protein staining in colon cancer specimens but little to no staining in matched-paired normal colon tissues. We explored the mechanism of VGSC-mediated invasive potential on the basis of reported links between VGSC activity and gene expression in excitable cells. Probabilistic modeling of loss-of-function screens and microarray data established an unequivocal role of VGSC SCN5A as a high level regulator of a colon cancer invasion network, involving genes that encompass Wnt signaling, cell migration, ectoderm development, response to biotic stimulus, steroid metabolic process and cell cycle control. siRNA-mediated knockdown of predicted downstream network components caused a loss of invasive behavior, demonstrating network connectivity and its function in driving colon cancer invasion. PMID:20651255

Response of the human circadian system to millisecond flashes of light.

Directory of Open Access Journals (Sweden)

Jamie M Zeitzer

Full Text Available Ocular light sensitivity is the primary mechanism by which the central circadian clock, located in the suprachiasmatic nucleus (SCN, remains synchronized with the external geophysical day. This process is dependent on both the intensity and timing of the light exposure. Little is known about the impact of the duration of light exposure on the synchronization process in humans. In vitro and behavioral data, however, indicate the circadian clock in rodents can respond to sequences of millisecond light flashes. In a cross-over design, we tested the capacity of humans (n = 7 to respond to a sequence of 60 2-msec pulses of moderately bright light (473 lux given over an hour during the night. Compared to a control dark exposure, after which there was a 3.5±7.3 min circadian phase delay, the millisecond light flashes delayed the circadian clock by 45±13 min (p<0.01. These light flashes also concomitantly increased subjective and objective alertness while suppressing delta and sigma activity (p<0.05 in the electroencephalogram (EEG. Our data indicate that phase shifting of the human circadian clock and immediate alerting effects can be observed in response to brief flashes of light. These data are consistent with the hypothesis that the circadian system can temporally integrate extraordinarily brief light exposures.

α1B-Adrenergic receptor signaling controls circadian expression of Tnfrsf11b by regulating clock genes in osteoblasts

Directory of Open Access Journals (Sweden)

Takao Hirai

2015-11-01

Full Text Available Circadian clocks are endogenous and biological oscillations that occur with a period of <24 h. In mammals, the central circadian pacemaker is localized in the suprachiasmatic nucleus (SCN and is linked to peripheral tissues through neural and hormonal signals. In the present study, we investigated the physiological function of the molecular clock on bone remodeling. The results of loss-of-function and gain-of-function experiments both indicated that the rhythmic expression of Tnfrsf11b, which encodes osteoprotegerin (OPG, was regulated by Bmal1 in MC3T3-E1 cells. We also showed that REV-ERBα negatively regulated Tnfrsf11b as well as Bmal1 in MC3T3-E1 cells. We systematically investigated the relationship between the sympathetic nervous system and the circadian clock in osteoblasts. The administration of phenylephrine, a nonspecific α1-adrenergic receptor (AR agonist, stimulated the expression of Tnfrsf11b, whereas the genetic ablation of α1B-AR signaling led to the alteration of Tnfrsf11b expression concomitant with Bmal1 and Per2 in bone. Thus, this study demonstrated that the circadian regulation of Tnfrsf11b was regulated by the clock genes encoding REV-ERBα (Nr1d1 and Bmal1 (Bmal1, also known as Arntl, which are components of the core loop of the circadian clock in osteoblasts.

Melatonin is a redundant entraining signal in the rat circadian system

Czech Academy of Sciences Publication Activity Database

Houdek, Pavel; Nováková, Marta; Polidarová, Lenka; Sládek, Martin; Sumová, Alena

2016-01-01

Roč. 83, Jul (2016), s. 1-5 ISSN 0018-506X R&D Projects: GA ČR(CZ) GA14-07711S Institutional support: RVO:67985823 Keywords : melatonin * pinealectomy * suprachiasmatic nucleus * liver * duodenum * clock gene Subject RIV: ED - Physiology Impact factor: 3.378, year: 2016

Normal sleep and its neurophysiological regulation

NARCIS (Netherlands)

Hofman, W.F.; Talamini, L.M.; Watson, R.R.

2015-01-01

Normal sleep consists of two states: NREM (light and deep sleep) and REM, alternating in a cyclical pattern. The sleep/wake rhythm is regulated by two processes: the sleep propensity, building up during wake, and the circadian rhythm, imposed by the suprachiasmatic nucleus. The arousal pathways in

The imaginary part of the nucleus - nucleus optical potential

International Nuclear Information System (INIS)

Phatak, S.C.; Sinha, B.

1978-01-01

The contribution to the imaginary nucleus - nucleus optical potential has been estimated by evaluating the energy - conserving seocond-order term in the perturbation series. The incoming nuclear field is supposed to excite nucleons in a nucleus in this calculation and the nuclear excitations are approximated by particle-hole excitations in a Fermi gas. The resulting imaginary potential compares favourably with phenomenological potentials. (author)

Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

Science.gov (United States)

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-05-01

Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

Quantitative light microscopic autoradiographic localization of binding sites labelled with [3H]vasopressin antagonist d(CH2)5Tyr(Me)VP in the rat brain, pituitary and kidney

International Nuclear Information System (INIS)

Leeuwen, F.W. van; Beek, E.M. van der; Heerikhuize, J.J. van; Wolters, P.; Meulen, G. van der; Wan, Yieh-Ping

1987-01-01

Binding sites for the vasopressin (VP) antagonist d(CH 2 ) 5 Tyr(Me)VP, were located in various brain areas (e.g. the lateral septum, amygdala, choroid plexus and nucleus of the solitary tract) using light microscopic autoradiography. A number of areas (e.g. suprachiasmatic and arcuate nucleus, pineal gland) which previously showed no VP binding were labelled in the present study. The olfactory nucleus and ventromedial hypothalamic nucleus were not labelled. It therefore appears that d(CH 2 ) 5 Tyr(Me)VP is capable of discriminating between VP and oxytocin binding sites and more sensitive means of detecting VP binding sites than VP alone. (Author)

Quasi-elastic shadowing in nucleus-nucleus elastic scattering

Energy Technology Data Exchange (ETDEWEB)

Dymarz, R; Malecki, A [Institute of Nuclear Physics, Krakow (Poland); Gluski, K [Institute of Nuclear Research, Warsaw (Poland); Picchi, P [Turin Univ. (Italy). Ist. di Fisica; Consiglio Nazionale delle Ricerche, Turin (Italy). Lab. di Cosmo-Geofisica)

1979-01-06

The complete evaluation of the Glauber multiple-scattering series for nucleus-nucleus collisions is a very difficult task and that is why various approximate formulae were proposed. In this work some of these approximations are discussed.

Solution-processed p-type copper(I) thiocyanate (CuSCN) for low-voltage flexible thin-film transistors and integrated inverter circuits

KAUST Repository

Petti, Luisa; Pattanasattayavong, Pichaya; Lin, Yen-Hung; Mü nzenrieder, Niko; Cantarella, Giuseppe; Yaacobi-Gross, Nir; Yan, Feng; Trö ster, Gerhard; Anthopoulos, Thomas D.

2017-01-01

, depending on the gate dielectric employed. The promising TFT characteristics enable fabrication of unipolar NOT gates on flexible free-standing plastic substrates with voltage gain of 3.4 at voltages as low as −3.5 V. Importantly, discrete CuSCN transistors

High density QCD and nucleus-nucleus scattering deeply in the saturation region

International Nuclear Information System (INIS)

Kormilitzin, Andrey; Levin, Eugene; Miller, Jeremy S.

2011-01-01

In this paper we solve the equations that describe nucleus-nucleus scattering, in high density QCD, in the framework of the BFKL Pomeron Calculus. We found that (i) the contribution of short distances to the opacity for nucleus-nucleus scattering dies at high energies, (ii) the opacity tends to unity at high energy, and (iii) the main contribution that survives comes from soft (long distance) processes for large values of the impact parameter. The corrections to the opacity Ω(Y,b)=1 were calculated and it turns out that they have a completely different form, namely (1-Ω→exp(-Const√(Y))) than the opacity that stems from the Balitsky-Kovchegov equation, which is (1-Ω→exp(-ConstY 2 )). We reproduce the formula for the nucleus-nucleus cross section that is commonly used in the description of nucleus-nucleus scattering, and there is no reason why it should be correct in the Glauber-Gribov approach.

High Prevalence of Long QT Syndrome Associated SCN5A Variants in Patients with Early-Onset Lone Atrial Fibrillation

DEFF Research Database (Denmark)

Olesen, Morten S; Yuan, Lei; Liang, Bo

2012-01-01

a mechanistic overlap between LQTS3 and early-onset lone AF. In 9 of 10 identified mutations and rare variants, we observed compromised biophysical properties affecting the transient peak current. CONCLUSIONS: In a cohort of patients with early-onset lone AF, we identified a high prevalence of SCN5A mutations...

Onuf's nucleus X

DEFF Research Database (Denmark)

Schrøder, H D

1981-01-01

in the length of the nucleus was observed. Based on the cytoarchitecture the nucleus could be divided in three parts, a cranial, a dorsomedial and a ventrolateral. All parts of the nucleus consisted of chromatin-rich medium-sized neurons, and apparent direct appositions between different cells bodies as well...

Solution-processed p-type copper(I) thiocyanate (CuSCN) for low-voltage flexible thin-film transistors and integrated inverter circuits

KAUST Repository

Petti, Luisa

2017-03-17

We report on low operating voltage thin-film transistors (TFTs) and integrated inverters based on copper(I) thiocyanate (CuSCN) layers processed from solution at low temperature on free-standing plastic foils. As-fabricated coplanar bottom-gate and staggered top-gate TFTs exhibit hole-transporting characteristics with average mobility values of 0.0016 cm2 V−1 s−1 and 0.013 cm2 V−1 s−1, respectively, current on/off ratio in the range 102–104, and maximum operating voltages between −3.5 and −10 V, depending on the gate dielectric employed. The promising TFT characteristics enable fabrication of unipolar NOT gates on flexible free-standing plastic substrates with voltage gain of 3.4 at voltages as low as −3.5 V. Importantly, discrete CuSCN transistors and integrated logic inverters remain fully functional even when mechanically bent to a tensile radius of 4 mm, demonstrating the potential of the technology for flexible electronics.

Hierarchical organization of the circadian timing system

NARCIS (Netherlands)

Steensel, Mariska van

2006-01-01

In order to cope with and to predict 24-hour rhythms in the environment, most, if not all, organisms have a circadian timing system. The most important mammalian circadian pacemaker is located in the suprachiasmatic nucleus at the base of the hypothalamus in the brain. Over the years, it has become

Classifiers for centrality determination in proton-nucleus and nucleus-nucleus collisions

Directory of Open Access Journals (Sweden)

Altsybeev Igor

2017-01-01

Full Text Available Centrality, as a geometrical property of the collision, is crucial for the physical interpretation of nucleus-nucleus and proton-nucleus experimental data. However, it cannot be directly accessed in event-by-event data analysis. Common methods for centrality estimation in A-A and p-A collisions usually rely on a single detector (either on the signal in zero-degree calorimeters or on the multiplicity in some semi-central rapidity range. In the present work, we made an attempt to develop an approach for centrality determination that is based on machine-learning techniques and utilizes information from several detector subsystems simultaneously. Different event classifiers are suggested and evaluated for their selectivity power in terms of the number of nucleons-participants and the impact parameter of the collision. Finer centrality resolution may allow to reduce impact from so-called volume fluctuations on physical observables being studied in heavy-ion experiments like ALICE at the LHC and fixed target experiment NA61/SHINE on SPS.

Partial inelasticity coefficients of negative pions produced in hadron-nucleus and nucleus-nucleus collisions at high energies

International Nuclear Information System (INIS)

OLIMOV, K.; LUTPULLAEV, S.L.; PETROV, V.I.; OLIMOV, A.K.

2015-01-01

New experimental data on the partial inelasticity coefficients of negative pions produced in "1"6Op-collisions at 3.25 A GeV/s, pC-interactions at 4.2 and 9.9 GeV/s, and d,α,C(C)-collisions at 4.2 A GeV/s are presented. It is established that the behavior of partial inelasticity coefficients of pions at intermediate energies (<10 GeV) in hadron-nucleus collisions has a transitional character, reaching the limiting value at ultrahigh energies. It is shown that the mean values of partial inelasticity coefficients of pions produced in nucleus-nucleus collisions decrease with an increase in mass number of the projectile nucleus. (authors)

Diabatic interaction potential for nucleus-nucleus collisions

International Nuclear Information System (INIS)

Noerenberg, W.; Lukasiak, A.

1984-01-01

Within a refined method for the construction of diabatic states allowing for the treatment of the full spin-orbit coupling, characteristic features of the diabatic potential for nucleus-nucleus collisions are investigated. Approximately 90% of the strong repulsion results from diabatic particle-hole excitations, while only 10% is due to compression. The diabatic interaction potential describes a physical situation intermediate between adiabatic and sudden approximations. (orig.)

Role of aging and hippocampus in Time-Place Learning: link to episodic-like memory?

Directory of Open Access Journals (Sweden)

Cornelis Kees Mulder

2016-01-01

Full Text Available Introduction: with time-place learning (TPL, animals link an event with the spatial location and the time of day. The what-where-when TPL components make the task putatively episodic-like in nature. Animals use an internal sense of time to master TPL, which is circadian system based. Finding indications for a role of the hippocampus and (early aging-sensitivity in TPL would strengthen the episodic-like memory nature of the paradigm. Methods: previously, we used C57Bl/6 mice for our TPL research. Here, we used CD1 mice which are less hippocampal-driven and age faster compared to C57Bl/6 mice. To demonstrate the low degree of hippocampal-driven performance in CD1 mice, a cross maze was used. The spontaneous alternation test was used to score spatial working memory in CD1 mice at four different age categories (young (3-6 months, middle-aged (7-11 months, aged (12-18 months and old (>19 months. TPL performance of middle-aged and aged CD1 mice was tested in a setup with either two or three time points per day (2-arm or 3-arm TPL task. Immunostainings was applied on brains of young and middle-aged C57Bl/6 mice that had successfully mastered the 3-arm TPL task. Results: in contrast to C57Bl/6 mice, middle-aged and aged CD1 mice were less hippocampus-driven and failed to master the 3-arm TPL task. They could, however, master the 2-arm TPL task primarily via an ordinal (non-circadian timing system. c-Fos, CRY2, vasopressin (AVP, and pCREB were investigated. We found no differences at the level of the suprachiasmatic nucleus (SCN; circadian master clock, whereas CRY2 expression was increased in the hippocampal dentate gyrus. The most pronounced difference between TPL trained and control mice was found in c-Fos expression in the paraventricular thalamic nucleus, a circadian system relay station. Conclusions: These results further indicate a key role of CRY proteins in TPL and confirm the limited role of the SCN in TPL. Based on the poor TPL performance of

The theoretical character of the X1Σ+ and A1Σ+ states of ScN

International Nuclear Information System (INIS)

Feng-Juan, Bai; Chuan-Lu, Yang; Qi, Qian; Ling, Zhang

2009-01-01

This paper calculates the potential energy curves (PECs) of the ground state (X 1 Σ + ) and excited state (A 1 Σ + ) of ScN molecule by multireference configuration interaction method. The correct character of the PECs has been gripped while they had been improperly reported in the literature. Based on the PECs, the spectroscopic parameters and vibrational energy levels are determined, and compared with experimental data and other theoretical works available at the present. (atomic and molecular physics)

Classical gluon production amplitude for nucleus-nucleus collisions:First saturation correction in the projectile

International Nuclear Information System (INIS)

Chirilli, Giovanni A.; Kovchegov, Yuri V.; Wertepny, Douglas E.

2015-01-01

We calculate the classical single-gluon production amplitude in nucleus-nucleus collisions including the first saturation correction in one of the nuclei (the projectile) while keeping multiple-rescattering (saturation) corrections to all orders in the other nucleus (the target). In our approximation only two nucleons interact in the projectile nucleus: the single-gluon production amplitude we calculate is order-g"3 and is leading-order in the atomic number of the projectile, while resumming all order-one saturation corrections in the target nucleus. Our result is the first step towards obtaining an analytic expression for the first projectile saturation correction to the gluon production cross section in nucleus-nucleus collisions.

A dual-color luciferase assay system reveals circadian resetting of cultured fibroblasts by co-cultured adrenal glands.

Directory of Open Access Journals (Sweden)

Takako Noguchi

Full Text Available In mammals, circadian rhythms of various organs and tissues are synchronized by pacemaker neurons in the suprachiasmatic nucleus (SCN of the hypothalamus. Glucocorticoids released from the adrenal glands can synchronize circadian rhythms in other tissues. Many hormones show circadian rhythms in their plasma concentrations; however, whether organs outside the SCN can serve as master synchronizers to entrain circadian rhythms in target tissues is not well understood. To further delineate the function of the adrenal glands and the interactions of circadian rhythms in putative master synchronizing organs and their target tissues, here we report a simple co-culture system using a dual-color luciferase assay to monitor circadian rhythms separately in various explanted tissues and fibroblasts. In this system, circadian rhythms of organs and target cells were simultaneously tracked by the green-emitting beetle luciferase from Pyrearinus termitilluminans (ELuc and the red-emitting beetle luciferase from Phrixothrix hirtus (SLR, respectively. We obtained tissues from the adrenal glands, thyroid glands, and lungs of transgenic mice that expressed ELuc under control of the promoter from a canonical clock gene, mBmal1. The tissues were co-cultured with Rat-1 fibroblasts as representative target cells expressing SLR under control of the mBmal1 promoter. Amplitudes of the circadian rhythms of Rat-1 fibroblasts were potentiated when the fibroblasts were co-cultured with adrenal gland tissue, but not when co-cultured with thyroid gland or lung tissue. The phases of Rat-1 fibroblasts were reset by application of adrenal gland tissue, whereas the phases of adrenal gland tissue were not influenced by Rat-1 fibroblasts. Furthermore, the effect of the adrenal gland tissue on the fibroblasts was blocked by application of a glucocorticoid receptor (GR antagonist. These results demonstrate that glucocorticoids are strong circadian synchronizers for fibroblasts and that

[Depression as chronobiological illness].

Science.gov (United States)

Kálmán, Janos; Kálmán, Sára

2009-06-01

Chronobiological problems are always present as aetiological or pathoplastic conditions almost in all psychiatric disorders and considered as the greatest contributors to the mood and sleep disorders associated problems. The present review summarise the recent advances in the chronobiology research from the point of the clinician with particular emphasis on the psychobiology and pharmacotherapy of the depression. Human behaviour builds up from different length of circadian, ultradian and seasonal rhytms, strictly controlled by a hierarchical organisation of sub-cellullar, cellular, neuro-humoral and neuro-immunological clock systems. These internal clock systems are orchestrated at molecular level by certain clock genes and on the other hand--at neuro-humoral level--by the effect of the sleep hormone, melatonine, produced by the neurons of the suprachiasmatic nucleus (SCN). Beside the biological factors, social interactions are also considered as important regulators of the biological clock systems. The pacemaker centers of the SCN receive efferents from the serotoninergic raphe nuclei in order to regulate stress responses and neuroimmunological functions. The direction and the level of the chronobiological desynchronisation could be totally divergent in the case of the different affective disorders. Different chronobiological interventions are required therefore in the case of the advanced and delayed sleep disorders. Sleeping disorders are considered as the most recognised signs of the chronobiological desynchronisation in depression, but these symptoms are only the tip of the iceberg, since other chronobiological symptoms could be present due to the hidden physiological abnormalities. The serum melatonine profile is considered to be characteristic to age, gender and certain neuropsychiatric disorders. The natural and synthetic agonist of the melatonine receptors could be used as chronobiotics. The recently marketed agomelatine with a highly selective receptor

Neural Damage in Experimental Trypanosoma brucei gambiense Infection: Hypothalamic Peptidergic Sleep and Wake-Regulatory Neurons

Directory of Open Access Journals (Sweden)

Claudia Laperchia

2018-02-01

Full Text Available Neuron populations of the lateral hypothalamus which synthesize the orexin (OX/hypocretin or melanin-concentrating hormone (MCH peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT, also called sleeping sickness, caused by extracellular Trypanosoma brucei (T. b. parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T. b. brucei subspecies. No information is available, however, on these peptidergic neurons after systemic infection with T. b. gambiense, the etiological agent of 97% of HAT cases. The present study was aimed at the investigation of immunohistochemically characterized OX and MCH neurons after T. b. gambiense or T. b. brucei infection of a susceptible rodent, the multimammate mouse, Mastomysnatalensis. Cell counts and evaluation of OX fiber density were performed at 4 and 8 weeks post-infection, when parasites had entered the brain parenchyma from the periphery. A significant decrease of OX neurons (about 44% reduction and MCH neurons (about 54% reduction was found in the lateral hypothalamus and perifornical area at 8 weeks in T. b. gambiense-infected M. natalensis. A moderate decrease (21% and 24% reduction, respectively, which did not reach statistical significance, was found after T. b. brucei infection. In two key targets of diencephalic orexinergic innervation, the peri-suprachiasmatic nucleus (SCN region and the thalamic paraventricular nucleus (PVT, densitometric analyses showed a significant progressive decrease in the density of orexinergic fibers in both infection paradigms, and especially during T. b. gambiense infection. Altogether the findings provide novel information showing that OX and MCH neurons are highly vulnerable to chronic

K+-nucleus interaction

International Nuclear Information System (INIS)

Gibbs, W.R.

