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Sample records for suprachiasmatic nuclei scn

  1. Multiplexing Visual Signals in the Suprachiasmatic Nuclei

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. Multiplexing Visual Signals in the Suprachiasmatic Nuclei.

    Science.gov (United States)

    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.

  4. 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

  5. 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,

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

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    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.

  7. The suprachiasmatic nucleus regulates sleep timing and amount in mice

    NARCIS (Netherlands)

    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

  8. 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.

  9. 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

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

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    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.

  11. Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression

    NARCIS (Netherlands)

    Wu, Xueyan; Balesar, R.A.; Lu, Jing; Farajnia, Sahar; Zhu, Qiongbin; Huang, Manli; Bao, Ai-Min; Swaab, D.F.

    2017-01-01

    In depression, disrupted circadian rhythms reflect abnormalities in the central circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN). Although many SCN neurons are said to be GABAergic, it was not yet known whether and how SCN GABA changes occur in the SCN in depression. We,

  12. Control of the Estradiol-Induced Prolactin Surge by the Suprachiasmatic Nucleus

    NARCIS (Netherlands)

    Palm, Inge F.; van der Beek, Eline M.; Swarts, Hans J. M.; van der Vliet, Jan; Wiegant, Victor M.; Buijs, Ruud M.; Kalsbeek, Andries

    2001-01-01

    In the present study we investigated how the suprachiasmatic nucleus (SCN) controls the E(2)-induced PRL surge in female rats. First, the role of vasopressin (VP), a SCN transmitter present in medial preoptic area (MPO) projections and rhythmically released by SCN neurons, as a circadian signal for

  13. 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

  14. 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, 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

  15. 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

  16. Physiological and anatomic evidence for regulation of the heart by suprachiasmatic nucleus in rats

    NARCIS (Netherlands)

    Scheer, F. A.; ter Horst, G. J.; van der Vliet, J.; Buijs, R. M.

    2001-01-01

    The suprachiasmatic nucleus (SCN) is the mammalian biological clock that generates the daily rhythms in physiology and behavior. Light can phase shift the rhythm of the SCN but can also acutely affect SCN activity and output, e.g., output to the pineal. Recently, multisynaptic SCN connections to

  17. Physiological and anatomic evidence for regulation of the heart by suprachiasmatic nucleus in rats

    NARCIS (Netherlands)

    Scheer, FAJL; Ter Horst, GJ; Van der Vliet, J

    The suprachiasmatic nucleus (SCN) is the mammalian biological clock that generates the daily rhythms in physiology and behavior. Light can phase shift the rhythm of the SCN but can also acutely affect SCN activity and output, e.g., output to the pineal. Recently, multisynaptic SCN connections to

  18. Suprachiasmatic Nucleus Interaction with the Arcuate Nucleus; Essential for Organizing Physiological Rhythms

    NARCIS (Netherlands)

    Buijs, Frederik N.; Guzmán-Ruiz, Mara; León-Mercado, Luis; Basualdo, Mari Carmen; Escobar, Carolina; Kalsbeek, Andries; Buijs, Ruud M.

    2017-01-01

    The suprachiasmatic nucleus (SCN) is generally considered the master clock, independently driving all circadian rhythms. We recently demonstrated the SCN receives metabolic and cardiovascular feedback adeptly altering its neuronal activity. In the present study, we show that microcuts effectively

  19. The suprachiasmatic nucleus-paraventricular nucleus interactions: a bridge to the neuroendocrine and autonomic nervous system

    NARCIS (Netherlands)

    Buijs, R. M.; Hermes, M. H.; Kalsbeek, A.

    1998-01-01

    Vasopressin (VP) is one of the principal neurotransmitters of the suprachiasmatic nucleus (SCN). By means of anatomical, physiological and electrophysiological techniques we have demonstrated that VP containing pathways from the SCN serve to affect neuroendocrine and 'autonomic' neurons in the

  20. 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.

  1. Circadian modulation of GABA function in the rat suprachiasmatic nucleus: excitatory effects during the night phase.

    NARCIS (Netherlands)

    De Jeu, M.T.G.; Pennartz, C.M.A.