1984-01-01

The K + -nucleus system is reviewed and comparison with data is made. The principal conclusions are that the theoretical uncertainties in relating the K + -nucleus interaction to the K + -nucleon interaction are very small and hence the positive kaon makes an excellent probe of the nucleus. It is suggested that this particle may be more sensitive to non-nucleonic degrees of freedom (especially quarks) than classical probes

TWO-PHOTON PHYSICS IN NUCLEUS-NUCLEUS COLLISIONS AT RHIC

International Nuclear Information System (INIS)

Nystrand, J.; Klein, S.

1998-01-01

Ultra-relativistic heavy-ions carry strong electromagnetic and nuclear fields. Interactions between these fields in peripheral nucleus-nucleus collisions can probe many interesting physics topics. This presentation will focus on coherent two-photon and photonuclear processes at RHIC. The rates for these interactions will be high. The coherent coupling of all the protons in the nucleus enhances the equivalent photon flux by a factor Z 2 up to an energy of ∼ 3 GeV. The plans for studying coherent interactions with the STAR experiment will be discussed. Experimental techniques for separating signal from background will be presented

Two-photon physics in nucleus-nucleus collisions at RHIC

International Nuclear Information System (INIS)

Nystrand, J.; Klein, S.

1998-01-01

Ultra-relativistic heavy-ions carry strong electromagnetic and nuclear fields. Interactions between these fields in peripheral nucleus-nucleus collisions can probe many interesting physics topics. This presentation will focus on coherent two-photon and photonuclear processes at RHIC. The rates for these interactions will be high. The coherent coupling of all the protons in the nucleus enhances the equivalent photon flux by a factor Z 2 up to an energy of ∼ 3 GeV. The plans for studying coherent interactions with the STAR experiment will be discussed. Experimental techniques for separating signal from background will be presented

Functionalized active-nucleus complex sensor

Science.gov (United States)

Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

2003-11-25

A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

Strangeness production in hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions in the dual parton model

International Nuclear Information System (INIS)

Moehring, H.; Ranft, J.; Capella, A.; Tran Thanh Van, J.

1993-01-01

Λ, bar Λ, and K S 0 production is studied in a Monte Carlo dual parton model for hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions with an SU(3) symmetric sea for chain formation (chain ends) but strangeness suppression in the chain fragmentation process. Additionally, (qq)-(bar q bar q) production from the sea was introduced into the chain formation process with the same probability as for the q→qq branching within the chain decay process. With these assumptions, multiplicity ratios and Feynman-x distributions for strange particles in h-h and multiplicity ratios in heavy ion collisions are reasonably well reproduced

The nuclear response and the imaginary potential for nucleus-nucleus collisions

International Nuclear Information System (INIS)

Phatak, S.C.; Sinha, B.

1983-01-01

The Fermi-gas model is used in this paper to study the nucleus-nucleus collision. The field produced by one of the nuclei is considered to act on nucleons in the other nucleus, which is treated as a Fermi gas of radius R. The imaginary part of the (non-local) nucleus-nucleus potential is then computed by evaluating the energy-conserving second-order term in which the intermediate states are particle-hole excitations produced in the Fermi gas. The equivalent local potential, obtained by using the Perey-Saxon method, is compared with phenomenological imaginary potentials. Later it is shown that, in the limit of small range of non-locality, the imaginary potential can be related to the nuclear response function. With this, one can write the nuclear friction coefficient that is used in phenomenological analyses of heavy-ion collisions in terms of the imaginary potential. (orig.)

Maternal Control of the Fetal and Neonatal Rat Suprachiasmatic Nucleus

Czech Academy of Sciences Publication Activity Database

El-Hennamy, Rehab; Matějů, Kristýna; Bendová, Zdena; Sosniyenko, Serhiy; Sumová, Alena

2008-01-01

Roč. 23, č. 5 (2008), s. 435-444 ISSN 0748-7304 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA309/05/0350; GA ČR GA309/08/0503 Grant - others:GA ČR(CZ) GD309/08/H079; EUCLOCK(XE) LSH-2004-115-4-018741 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian system * ontogenesis * maternal entrainment Subject RIV: FH - Neurology Impact factor: 4.211, year: 2008

Hole-transporting transistors and circuits based on the transparent inorganic semiconductor copper(I) thiocyanate (CuSCN) processed from solution at room temperature

KAUST Repository

Pattanasattayavong, Pichaya; Yaacobi-Gross, Nir; Zhao, Kui; Ndjawa, Guy Olivier Ngongang; Li, Jinhua; Yan, Feng; O'Regan, Brian C.; Amassian, Aram; Anthopoulos, Thomas D.

2012-01-01

ferroelectric polymeric dielectric P(VDF-TrFE-CFE), we demonstrate low-voltage transistors with hole mobilities on the order of 0.1 cm2 V-1 s-1. By integrating two CuSCN transistors, unipolar logic NOT gates are also demonstrated. Copyright © 2013 WILEY

Effective nucleus-nucleus potentials derived from the generator coordinate method

Energy Technology Data Exchange (ETDEWEB)

Friedrich, H; Canto, L F [Oxford Univ. (UK). Dept. of Theoretical Physics

1977-11-07

The equivalence of the generator coordinate method (GCM) and the resonating group method (RGM) and the formal equivalence of the RGM and the orthogonality condition model (OCM) lead to a relation connecting the effective nucleus-nucleus potentials of the OCM with matrix elements of the GCM. This relation may be used to derive effective nucleus-nucleus potentials directly from GCM matrix elements without explicit reference to the potentials of the RGM. In a first application local and l-independent effective potentials are derived from diagonal GCM matrix elements which represent the energy surfaces of a two-centre shell model. Using these potentials the OCM can reproduce the results of a full RGM calculation very well for the elastic scattering of two ..cap alpha..-particles and fairly well for elastic /sup 16/O-/sup 16/O scattering.

Muon-spin rotation studies of the flux lattice in {kappa}-(BEDT-TTF){sub 2}Cu(SCN){sub 2}

Energy Technology Data Exchange (ETDEWEB)

Lee, S.L. [Saint Andrews Univ. (United Kingdom). Sch. of Phys. and Astron.; Blundell, S.J. [Oxford Univ. (United Kingdom). Dept. of Physics; Pratt, F.L. [RIKEN-RAL, Didcot (United Kingdom); Pattenden, P.A. [Oxford Univ. (United Kingdom). Dept. of Physics; Forgan, E.M. [Birmingham Univ. (United Kingdom). School of Physics and Space Research; Sasaki, T. [Tohoku Univ., Sendai (Japan). Inst. for Materials Research; Aegerter, C.M. [Zurich Univ. (Switzerland). Inst. fuer Physik; Hunt, M. [Zurich Univ. (Switzerland). Inst. fuer Physik; Chow, K.H. [Oxford Univ. (United Kingdom). Dept. of Physics; Hayes, W. [Oxford Univ. (United Kingdom). Dept. of Physics; Singleton, J. [Oxford Univ. (United Kingdom). Dept. of Physics; Keller, H. [Zurich Univ. (Switzerland). Inst. fuer Physik; Savic, I.M. [Zurich Univ. (Switzerland). Inst. fuer Physik

1997-02-15

Muon spin rotation ({mu}SR) studies of the vortex lattice in the superconductor {kappa}-(BEDT-TTF){sub 2}Cu(SCN){sub 2} have revealed a crossover from a quasi-2d to a vortex-line lattice structure for fields below a characteristic field B{sub cr}. The {mu}SR-lineshapes measured from the vortex-line lattice have allowed a re-evaluation of the in-plane penetration depth. (orig.)

Experimental search for compression phenomena in fast nucleus--nucleus collisions

International Nuclear Information System (INIS)

Schopper, E.; Baumgardt, H.G.; Obst, E.

1977-01-01

The occurrence of compression phenomena and shock waves, connected with the increase of the density of the nuclear matter during the interpenetration of two fast nuclei, are discussed. Current experiments dealing with this problem are reviewed. Before considering the mechanism of the interpenetration of two fast nuclei it may be useful to look at more simple situations, i.e., proton-proton interactions, then to envelop them with nuclear matter, considering proton-nucleus interactions. Only very general features are described, which may give suggestions for the understanding of the nucleus-nucleus impact

Biological Rhythms in the Skin

Directory of Open Access Journals (Sweden)

Mary S. Matsui

2016-05-01

Full Text Available Circadian rhythms, ≈24 h oscillations in behavior and physiology, are reflected in all cells of the body and function to optimize cellular functions and meet environmental challenges associated with the solar day. This multi-oscillatory network is entrained by the master pacemaker located in the suprachiasmatic nucleus (SCN of the hypothalamus, which directs an organism’s rhythmic expression of physiological functions and behavior via a hierarchical system. This system has been highly conserved throughout evolution and uses transcriptional–translational autoregulatory loops. This master clock, following environmental cues, regulates an organism’s sleep pattern, body temperature, cardiac activity and blood pressure, hormone secretion, oxygen consumption and metabolic rate. Mammalian peripheral clocks and clock gene expression have recently been discovered and are present in all nucleated cells in our body. Like other essential organ of the body, the skin also has cycles that are informed by this master regulator. In addition, skin cells have peripheral clocks that can function autonomously. First described in 2000 for skin, this review summarizes some important aspects of a rapidly growing body of research in circadian and ultradian (an oscillation that repeats multiple times during a 24 h period cutaneous rhythms, including clock mechanisms, functional manifestations, and stimuli that entrain or disrupt normal cycling. Some specific relationships between disrupted clock signaling and consequences to skin health are discussed in more depth in the other invited articles in this IJMS issue on Sleep, Circadian Rhythm and Skin.

Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice.

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Naoto Hayasaka

Full Text Available Regulators of G protein signaling (RGS are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs of G protein α-subunits to terminate G protein signaling. Previous studies have demonstrated that the Rgs16 transcripts exhibit robust circadian rhythms both in the suprachiasmatic nucleus (SCN, the master circadian light-entrainable oscillator (LEO of the hypothalamus, and in the liver. To investigate the role of RGS16 in the circadian clock in vivo, we generated two independent transgenic mouse lines using lentiviral vectors expressing short hairpin RNA (shRNA targeting the Rgs16 mRNA. The knockdown mice demonstrated significantly shorter free-running period of locomotor activity rhythms and reduced total activity as compared to the wild-type siblings. In addition, when feeding was restricted during the daytime, food-entrainable oscillator (FEO-driven elevated food-anticipatory activity (FAA observed prior to the scheduled feeding time was significantly attenuated in the knockdown mice. Whereas the restricted feeding phase-advanced the rhythmic expression of the Per2 clock gene in liver and thalamus in the wild-type animals, the above phase shift was not observed in the knockdown mice. This is the first in vivo demonstration that a common regulator of G protein signaling is involved in the two separate, but interactive circadian timing systems, LEO and FEO. The present study also suggests that liver and/or thalamus regulate the food-entrained circadian behavior through G protein-mediated signal transduction pathway(s.

Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks.

Science.gov (United States)

de Assis, Leonardo Vinícius Monteiro; Moraes, Maria Nathália; Magalhães-Marques, Keila Karoline; Kinker, Gabriela Sarti; da Silveira Cruz-Machado, Sanseray; Castrucci, Ana Maria de Lauro

2018-04-03

The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis), and the suprachiasmatic nucleus (SCN) were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism's biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

Directory of Open Access Journals (Sweden)

Leonardo Vinícius Monteiro de Assis

2018-04-01

Full Text Available The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME and macro-environments (TMaE in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis, and the suprachiasmatic nucleus (SCN were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism’s biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

The mechanism of nuclear energy release in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Strugalski, Z.; Strugalska-Gola, E.

1998-01-01

The mechanism of intranuclear energy release in reactions induced by nucleus-nucleus collisions at energies higher than ∼ 0.5 GeV/nucl. is presented - as prompted experimentally. The intranuclear energy release goes through local damages of the colliding nuclei

The correlation between the transverse polarization and transverse momentum of lambda produced in relativistic nucleus-nucleus collisions

International Nuclear Information System (INIS)

Ye Yunxiu; Zhou Xin; Ji Gang; Su Shufang; Zhu Guohuai

1996-01-01

The transverse polarization of lambda produced in relativistic nucleus-nucleus collisions is determined. The effect from the interaction between spin moment and magnetic field is corrected. The near zero transverse polarization and non-correlation between transverse polarization and transverse momentum are obtained and compared to ones obtained from the nucleus-nucleus interactions at lower energies. This comparison shows that the production mechanism of lambdas in the relativistic nucleus-nucleus collisions is different from one in the nucleus-nucleus reactions at lower energies

Formation of proton-fragments in hadron-nucleus and nucleus-nucleus collisions at high energies

International Nuclear Information System (INIS)

Bazarov, E.Kh.; Olimov, K.; Petrov, V.I.; Lutpullaev, S.L.

2006-01-01

Full text: The investigation of production of protons in hadron- and nucleus-nucleus interactions is a key problem allowing one to establish the singularities of dynamics of nuclear interactions. The formation of proton-fragments at high energies of colliding particles proceeds within both the interaction of hadrons with nuclei and in the process of decay of the nucleus or its de-excitation at peripheral interactions. At different stages of interaction of impinging particle with target nucleus, the different mechanisms of formation of proton-fragments: the direct knock-out of intranuclear nucleons in the process of high energy cascade of an initial hadron, intranuclear cascade of produced particles, decay of the excited multi-nucleon fragments and of the thermalized remnant nucleus, and the coalescence of nuclear fragments to the new clusters are realized with the certain probability, connected to the interaction parameters (the interaction energy, the parameter of collision, the intranuclear density, the configuration of Fermi momentum of nucleons and clusters of target nucleus et al.). In its turn, the mechanisms of formation of the final nuclear fragments are closely related to the type of excitation of an initial nucleus. The peripheral interactions proceed at small transfers of the momentum of an impinging particle and represent the wide class of reactions covering the processes from diffractive or coulomb collective excitations of the whole nucleus to the direct quasi-elastic knock-out of the separate nucleons. Non-peripheral interactions are caused by comparatively high local transfers of momentum to the intranuclear clusters allowing the development of intranuclear cascade and the asymmetric redistribution of energy of an impinging particle. The central collisions causing the full decay of nucleus on nucleons or few-nucleon fragments, are the limiting case of the maximal development of the intranuclear cascade. The interaction of the initial particles with

Nucleus-nucleus interactions in the transition energy regime

International Nuclear Information System (INIS)

Volant, C.

1985-02-01

There are at least two ways for studying large interactions in nucleus-nucleus collisions. One way is to use the method of angular correlations between fission fragments. The aim of the experiments presented here was to make a survey on the role of the various experimental parameters. In that respect three targets have been studied and different projectiles and bombarding energies have been used. Results are presented and discussed

Setting the biological time in central and peripheral clocks during ontogenesis

Czech Academy of Sciences Publication Activity Database

Sumová, Alena; Bendová, Zdeňka; Sládek, Martin; El-Hennamy, Rehab; Laurinová, Kristýna; Jindráková, Zuzana; Illnerová, Helena

2006-01-01

Roč. 580, č. 12 (2006), s. 2836-2842 ISSN 0014-5793 R&D Projects: GA ČR(CZ) GA309/05/0350; GA MŠk(CZ) LC554 Grant - others:EUCLOCK(XE) 018741 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian system * suprachiasmatic nucleus * ontogenesis Subject RIV: FH - Neurology Impact factor: 3.372, year: 2006

Vesicular glutamate transporter 2 (VGLUT2) is co-stored with PACAP in projections from the rat melanopsin-containing retinal ganglion cells

DEFF Research Database (Denmark)

Engelund, Anna Iversen; Fahrenkrug, Jan; Harrison, Adrian Paul

2010-01-01

The retinal ganglion cell layer of the eye comprises a subtype of cells characterized by their intrinsic photosensitivity and expression of melanopsin (ipRGCs). These cells regulate a variety of non-image-forming (NIF) functions such as light entrainment of circadian rhythms, acute suppression......-localized in their projections in the suprachiasmatic nucleus, the intergeniculate leaflet, and the olivary pretectal nucleus. We conclude that there is evidence to support the use of glutamate and PACAP as neurotransmitters in NIF photoperception by rat ipRGCs, and that these neurotransmitters are co-stored and probably...

Anatomy of the human hypothalamus (chiasmatic and tuberal region).

Science.gov (United States)

Braak, H; Braak, E

1992-01-01

The hypothalamus sensu stricto consists of the chiasmatic, the tuberal and the mamillary region. The present study is confined to the poorly myelinated chiasmatic and tuberal region. Both regions harbor many nuclear grays with relatively clear-cut boundaries embedded in an ill-defined nerve cell assembly referred to as the hypothalamic gray. Prominent components of the chiasmatic region are the magnocellular neurosecretory complex (supraoptic nucleus, paraventricular nucleus, accessory neurosecretory nucleus), the sexually dimorphic intermediate nucleus, the suprachiasmatic and retrochiasmatic nuclei. The dominating structure of the tuberal region is the complex of the ventromedial, posteromedial and dorsomedial nuclei supplemented by the periventricular and infundibular nuclei. Lateral portions of the tuber cinereum harbor the lateral tuberal nucleus and the tuberomamillary nucleus. The lateral tuberal nucleus exhibits pronounced cell loss in Huntington's chorea and is also severely involved in cases of dementia with argyrophilic grains. The large nerve cells of the tuberomamillary nucleus show particularly severe affection in both Alzheimer's (intraneuronal neurofibrillary changes) and Parkinson's disease (Lewy bodies).

The application of a phenomenological model to inelastic nucleus-nucleus interactions for laboratory momenta below 5 GeV/c per nucleon of the incident nucleus

International Nuclear Information System (INIS)

Grishin, V.G.; Kladnitskaya, E.N.

1985-01-01

A phenomenological model for inelastic nucleus-nucleus interactions at momenta below 5 GeV/c per nucleon is described. Particle interactions inside the interacting nuclei are described by phenomenological models of hadron-nucleus and hadron-nucleon interactions. The Monte-Carlo model provides the kinematic variables for a set of events under study. The comparison of the model inclusive distri-- butions for different particles and nucleus-nucleus interactions agrees well with the experimental data

Nucleus Ruber of Actinopterygians.

Science.gov (United States)

Nakayama, Tomoya; Miyajima, Satoshi; Nishino, Hirotaka; Narita, Junya; Abe, Hideki; Yamamoto, Naoyuki

2016-01-01

Nucleus ruber is known as an important supraspinal center that controls forelimb movements in tetrapods, and the rubral homologue may serve similar functions in fishes (motor control of pectoral fin). However, two apparently different structures have been identified as 'nucleus ruber' in actinopterygians. One is nucleus ruber of Goldstein (1905) (NRg), and the other nucleus ruber of Nieuwenhuys and Pouwels (1983) (NRnp). It remains unclear whether one of these nuclei (or perhaps both) is homologous to tetrapod nucleus ruber. To resolve this issue from a phylogenetic point of view, we have investigated the distribution of tegmental neurons retrogradely labeled from the spinal cord in eight actinopterygian species. We also investigated the presence/absence of the two nuclei with Nissl- or Bodian-stained brain section series of an additional 28 actinopterygian species by comparing the morphological features of candidate rubral neurons with those of neurons revealed by the tracer studies. Based on these analyses, the NRg was identified in all actinopterygians investigated in the present study, while the NRnp appears to be absent in basal actinopterygians. The phylogenetic distribution pattern indicates that the NRg is the more likely homologue of nucleus ruber, and the NRnp may be a derived nucleus that emerged during the course of actinopterygian evolution. © 2016 S. Karger AG, Basel.

The stress system in depression and neurodegeneration: focus on the human hypothalamus.

Science.gov (United States)

Bao, A-M; Meynen, G; Swaab, D F

2008-03-01

The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH) release from the pituitary, which subsequently causes cortisol release from the adrenal cortex. The CRH neurons co-express vasopressin (AVP) which potentiates the CRH effects. CRH neurons project not only to the median eminence but also into brain areas where they, e.g., regulate the adrenal innervation of the autonomic system and affect mood. The hypothalamo-neurohypophysial system is also involved in stress response. It releases AVP from the PVN and the supraoptic nucleus (SON) and oxytocin (OXT) from the PVN via the neurohypophysis into the bloodstream. The suprachiasmatic nucleus (SCN), the hypothalamic clock, is responsible for the rhythmic changes of the stress system. Both centrally released CRH and increased levels of cortisol contribute to the signs and symptoms of depression. Symptoms of depression can be induced in experimental animals by intracerebroventricular injection of CRH. Depression is also a frequent side effect of glucocorticoid treatment and of the symptoms of Cushing's syndrome. The AVP neurons in the hypothalamic PVN and SON are also activated in depression, which contributes to the increased release of ACTH from the pituitary. Increased levels of circulating AVP are also associated with the risk for suicide. The prevalence, incidence and morbidity risk for depression are higher in females than in males and fluctuations in sex hormone levels are considered to be involved in the etiology. About 40% of the activated CRH neurons in mood disorders co-express nuclear estrogen receptor (ER)-alpha in the PVN, while estrogen-responsive elements have been found in the CRH gene promoter region, and estrogens stimulate CRH production. An androgen

A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus

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Guilding Clare

2009-08-01

Full Text Available Abstract Background In mammals, the synchronized activity of cell autonomous clocks in the suprachiasmatic nuclei (SCN enables this structure to function as the master circadian clock, coordinating daily rhythms in physiology and behavior. However, the dominance of this clock has been challenged by the observations that metabolic duress can over-ride SCN controlled rhythms, and that clock genes are expressed in many brain areas, including those implicated in the regulation of appetite and feeding. The recent development of mice in which clock gene/protein activity is reported by bioluminescent constructs (luciferase or luc now enables us to track molecular oscillations in numerous tissues ex vivo. Consequently we determined both clock activities and responsiveness to metabolic perturbations of cells and tissues within the mediobasal hypothalamus (MBH, a site pivotal for optimal internal homeostatic regulation. Results Here we demonstrate endogenous circadian rhythms of PER2::LUC expression in discrete subdivisions of the arcuate (Arc and dorsomedial nuclei (DMH. Rhythms resolved to single cells did not maintain long-term synchrony with one-another, leading to a damping of oscillations at both cell and tissue levels. Complementary electrophysiology recordings revealed rhythms in neuronal activity in the Arc and DMH. Further, PER2::LUC rhythms were detected in the ependymal layer of the third ventricle and in the median eminence/pars tuberalis (ME/PT. A high-fat diet had no effect on the molecular oscillations in the MBH, whereas food deprivation resulted in an altered phase in the ME/PT. Conclusion Our results provide the first single cell resolution of endogenous circadian rhythms in clock gene expression in any intact tissue outside the SCN, reveal the cellular basis for tissue level damping in extra-SCN oscillators and demonstrate that an oscillator in the ME/PT is responsive to changes in metabolism.

Description of inelastic nucleus-nucleus interactions at medium energy using dual parton model

International Nuclear Information System (INIS)

Polanski, A.; Shmakov, S.Yu.; Uzhinskij, V.V.

1989-01-01

It is shown that the dual parton model taking into account the processes of diffraction dissociation to the low mass states and finite energy corrections to the asymptotic Abramovski-Gribov-Kancheli cutting rules allows satisfactory description of existing experimental data on hadron-nucleus and nucleus-nucleus interactions at medium energy. (orig.)

Diurnal rhythms in neurexins transcripts and inhibitory/excitatory synapse scaffold proteins in the biological clock.

Directory of Open Access Journals (Sweden)

Mika Shapiro-Reznik

Full Text Available The neurexin genes (NRXN1/2/3 encode two families (α and β of highly polymorphic presynaptic proteins that are involved in excitatory/inhibitory synaptic balance. Recent studies indicate that neuronal activation and memory formation affect NRXN1/2/3α expression and alternative splicing at splice sites 3 and 4 (SS#3/SS#4. Neurons in the biological clock residing in the suprachiasmatic nuclei of the hypothalamus (SCN act as self-sustained oscillators, generating rhythms in gene expression and electrical activity, to entrain circadian bodily rhythms to the 24 hours day/night cycles. Cell autonomous oscillations in NRXN1/2/3α expression and SS#3/SS#4 exons splicing and their links to rhythms in excitatory/inhibitory synaptic balance in the circadian clock were explored. NRXN1/2/3α expression and SS#3/SS#4 splicing, levels of neurexin-2α and the synaptic scaffolding proteins PSD-95 and gephyrin (representing excitatory and inhibitory synapses, respectively were studied in mRNA and protein extracts obtained from SCN of C3H/J mice at different times of the 24 hours day/night cycle. Further studies explored the circadian oscillations in these components and causality relationships in immortalized rat SCN2.2 cells. Diurnal rhythms in mNRXN1α and mNRXN2α transcription, SS#3/SS#4 exon-inclusion and PSD-95 gephyrin and neurexin-2α levels were found in the SCN in vivo. No such rhythms were found with mNRXN3α. SCN2.2 cells also exhibited autonomous circadian rhythms in rNRXN1/2 expression SS#3/SS#4 exon inclusion and PSD-95, gephyrin and neurexin-2α levels. rNRXN3α and rNRXN1/2β were not expressed. Causal relationships were demonstrated, by use of specific siRNAs, between rNRXN2α SS#3 exon included transcripts and gephyrin levels in the SCN2.2 cells. These results show for the first time dynamic, cell autonomous, diurnal rhythms in expression and splicing of NRXN1/2 and subsequent effects on the expression of neurexin-2α and postsynaptic

Dimuon enhancement in nucleus-nucleus ultrarelativistic interactions

International Nuclear Information System (INIS)

Bordalo, Paula; Abreu, M.C.; Alessandro, B.; Alexa, C.; Arnaldi, R.; Astruc, J.; Atayan, M.; Baglin, C.; Baldit, A.; Bedjidian, M.; Bellaiche, F.; Beole, S.; Bohrani, A.; Boldea, V.; Bussiere, A.; Capelli, L.; Caponi, V.; Casagrande, L.; Castor, J.; Chambon, T.; Chaurand, B.; Chevrot, I.; Cheynis, B.; Chiavassa, E.; Cicalo, C.; Comets, M.P.; Constans, N.; Constantinescu, S.; Contardo, D.; Cruz, J.; De Falco, A.; De Marco, N.; Dellacasa, G.; Devaux, A.; Dita, S.; Drapier, O.; Ducroux, L.; Espagnon, B.; Fargeix, J.; Ferreira, R.; Filippov, S.N.; Fleuret, F.; Force, P.; Gallio, M.; Gavrilov, Y.K.; Gerschel, C.; Giubellino, P.; Golubeva, M.B.; Gonin, M.; Gorodetzky, P.; Grigorian, A.A.; Grossiord, J.Y.; Guber, F.F.; Guichard, A.; Gulkanyan, H.; Hakobyan, R.; Haroutunian, R.; Idzik, M.; Jouan, D.; Karavitcheva, T.L.; Kluberg, L.; Kossakowski, R.; Kurepin, A.B.; Landau, G.; Le Bornec, Y.; Lourenco, C.; Luquin, L.; Macciotta, P.; Mac Cormick, M.; Mandry, R.; Marzari-Chiesa, A.; Masera, M.; Masoni, A.; Mehrabyan, S.; Monteno, M.; Mourgues, S.; Musso, A.; Ohlsson-Malek, F.; Petiau, P.; Piccotti, A.; Pizzi, J.R.; Prado da Silva, W.L.; Puddu, G.; Quintans, C.; Racca, C.; Ramello, L.; Ramos, S.; Rato-Mendes, P.; Riccati, L.; Romana, A.; Ropotar, I.; Saturnini, P.; Scomparin, E.; Serci, S.; Shahoyan, R.; Silva, S.; Sitta, M.; Soave, C.; Sonderegger, P.; Tarrago, X.; Topilskaya, N.S.; Usai, G.L.; Varela, J.; Vercellin, E.; Villatte, L.

1999-01-01

The study of muon pairs in the mass region 1.5 μμ 2 in 450 GeV/c p-A, 200 GeV/nucleon S-U and 158 GeV/nucleon Pb-Pb collisions is presented. In p-A interactions, the dimuon signal mass spectra are well described by a superposition of Drell-Yan and charmed meson semi-leptonic decay contributions, in agreement with previous experiments when considering a linear A dependence. In nucleus-nucleus reactions, taking only into account these two physical ingredients, a dimuon enhancement both with increasing A·B and centrality is observed

Nucleus and nucleus-cytoskeleton connections in 3D cell migration

Energy Technology Data Exchange (ETDEWEB)

Liu, Lingling, E-mail: liulingling2012@163.com; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Sun, Jinghui, E-mail: sunjhemail@163.com; Song, Guanbin, E-mail: song@cqu.edu.cn

2016-10-15

Cell migration plays an important role in many physiological and pathological settings, ranging from embryonic development to cancer metastasis. Currently, accumulating data suggest that cells migrating in three-dimensional (3D) environments show well-defined differences compared to their well-established two-dimensional (2D) counterparts. During 3D migration, the cell body and nucleus must deform to allow cellular passage through the available spaces, and the deformability of the relatively rigid nucleus may constitute a limiting step. Here, we highlight the key evidence regarding the role of the nuclear mechanics in 3D migration, including the molecular components that govern the stiffness of the nucleus and review how the nuclear dynamics are connected to and controlled by cytoskeleton-based migration machinery. Intriguingly, nuclear movement must be coordinated with the cytoskeletal dynamics at the leading and trailing edges, which in turn impact the cytoplasmic dynamics that affect the migration efficiency. Thus, we suggest that alterations in the nuclear structure may facilitate cellular reorganizations that are necessary for efficient migration. - Graphical abstract: Schematic representations of a cell migrating on a 2D substrate and a cell migrating in a 3D extracellular matrix environment. (A) Nucleus-cytoskeleton connections are essential to 3D migration. Mechanical signals are transduced by integrins at the cell surface and channeled to cytoskeletal proteins, which generates prestress. The nucleus-cytoskeleton connections can either act as a stable skeleton to anchor the nuclei or provide active force to move the nuclei. The LINC complex is responsible for the nucleo-cytoskeletal coupling. Nesprins connect the cytoskeletal proteins to the inner nuclear membrane proteins SUN1 and SUN2. The SUN proteins connect to the lamins that form the lamina, which attaches to the chromatin. This physical connectivity transmits the mechanical signals from receptors at

Nucleus and nucleus-cytoskeleton connections in 3D cell migration

International Nuclear Information System (INIS)

Liu, Lingling; Luo, Qing; Sun, Jinghui; Song, Guanbin

2016-01-01

Cell migration plays an important role in many physiological and pathological settings, ranging from embryonic development to cancer metastasis. Currently, accumulating data suggest that cells migrating in three-dimensional (3D) environments show well-defined differences compared to their well-established two-dimensional (2D) counterparts. During 3D migration, the cell body and nucleus must deform to allow cellular passage through the available spaces, and the deformability of the relatively rigid nucleus may constitute a limiting step. Here, we highlight the key evidence regarding the role of the nuclear mechanics in 3D migration, including the molecular components that govern the stiffness of the nucleus and review how the nuclear dynamics are connected to and controlled by cytoskeleton-based migration machinery. Intriguingly, nuclear movement must be coordinated with the cytoskeletal dynamics at the leading and trailing edges, which in turn impact the cytoplasmic dynamics that affect the migration efficiency. Thus, we suggest that alterations in the nuclear structure may facilitate cellular reorganizations that are necessary for efficient migration. - Graphical abstract: Schematic representations of a cell migrating on a 2D substrate and a cell migrating in a 3D extracellular matrix environment. (A) Nucleus-cytoskeleton connections are essential to 3D migration. Mechanical signals are transduced by integrins at the cell surface and channeled to cytoskeletal proteins, which generates prestress. The nucleus-cytoskeleton connections can either act as a stable skeleton to anchor the nuclei or provide active force to move the nuclei. The LINC complex is responsible for the nucleo-cytoskeletal coupling. Nesprins connect the cytoskeletal proteins to the inner nuclear membrane proteins SUN1 and SUN2. The SUN proteins connect to the lamins that form the lamina, which attaches to the chromatin. This physical connectivity transmits the mechanical signals from receptors at

Physical meaning of the yields from hadron-nucleon, hadron-nucleus, and nucleus-nucleus collisions observed in experiments

International Nuclear Information System (INIS)

Strugalski, Z.

1995-01-01

A physical meaning of the outcomes from hadronic and nuclear collision processes at high energies is presented, as prompted experimentally. The fast and slow stages in hadron-nucleus collisions are distinguished. Hadrons are produced via intermediate objects observed in hadron-nucleus collisions. The intermediate objects may be treated as the groups of quarks or the quark bags. 37 refs

Meson-nucleus potentials and the search for meson-nucleus bound states

Science.gov (United States)

Metag, V.; Nanova, M.; Paryev, E. Ya.

2017-11-01

Recent experiments studying the meson-nucleus interaction to extract meson-nucleus potentials are reviewed. The real part of the potentials quantifies whether the interaction is attractive or repulsive while the imaginary part describes the meson absorption in nuclei. The review is focused on mesons which are sufficiently long-lived to potentially form meson-nucleus quasi-bound states. The presentation is confined to meson production off nuclei in photon-, pion-, proton-, and light-ion induced reactions and heavy-ion collisions at energies near the production threshold. Tools to extract the potential parameters are presented. In most cases, the real part of the potential is determined by comparing measured meson momentum distributions or excitation functions with collision model or transport model calculations. The imaginary part is extracted from transparency ratio measurements. Results on K+ ,K0 ,K- , η ,η‧ , ω, and ϕ mesons are presented and compared with theoretical predictions. The interaction of K+ and K0 mesons with nuclei is found to be weakly repulsive, while the K- , η ,η‧ , ω and ϕ meson-nucleus potentials are attractive, however, with widely different strengths. Because of meson absorption in the nuclear medium the imaginary parts of the meson-nucleus potentials are all negative, again with a large spread. An outlook on planned experiments in the charm sector is given. In view of the determined potential parameters, the criteria and chances for experimentally observing meson-nucleus quasi-bound states are discussed. The most promising candidates appear to be the η and η‧ mesons.

Effective number of inelastically interacting nucleons in rare nucleus-nucleus production processes

International Nuclear Information System (INIS)

Korotkikh, V.L.; Lokhtin, I.P.

1992-01-01

A model of nucleus-nucleus interaction using one inelastic NN-interaction is suggested for the exclusive production processes with small cross-section. A-dependence nuclear coherent and incoherent production cross-section are predicted. 20 refs.; 4 figs

Double folding model of nucleus-nucleus potential: formulae, iteration method and computer code

International Nuclear Information System (INIS)

Luk'yanov, K.V.

2008-01-01

Method of construction of the nucleus-nucleus double folding potential is described. Iteration procedure for the corresponding integral equation is presented. Computer code and numerical results are presented

Theory of and effects from elastoplasticity in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Noerenberg, W.; Technische Hochschule Darmstadt

1985-02-01

Elastoplasticity of finite Fermi systems results from a coherent coupling between collective and intrinsic degrees of freedom and subsequent equilibration essentially due to two-body collisions. Within a non-markovian transport-theoretical approach referred to as dissipative diabatic dynamics (DDD), elastoplastical forms the link between giant vibrations and overdamped motion of nuclear. Obersvable effects resulting from this non-markovian behaviour in nucleus-nucleus collisions are discussed. (orig.)

Study of η-nucleus interaction through the formation of η-nucleus ...

Indian Academy of Sciences (India)

Answer to this question will deeply enrich our understanding of -nucleus interaction which is not so well-understood. We review the experimental efforts for the search of -mesic nuclei and describe the physics motivation behind it. We present the description of an experiment for the search of -nucleus bound state using ...

Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome.

Directory of Open Access Journals (Sweden)

Junhong Gui

2010-06-01

Full Text Available To identify molecular mechanisms underlying SCN5A-related sick sinus syndrome (SSS, a rare type of SSS, in parallel experiments we elucidated the electrophysiological properties and the cell surface localization of thirteen human Na(v1.5 (hNa(v1.5 mutant channels previously linked to this disease.Mutant hNa(v1.5 channels expressed by HEK293 cells and Xenopus oocytes were investigated by whole-cell patch clamp and two-microelectrode voltage clamp, respectively. HEK293 cell surface biotinylation experiments quantified the fraction of correctly targeted channel proteins. Our data suggested three distinct mutant channel subtypes: Group 1 mutants (L212P, P1298L, DelF1617, R1632H gave peak current densities and cell surface targeting indistinguishable from wild-type hNa(v1.5. Loss-of-function of these mutants resulted from altered channel kinetics, including a negative shift of steady-state inactivation and a reduced voltage dependency of open-state inactivation. Group 2 mutants (E161K, T220I, D1275N gave significantly reduced whole-cell currents due to impaired cell surface localization (D1275N, altered channel properties at unchanged cell surface localization (T220I, or a combination of both (E161K. Group 3 mutant channels were non-functional, due to an almost complete lack of protein at the plasma membrane (T187I, W1421X, K1578fs/52, R1623X or a probable gating/permeation defect with normal surface localisation (R878C, G1408R.This study indicates that multiple molecular mechanisms, including gating abnormalities, trafficking defects, or a combination of both, are responsible for SCN5A-related familial SSS.

Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation

DEFF Research Database (Denmark)

Gardella, Elena; Becker, Felicitas; Møller, Rikke S

2016-01-01

by stretching, motor initiation or by emotional stimuli. In one case, we recorded typical PKD spells by video-EEG-polygraphy, documenting a cortical involvement. INTERPRETATION: Our study establishes SCN8A as a novel gene in which a recurrent mutation causes BFIS/ICCA, expanding the clinical-genetic spectrum...... patient had seizures only at school age. All patients stayed otherwise seizure-free, most without medication. Interictal EEG was normal in all cases but two. Five/16 patients developed additional brief paroxysmal episodes in puberty, either dystonic/dyskinetic or "shivering" attacks, triggered...... identified as the major gene in all three conditions, found to be mutated in 80-90% of familial and 30-35% of sporadic cases. METHODS: We searched for the genetic defect in PRRT2-negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed...

Quark matter formation in high energy nucleus-nucleus collisions - predictions and observations

International Nuclear Information System (INIS)

Otterlund, I.