    2002-01-01

    Gramicidin-perforated patch-clamp recordings were made from slices of the suprachiasmatic nucleus (SCN) of adult rats to characterize the role of gamma-amino butyric acid (GABA) in the circadian timing system. During the day, activation of GABA(A) receptors hyperpolarized the membrane of SCN

  2. Reduced neurophysin immunoreactivity in rat suprachiasmatic nucleus parallels dissociation of circadian feeding rhythm in constant light

    NARCIS (Netherlands)

    Steinhorst, B; Mai, JK; Rietveld, WJ

    Several distinct neuronal populations can be outlined in the suprachiasmatic nucleus (SCN) by employing immunohistochemistry. Understanding their interaction may serve as the key to the proc esses involved in the generation of circadian rhythms by the SCN. 15 adult rats were exposed to constant dim

  3. Vasopressin immunoreactivity and release in the suprachiasmatic nucleus of wild-type and tau mutant Syrian hamsters

    NARCIS (Netherlands)

    Van der Zee, EA; Oklejewicz, M; Jansen, K; Daan, S; Gerkema, MP

    2002-01-01

    Despite the prominent role of the Syrian hamster (Mesocricetus auratus) in studies of circadian rhythms, there are no data available on the temporal dynamics of the neuropeptide vasopressin (AVP), a major output system of the suprachiasmatic nucleus (SCN). We studied the hamster SCN-AVP system in

  4. Circadian Rhythm Disturbances in Mood Disorders: Insights into the Role of the Suprachiasmatic Nucleus

    Science.gov (United States)

    2017-01-01

    Circadian rhythm disturbances are a common symptom among individuals with mood disorders. The suprachiasmatic nucleus (SCN), in the ventral part of the anterior hypothalamus, orchestrates physiological and behavioral circadian rhythms. The SCN consists of self-sustaining oscillators and receives photic and nonphotic cues, which entrain the SCN to the external environment. In turn, through synaptic and hormonal mechanisms, the SCN can drive and synchronize circadian rhythms in extra-SCN brain regions and peripheral tissues. Thus, genetic or environmental perturbations of SCN rhythms could disrupt brain regions more closely related to mood regulation and cause mood disturbances. Here, we review clinical and preclinical studies that provide evidence both for and against a causal role for the SCN in mood disorders. PMID:29230328

  5. Sex hormone receptors are present in the human suprachiasmatic nucleus

    NARCIS (Netherlands)

    Kruijver, Frank P. M.; Swaab, Dick F.

    2002-01-01

    The suprachiasmatic nucleus (SCN) is the clock of the brain that orchestrates circadian and circannual biological rhythms, such as the rhythms of hormones, body temperature, sleep and mood. These rhythms are frequently disturbed in menopause and even more so in dementia and can be restored in

  6. Environmental light and suprachiasmatic nucleus interact in the regulation of body temperature.

    NARCIS (Netherlands)

    Scheer, F.A.J.L.; Pirovano, C.; Someren, E.J.W. van; Buijs, R.M.

    2005-01-01

    The mammalian biological clock, located in the suprachiasmatic nucleus (SCN), is crucial for circadian rhythms in physiology and behavior. However, equivocal findings have been reported on its role in the circadian regulation of body temperature. The goal of the present studies was to investigate

  7. Alteration of circadian rhythm during epileptogenesis: implications for the suprachiasmatic nucleus circuits.

    Science.gov (United States)

    Xiang, Yan; Li, Zhi-Xiao; Zhang, Ding-Yu; He, Zhi-Gang; Hu, Ji; Xiang, Hong-Bing

    2017-01-01

    It is important to realize that characterization of the circadian rhythm patterns of seizure occurrence can implicate in diagnosis and treatment of selected types of epilepsy. Evidence suggests a role for the suprachiasmatic nucleus (SCN) circuits in overall circadian rhythm and seizure susceptibility both in animals and humans. Thus, we conclude that SCN circuits may exert modifying effects on circadian rhythmicity and neuronal excitability during epileptogenesis. SCN circuits will be studied in our brain centre and collaborating centres to explore further the interaction between the circadian rhythm and epileptic seizures. More and thorough research is warranted to provide insight into epileptic seizures with circadian disruption comorbidities such as disorders of cardiovascular parameters and core body temperature circadian rhythms.