1983-01-01

In this talk I give a short summary of the recent discussion around predictions and possible observations of quark-gluon plasma and fireballs in ultrarelativistic nucleus-nucleus collisions. In particular this talk is focused on heavy ion reactions at 200 A GeV. (orig./HSI)

Early Chronotype and Tissue-Specific Alterations of Circadian Clock Function in Spontaneously Hypertensive Rats

Czech Academy of Sciences Publication Activity Database

Sládek, Martin; Polidarová, Lenka; Nováková, Marta; Parkanová, Daniela; Sumová, Alena

2012-01-01

Roč. 7, č. 10 (2012), e46951 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP303/11/0668; GA ČR(CZ) GPP305/10/P244 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : SHR * circadian system * clock gene * metabolism * colon * liver * suprachiasmatic nucleus Subject RIV: ED - Physiology Impact factor: 3.730, year: 2012

Copper diffusion in In2S3 and charge separation at In2S3/CuSCN and TiO2/In2S3 interfaces

International Nuclear Information System (INIS)

Juma, Albert Owino

2013-01-01

The concept of inorganic nanostructured solar cells consists of a very thin absorber layer sandwiched between highly structured electron and hole conductors. When a TiO 2 /In 2 S 3 /CuSCN nanocomposite heterostructure is illuminated with light, photo-generated electrons in In 2 S 3 can be injected into the conduction band of TiO 2 and holes into the valence band of CuSCN. Charge transfer at the interfaces is limited by the deposition parameters, band alignment and diffusion of Cu from CuSCN into In 2 S 3 , which was the focus of this work. TiO 2 nanoparticles were screen printed onto SnO 2 :F (FTO)-coated glass substrates to give a layer of nanoporous (np) TiO 2 . In 2 S 3 layers were deposited by thermal evaporation or ion layer gas reaction (ILGAR) methods producing Cl-free (In(acac) 3 precursor) and Cl-containing (InCl 3 precursor) layers. A spray-spin method was developed for deposition of CuSCN onto In 2 S 3 . Diffusion of Cu into In 2 S 3 layers was investigated by Rutherford backscattering spectrometry (RBS) while charge transport mechanisms were studied with surface photovoltage (SPV) technique in the fixed capacitor configuration. The activation energy (Ea) for Cu diffusion in thermally evaporated and Cl-free ILGAR In 2 S 3 layers was 0.30 and 0.24 eV, respectively but increased to between 0.72 and 0.78 eV for Cl-containing In 2 S 3 with residual Cl concentrations of 7.8 - 13.8 at.%. The diffusion prefactor (D 0 ) was six orders of magnitude higher for Cl-containing compared to Cl-free layers. The relationship between E a and D 0 was described by the Meyer-Neldel rule with a Meyer-Neldel energy of 40 meV. The presence of Cl has no significant influence on the structural properties of In 2 S 3 but resulted in a modified diffusion mechanism for Cu diffusion. The photovoltage of In 2 S 3 /CuSCN samples decreased after annealing for longer than 2 min at 200 C. A defect band was formed near the interface where holes accumulated and electrons tunneled through

Counterregulation of insulin by leptin as key component of autonomic regulation of body weight

Science.gov (United States)

Borer, Katarina T

2014-01-01

A re-examination of the mechanism controlling eating, locomotion, and metabolism prompts formulation of a new explanatory model containing five features: a coordinating joint role of the (1) autonomic nervous system (ANS); (2) the suprachiasmatic (SCN) master clock in counterbalancing parasympathetic digestive and absorptive functions and feeding with sympathetic locomotor and thermogenic energy expenditure within a circadian framework; (3) interaction of the ANS/SCN command with brain substrates of reward encompassing dopaminergic projections to ventral striatum and limbic and cortical forebrain. These drive the nonhomeostatic feeding and locomotor motivated behaviors in interaction with circulating ghrelin and lateral hypothalamic neurons signaling through melanin concentrating hormone and orexin-hypocretin peptides; (4) counterregulation of insulin by leptin of both gastric and adipose tissue origin through: potentiation by leptin of cholecystokinin-mediated satiation, inhibition of insulin secretion, suppression of insulin lipogenesis by leptin lipolysis, and modulation of peripheral tissue and brain sensitivity to insulin action. Thus weight-loss induced hypoleptimia raises insulin sensitivity and promotes its parasympathetic anabolic actions while obesity-induced hyperleptinemia supresses insulin lipogenic action; and (5) inhibition by leptin of bone mineral accrual suggesting that leptin may contribute to the maintenance of stability of skeletal, lean-body, as well as adipose tissue masses. PMID:25317239

The intercalatus nucleus of Staderini.

Science.gov (United States)

Cascella, Marco

2016-01-01

Rutilio Staderini was one of the leading Italian anatomists of the twentieth century, together with some scientists, such as Giulio Chiarugi, Giovanni Vitali, and others. He was also a member of a new generation of anatomists. They had continued the tradition of the most famous Italian scientists, which started from the Renaissance up until the nineteenth century. Although he carried out important studies of neuroanatomy and comparative anatomy, as well as embryology, his name is rarely remembered by most medical historians. His name is linked to the nucleus he discovered: the Staderini nucleus or intercalated nucleus, a collection of nerve cells in the medulla oblongata located lateral to the hypoglossal nucleus. This article focuses on the biography of the neuroanatomist as well as the nucleus that carries his name and his other research, especially on comparative anatomy and embryology.

Neurobiology of circadian systems.

Science.gov (United States)

Schulz, Pierre; Steimer, Thierry

2009-01-01

Time is a dimension tightly associated with the biology of living species. There are cycles of varied lengths in biological activities, from very short (ultradian) rhythms to rhythms with a period of approximately one day (circadian) and rhythms with longer cycles, of a week, a month, a season, or even longer. These rhythms are generated by endogenous biological clocks, i.e. time-keeping structures, rather than being passive reactions to external fluctuations. In mammals, the suprachiasmatic nucleus (SCN) is the major pacemaker. The pineal gland, which secretes melatonin, is the major pacemaker in other phyla. There also exist biological clocks generating circadian rhythms in peripheral tissues, for example the liver. A series of clock genes generates the rhythm through positive and negative feedback effect of proteins on their own synthesis, and this system oscillates with a circadian period. External factors serve as indicators of the astronomical (solar) time and are called zeitgebers, literally time-givers. Light is the major zeitgeber, which resets daily the SCN circadian clock. In the absence of zeitgebers, the circadian rhythm is said to be free running; it has a period that differs from 24 hours. The SCN, together with peripheral clocks, enables a time-related homeostasis, which can become disorganized in its regulation by external factors (light, social activities, food intake), in the coordination and relative phase position of rhythms, or in other ways. Disturbances of rhythms are found in everyday life (jet lag, shift work), in sleep disorders, and in several psychiatric disorders including affective disorders. As almost all physiological and behavioural functions in humans occur on a rhythmic basis, the possibility that advances, delays or desynchronization of circadian rhythms might participate in neurological and psychiatric disorders has been a theme of research. In affective disorders, a decreased circadian amplitude of several rhythms as well as a

Dynamics of hadronization in ultra-relativistic nucleus-nucleus collisions

International Nuclear Information System (INIS)

Friman, B.L.

1986-01-01

One of the main problems in the search for quark-gluon plasma in ultra-relativistic nucleus-nucleus collisions is finding a reliable signature for deconfinement. Several signatures have been suggested, e.g., dileptons with a spectrum characteristic of the plasma, an increase in the number of strange particles and effects due to the hadronization of the plasma. In this talk I will describe some recent work on the effects of the hadronization transition in the central rapidity region within the hydrodynamic model of Bjorken, Kajantie and McLerran. (orig.)

Brugada syndrome with a novel missense mutation in SCN5A gene: A case report from Bangladesh

Directory of Open Access Journals (Sweden)

Md. Zahidus Sayeed

2014-01-01

Full Text Available Brugada syndrome is an inherited cardiac arrhythmia that follows autosomal dominant transmission and can cause sudden death. We report a case of Brugada syndrome in a 55-year-old male patient presented with recurrent palpitation, atypical chest pain and presyncope. ECG changes were consistent with type 1 Brugada. Gene analysis revealed a novel missense mutation in SCN5A gene with a genetic variation of D785N and a nucleotide change at 2353G-A. One of his children also had the same mutation. To our knowledge this is the first genetically proved case of Brugada syndrome in Bangladesh.

The picture of the nuclei disintegration mechanism - from hadron-nucleus and nucleus-nucleus collisions experimental investigations at high energies

International Nuclear Information System (INIS)

Strugalska-Gola, E.; Strugalski, Z.; Chmielowski, W.

1997-01-01

The mechanism of the nuclei disintegration process in collisions of high-energy hadrons with nuclei is revealed experimentally. The disintegration appears as a complicated nuclear process developing in time and space in intranuclear matter, consisting at least of three stages which last together about 10 -24 - 10 -17 s after the impact. At the first stage, which lasts about 10 -24 - 10 -22 s, fast nucleons are densely emitted and the target-nucleus is locally damaged. At the second stage, lasting about 10 -22 - 10 -1 7 s, the damaged and unstable residual target nucleus uses to evaporate light fragments - mainly nucleons, deuterons, tritons, α-particles. At the final stage, the residual target-nucleus uses to split sometimes into two or more nuclear fragments

The role of biological clock in glucose homeostasis 

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Piotr Chrościcki

2013-06-01

Full Text Available The mechanism of the biological clock is based on a rhythmic expression of clock genes and clock-controlled genes. As a result of their transcripto-translational associations, endogenous rhythms in the synthesis of key proteins of various physiological and metabolic processes are created. The major timekeeping mechanism for these rhythms exists in the central nervous system. The master circadian clock, localized in suprachiasmatic nucleus (SCN, regulates multiple metabolic pathways, while feeding behavior and metabolite availability can in turn regulate the circadian clock. It is also suggested that in the brain there is a food entrainable oscillator (FEO or oscillators, resulting in activation of both food anticipatory activity and hormone secretion that control digestion processes. Moreover, most cells and tissues express autonomous clocks. Maintenance of the glucose homeostasis is particularly important for the proper function of the body, as this sugar is the main source of energy for the brain, retina, erythrocytes and skeletal muscles. Thus, glucose production and utilization are synchronized in time. The hypothalamic excited orexin neurons control energy balance of organism and modulate the glucose production and utilization. Deficiency of orexin action results in narcolepsy and weight gain, whereas glucose and amino acids can affect activity of the orexin cells. Large-scale genetic studies in rodents and humans provide evidence for the involvement of disrupted clock gene expression rhythms in the pathogenesis of obesity and type 2 diabetes. In general, the current lifestyle of the developed modern societies disturbs the action of biological clock. 

Evolution of circadian organization in vertebrates

Directory of Open Access Journals (Sweden)

M. Menaker

1997-03-01

Full Text Available Circadian organization means the way in which the entire circadian system above the cellular level is put together physically and the principles and rules that determine the interactions among its component parts which produce overt rhythms of physiology and behavior. Understanding this organization and its evolution is of practical importance as well as of basic interest. The first major problem that we face is the difficulty of making sense of the apparently great diversity that we observe in circadian organization of diverse vertebrates. Some of this diversity falls neatly into place along phylogenetic lines leading to firm generalizations: i in all vertebrates there is a "circadian axis" consisting of the retinas, the pineal gland and the suprachiasmatic nucleus (SCN, ii in many non-mammalian vertebrates of all classes (but not in any mammals the pineal gland is both a photoreceptor and a circadian oscillator, and iii in all non-mammalian vertebrates (but not in any mammals there are extraretinal (and extrapineal circadian photoreceptors. An interesting explanation of some of these facts, especially the differences between mammals and other vertebrates, can be constructed on the assumption that early in their evolution mammals passed through a "nocturnal bottleneck". On the other hand, a good deal of the diversity among the circadian systems of vertebrates does not fall neatly into place along phylogenetic lines. In the present review we will consider how we might better understand such "phylogenetically incoherent" diversity and what sorts of new information may help to further our understanding of the evolution of circadian organization in vertebrates

Rhythms of mammalian body temperature can sustain peripheral circadian clocks.

Science.gov (United States)

Brown, Steven A; Zumbrunn, Gottlieb; Fleury-Olela, Fabienne; Preitner, Nicolas; Schibler, Ueli

2002-09-17

Low-amplitude temperature oscillations can entrain the phase of circadian rhythms in several unicellular and multicellular organisms, including Neurospora and Drosophila. Because mammalian body temperature is subject to circadian variations of 1 degrees C-4 degrees C, we wished to determine whether these temperature cycles could serve as a Zeitgeber for circadian gene expression in peripheral cell types. In RAT1 fibroblasts cultured in vitro, circadian gene expression could be established by a square wave temperature rhythm with a (Delta)T of 4 degrees C (12 hr 37 degrees C/12 hr 33 degrees C). To examine whether natural body temperature rhythms can also affect circadian gene expression, we first measured core body temperature cycles in the peritoneal cavities of mice by radiotelemetry. We then reproduced these rhythms with high precision in the liquid medium of cultured fibroblasts for several days by means of a homemade computer-driven incubator. While these "in vivo" temperature rhythms were incapable of establishing circadian gene expression de novo, they could maintain previously induced rhythms for multiple days; by contrast, the rhythms of control cells kept at constant temperature rapidly dampened. Moreover, circadian oscillations of environmental temperature could reentrain circadian clocks in the livers of mice, probably via the changes they imposed upon both body temperature and feeding behavior. Interestingly, these changes in ambient temperature did not affect the phase of the central circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. We postulate that both endogenous and environmental temperature cycles can participate in the synchronization of peripheral clocks in mammals.

Proton rapidity distribution in nucleus-nucleus collisions at high energy

International Nuclear Information System (INIS)

Liu, F.H.

2002-01-01

The proton rapidity distributions in nucleus-nucleus collisions at the Alternating Gradient Synchrotron (AGS) and the Super Proton Synchrotron (SPS) energies are analysed by the revised thermalized cylinder model. The calculated results are compared and found to he in agreement with the experimental data of Si-AI and Si-Pb collisions at 14.6 A GeV/c, Pb-Pb collisions at 158 A GeV/c, and S-S collisions at 200 A GeV/c. (Author)

ψ' and J/ψ suppression in high-energy nucleon-nucleus and nucleus-nucleus collisions

International Nuclear Information System (INIS)

Wong, Cheuk-Yin.

1995-01-01

The observed features of ψ' to J/ψ suppression in pA and nucleus-nucleus collisions can be explained in terms of a two-component absorption model. For the hard component of the absorption due to the interaction of the produced c bar c systems with baryons at high relative energies, the absorption cross sections are insensitive to the radii of the c bar c systems, as described by the Additive Quark Model. For the soft component due to the low energy c bar c interactions with soft particles produced by other baryon-baryon collisions, the absorption cross sections are greater for ψ' than for J/ψ, because the breakup threshold for ψ' is much smaller than for ψ

Flow-injection spectrophotometric determination of captopril in pharmaceutical formulations using a new solid-phase reactor containing AgSCN immobilized in a polyurethane resin

Directory of Open Access Journals (Sweden)

Fernando Campanhã Vicentini

2012-06-01

Full Text Available A simple flow-injection analysis procedure was developed for determining captopril in pharmaceutical formulations employing a novel solid-phase reactor containing silver thiocyanate immobilized in a castor oil derivative polyurethane resin. The method was based on silver mercaptide formation between the captopril and Ag(I in the solid-phase reactor. During such a reaction, the SCN- anion was released and reacted with Fe3+, which generated the FeSCN2+ complex that was continuously monitored at 480 nm. The analytical curve was linear in the captopril concentration range from 3.0 × 10-4 mol L-1 to 1.1 × 10-3 mol L-1 with a detection limit of 8.0 × 10-5 mol L-1. Recoveries between 97.5% and 103% and a relative standard deviation of 2% for a solution containing 6.0 × 10-4 mol L-1 captopril (n = 12 were obtained. The sample throughput was 40 h-1 and the results obtained for captopril in pharmaceutical formulations using this procedure and those obtained using a pharmacopoeia procedure were in agreement at a 95% confidence level.Um procedimento simples de análise por injeção em fluxo foi desenvolvido para a determinação de captopril em formulações farmacêuticas empregando um novo reator em fase sólida contendo tiocianato de prata imobilizado em resina poliuretana obtida a partir de óleo de mamona. O método foi baseado na formação de um mercapto composto de prata, no reator em fase sólida, obtido entre o captopril e Ag (I imobilizada. Durante a reação, íons SCN- eram liberados e reagiam com Fe3+, gerando o complexo FeSCN2+, que foi continuamente monitorado em 480 nm. A curva analítica foi linear no intervalo de concentração de captopril entre 3,0 × 10-4 a 1,1 × 10-3 mol L-1 com um limite de detecção de 8,0 × 10-5 mol L-1. Recuperações entre 97,5-103% e desvio padrão relativo de 2% para uma solução contendo 6,0 × 10-4 mol L-1 de captopril (n = 12 foram obtidos. A frequência de amostragem foi de 40 h-1 e os resultados

Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3

Czech Academy of Sciences Publication Activity Database

Christé, G.; Chahine, M.; Chevalier, P.; Pásek, Michal

2008-01-01

Roč. 96, - (2008), s. 281-293 ISSN 0079-6107 Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac cell * SCN5A mutation * Long QT syndrome * quantitative modelling Subject RIV: BO - Biophysics Impact factor: 6.388, year: 2008

The Baryon Production and Baryon Number Transfer in Hadron-Hadron, Hadron-Nucleus and Nucleus-Nucleus Collisions

International Nuclear Information System (INIS)

Szymanski, P.

2006-09-01

This work concerns soft hadronic interactions which in the Standard Model carry most of the observable cross-section but are not amenable to quantitative predictions due to the very nature of the QCD (Theory of Strong Interactions). In the low momentum transfer region the evolving coupling constant caused perturbation theory to break down. In this situation better experimental understanding of the physics phenomena is needed. One aspect of the soft hadronic interactions will be discussed in this work: transfer of the baryon number from the initial to the final state of the interaction. The past experimental knowledge on this process is presented, reasons for its unsatisfactory status are discussed and condition necessary for improvement are outlined: that is experimental apparatus with superior performance over the full range of available interactions: hadron-hadron collision, hadron-nucleus and nucleus-nucleus interactions. A consistent model-independent picture of the baryon number transfer process emerging from the data on the full range of interactions is shown. It offers serious challenge to theory to provide quantitative and detailed explanation of the measurements. (author)

Production of strange and multistrange hadrons in nucleus-nucleus collisions at the SPS

Czech Academy of Sciences Publication Activity Database

Antinori, F.; Bakke, H.; Beusch, W.; Staroba, Pavel; Závada, Petr

1999-01-01

Roč. 661, - (1999), 130c-139c ISSN 0375-9474 Institutional research plan: CEZ:AV0Z1010920 Keywords : production * nucleus-nucleus collisions * hadrons * strangeness * model predictions Subject RIV: BF - Elementary Particles and High Energy Physics Impact factor: 2.088, year: 1999

Particle production in high energy nucleus--nucleus experiments at Berkeley

International Nuclear Information System (INIS)

Schroeder, L.S.

1976-09-01

A review of high energy nucleus-nucleus experiments performed at the Berkeley Bevalac is presented. Earlier results on projectile and target fragmentation and pion production are briefly summarized. More recent results on Coulomb effects in projectile fragmentation, heavy ion total cross-sections, γ-ray production, and charged particle multiplicities are presented. Also, recent experiments which may shed light on phenomena arising from the central collision of two energetic nuclei, including recent evidence for and against the observation of nuclear shock waves, are reviewed

Kaonic nuclei and kaon-nucleus interactions

CERN Document Server

Ikuta, K; Masutani, K

2002-01-01

Although kaonic atoms provide valuable information concerning the K sup - -nucleus interaction at low energies, they cannot fully determine the K sup - - nucleus optical potential. We demonstrate that K sup - nuclear bound states, if they exist, can be useful in investigating the K sup - -nucleus interaction, especially in the interior of the nucleus. In order to show this possibility, we calculate the double differential cross sections for (K sup - , P) using the Green function method. (author)

Insulin-regulated aminopeptidase immunoreactivity is abundantly present in human hypothalamus and posterior pituitary gland, with reduced expression in paraventricular and suprachiasmatic neurons in chronic schizophrenia.

Science.gov (United States)

Bernstein, Hans-Gert; Müller, Susan; Dobrowolny, Hendrik; Wolke, Carmen; Lendeckel, Uwe; Bukowska, Alicja; Keilhoff, Gerburg; Becker, Axel; Trübner, Kurt; Steiner, Johann; Bogerts, Bernhard

2017-08-01

The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls. By using immunohistochemistry and Western blot analysis, IRAP was immunolocalized in postmortem human brains. Cell countings were performed to estimate numbers and numerical densities of IRAP immunoreactive hypothalamic neurons in schizophrenia patients and control cases. Shape, size and regional distribution of IRAP-expressing cells, as well the lack of co-localization with the glia marker glutamine synthetase, show that IRAP is expressed in neurons. IRAP immunoreactive cells were observed in the hippocampal formation, cerebral cortex, thalamus, amygdala and, abundantly, hypothalamus. Double labeling experiments (IRAP and oxytocin/neurophysin 1, IRAP with vasopressin/neurophysin 2) revealed that IRAP is present in oxytocinergic and in vasopressinergic neurons. In schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. The pathophysiological role of lowered hypothalamic IRAP expression in schizophrenia remains to be established.

Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson's Disease

Institute of Scientific and Technical Information of China (English)

Si-Yue Li; Ya-Li Wang; Wen-Wen Liu; Dong-Jun Lyu; Fen Wang; Cheng-Jie Mao; Ya-Ping Yang; Li-Fang Hu; Chun-Feng Liu

2017-01-01

Background:Parkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction.However,it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself,or is affected by L-DOPA replacement therapy.This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD.Methods:The rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA),followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days.Rotarod test,footprint test,and open-field test were carried out to evaluate the motor function.Striatum,suprachiasmatic nucleus (SCN),liver,and plasma were collected at 6:00,12:00,18:00,and 24:00.Quantitative real-time polymerase chain reaction was used to examine the expression of clock genes.Enzyme-linked immunosorbent assay was used to determine the secretion level of cortisol and melatonin.High-performance liquid chromatography was used to measure the neurotransmitters.Analysis of variance was used for data analysis.Results:L-DOPA alleviated the motor deficits induced by 6-OHDA lesions in the footprint and open-field test (P ＜ 0.01,P ＜ 0.001,respectively).After L-DOPA treatment,Bmal1 decreased in the SCN compared with 6-OHDA group at 12:00 (P ＜ 0.01) and 24:00 (P ＜ 0.001).In the striatum,the expression ofBmal1,Rorα was lower than that in the 6-OHDA group at 18:00 (P ＜ 0.05) and L-DOPA seemed to delay the peak of Per2 to 24:00.In liver,L-DOPA did not affect the rhythmicity and expression of these clock genes (P ＞ 0.05).In addition,the cortisol secretion was increased (P ＞ 0.05),but melatonin was further inhibited after L-DOPA treatment at 6:00 (P ＜ 0.01).Conclusions:In the circadian system of advanced PD rat models,circadian dysfunction is not only contributed by the degeneration of the disease itself but also long-term L-DOPA therapy may further aggravate it.

The nucleus

International Nuclear Information System (INIS)

Marano, S.

1998-01-01

In 1911 E.Rutherford discovered the nucleus. Since then the nucleus has been investigated with more and more powerful tools but it remains the main field of study of nuclear physics. As it is impossible to take into account the interaction of all the nucleons, a theory based on the hypothesis that each nucleon undergoes an average interaction force has been set up. 2 representations have emerged: the Skyrme force and the Gogny force. Both representations match experimental results but are unable to describe fission yields or the multi-fragmentation of very hot nuclei. The mean-field theory can predict the shape of the nuclei according to its energy level. An experimental program involving the Vivitron accelerator and the Euroball detector is due to begin to validate it. By bombarding targets with exotic nuclei nuclear physicists detect new structures and test their collision models. About ten years ago nuclear halos were observed with lithium 11 nuclei. In this nucleus 2 neutrons move in a space larger than the nucleus itself. This discovery has triggered the elaboration of new theories based on nuclear clusters. At very high temperatures the mean-field theory predicts that nuclear matter acts as a fluid. Following the nuclei temperature different ways of decay appear: first evaporation then multi-fragmentation and vaporization. This ultimate stage occurs around 100 milliard celsius degree temperature when the nuclei decays in a multitude of light particles. Isomeric states are studied and could be seen as a way of storing energy. In a very pedagogical way this article gives information to understand the challenges that face nuclear physics today and highlights the contributions of Cea in this field. (A.C.)

Dissipation in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Santanu Pal

1984-01-01

This paper deals with the mechanism of one- and two-body dissipations in nucleus-nucleus collisions. The average energy transferred to nuclear excitations is calculated using a time-dependent density matrix approach with lowest-order approximations. Considering the nuclei as Fermi gases, and using a gaussian-type NN interaction as the basic perturbation, simplified expressions are obtained for energy dissipations. These expressions are quite instructive to follow a number of interesting aspects of one- and two-body dissipations. It is theoretically observed that the memory time for the two-body dissipation is significantly smaller than that of one-body dissipation. A threshold-type dependence of the transferred energy on the relative velocity between the two nuclei is also observed. This threshold velocity is found to be related with the intrinsic nucleon kinetic energy for two-body dissipation and with the nuclear size for the one-body case. This observation further suggests that the total dissipated energy is shared between the two nuclei approximately in the ratio of their masses. The physical origin of these observations is also explained. Numerical calculations further illustrate some characteristic features of one- and two-body dissipations. (orig.)

Single nucleon emission in relativistic nucleus-nucleus reactions

International Nuclear Information System (INIS)

Anon.

1992-01-01

Significant discrepancies between theory and experiment have previously been noted for nucleon emission via electromagnetic processes in relativistic nucleus-nucleus collisions. The present work investigates the hypothesis that these discrepancies have arisen due to uncertainties about how to deduce the experimental electromagnetic cross section from the total measured cross section. An optical-model calculation of single neutron removal is added to electromagnetic cross sections and compared to the total experimental cross sections. Good agreement is found thereby resolving some of the earlier noted discrepancies. A detailed comparison to the recent work of Benesh, Cook, and Vary is made for both the impact parameter and the nuclear cross section. Good agreement is obtained giving an independent confirmation of the parameterized formulas developed by those authors

cGMP-phosphodiesterase inhibition enhances photic responses and synchronization of the biological circadian clock in rodents.

Directory of Open Access Journals (Sweden)

Santiago A Plano

Full Text Available The master circadian clock in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN and is synchronized by several environmental stimuli, mainly the light-dark (LD cycle. Light pulses in the late subjective night induce phase advances in locomotor circadian rhythms and the expression of clock genes (such as Per1-2. The mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase (GC, cGMP and its related protein kinase (PKG. Pharmacological manipulation of cGMP by phosphodiesterase (PDE inhibition (e.g., sildenafil increases low-intensity light-induced circadian responses, which could reflect the ability of the cGMP-dependent pathway to directly affect the photic sensitivity of the master circadian clock within the SCN. Indeed, sildenafil is also able to increase the phase-shifting effect of saturating (1200 lux light pulses leading to phase advances of about 9 hours, as well as in C57 a mouse strain that shows reduced phase advances. In addition, sildenafil was effective in both male and female hamsters, as well as after oral administration. Other PDE inhibitors (such as vardenafil and tadalafil also increased light-induced phase advances of locomotor activity rhythms and accelerated reentrainment after a phase advance in the LD cycle. Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked light-induced expression of Per1. Our results indicate that the cGMP-dependent pathway can directly modulate the light-induced expression of clock-genes within the SCN and the magnitude of light-induced phase advances of overt rhythms, and provide promising tools to design treatments for human circadian disruptions.

A distinct boundary between the higher brain's susceptibility to ischemia and the lower brain's resistance.

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C Devin Brisson

Full Text Available Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD revealed a rapid anoxic depolarization (AD from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons and suprachiasmatic nucleus (SCN, n= 18 only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na(+/K(+ pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K(+]o caused spreading depression (SD, a milder, AD-like event only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus. In contrast hypothalamic neurons are

Effect of monochromatic light on circadian rhythmic expression of clock genes in the hypothalamus of chick.

Science.gov (United States)

Jiang, Nan; Wang, Zixu; Cao, Jing; Dong, Yulan; Chen, Yaoxing

2017-08-01

To clarify the effect of monochromatic light on circadian clock gene expression in chick hypothalamus, a total 240 newly hatched chickens were reared under blue light (BL), green light (GL), red light (RL) and white light (WL), respectively. On the post-hatched day 14, 24-h profiles of seven core clock genes (cClock, cBmal1, cBmal2, cCry1, cCry2, cPer2 and cPer3) were measured at six time points (CT 0, CT 4, CT 8, CT 12, CT 16, CT 20, circadian time). We found all these clock genes expressed with a significant rhythmicity in different light wavelength groups. Meanwhile, cClock and cBmal1 showed a high level under GL, and followed a corresponding high expression of cCry1. However, RL decreased the expression levels of these genes. Be consistent with the mRNA level, CLOCK and BMAL1 proteins also showed a high level under GL. The CLOCK-like immunoreactive neurons were observed not only in the SCN, but also in the non-SCN brain region such as the nucleus anterior medialis hypothalami, the periventricularis nucleus, the paraventricular nucleus and the median eminence. All these results are consistent with the auto-regulatory circadian feedback loop, and indicate that GL may play an important role on the circadian time generation and development in the chick hypothalamus. Our results also suggest that the circadian clock in the chick hypothalamus such as non-SCN brain region were involved in the regulation of photo information. Copyright © 2017 Elsevier B.V. All rights reserved.

Distribution of angiotensin converting enzyme in sheep hypothalamus and medulla oblongata visualized by in vitro autoradiography

International Nuclear Information System (INIS)

Chai, S.Y.; McKinley, M.J.; Mendelsohn, F.A.

1987-01-01

In vitro autoradiographic mapping of angiotensin converting enzyme (ACE) in sheep brain using the specific ACE inhibitor, 125 I-351A, revealed very high densities of binding in large blood vessels and choroid plexus. In the a very high density of labelling occurred in the organum vasculosum of the lamina terminalis and median eminence and a high density in the subfornical organ and moderate density in supraoptic, suprachiasmatic, arcuate and paraventricular nuclei. All fiber tracts were unlabelled. In the medulla oblongata, a very high density of binding was detected in the area postrema and a high density in the nucleus of the solitary tract and dorsal motor nucleus of the vagus; a moderate density was found in the substantia gelatinosa of the spinal tract and the inferior olivary nucleus

Thyrotoxic periodic paralysis associated with a mutation in the sodium channel gene SCN4A.

Science.gov (United States)

Lane, Andrew H; Markarian, Katherine; Braziunene, Ieva

2004-12-01

Thyrotoxic hypokalemic periodic paralysis (THypoKPP) is an uncommon disorder with an unknown etiology. We describe a family in which the proband presented with paralysis and thyrotoxicosis. Because of similarities between familial hypokalemic periodic paralysis (FHypoKPP) and THypoKPP, we sequenced exon 12 of the SCN4A gene, which is known to be mutated in FHypoKPP. We identified an Arg672Ser mutation in the proband and his affected father, as well as the proband's brother. As the brother has paralysis without thyrotoxicosis, our finding suggests that the genetic spectrum of FHypoKPP and THypoKPP overlap. We speculate that thyroid hormone may exert a threshold or permissive effect in hypokalemic periodic paralysis. Non-thyrotoxic family members of individuals with THypoKPP may have an unrecognized risk for paralysis.

PPARg mRNA in the adult mouse hypothalamus: distribution and regulation in response to dietary challenges

Directory of Open Access Journals (Sweden)

Yang eLiu

2015-09-01

Full Text Available Peroxisome proliferator-activated receptor gamma (PPARg is a ligand-activated transcription factor that was originally identified as a regulator of peroxisome proliferation and adipocyte differentiation. Emerging evidence suggests that functional PPARg signaling also occurs within the hypothalamus. However, the exact distribution and identities of PPARg-expressing hypothalamic cells remains under debate. The present study systematically mapped PPARg mRNA expression in the adult mouse brain using in situ hybridization histochemistry. PPARg mRNA was found to be expressed at high levels outside the hypothalamus including the neocortex, the olfactory bulb, the organ of the vasculosum of the lamina terminalis, and the subfornical organ. Within the hypothalamus, PPARg was present at moderate levels in the suprachiasmatic nucleus and the ependymal of the 3rd ventricle. In all examined feeding-related hypothalamic nuclei, PPARg was expressed at very low levels that were close to the limit of detection. Using qPCR techniques, we demonstrated that PPARg mRNA expression was upregulated in the suprachiasmatic nucleus in response to fasting. Double in situ hybridization further demonstrated that PPARg was primarily expressed in neurons. Collectively, our observations provide a comprehensive map of PPARg distribution and regulation in the intact adult mouse hypothalamus.

Serotonin projection patterns to the cochlear nucleus.

Science.gov (United States)

Thompson, A M; Thompson, G C

2001-07-13

The cochlear nucleus is well known as an obligatory relay center for primary auditory nerve fibers. Perhaps not so well known is the neural input to the cochlear nucleus from cells containing serotonin that reside near the midline in the midbrain raphe region. Although the specific locations of the main, if not sole, sources of serotonin within the dorsal cochlear nucleus subdivision are known to be the dorsal and median raphe nuclei, sources of serotonin located within other cochlear nucleus subdivisions are not currently known. Anterograde tract tracing was used to label fibers originating from the dorsal and median raphe nuclei while fluorescence immunohistochemistry was used to simultaneously label specific serotonin fibers in cat. Biotinylated dextran amine was injected into the dorsal and median raphe nuclei and was visualized with Texas Red, while serotonin was visualized with fluorescein. Thus, double-labeled fibers were unequivocally identified as serotoninergic and originating from one of the labeled neurons within the dorsal and median raphe nuclei. Double-labeled fiber segments, typically of fine caliber with oval varicosities, were observed in many areas of the cochlear nucleus. They were found in the molecular layer of the dorsal cochlear nucleus, in the small cell cap region, and in the granule cell and external regions of the cochlear nuclei, bilaterally, of all cats. However, the density of these double-labeled fiber segments varied considerably depending upon the exact region in which they were found. Fiber segments were most dense in the dorsal cochlear nucleus (especially in the molecular layer) and the large spherical cell area of the anteroventral cochlear nucleus; they were moderately dense in the small cell cap region; and fiber segments were least dense in the octopus and multipolar cell regions of the posteroventral cochlear nucleus. Because of the presence of labeled fiber segments in subdivisions of the cochlear nucleus other than the

Actomyosin contractility rotates the cell nucleus.

Science.gov (United States)

Kumar, Abhishek; Maitra, Ananyo; Sumit, Madhuresh; Ramaswamy, Sriram; Shivashankar, G V

2014-01-21

The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells.

Multi-quark effects in high energy nucleon-nucleon and nucleus-nucleus collisions

International Nuclear Information System (INIS)

Besliu, C.; Caraciuc, I.; Jipa, A.; Olariu, A.; Topor-Pop, R.; Cotorobai, F.; Pantea, D.; Popa, L.; Popa, V.; Topor-Pop, V.

1988-02-01

Recent data obtained in two experiments performed in the framework of the Bucharest-Dubna collaboration are presented, i.e.: the observation of narrow dibaryonic resonances is neutron-proton interactions in 1mHBC at different momenta of incident neutrons in the range 1-5 GeV/c, and the cumulative production of negative pions in nucleus-nucleus interactions in SKM-200 streamer chamber at 4.5 GeV/c. (authors)

Copper(I) Thiocyanate (CuSCN) Hole-Transport Layers Processed from Aqueous Precursor Solutions and Their Application in Thin-Film Transistors and Highly Efficient Organic and Organometal Halide Perovskite Solar Cells

KAUST Repository

Wijeyasinghe, Nilushi; Regoutz, Anna; Eisner, Flurin; Du, Tian; Tsetseris, Leonidas; Lin, Yen-Hung; Faber, Hendrik; Pattanasattayavong, Pichaya; Li, Jinhua; Yan, Feng; McLachlan, Martyn A.; Payne, David J.; Heeney, Martin; Anthopoulos, Thomas D.

2017-01-01

spectra agree with first-principles calculations. Study of the hole-transport properties using field-effect transistor measurements reveals that the aqueous-processed CuSCN layers exhibit a fivefold higher hole mobility than films processed from diethyl

Microscopic model of nucleus-nucleus collisions

International Nuclear Information System (INIS)

Harvey, B.G.

1986-04-01

The collision of two nuclei is treated as a collection of collisions between the nucleons of the projectile and those of the target nucleus. The primary projectile fragments contain only those nucleons that did not undergo a collision. The inclusive and coincidence cross sections result from the decay of the excited primary fragments. 15 refs., 5 figs

Severe congenital neutropenia

DEFF Research Database (Denmark)

Borregaard, Niels

2014-01-01

In this issue of Blood, Tidwell et al1 demonstrate that mutations in the start codon (protein synthesis is initiated at the codon ATG) of neutrophil elastase (ELANE) result in the production of N-terminally truncated elastase, which mislocates to the nucleus and results in severe congenital neutr...... neutropenia (SCN)....

K+ nucleus total cross sections

International Nuclear Information System (INIS)

Sawafta, R.

1990-01-01

The scattering of K + mesons from nuclei has attracted considerable interest in the last few years. The K + holds a very special position as the weakest of all strongly interaction probes. The average cross section is not larger than about 10 mb at lab momenta below 800 MeV/c, corresponding to a mean free path in the nucleus larger than 5 fm. Thus the K + is capable of probing the entire volume of the nucleus. Single scattering of the K + with a nucleon in the nucleus dominates the nuclear scattering, and only small and calculable higher order corrections are needed. The nucleon is a dynamical entity and its internal structure can, in principle, be altered by its surrounding nuclear environment. This work reports an experiment in which the K + is used to compare the nucleon in the nucleus with a free nucleon

Molecular Basis of Circadian Photoreception

Science.gov (United States)

2006-06-30

267, 16237-16243. Murakami, D.M., Miller, J.D., Fuller, C.A., 1989. The retinohypothalamic tract in the cat: retinal ganglion cell morphology and...Photochem Photobiol B 13, 5-17. Pickard, G.E., 1980. Morphological characteristics of retinal ganglion cells projecting to the suprachiasmatic nucleus: a...from archaea to humans. Annu Rev Cell Dev Biol 16, 365-392. Takahashi, J.S., DeCoursey, P.J., Bauman, L., Menaker, M., 1984. Spectral sensitivity

Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography

International Nuclear Information System (INIS)

Corp, E.S.; Woods, S.C.; Figlewicz, D.P.; Porte, D. Jr.; Baskin, D.G.; Dorsa, D.M.

1986-01-01

In vitro autoradiography and computer video densitometry were used to localize and quantify binding of 125 I-insulin in the hypothalamus of the rat brain. Highest specific binding was found in the arculate, dorsomedial, suprachiasmatic, paraventricular and periventricular regions. Significantly lower binding was present in the ventromedial nucleus and median eminence. The results are consistent with the hypothesis that insulin modulates the neural regulation of feeding by acting at sites in the hypothalamus. (author)

Random matrix theory and analysis of nucleus-nucleus collision at high energies

International Nuclear Information System (INIS)

Shahaliev, E.I.; Inst. of Radiation Problems, Baku; ); Kuznetsov, A.A.; Suleymanov, M.K.; ); Teryaev, O.V.; )

2006-01-01

A novel method for analysis of experimental data obtained at relativistic nucleus-nucleus collisions is proposed. The method, based on the ideas of Random Matrix Theory, is applied to detect systematic errors that occur at measurements of momentum distributions of emitted particles. The unfolded momentum distribution is well described by the Gaussian orthogonal ensemble of random matrices, when the uncertainty in the momentum distribution is maximal. The method is free from unwanted background contributions [ru

Color oscillations of nucleons in a nucleus

International Nuclear Information System (INIS)

Petrov, V.A.; Smirnov, A.Yu.

1987-01-01

Possibility of nucleus description as an object consisting of quarks and gluons is considered. A model of two-nucleon interaction in a nucleus is presented and analytical expressions for the nucleus nucleon ground state wave functions and also for nuclear nucleon structure functions are obtained. The carried out analysis shows that the suggested model permits to express the nucleus structure functions at quark level only by means of nucleon and Δ-isobaric degrees of freedom

Percolation Model of Nuclear Multifragmentation in High Energy Nucleus-Nucleus Interactions

International Nuclear Information System (INIS)

Abdel-Waged, Kh.