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

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    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.

  9. Suprachiasmatic modulation of noradrenaline release in the ventrolateral preoptic nucleus.

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    Saint-Mleux, Benoît; Bayer, Laurence; Eggermann, Emmanuel; Jones, Barbara E; Mühlethaler, Michel; Serafin, Mauro

    2007-06-13

    As the major brain circadian pacemaker, the suprachiasmatic nucleus (SCN) is known to influence the timing of sleep and waking. We thus investigated here the effect of SCN stimulation on neurons of the ventrolateral preoptic nucleus (VLPO) thought to be involved in promoting sleep. Using an acute in vitro preparation of the rat anterior hypothalamus/preoptic area, we found that whereas single-pulse stimulations of the SCN evoked standard fast ionotropic IPSPs and EPSPs, train stimulations unexpectedly evoked a long-lasting inhibition (LLI). Such LLIs could also be evoked in VLPO neurons by pressure application of NMDA within the SCN, indicating the specific activation of SCN neurons. This LLI was shown to result from the presynaptic facilitation of noradrenaline release, because it was suppressed in presence of yohimbine, a selective antagonist of alpha2-adrenoreceptors. The LLI depended on the opening of a potassium conductance, because it was annulled at E(K) and could be reversed below E(K). These results show that the SCN can provide an LLI of the sleep-promoting VLPO neurons that could play a role in the circadian organization of the sleep-waking cycle.

  10. 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

  11. 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.

  12. Differential Involvement of the Suprachiasmatic Nucleus in Lipopolysaccharide-Induced Plasma Glucose and Corticosterone Responses

    NARCIS (Netherlands)

    Kalsbeek, Andries; Liu, Ji; Lei, Jun; Timmermans, Loes; Foppen, Ewout; Cailotto, Cathy; Fliers, Eric

    2012-01-01

    The hypothalamic suprachiasmatic nucleus (SCN) is an essential component of the circadian timing system, and an important determinant of neuroendocrine and metabolic regulation. Recent data indicate a modulatory role for the immune system on the circadian timing system. The authors investigated how

  13. Interaction between hypothalamic dorsomedial nucleus and the suprachiasmatic nucleus determines intensity of food anticipatory behavior

    NARCIS (Netherlands)

    Acosta-Galvan, Guadalupe; Yi, Chun-Xia; van der Vliet, Jan; Jhamandas, Jack H.; Panula, Pertti; Angeles-Castellanos, Manuel; del Carmen Basualdo, María; Escobar, Carolina; Buijs, Ruud M.

    2011-01-01

    Food anticipatory behavior (FAA) is induced by limiting access to food for a few hours daily. Animals anticipate this scheduled meal event even without the suprachiasmatic nucleus (SCN), the biological clock. Consequently, a food-entrained oscillator has been proposed to be responsible for meal time

  14. The Suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons

    NARCIS (Netherlands)

    Buijs, Ruud M.; la Fleur, Susanne E.; Wortel, Joke; van Heyningen, Caroline; Zuiddam, Laura; Mettenleiter, Thomas C.; Kalsbeek, Andries; Nagai, Katsuya; Niijima, Akira

    2003-01-01

    Opposing parasympathetic and sympathetic signals determine the autonomic output of the brain to the body and the change in balance over the sleep-wake cycle. The suprachiasmatic nucleus (SCN) organizes the activity/inactivity cycle and the behaviors that go along with it, but it is unclear how the

  15. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  19. 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

  20. Functional Peptidomics: Combining Discovery-Based Mass Spectrometry and Neurophysiology to Explore Communication of Phase-Resetting Cues in the Rat Suprachiasmatic Nucleus

    Science.gov (United States)

    Atkins, Norman, Jr.

    2009-01-01

    Intercellular signaling is vital to communication within neuronal circuits. The suprachiasmatic nucleus (SCN), the master circadian clock of mammals, contains a dense collection of neurons that align their intrinsic rhythmicity with environmental stimulus and physiological state. While peptide physiology has been demonstrated as a contributor to…

  1. The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus

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    Albers, H. Elliott; Walton, James C.; Gamble, Karen L.; McNeill, John K.; Hummer, Daniel L.