1994-01-01

A hybrid model based on Reggeon theory inspired model of nuclear distribution, which was successful in explaining the cascading of particles in high energy nucleus-nucleus interactions, and percolation model is proposed. In the framework of this model the yield of the fragment in p + Ag, Au at 350 GeV and C + Ag, Au at 3.6 GeV/nucleon as well as the charge distribution of fragments in Kr, Xe and U interactions with emulsion at ∼ 1 GeV/nucleon is correctly described. 32 refs., 3 figs

Energy loss, range and fluence distributions, total reaction and projectile fragment production cross sections for proton-nucleus and nucleus-nucleus interactions

International Nuclear Information System (INIS)

Sihver, L.; Kanai, T.

1992-07-01

We have developed a computer code for calculations of energy loss (dE/dx) and range distributions for heavy ions in any media. The results from our calculations are in very good agreement with previous calculations. We have developed semiempirical total reaction cross section formulae for proton-nucleus (with Z p ≤26) and nucleus-nucleus (with Z p and Z t ≤26) reactions. These formulae apply for incident energies above 15 MeV and 100 MeV/nucleon respectively. From the total reaction cross sections, we can calculate the mean free paths and the fluence distributions of protons and heavy ions in any media. We have compared all the calculated reaction cross sections and the mean free paths with experimental data, and the agreement is good. We have also constructed a procedure for calculating projectile fragment production cross sections, by scaling semiempirical proton-nucleus partial cross section systematics. The scaling is performed using a scaling parameter deduced from our reaction cross sections formulae, and additional enhancements factors. All products with atomic number ranging from that of the projectile (Z p ) down to Z=2 can be calculated. The agreement between the calculated cross sections and the experimental data is better than earlier published results. (author)

Transverse Energy in nucleus-nucleus collisions: A review

International Nuclear Information System (INIS)

Tincknell, M.

1988-01-01

The status of Transverse Energy (E/sub T/) in relativistic nucleus-nucleus collisions at the Brookhaven AGS and the CERN SPS is reviewed. The definition of E/sub T/ and its physical significance are discussed. The basic techniques and limitations of the experimental measurements are presented. The acceptances of the major experiments to be discussed are shown, along with remarks about their idiosyncrasies. The data demonstrate that the nuclear geometry of colliding spheres primarily determines the shapes of the observed spectra. Careful account of the acceptances is crucial to comparing and interpreting results. It is concluded that nuclear stopping power is high, and that the amount of energy deposited into the interaction volume is increasing with beam energy even at SPS energies. The energy densities believed to be obtained at the SPS are close to the critical values predicted for the onset of a quark-gluon plasma. 25 refs., 8 figs

Two Sets of Piwi Proteins Are Involved in Distinct sRNA Pathways Leading to Elimination of Germline-Specific DNA

Directory of Open Access Journals (Sweden)

Dominique I. Furrer

2017-07-01

Full Text Available Piwi proteins and piRNAs protect eukaryotic germlines against the spread of transposons. During development in the ciliate Paramecium, two Piwi-dependent sRNA classes are involved in the elimination of transposons and transposon-derived DNA: scan RNAs (scnRNAs, associated with Ptiwi01 and Ptiwi09, and iesRNAs, whose binding partners we now identify as Ptiwi10 and Ptiwi11. scnRNAs derive from the maternal genome and initiate DNA elimination during development, whereas iesRNAs continue DNA targeting until the removal process is complete. Here, we show that scnRNAs and iesRNAs are processed by distinct Dicer-like proteins and bind Piwi proteins in a mutually exclusive manner, suggesting separate biogenesis pathways. We also demonstrate that the PTIWI10 gene is transcribed from the developing nucleus and that its transcription depends on prior DNA excision, suggesting a mechanism of gene expression control triggered by the removal of short DNA segments interrupting the gene.

Aspects of Coulomb dissociation and interference in peripheral nucleus-nucleus collisions

International Nuclear Information System (INIS)

Nystrand, Joakim; Baltz, Anthony; Klein, Spencer R.

2001-01-01

Coherent vector meson production in peripheral nucleus-nucleus collisions is discussed. These interactions may occur for impact parameters much larger than the sum of the nuclear radii. Since the vector meson production is always localized to one of the nuclei, the system acts as a two-source interferometer in the transverse plane. By tagging the outgoing nuclei for Coulomb dissociation it is possible to obtain a measure of the impact parameter and thus the source separation in the interferometer. This is of particular interest since the life-time of the vector mesons are generally much shorter than the impact parameters of the collisions

Receptors for GRP/bombesin-like peptides in the rat forebrain

International Nuclear Information System (INIS)

Wolf, S.S.; Moody, T.W.

1985-01-01

Binding sites in the rat forebrain were characterized using ( 125 I-Tyr4)bombesin as a receptor probe. Pharmacology experiments indicate that gastrin releasing peptide (GRP) and the GRP fragments GRP as well as Ac-GRP inhibited radiolabeled (Tyr4)bombesin binding with high affinity. Biochemistry experiments indicated that heat, N-ethyl maleimide or trypsin greatly reduced radiolabeled (Tyr4)bombesin binding. Also, autoradiographic studies indicated that highest grain densities were present in the stria terminalis, periventricular and suprachiasmatic nucleus of the hypothalamus, dorsomedial and rhomboid thalamus, dentate gyrus, hippocampus and medial amygdaloid nucleus. The data suggest that CNS protein receptors, which are discretely distributed in the rat forebrain, may mediate the action of endogenous GRP/bombesin-like peptides

Neutrino-nucleus collision at intermediate energy

International Nuclear Information System (INIS)

Kosmas, T.S.; Oset, E.

1999-01-01

Neutrino-nucleus reactions at low and intermediate energy up to E ν = 500 MeV are studied for the most interesting nuclei from an experimental point of view. We focus on neutrino-nucleus cross-sections of semi-inclusive processes, for which recent measurements from radiochemical experiments at LAMPF and KARMEN laboratories are available. The method employed uses the modified Lindhard function for the description of the particle-hole excitations of the final nucleus via a local density approximation. (authors)

Transverse and radial flow in intermediate energy nucleus-nucleus collisions

International Nuclear Information System (INIS)

Vestfall, D. Gary

1997-01-01

We have studied transverse and radial flow in nucleus-nucleus collisions ranging in energy from 15 to 155 MeV/nucleon. We have measured the impact parameter dependence of the balance energy for Ar + Sc and compared the results with Quantum Molecular Dynamics calculations with and without momentum dependence. We have shown that transverse flow and the balance energy dependence on the isospin of the system using the systems 58 Fe + 58 Fe, 58 Ni + 58 Ni, and 58 Mn + 58 Fe. These results are compared with Boltzmann-Uehling-Uehlenbeck calculations incorporating isospin-dependence. We have measured radial flow for Ar + Sc and find that about 50% of the observed energy is related to radial flow. (author)

Nuclear energy release in hadron-nucleus collisions

International Nuclear Information System (INIS)

Strugalski, Z.; Strugalska-Gola, E.

1998-01-01

Energy release process in nuclear reactions induced by fast hadrons in hadron-nucleus collisions is discussed. Some portion of the internal nuclear energy is released when the locally damaged in a collision, and instable therefore, residual target nucleus transits itself into light nuclear fragments (nucleons, D, T) and a stable lighter final nucleus or some number of stable lighter nuclei. It is not excluded that in some of the collisions the induced intranuclear nuclear reactions may be energy overcompensating. Corresponding reconnaissance should be made - in analysing the nuclear reactions induced in hadron-nucleus collisions

Influence of simulated microgravity on clock genes expression rhythmicity and underlying blood circulating miRNAs-mRNA co-expression regulatory mechanism in C57BL/6J mice

Science.gov (United States)

Lv, Ke; Qu, Lina

Purpose: It is vital for astronauts to maintain the optimal alertness and neurobehavioral function. Among various factors that exist in the space flight and long-duration mission environment, gravity changes may probably an essential environmental factor to interfere with internal circadian rhythms homeostasis and sleep quality, but the underlying mechanism is unclear. Mammals' biological clock is controlled by the suprachiasmatic nucleus (SCN), and peripheral organs adjust their own rhythmicity with the central signals. Nevertheless the mechanism underlying this synchronizition process is still unknown. microRNAs (miRNAs) are about 19˜22nt long regulatory RNAs that serve as critical modulators of post-transcriptional gene regulation. Recently, circulating miRNAs were found to have the regulatory role between cells and peripheral tissues, besides its function inside the cells. This study aims to investigate the regulatory signal transduction role of miRNAs between SCN and peripheral biological clock effecter tissues and to further decipher the mechanism of circadian disturbance under microgravity. Method: Firstly, based on the assumption that severe alterations in the expression of genes known to be involved in circadian rhythms may affect the expression of other genes, the labeled cDNA from liver and suprachiasmatic nucleus (SCN) of clock-knockout mice and control mice in different time points were cohybridized to microarrays. The fold change exceeding 2 (FC>2) was used to identify genes with altered expression levels in the knockout mice compared with control mice. Secondly, male C57BL/6J mice at 8 weeks of age were individually caged and acclimatized to the laboratory conditions (12h light/dark cycle) before being used for continuous core body temperature and activity monitoring. The mice were individually caged and tail suspended using a strip of adhesive surgical tape attached to a chain hanging from a pulley. Peripheral blood and liver tissues collection

Thermal Bremsstrahlung probing nuclear multifragmentation in nucleus-nucleus collisions around the Fermi energy

International Nuclear Information System (INIS)

D'Enterria, D.G.

2000-05-01

The thermodynamical properties of nuclear matter at moderate temperatures and densities, in the vicinity of the predicted nuclear liquid-gas phase transition, are studied using as experimental probe the hard-photons (E γ > 30 MeV) emitted in nucleus-nucleus collisions. Photon and charged-particle production in four different heavy-ion reactions (Ar 36 + Au 197 , Ag 107 , Ni 58 , C 12 at 60 A*MeV) is measured exclusively and inclusively coupling the TAPS photon spectrometer with two charged-particle and intermediate-mass-fragment detectors covering nearly 4π. We confirm that Bremsstrahlung emission in first-chance (off-equilibrium) proton-neutron collisions (pnγ) is the dominant origin of hard photons. We also firmly establish the existence of a thermal radiation component emitted in second-chance proton-neutron collisions. This thermal Bremsstrahlung emission takes place in semi-central and central nucleus-nucleus reactions involving heavy targets. We exploit this observation i) to demonstrate that thermal equilibrium is reached during the reaction, ii) to establish a new thermometer of nuclear matter based on Bremsstrahlung photons, iii) to derive the thermodynamical properties of the excited nuclear sources and, in particular, to establish a 'caloric curve' (temperature versus excitation energy), and iv) to assess the time-scales of the nuclear break-up process. (author)

Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system

NARCIS (Netherlands)

Bezzina, Connie R.; Rook, Martin B.; Groenewegen, W. Antoinette; Herfst, Lucas J.; van der Wal, Allard C.; Lam, Jan; Jongsma, Habo J.; Wilde, Arthur A. M.; Mannens, Marcel M. A. M.

2003-01-01

Cardiac conduction defects associate with mutations in SCN5A, the gene encoding the cardiac Na+ channel. In the present study, we characterized a family in which the proband was born in severe distress with irregular wide complex tachycardia. His older sister died at 1 year of age from severe

Nucleon molecular orbitals and the transition mechanism between molecular orbitals in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Imanishi, B.; Misono, S.; von Oertzen, W.; Voit, H.

1988-08-01

The molecular orbitals of the nucleon(s) in nucleus-nucleus collisions are dynamically defined as a linear combination of nucleon single-particle orbits (LCNO) in a rotating frame by using the coupled-reaction-channel (CRC) theory. Nucleon molecular orbitals and the promotions of nucleon, - especially due to the Landau-Zener radial coupling are discussed with the method above mentioned. (author)

Tyrosine Hydroxylase (TH)- and Aromatic-L-Amino Acid Decarboxylase (AADC)-Immunoreactive Neurons of the Common Marmoset (Callithrix jacchus) Brain: An Immunohistochemical Analysis

Science.gov (United States)

Karasawa, Nobuyuki; Hayashi, Motoharu; Yamada, Keiki; Nagatsu, Ikuko; Iwasa, Mineo; Takeuchi, Terumi; Uematsu, Mitsutoshi; Watanabe, Kazuko; Onozuka, Minoru

2007-01-01

From the perspective of comparative morphology, the distribution of non-monoaminergic neurons in the common marmoset (Callithrix jacchus) was investigated using an immunohistochemical method with specific antibodies to tyrosine hydroxylase (TH) and aromatic-L-amino acid decarboxylase (AADC). TH-immunoreactive (IR) neurons (but not AADC-IR) neurons were observed in the olfactory tubercle, preoptic suprachiasmatic nucleus, periventricular hypothalamic nucleus, arcuate nucleus, paraventricular nucleus, periaqueductal gray matter, medial longitudinal fasciculus, substantia nigra, and nucleus solitaris. In contrast, AADC-IR (but not TH-IR), small, oval and spindle-shaped neurons were sparsely distributed in the following areas: the hypothalamus from the anterior nucleus to the lateral nucleus, the dorsomedial nucleus, the dorsomedial area of the medial mammillary nucleus and the arcuate nucleus; the midbrain, including the stria medullaris and substantia nigra; and the medulla oblongata, including the dorsal area of the nucleus solitaris and the medullary reticular nucleus. The distribution of AADC-IR neurons was not as extensive in the marmoset as it is in rats. However, these neurons were located in the marmoset, but not the rat substantia nigra. Furthermore, AADC-IR neurons that are present in the human striatum were absent in that of the marmoset. The present results indicate that the distribution of non-monoaminergic neurons in the brain of the common marmoset is unique and different from that in humans and rodents. PMID:17653300

Altered hippocampal replay is associated with memory impairment in mice heterozygous for the Scn2a gene.

Science.gov (United States)

Middleton, Steven J; Kneller, Emily M; Chen, Shuo; Ogiwara, Ikuo; Montal, Mauricio; Yamakawa, Kazuhiro; McHugh, Thomas J

2018-06-04

An accumulating body of experimental evidence has implicated hippocampal replay occurring within sharp wave ripples (SPW-Rs) as crucial for learning and memory in healthy subjects. This raises speculation that neurological disorders impairing memory disrupt either SPW-Rs or their underlying neuronal activity. We report that mice heterozygous for the gene Scn2a, a site of frequent de novo mutations in humans with intellectual disability, displayed impaired spatial memory. While we observed no changes during encoding, to either single place cells or cell assemblies, we identified abnormalities restricted to SPW-R episodes that manifest as decreased cell assembly reactivation strengths and truncated hippocampal replay sequences. Our results suggest that alterations to hippocampal replay content may underlie disease-associated memory deficits.

Transverse-momentum distribution of produced particles in ultrarelativistic nucleus-nucleus collisions

International Nuclear Information System (INIS)

Ban-Hao, S.; Wong, C.

1985-01-01

In order to discern coherent or collective processes from incoherent processes in nucleus-nucleus reactions at high energies, we study the transverse-momentum distribution of the produced particles with an incoherent-multiple-collision model. In this model, the projectile nucleon makes successive inelastic collisions with nucleons in the target nucleus, the probability of such collisions being given by the thickness function and the nucleon-nucleon inelastic cross section. It is assumed that each baryon-baryon collision produces particles and degrades momenta just as a baryon-baryon collision in free space, and that there are no secondary collisions between the produced particles and the nucleons. We found that the average transverse momentum and the charged-multiplicity data at Fermilab and CERN ISR energies can be well explained by such a model. However, the average transverse momentum for some events observed by the Japanese-American cooperative emulsion experiment (JACEE) associated with large energy density in the central rapidity region differ markedly from the model results. Such a deviation indicates the presence of coherent or collective effects for these collisions and may indicate the possibility of a formation of quark-gluon plasma

Fast detector for triggering on charged particle multiplicity for relativistic nucleus-nucleus collisions

International Nuclear Information System (INIS)

Agakishiev, G.; Man'yakov, P.K.; Drees, A.

1997-01-01

The simple and fast detector of charged particle multiplicity for relativistic nucleus-nucleus collision studies is performed. The multiplicity detector has been designed for the first level trigger of the CERES/NA45 experiment to study Pb-Au collisions at CERN SPS energies. The detector has allowed a realization of the 40 ns trigger for selection of events with definite impact parameter. The construction, operation characteristics, method of calibration, and testing results are described in detail

Electromagnetic processes in nucleus-nucleus collisions relating to space radiation research

Science.gov (United States)

Norbury, John W.

1992-01-01

Most of the papers within this report deal with electromagnetic processes in nucleus-nucleus collisions which are of concern in the space radiation program. In particular, the removal of one and two nucleons via both electromagnetic and strong interaction processes has been extensively investigated. The theory of relativistic Coulomb fission has also been developed. Several papers on quark models also appear. Finally, note that the theoretical methods developed in this work have been directly applied to the task of radiation protection of astronauts. This has been done by parameterizing the theoretical formalism in such a fashion that it can be used in cosmic ray transport codes.

Model of homogeneous nucleus. Total and inelastic cross sections of nucleon-nucleus scattering

International Nuclear Information System (INIS)

Ponomarev, L.A.; Smorodinskaya, N.Ya.

1985-01-01

It is shown that the nucleon-nuckleus scattering amplitude at high energy can be easily calculated by generalization of the nucleon-nucleon scattering amplitude and satisfies a simple factorization relation. As distinct from the Glauber model, the suggested approach makes no use of the nucleonic structure of the nucleus and the hadron-nucleus scattering amplitude is not expressed in terms of hadron-nucleon scattering amplitudes. The energy dependence of total and inelastic cross sections is successfully described for a number of nuclei

Characterization of proton conducting blend polymer electrolyte using PVA-PAN doped with NH{sub 4}SCN

Energy Technology Data Exchange (ETDEWEB)

Premalatha, M. [PG & Research Department of Physics, N.M.S.S.Vellaichamy Nadar College, Madurai-625 019 (India); Materials Research Center, Coimbatore-641 045 (India); Mathavan, T., E-mail: tjmathavan@gmail.com, E-mail: kingslin.genova20@gmail.com [PG & Research Department of Physics, N.M.S.S.Vellaichamy Nadar College, Madurai-625 019 (India); Selvasekarapandian, S. [Materials Research Center, Coimbatore-641 045 (India); Genova, F. Kingslin Mary, E-mail: tjmathavan@gmail.com, E-mail: kingslin.genova20@gmail.com; Umamaheswari, R. [Department of physics, S.F.R College for Women, Sivakasi-626 128 (India)

2016-05-23

Polymer electrolytes with proton conductivity based on blend polymer using polyvinyl alcohol (PVA) and poly acrylo nitrile (PAN) doped with ammonium thiocyanate have been prepared by solution casting method using DMF as solvent. The complex formation between the blend polymer and the salt has been confirmed by FTIR Spectroscopy. The amorphous nature of the blend polymer electrolytes have been confirmed by XRD analysis. The highest conductivity at 303 K has been found to be 3.25 × 10{sup −3} S cm{sup −1} for 20 mol % NH{sub 4}SCN doped 92.5PVA:7.5PAN system. The increase in conductivity of the doped blend polymer electrolytes with increasing temperature suggests the Arrhenius type thermally activated process. The activation energy is found to be low (0.066 eV) for the highest conductivity sample.

Interesting correlations among various parameters of charged secondaries in nucleus - nucleus interactions at 4.5 A GeV

International Nuclear Information System (INIS)

Khan, M. Saleem; Shukla, Praveen Prakash; Khushnood, H.

2015-01-01

The study of the characteristic of charged secondaries was the aim of most of the experiments on high energy nucleon-nucleon and nucleus-nucleus collisions. Investigation are carried out on the produced secondary charged particles with a common belief that these particles are more informative about the collisional dynamics and thus, could be effective in revealing the underlying physics of high energy relativistic interactions. So for understanding the mechanism of multiparticle production in high energy hadron-nucleus collisions, the correlations amongst the secondary charged particles are studied. Several workers have attempted to study the multiplicity correlations over widely different incident energies with different projectiles. The AALMT collaboration have also studied the multiplicity correlations in 200 GeV proton-nucleus collisions

K sup + nucleus total cross sections

Energy Technology Data Exchange (ETDEWEB)

Sawafta, R.

1990-01-01

The scattering of K{sup +} mesons from nuclei has attracted considerable interest in the last few years. The K{sup +} holds a very special position as the weakest of all strongly interaction probes. The average cross section is not larger than about 10 mb at lab momenta below 800 MeV/c, corresponding to a mean free path in the nucleus larger than 5 fm. Thus the K{sup +} is capable of probing the entire volume of the nucleus. Single scattering of the K{sup +} with a nucleon in the nucleus dominates the nuclear scattering, and only small and calculable higher order corrections are needed. The nucleon is a dynamical entity and its internal structure can, in principle, be altered by its surrounding nuclear environment. This work reports an experiment in which the K{sup +} is used to compare the nucleon in the nucleus with a free nucleon.

Microtubules move the nucleus to quiescence.

Science.gov (United States)

Laporte, Damien; Sagot, Isabelle

2014-01-01

The nucleus is a cellular compartment that hosts several macro-molecular machines displaying a highly complex spatial organization. This tight architectural orchestration determines not only DNA replication and repair but also regulates gene expression. In budding yeast microtubules play a key role in structuring the nucleus since they condition the Rabl arrangement in G1 and chromosome partitioning during mitosis through their attachment to centromeres via the kinetochore proteins. Recently, we have shown that upon quiescence entry, intranuclear microtubules emanating from the spindle pole body elongate to form a highly stable bundle that spans the entire nucleus. Here, we examine some molecular mechanisms that may underlie the formation of this structure. As the intranuclear microtubule bundle causes a profound re-organization of the yeast nucleus and is required for cell survival during quiescence, we discuss the possibility that the assembly of such a structure participates in quiescence establishment.

High energy nucleus-nucleus collisions at CERN: Signatures, physical observables and experimental results

International Nuclear Information System (INIS)

Harris, J.W.

1988-02-01

Experimental results on high energy nucleus-nucleus collisions have become available with the recent experiments at CERN utilizing 200 GeV/n oxygen and sulfur beams. Physics motivations for these experiments are presented: a description of predicted signatures for possible formation of a quark-gluon plasma and physical observables that are expected to provide important information for understanding the dynamics of these collisions. A presentation will be made of some of the first experimental results to emerge from this new field. 28 refs., 9 figs

The isospin dependence of the nucleus-nucleus inelastic cross-section at high energy

International Nuclear Information System (INIS)

Rashdan, M.; Farhan, A.M.; Hassib, E.; Kareem, W. Abdel

2006-01-01

The isospin dependence of the nucleus-nucleus inelastic cross-section at high energy is investigated within the multiple scattering theory. The multiple integrals are evaluated by Monte Carlo method as well as by the optical limit approximation of the Glauber model. Calculations are performed for 14-23 N, 16-24 O and 18-26 F isotopes colliding with carbon target around 1 GeV. It is found that rms radii and the density distributions show a halo structure of 22 N, 23 O and 24 F

Strangeness and charm production in nucleus-nucleus collisions at beam energies near the thresholds

International Nuclear Information System (INIS)

Senger, P.

2001-01-01

The creation of strangeness and charm in nucleus-nucleus collisions at threshold beam energies is discussed as a probe for compressed baryonic matter. Experimental data on strangeness production at SIS energies indicate that the properties of kaons and antikaons are modified in the dense nuclear medium. An experiment is proposed to explore the QCD phase diagram in the region of highest baryon densities. An important observable will be charm production close to threshold. (orig.)

Anti p-nucleus interaction

International Nuclear Information System (INIS)

Peng, J.C.

1986-05-01

Status and future prospects of antiproton-nucleus scattering experiments are presented. These scattering experiments were conducted at antiproton beam momentums of 300 and 600 MeV/c on target nuclei of 6 Li, 12 C, 16 O, 18 O, 40 Ca, 48 Ca, and 208 Pb. Antiproton-proton reactions investigated antiproton-nucleus bound or resonant states in antiproton reactions with d, 6 Li, 12 C, 63 Cu, and 209 Bi. Inelastic scattering experiments investigated the spin-isospin dependence of the NN interactions. 19 refs., 1 fig., 1 tab

Hadron-nucleus interactions with a small target-nucleus excitation

International Nuclear Information System (INIS)

Anzon, Z.V.; Chasnikov, I.Ya.; Shakhova, Ts.I.

1981-01-01

Hadron inelastic interactions in nuclear emulsion with a small target-nucleus excitation in the energy range 7.5-200 GeV have been studied. Possible reasons for the differences in production cross-section for events with even and odd number of S-particles are analysed

Formation, structure, and evolution of boiling nucleus and interfacial tension between bulk liquid phase and nucleus

Science.gov (United States)

Wang, Xiao-Dong; Peng, Xiao-Feng; Tian, Yong; Wang, Bu-Xuan

2005-05-01

In this paper, the concept of the molecular free path is introduced to derive a criterion distinguishing active molecules from inactive molecules in liquid phase. A concept of the critical aggregation concentration (CAC) of active molecules is proposed to describe the physical configuration before the formation of a nucleus during vapor-liquid phase transition. All active molecules exist as monomers when the concentration of active molecules is lower than CAC, while the active molecules will generate aggregation once the concentration of the active molecules reaches CAC. However, these aggregates with aggregation number, N, smaller than five can steadily exist in bulk phase. The other excess active molecules can only produce infinite aggregation and form a critical nucleus of vapor-liquid phase transition. Without any outer perturbation the state point of CAC corresponds to the critical superheated or supercooled state. Meanwhile, a model of two-region structure of a nucleus is proposed to describe nucleus evolution. The interfacial tension between bulk liquid phase and nucleus is dependent of the density gradient in the transition region and varies with the structure change of the transition region. With the interfacial tension calculated using this model, the predicted nucleation rate is very close to the experimental measurement. Furthermore, this model and associated analysis provides solid theoretical evidences to clarify the definition of nucleation rate and understand nucleation phenomenon with the insight into the physical nature.

Luminescence studies of Sm(III) and Cm(III) complexes in NaSCN/DHDECMP extraction systems

CERN Document Server

Chung, D Y; Kimura, T

1999-01-01

Laser-induced fluorescence (LIF) studies of Sm(III) and Cm(III) complexes in the NaSCN/DHDECMP solvent extraction system were carried out. Luminescence lifetimes were measured to determine the number of water molecules coordinated to Sm(III), Tb(III), Dy(III), and Cm(III) in the sodium thiocyanate solution and in the DHDECMP phase. The hydration number of Sm(III), Tb(III), Dy(III), and Cm(III) in the sodium thiocyanate solution decreased linearly with increasing sodium thiocyanate concentration. The hydration numbers of Sm(III), Dy(III), and Cm(III) in the DHDECMP phase decreased with increasing sodium thiocyanate concentration. The water molecules in the inner coordination sphere of Sm(III) and Dy(III) extracted into the DHDECMP were not completely removed at low sodium thiocyanate concentration but decreased with increasing sodium thiocyanate concentration. However, in the case of Cm(III) extracted into the DHDECMP phase from the sodium thiocyanate solution, there was no water in the inner coordination sphe...

On the possible detection of quantum-mechanical interferences between gravitational forces and nucleus-nucleus Coulomb forces

International Nuclear Information System (INIS)

Silveira, R. da

1996-07-01

Possible effects of quantum-mechanical interferences between gravitational forces and the nucleus-nucleus Coulomb interaction are discussed. It is shown that, although very small, these effects could be measured using low energy scattering between identical heavy nuclei, e.g. for the system 208 Pb + 208 Pb (E L = 5 MeV). (author)

Dynamics of hadron-nucleus interactions

International Nuclear Information System (INIS)

Wallace, S.J.

1981-07-01

Recent progress in diffraction theory shows that proton-nucleus scattering at nonforward angles is dominated by the interference of waves from two or more bright spots. Analytic formulas based on asymptotic theories of diffraction yield valuable new insights into the scattering and these formulas can be readily extended to illuminate the role of dynamical ingredients, i.e., the nucleon-nucleon amplitudes. The governing parameters of the diffraction and some direct connections between the observed cross sections and the input dynamics are reviewed. New information regarding the nucleon-nucleon parameters based on recent phase shift analyses show some systematic differences from the effective NN amplitudes which produce fits to proton-nucleus diffraction data. Recent progress in understanding the role of Δ-isobars in proton-nucleus dynamics is reviewed. 126 references

Circadian system from conception till adulthood

Czech Academy of Sciences Publication Activity Database

Sumová, Alena; Sládek, Martin; Polidarová, Lenka; Nováková, Marta; Houdek, Pavel

2012-01-01

Roč. 199, č. 2012 (2012), s. 83-103 ISSN 0079-6123 R&D Projects: GA ČR(CZ) GA305/09/0321; GA ČR(CZ) GAP303/11/0668; GA MŠk(CZ) LC554; GA MZd(CZ) NT11474; GA ČR(CZ) GAP303/12/1108 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : ontogenesis * suprachiasmatic nucleus * peripheral circadian clocks * clock gene Subject RIV: ED - Physiology Impact factor: 4.191, year: 2012

Uniform and pitting corrosion events induced by SCN- anions on Al alloys surfaces and the effect of UV light

International Nuclear Information System (INIS)

Amin, Mohammed A.

2011-01-01

The influence of the alloying elements on the uniform and pitting corrosion processes of Al-6061, Al-4.5%Cu, Al-7.5%Cu, Al-6%Si and Al-12%Si alloys was studied in 0.50 M KSCN solution at 25 o C. Open-circuit potential, Tafel polarization, linear polarization resistance (LPR) and ICP-AES measurements were used to study the uniform corrosion process on the surfaces of the tested alloys. Cyclic polarization, potentiostatic current-time transients and impedance techniques were employed for pitting corrosion studies. Obtained results were compared with pure Al. Passivation kinetics of the tested Al samples were also studied as a function of applied potential, [SCN - ] and sample composition by means of potentiostatic current transients. The induction time, after which the growth of stable pits occurs, decreased with increasing applied potential and [SCN - ]. Regarding to uniform corrosion, alloyed Cu was found to enhance the corrosion rate, while alloyed Si suppressed it. Alloying elements of the tested samples diminished pitting attack to an extent depending on the percentage of the alloying element in the sample. Among the investigated materials, Al-Si alloys exhibited the highest corrosion resistance towards uniform and pitting corrosion processes in KSCN solutions. The passive and dissolution behaviour of Al was also studied under the conditions of continuous illumination (300-450 nm) based on cyclic polarization and potentiostatic techniques. The incident photons had a little influence on pit initiation and a marked effect on pit growth. These explained in terms of a photo-induced modification of the passive film formed on the anode surface, which render it more resistant to pitting. The effects of UV photons energy and period of illumination on the morphology of the pitted surfaces were also studied.

Transport of glutathione into the nucleus.

Science.gov (United States)

Queval, Guillaume; Foyer, Christine

2014-10-01

The tripeptide thiol glutathione (GSH) is present in the nucleus of plant and animal cells. However, the functions of GSH in the nucleus remain poorly characterised. GSH appears to become sequestered in the nucleus at the early stages of the cell cycle. As part of our search for proteins that may be involved in GSH transport into the nucleus, we studied the functions of the nucleoporin called Alacrima Achalasia aDrenal Insufficiency Neurologic disorder (ALADIN). ALADIN is encoded by the Achalasia-Addisonianism-Alacrimia (AAAS) gene in mammalian cells. Defects in ALADIN promote adrenal disorders and lead to the triple A syndrome in humans. The ALADIN protein localizes to the nuclear envelope in Arabidopsis thaliana and interacts with other components of the nuclear pore complex (NPC). We characterised the functions of the ALADIN protein in an Arabidopsis thaliana T-DNA insertion knockout mutant, which shows slow growth compared to the wild type. Copyright © 2014. Published by Elsevier Inc.

Circadian clock, cell cycle and cancer

Directory of Open Access Journals (Sweden)

Cansu Özbayer

2011-12-01

Full Text Available There are a few rhythms of our daily lives that we are under the influence. One of them is characterized by predictable changes over a 24-hour timescale called circadian clock. This cellular clock is coordinated by the suprachiasmatic nucleus in the anterior hypothalamus. The clock consist of an autoregulatory transcription-translation feedback loop compose of four genes/proteins; BMAL1, Clock, Cyrptochrome, and Period. BMAL 1 and Clock are transcriptional factors and Period and Cyrptochrome are their targets. Period and Cyrptochrome dimerize in the cytoplasm to enter the nucleus where they inhibit Clock/BMAL activity.It has been demonstrate that circadian clock plays an important role cellular proliferation, DNA damage and repair mechanisms, checkpoints, apoptosis and cancer.

Nucleus management with irrigating vectis

Directory of Open Access Journals (Sweden)

Srinivasan Aravind

2009-01-01

Full Text Available The main objective in modern cataract surgery is to achieve a better unaided visual acuity with rapid post-surgical recovery and minimal surgery-related complications. Early visual rehabilitation and better unaided vision can be achieved only by reducing the incision size. In manual small incision cataract surgery (MSICS, incision is between 5.5 to 7 mm. Once the nucleus is prolapsed into the anterior chamber, it can be extracted through the tunnel. Nucleus extraction with an irrigating vectis is a very simple technique, which combines mechanical and hydrostatic forces to express out the nucleus. This technique is time-tested with good results and more than 95% of nuclei in MSICS are extracted in this way offering all the merits of phacoemulsification with the added benefits of having wider applicability, better safety, shorter learning curve and lower cost.

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

Science.gov (United States)

Wolff, Markus; Johannesen, Katrine M; Hedrich, Ulrike B S; Masnada, Silvia; Rubboli, Guido; Gardella, Elena; Lesca, Gaetan; Ville, Dorothée; Milh, Mathieu; Villard, Laurent; Afenjar, Alexandra; Chantot-Bastaraud, Sandra; Mignot, Cyril; Lardennois, Caroline; Nava, Caroline; Schwarz, Niklas; Gérard, Marion; Perrin, Laurence; Doummar, Diane; Auvin, Stéphane; Miranda, Maria J; Hempel, Maja; Brilstra, Eva; Knoers, Nine; Verbeek, Nienke; van Kempen, Marjan; Braun, Kees P; Mancini, Grazia; Biskup, Saskia; Hörtnagel, Konstanze; Döcker, Miriam; Bast, Thomas; Loddenkemper, Tobias; Wong-Kisiel, Lily; Baumeister, Friedrich M; Fazeli, Walid; Striano, Pasquale; Dilena, Robertino; Fontana, Elena; Zara, Federico; Kurlemann, Gerhard; Klepper, Joerg; Thoene, Jess G; Arndt, Daniel H; Deconinck, Nicolas; Schmitt-Mechelke, Thomas; Maier, Oliver; Muhle, Hiltrud; Wical, Beverly; Finetti, Claudio; Brückner, Reinhard; Pietz, Joachim; Golla, Günther; Jillella, Dinesh; Linnet, Karen M; Charles, Perrine; Moog, Ute; Õiglane-Shlik, Eve; Mantovani, John F; Park, Kristen; Deprez, Marie; Lederer, Damien; Mary, Sandrine; Scalais, Emmanuel; Selim, Laila; Van Coster, Rudy; Lagae, Lieven; Nikanorova, Marina; Hjalgrim, Helle; Korenke, G Christoph; Trivisano, Marina; Specchio, Nicola; Ceulemans, Berten; Dorn, Thomas; Helbig, Katherine L; Hardies, Katia; Stamberger, Hannah; de Jonghe, Peter; Weckhuysen, Sarah; Lemke, Johannes R; Krägeloh-Mann, Ingeborg; Helbig, Ingo; Kluger, Gerhard; Lerche, Holger; Møller, Rikke S

2017-05-01

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more frequent than previously reported; (ii) distinct phenotypes can be seen within the late onset group, including myoclonic-atonic epilepsy (two patients), Lennox-Gastaut not emerging from West syndrome (two patients), and focal epilepsies with an electrical status epilepticus during slow sleep-like EEG pattern (six patients); and (iii) West syndrome constitutes a common phenotype with a major recurring mutation (p.Arg853Gln: two new and four previously reported children). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (<3 months), whereas other antiepileptic drugs were less effective. In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers. Functional characterization of four selected missense mutations using whole cell patch-clamping in tsA201 cells-together with data from the literature-suggest that

Open-nucleus theory for beef cattle breeding systems: A revisitation

International Nuclear Information System (INIS)

Recami, E.; Packer, I.U.; Tenorio Vasconselos, M.

1990-07-01

A theoretical model for Open-Nucleus Systems is herein described in the case of beef cattle breeding. One of the starting points is the observation that the majority of the standard theoretical models for open-nucleus breeding systems were constructed for the case of discrete generations, i.e. for the cases in which the dam average fertility coefficient is f>2. In the case of cattle herds, when only a fraction of the breeding dams can be replaced, it is therefore worthwhile to build up anew a rather rigorous theoretical model, with overlapping generations, and check its predictions. Namely, we apply the new formulae - explicitly depending on β F , ν F , ν M , K and R - to the system in which all breeding sires are in the Nucleus (and are reared in the nucleus itself), and are mated to both Nucleus and Base dams via artificial insemination. Optimal system design has been looked for by the NAG and MINOS computation programs, operated on Vax computers. Opening the nucleus in this situation results to be very effective since the (optimum) asymptotic genetic gain per generation for ''closed nucleus'' systems (x=0) results to be, when e.g. R≡F/M≅200, more than 40% lower than the (optimum) asymptotic genetic gain, G*, for open nucleus systems. Optimal design corresponds to: (i) having a fraction p≅16% of the female population in the nucleus; (ii) replacing practically all the (nucleus) breeding sires by the best (nucleus born) males: ν M =97/98%; (iii) using for dam replacement all (b≅100%) the (base and nucleus born) females; (iv) implementing a high upward gene migration (x≅80%), while all the surplus nucleus-born females are to be used as base replacements. This corresponds to replace, at each generation, also almost all the nucleus dams (ν F ≅95/100%), and the largest possible fraction of base dams (β F ≅30%, a value changing with p). 17 refs

Calculations of nucleus-nucleus microscopic optical potentials at intermediate energies

International Nuclear Information System (INIS)

Hanna, K.M.; Kuhtina, I.N.; Lukyanov, K.V.; Lukyanov, V.K.; Zemlyanaya, E.V.; Slowinski, B.

2006-01-01

Three types of microscopic nucleus-nucleus optical potentials are constructed using three patterns for their real and imaginary parts. Two of these patterns are the real V H and imaginary W H parts of the potential which reproduces the high-energy amplitude of scattering in the microscopic Glauber-Sitenko theory. Another template VDF is calculated within the standard double-folding model with the exchange term included. For either of the three tested potentials, the contribution of real and imaginary patterns is adjusted by introducing two fitted factors. Correspondingly, using numerical code ECIS, the elastic differential cross-sections were fitted to the experimental data on scattering of the 16,17 O heavy-ions at about hundred Mev/nucleon on various target-nuclei. The relativization effect is also included. The tables of the obtained factors which renormalize the strengths of the real and (or) imaginary parts of the calculated microscopic potentials are given

The momentum distribution inside nucleus

International Nuclear Information System (INIS)

Fujita, T.

1985-01-01

Discussions are made on several reactions which can determine the momentum distribution inside nucleus. The first reaction discussed is the high energy heavy ion collision. This reaction involves many nucleons which interact strongly. Therefore, one must be careful for any possible final state interactions. The expression for the single particle momentum distribution is given. And it can be said that the expression is consistent with the description of the energetic neutrons from muon capture by heavy nucleus. The best way to determine the momentum distribution would be the lepton-nucleus scattering since it does not involve the strong interaction in the initial channel. Another reaction discussed is the backward proton production, which is governed by quite complicated reaction processes. Therefore, the determination of the momentum distribution is only indirect. Noverthless, it is found that this reaction presents a very interesting and important information on the momentum distribution. (Aoki, K.)

Local effect of enhancer of zeste-like reveals cooperation of epigenetic and cis-acting determinants for zygotic genome rearrangements.