    2016-01-01

    Virtually every neuron within the suprachiasmatic nucleus (SCN) communicates via GABAergic signaling. The extracellular levels of GABA within the SCN are determined by a complex interaction of synthesis and transport, as well as synaptic and non-synaptic release. The response to GABA is mediated by GABAA receptors that respond to both phasic and tonic GABA release and that can produce excitatory as well as inhibitory cellular responses. GABA also influences circadian control through the exclusively inhibitory effects of GABAB receptors. Both GABA and neuropeptide signaling occur within the SCN, although the functional consequences of the interactions of these signals are not well understood. This review considers the role of GABA in the circadian pacemaker, in the mechanisms responsible for the generation of circadian rhythms, in the ability of non-photic stimuli to reset the phase of the pacemaker, and in the ability of the day-night cycle to entrain the pacemaker. PMID:27894927

  2. The suprachiasmatic nucleus drives day-night variations in postprandial triglyceride uptake into skeletal muscle and brown adipose tissue.

    Science.gov (United States)

    Moran-Ramos, Sofía; Guerrero-Vargas, Natali N; Mendez-Hernandez, Rebeca; Basualdo, Maria Del Carmen; Escobar, Carolina; Buijs, Ruud M

    2017-12-01

    What is the central question of this study? What are the factors influencing day-night variations in postprandial triglycerides? What is the main finding and its importance? Rats show low postprandial plasma triglyceride concentrations early in the active period that are attributable to a higher uptake by skeletal muscle and brown adipose tissue. We show that these day-night variations in uptake are driven by the suprachiasmatic nucleus, probably via a Rev-erbα-mediated mechanism and independent of locomotor activity. These findings highlight that the suprachiasmatic nucleus has a major role in day-night variations in plasma triglycerides and that disturbances in our biological clock might be an important risk factor contributing to development of postprandial hyperlipidaemia. Energy metabolism follows a diurnal pattern, mainly driven by the suprachiasmatic nucleus (SCN), and disruption of circadian regulation has been linked to metabolic abnormalities. Indeed, epidemiological evidence shows that night work is a risk factor for cardiovascular disease, and postprandial hyperlipidaemia is an important contributor. Therefore, the aim of this work was to investigate the factors that drive day-night variations in postprandial triglycerides (TGs). Intact and SCN-lesioned male Wistar rats were subjected to an oral fat challenge during the beginning of the rest phase (day) or the beginning of the active phase (night). The plasma TG profile was evaluated and tissue TG uptake assayed. After the fat challenge, intact rats showed lower postprandial plasma TG concentrations early in the night when compared with the day. However, no differences were observed in the rate of intestinal TG secretion between day and night. Instead, there was a higher uptake of TG by skeletal muscle and brown adipose tissue early in the active phase (night) when compared with the rest phase (day), and these variations were abolished in rats bearing bilateral SCN lesions. Rev-erbα gene expression

  3. 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

    DEFF Research Database (Denmark)

    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...

  4. 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)

  5. 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)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  8. 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.

  9. 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

  10. 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....

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

    Science.gov (United States)

    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.

  12. 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

  13. Circadian pacemaking in cells and circuits of the suprachiasmatic nucleus.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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).

  15. 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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. 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

  4. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. 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

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  12. A colourful clock.

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  15. 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

  16. A case of recurrent encephalopathy with SCN2A missense mutation.

    Science.gov (United States)

    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.

  17. 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.

  18. 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....

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

    Science.gov (United States)

    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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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...

  14. 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

  15. 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

  16. 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.

  17. 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

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

    CERN Document Server

    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...

  19. 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.

  20. Causes and consequences of hyperexcitation in central clock neurons.

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

  2. 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

  3. 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.

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

    Science.gov (United States)

    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.

  5. A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  8. 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 .

  9. 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....

  10. 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.

  11. 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.

  12. 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.

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

    Science.gov (United States)

    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.

  14. 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.

  15. 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

  16. 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....

  17. 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

  18. 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...

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

    DEFF Research Database (Denmark)

    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...

  20. 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...

  1. Identification of novel light-induced genes in the suprachiasmatic nucleus

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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...

  7. 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.

  8. 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....

  9. 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

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

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

    NARCIS (Netherlands)

    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

  14. 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....

  15. 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.