Directory of Open Access Journals (Sweden)

Maoussi Lhuillier-Akakpo

2014-09-01

Full Text Available In the ciliate Paramecium tetraurelia, differentiation of the somatic nucleus from the zygotic nucleus is characterized by massive and reproducible deletion of transposable elements and of 45,000 short, dispersed, single-copy sequences. A specific class of small RNAs produced by the germline during meiosis, the scnRNAs, are involved in the epigenetic regulation of DNA deletion but the underlying mechanisms are poorly understood. Here, we show that trimethylation of histone H3 (H3K27me3 and H3K9me3 displays a dynamic nuclear localization that is altered when the endonuclease required for DNA elimination is depleted. We identified the putative histone methyltransferase Ezl1 necessary for H3K27me3 and H3K9me3 establishment and show that it is required for correct genome rearrangements. Genome-wide analyses show that scnRNA-mediated H3 trimethylation is necessary for the elimination of long, repeated germline DNA, while single copy sequences display differential sensitivity to depletion of proteins involved in the scnRNA pathway, Ezl1- a putative histone methyltransferase and Dcl5- a protein required for iesRNA biogenesis. Our study reveals cis-acting determinants, such as DNA length, also contribute to the definition of germline sequences to delete. We further show that precise excision of single copy DNA elements, as short as 26 bp, requires Ezl1, suggesting that development specific H3K27me3 and H3K9me3 ensure specific demarcation of very short germline sequences from the adjacent somatic sequences.

Structural dynamics of the cell nucleus

Science.gov (United States)

Wiegert, Simon; Bading, Hilmar

2011-01-01

Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions. In neurons, intracellular calcium levels are controlled by ion channels in the plasma membrane such as NMDA receptors (NMDARs), voltage-gated calcium channels (VGCCs) and certain α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by calcium exchange pathways between the cytosol and internal calcium stores including the endoplasmic reticulum and mitochondria. Synaptic activity and the subsequent opening of ligand and/or voltage-gated calcium channels can initiate cytosolic calcium transients which propagate towards the cell soma and enter the nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope. We recently described the discovery that in hippocampal neurons the morphology of the nucleus affects the calcium dynamics within the nucleus. Here we propose that nuclear infoldings determine whether a nucleus functions as an integrator or detector of oscillating calcium signals. We outline possible ties between nuclear mophology and transcriptional activity and discuss the importance of extending the approach to whole cell calcium signal modeling in order to understand synapse-to-nucleus communication in healthy and dysfunctional neurons. PMID:21738832

Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

Energy Technology Data Exchange (ETDEWEB)

Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B. (Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD (USA))

1991-05-01

Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-(1-14C) glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection.

Restricted expression of Neuroglobin in the mouse retina and co-localization with Melanopsin and Tyrosine Hydroxylase

DEFF Research Database (Denmark)

Hundahl, C A; Fahrenkrug, J; Luuk, H

2012-01-01

level of Melanopsin and Tyrosine Hydroxylase were investigated in Ngb-null mice. Ngb-immunoreactivity was found in a few neurons of the ganglion cell and inner nuclear layers co-expressing Melanopsin and Tyrosine Hydroxylase, respectively. Ngb deficiency neither affected the level of Melanopsin...... and Tyrosine Hydroxylase proteins nor the intactness of PACAP-positive retinohypothalamic projections in the suprachiasmatic nucleus. Based on the present results, it seems unlikely that Ngb could have a major role in retinal oxygen homeostasis and neuronal survival under normal conditions. The present study...

Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

International Nuclear Information System (INIS)

Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B.

1991-01-01

Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-[1-14C] glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection

Strangeness production in nucleus-nucleus collisions: An experimental review

International Nuclear Information System (INIS)

Odyniec, G.

1990-12-01

In experiments with oxygen (60 and 200 GeV/N) and sulphur (200 GeV/N) ions at CERNSPS, large energy densities of the order of 2--3 GeV/fm 3 have been observed, which according to QCD calculations, satisfy necessary conditions for the formation of a quark gluon plasma (QGP) phase. Under such conditions, colour would no longer be confined to hadronic dimensions, and quarks and gluons will propagate freely throughout an extended volume. Somehow lower energy densities, of the order of 0.7--1 GeV/fm 3 , were observed in AGS experiments with 15 GeV/N silicon beams and heavy targets. These energy densities might be adequate for investigations of the pre-equilibrium stage, during which the momentum space distribution has been degradated from its initial value but is not yet thermal. First experimental results, available now, show promise of seeing signs of a new phase of matter. In this review the current status of the selective experimental results on strange-particle production, which are relevant to equilibration and QGP formation in nucleus-nucleus collisions, is presented

Applying the elastic model for various nucleus-nucleus fusion

International Nuclear Information System (INIS)

HASSAN, G.S.; RAGAB, H.S.; SEDDEEK, M.K.

2000-01-01

The Elastic Model of two free parameters m,d given by Scalia has been used for wider energy regions to fit the available experimental data for potential barriers and cross sections. In order to generalize Scalia's formula in both sub- and above-barrier regions, we calculated m, d for pairs rather than those given by Scalia and compared the calculated cross sections with the experimental data. This makes a generalization of the Elastic Model in describing fusion process. On the other hand, Scalia's range of interacting systems was 24 ≤ A ≤194 where A is the compound nucleus mass number. Our extension of that model includes an example of the pairs of A larger than his final limit aiming to make it as a general formula for any type of reactants: light, intermediate or heavy systems. A significant point is the comparison of Elastic Model calculations with the well known methods studying complete fusion and compound nucleus formation, namely with the resultants of using Proximity potential with either Sharp or Smooth cut-off approximations

A New Perspective for Parkinson's Disease: Circadian Rhythm.

Science.gov (United States)

Li, Siyue; Wang, Yali; Wang, Fen; Hu, Li-Fang; Liu, Chun-Feng

2017-02-01

Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative consequences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

Neuroglobin expression in the rat suprachiasmatic nucleus: colocalization, innervation, and response to light

DEFF Research Database (Denmark)

Hundahl, C A; Hannibal, J; Fahrenkrug, J

2010-01-01

Neuroglobin (Ngb) is a myoglobin-like (Mb) heme-globin, belonging the globin family located only in neuronal tissue of the central nervous system. Ngb has been shown to be upregulated in and to protect neurons from hypoxic and ischemic injury, but the function of Ngb-in particular how Ngb may...... protect neurons-remains largely elusive. We have previously described the localization of Ngb in the rat brain and found it to be expressed in areas primarily involved in sleep/wake, circadian, and food regulation. The present study was undertaken, using immunohistochemistry, to characterize......-containing cells received input from neuropeptide Y (NPY)-containing nerve fibers of the geniticulo-hypothalamic tract (GHT), whereas no direct input from the eye or the midbrain raphe system was demonstrated. The results indicate that the Ngb could be involved in both photic and nonphotic entrainment via input...

Nucleus-size pinning for determination of nucleation free-energy barriers and nucleus geometry

Science.gov (United States)

Sharma, Abhishek K.; Escobedo, Fernando A.

2018-05-01

Classical Nucleation Theory (CNT) has recently been used in conjunction with a seeding approach to simulate nucleation phenomena at small-to-moderate supersaturation conditions when large free-energy barriers ensue. In this study, the conventional seeding approach [J. R. Espinosa et al., J. Chem. Phys. 144, 034501 (2016)] is improved by a novel, more robust method to estimate nucleation barriers. Inspired by the interfacial pinning approach [U. R. Pedersen, J. Chem. Phys. 139, 104102 (2013)] used before to determine conditions where two phases coexist, the seed of the incipient phase is pinned to a preselected size to iteratively drive the system toward the conditions where the seed becomes a critical nucleus. The proposed technique is first validated by estimating the critical nucleation conditions for the disorder-to-order transition in hard spheres and then applied to simulate and characterize the highly non-trivial (prolate) morphology of the critical crystal nucleus in hard gyrobifastigia. A generalization of CNT is used to account for nucleus asphericity and predict nucleation free-energy barriers for gyrobifastigia. These predictions of nuclei shape and barriers are validated by independent umbrella sampling calculations.

Generation of the SCN1A epilepsy mutation in hiPS cells using the TALEN technique

Science.gov (United States)

Chen, Wanjuan; Liu, Jingxin; Zhang, Longmei; Xu, Huijuan; Guo, Xiaogang; Deng, Sihao; Liu, Lipeng; Yu, Daiguan; Chen, Yonglong; Li, Zhiyuan

2014-06-01

Human induced pluripotent stem cells (iPSC) can be used to understand the pathological mechanisms of human disease. These cells are a promising source for cell-replacement therapy. However, such studies require genetically defined conditions. Such genetic manipulations can be performed using the novel Transcription Activator-Like Effector Nucleases (TALENs), which generate site-specific double-strand DNA breaks (DSBs) with high efficiency and precision. Combining the TALEN and iPSC methods, we developed two iPS cell lines by generating the point mutation A5768G in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1 α subunit. The engineered iPSC maintained pluripotency and successfully differentiated into neurons with normal functional characteristics. The two cell lines differ exclusively at the epilepsy-susceptibility variant. The ability to robustly introduce disease-causing point mutations in normal hiPS cell lines can be used to generate a human cell model for studying epileptic mechanisms and for drug screening.

Do migrating cells need a nucleus?

Science.gov (United States)

Hawkins, Rhoda J

2018-03-05

How the nucleus affects cell polarity and migration is unclear. In this issue, Graham et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201706097) show that enucleated cells polarize and migrate in two but not three dimensions and propose that the nucleus is a necessary component of the molecular clutch regulating normal mechanical responses. © 2018 Hawkins.

Study of high energy densities over extended nuclear volumes via nucleus-nucleus collisions at the SPS

CERN Multimedia

2002-01-01

This experiment examines in detail the characteristics of ultra-relativistic nucleus-nucleus interactions using $^{16}$O beams of 200 GeV/A from the SPS. The experiment combines 4$\\pi$ calorimeter coverage with measurements of inclusive particle spectra, two-particle correlations, low and high-mass lepton pairs and photons. A multiwire active target allows maximum interaction rates with a minimum of secondary interactions. Additional data are taken with an emulsion target.

International Halley Watch: Discipline specialists for near-nucleus studies

Science.gov (United States)

Larson, S.; Sekanina, Z.; Rahe, J.

1986-01-01

The purpose of the Near-Nucleus Studies Net is to study the processes taking place in the near-nucleus environment as they relate to the nature of nucleus. This is accomplisghed by measuring the spatial and temporal distribution of dust, gases and ions in the coma on high resolution images taken from many observatories around the world. By modeling the motions of discrete dust features in Comet Halley, it is often possible to determine the locations of the emission sources on the surface and learn about the nucleus structure. In addition to the general goals shared by all IHW nets, the scientific goals of the net has been to determine (1)the gross surface structure of the nucleus, (2)the nucleus spin vector, (3)the distribution and evolution of jet sources and (4)the interrelationships between the gas, dust and ion components of the coma. An additional Comet Giacobini-Zinner watch was carried out by the NNSN in support of the NASA International Cometary Explorer flyby.

Diabatic emission of neutrons: A probe for the energy dissipation mechanism in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Noerenberg, W.; Cassing, W.

1984-05-01

The precompound emission of neutrons in central nucleus-nucleus collisions is investigated within the framework of dissipative diabatic dynamics. For 92 Mo + 92 Mo at bombarding energies between 7.5 and 20 MeV/u the differential neutron multiplicities dMsub(n)/dEsub(n) are estimated from the decay of highly excited diabatic single-particle states. The energy spectra have an almost exponential high-energy tail with effective temperatures up to 10 MeV for 20 MeV/u bombarding energy. (orig.)

Study of Strange and Multistrange Particles in Ultrarelativistic Nucleus-Nucleus Collisions

CERN Multimedia

Vande vyvre, P; Feofilov, G; Snoeys, W; Hetland, K F; Campbell, M; Klempt, W

2002-01-01

% NA57\\\\ \\\\ The goal of the experiment is to study the production of strange and multi-strange particles in nucleus-nucleus collisions. This study was initiated at the OMEGA spectrometer, where three ion experiments have been performed: WA85 (S-W and p-W collisions at 200 A GeV/c), WA94 (S-S and p-S collisions at 200 A GeV/c) and WA97 (Pb-Pb, p-Pb and p-Be collisions at 160 A GeV/c).\\\\ \\\\ The experiment aims at extending the scope of WA97 by:\\\\ \\\\ - investigating the beam energy dependence of the enhancements of multi-strange particle production reported by the previous experiments, and by\\\\ \\\\\\\\ \\\\- measuring the yields of strange and multi-strange particles over an extended centrality range compared with the previous experiments.\\\\ \\\\ The apparatus consists mainly of silicon pixel detector planes.

Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture.

Science.gov (United States)

Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

2017-01-01

Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC)-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER) protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF), which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the intact circadian

Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

Directory of Open Access Journals (Sweden)

Virginie Sabado

2017-10-01

Full Text Available Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF, which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells.

Science.gov (United States)

Fang, Mingzhu; Kang, Hwan-Goo; Park, Youngil; Estrella, Brian; Zarbl, Helmut

2017-09-28

The circadian rhythm is a fundamental physiological process present in all organisms that regulates biological processes ranging from gene expression to sleep behavior. In vertebrates, circadian rhythm is controlled by a molecular oscillator that functions in both the suprachiasmatic nucleus (SCN; central pacemaker) and individual cells comprising most peripheral tissues. More importantly, disruption of circadian rhythm by exposure to light-at-night, environmental stressors and/or toxicants is associated with increased risk of chronic diseases and aging. The ability to identify agents that can disrupt central and/or peripheral biological clocks, and agents that can prevent or mitigate the effects of circadian disruption, has significant implications for prevention of chronic diseases. Although rodent models can be used to identify exposures and agents that induce or prevent/mitigate circadian disruption, these experiments require large numbers of animals. In vivo studies also require significant resources and infrastructure, and require researchers to work all night. Thus, there is an urgent need for a cell-type appropriate in vitro system to screen for environmental circadian disruptors and enhancers in cell types from different organs and disease states. We constructed a vector that drives transcription of the destabilized luciferase in eukaryotic cells under the control of the human PERIOD 2 gene promoter. This circadian reporter construct was stably transfected into human mammary epithelial cells, and circadian responsive reporter cells were selected to develop the in vitro bioluminescence assay. Here, we present a detailed protocol to establish and validate the assay. We further provide details for proof of concept experiments demonstrating the ability of our in vitro assay to recapitulate the in vivo effects of various chemicals on the cellular biological clock. The results indicate that the assay can be adapted to a variety of cell types to screen for both

The picture of the nuclei disintegration mechanism - from nucleus-nucleus collision experimental data at high energies

International Nuclear Information System (INIS)

Strugalska-Gola, E.; Strugalski, Z.

1997-01-01

Experimental data on nuclear collisions at high energies, mainly obtained from photographic emulsions, are considered from the point of view of the picture of the nuclear collision processes mechanisms prompted experimentally. In fact, the disintegration products of each nucleus involved in a nuclear collision, in its own rest-frame, are similar to that produced by the impact of a number of nucleons of velocity equal to that of the moving primary nucleus

The nucleus in Finland - The second report

International Nuclear Information System (INIS)

Aurela, Jorma; Korteniemi, Virpi; Halme-Tapanainen, Kristina

1993-01-01

The Finnish Nuclear Society (FNS) started the distribution of the Nucleus bulletin at the beginning of 1988. The volume of distribution has been extended since, including today nearly 1,000 persons. Both the English and the Finnish version of the bulletin is sent to various opinion leaders of society, i.e. the members of the parliament, ministries, the media, representatives of industry and other decision-makers of the energy field. After the five-year history of the Nucleus in Finland, it is time to look back and sum up the present status of the Nucleus. This report gives a short summary concerning the present distribution and its efficiency, the experiences gained and the influence of the bulletin in Finland. The first questionnaire was sent in November 1988, and the survey was repeated among the Finnish readers of the Nucleus in autumn 1992. The results of the latter survey are given in this report

Experimental and phenomenological investigations of QCD matter in high-energy nucleus-nucleus collisions

Energy Technology Data Exchange (ETDEWEB)

Andronic, Anton

2014-07-15

This thesis is heterogeneous, comprising experimental papers at low energies (SIS-18 at GSI) and at the LHC, papers on phenomenology of high-energy nucleus-nucleus collisions, and papers on detectors. The overview covers the experimental papers and those on phenomenology. I have chosen to write it in a general manner, intended to be accessible to non-experts. It emphasizes recent measurements and their understanding at the LHC. The detector papers, which address many principle aspects of gaseous detectors, are summarized and placed in context in the review I co-wrote and which closes the stack. The detector papers included here are the outcome of an R and D program for the Transition Radiation Detector of ALICE.

Experimental and phenomenological investigations of QCD matter in high-energy nucleus-nucleus collisions

International Nuclear Information System (INIS)

Andronic, Anton

2014-07-01

This thesis is heterogeneous, comprising experimental papers at low energies (SIS-18 at GSI) and at the LHC, papers on phenomenology of high-energy nucleus-nucleus collisions, and papers on detectors. The overview covers the experimental papers and those on phenomenology. I have chosen to write it in a general manner, intended to be accessible to non-experts. It emphasizes recent measurements and their understanding at the LHC. The detector papers, which address many principle aspects of gaseous detectors, are summarized and placed in context in the review I co-wrote and which closes the stack. The detector papers included here are the outcome of an R and D program for the Transition Radiation Detector of ALICE.

Dissipation and fluctuation of the relative momentum in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Feldmeier, H.; Spangenberger, H.

1984-07-01

The dissipation of the relative momentum in nucleus-nucleus collisions is treated in terms of a Langevin equation with a fluctuating force. Equations of motion for first and second moments of the macroscopic variables are derived directly from the Langevin equation. The properties of the fluctuating force which results from random particle exchange are investigated in detail. Drift and diffusion coefficients are calculated microscopically and analytical expressions are given which can be used in any trajectory calculation. An important feature of the model is that the Einstein relation between dissipation and fluctuation turns out to be only a limiting case of a more general expression which included nonthermal fluctuations. By treating the two nuclei as intrinsically equilibrated but not in thermal equilibrium with respect to each other several important aspects of the dissipative behaviour, seen in heavy ion collisions with final energies above the Coloumb barrier, can be understood. (orig.)

Dynamical and statistical aspects in nucleus-nucleus collisions around the Fermi energy

Energy Technology Data Exchange (ETDEWEB)

Tamain, B.; Bocage, F.; Bougault, R.; Brou, R. [Caen Univ., 14 (France). Lab. de Physique Corpusculaire; Assenard, M. [Centre National de la Recherche Scientifique, 44 - Nantes (France). Lab. de Physique Subatomique et des Technologies Associees; Auger, G.; Benlliure, J. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France); Bacri, C.O.; Borderie, B. [Paris-11 Univ., 91 - Orsay (France). Inst. de Physique Nucleaire; Bisquer, E. [Lyon-1 Univ., 69 - Villeurbanne (France). Inst. de Physique Nucleaire] [and others

1997-12-31

Nucleus-nucleus collisions at low incident energy are mainly governed by statistical dissipative processes, fusion and deep inelastic reactions being the most important ones. Conversely, in the relativistic energy regime, dynamical effects play a dominant role and one should apply a participant-spectator picture in order to understand the data. In between, the intermediate energy region is a transition one in which it is necessary to disentangle dynamics from statistical effects. Moreover, the Fermi energy region corresponds to available energies comparable with nuclear binding energies and one may except to observe phase transition effects. Experiments performed recently with 4{pi} devices have given quite new data and a much better insight into involved mechanisms and hot nuclear matter properties. INDRA data related to reaction mechanisms and multifragmentation are presented. (author) 53 refs.

Dynamical and statistical aspects in nucleus-nucleus collisions around the Fermi energy

International Nuclear Information System (INIS)

Tamain, B.; Bocage, F.; Bougault, R.; Brou, R.; Bacri, C.O.; Borderie, B.; Bisquer, E.

1997-01-01

Nucleus-nucleus collisions at low incident energy are mainly governed by statistical dissipative processes, fusion and deep inelastic reactions being the most important ones. Conversely, in the relativistic energy regime, dynamical effects play a dominant role and one should apply a participant-spectator picture in order to understand the data. In between, the intermediate energy region is a transition one in which it is necessary to disentangle dynamics from statistical effects. Moreover, the Fermi energy region corresponds to available energies comparable with nuclear binding energies and one may except to observe phase transition effects. Experiments performed recently with 4π devices have given quite new data and a much better insight into involved mechanisms and hot nuclear matter properties. INDRA data related to reaction mechanisms and multifragmentation are presented. (author)