  16. 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.

  17. 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.

  18. 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

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

    Science.gov (United States)

    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.

  20. 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.

  1. 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…

  2. 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

  3. 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...

  4. 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.

  5. 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)

  6. 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....

  7. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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.

  14. 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...

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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...

  20. 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.

  1. 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

  2. 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

  3. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  7. 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.

  8. 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

  9. 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.

  10. 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...

  11. 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

  12. Linkage between increased nociception and olfaction via a SCN9A haplotype.

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. (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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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

  19. 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

  20. 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...

  1. 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.

  2. 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.

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

    Science.gov (United States)

    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.

  4. 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...

  5. 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

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

    Directory of Open Access Journals (Sweden)

    Nicole Purrier

    Full Text Available Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods. Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

  12. 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

  13. 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,...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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).

  20. 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

  1. 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.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    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.

  5. 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...

  6. The retinal clock in mammals: role in health and disease

    Directory of Open Access Journals (Sweden)

    Felder-Schmittbuhl MP

    2017-05-01

    Full Text Available Marie-Paule Felder-Schmittbuhl,1,* Hugo Calligaro,2 Ouria Dkhissi-Benyahya2,* 1Institute of Cellular and Integratives Neurosciences, UPR3212, CNRS, Université de Strasbourg, Strasbourg, 2University of Lyon, Stem Cell and Brain Research Institute, INSERM U1208, Bron, France *These authors contributed equally to this work Abstract: The mammalian retina contains an extraordinary diversity of cell types that are highly organized into precise circuits to perceive and process visual information in a dynamic manner and transmit it to the brain. Above this builds up another level of complex dynamic, orchestrated by a circadian clock located within the retina, which allows retinal physiology, and hence visual function, to adapt to daily changes in light intensity. The mammalian retina is a remarkable model of circadian clock because it harbors photoreception, self-sustained oscillator function, and physiological outputs within the same tissue. However, the location of the retinal clock in mammals has been a matter of long debate. Current data have shown that clock properties are widely distributed among retinal cells and that the retina is composed of a network of circadian clocks located within distinct cellular layers. Nevertheless, the identity of the major pacemaker, if any, still warrants identification. In addition, the retina coordinates rhythmic behavior by providing visual input to the master hypothalamic circadian clock in the suprachiasmatic nuclei (SCN. This light entrainment of the SCN to the light/dark cycle involves a network of retinal photoreceptor cells: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs. Although it was considered that these photoreceptors synchronized both retinal and SCN clocks, new data challenge this view, suggesting that none of these photoreceptors is involved in photic entrainment of the retinal clock. Because circadian organization is a ubiquitous feature of the retina and controls

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

    Science.gov (United States)

    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.

  8. 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...

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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.

  4. Central control of circadian phase in arousal-promoting neurons.

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

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

    Science.gov (United States)

    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.

  8. 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

  9. 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

  10. Simulated shift work in rats perturbs multiscale regulation of locomotor activity

    Science.gov (United States)

    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

  11. 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...

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators

    Science.gov (United States)

    Saini, Camille; Morf, Jörg; Stratmann, Markus; Gos, Pascal; Schibler, Ueli

    2012-01-01

    The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles. PMID:22379191

  15. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators.

    Science.gov (United States)

    Saini, Camille; Morf, Jörg; Stratmann, Markus; Gos, Pascal; Schibler, Ueli

    2012-03-15

    The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles.

  16. 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

  17. 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...

  18. 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

  19. 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

  20. Masking responses to light in period mutant mice.

    Science.gov (United States)

    Pendergast, Julie S; Yamazaki, Shin

    2011-10-01

    Masking is an acute effect of an external signal on an overt rhythm and is distinct from the process of entrainment. In the current study, we investigated the phase dependence and molecular mechanisms regulating masking effects of light pulses on spontaneous locomotor activity in mice. The circadian genes, Period1 (Per1) and Per2, are necessary components of the timekeeping machinery and entrainment by light appears to involve the induction of the expression of Per1 and Per2 mRNAs in the suprachiasmatic nuclei (SCN). We assessed the roles of the Per genes in regulating masking by assessing the effects of light pulses on nocturnal locomotor activity in C57BL/6J Per mutant mice. We found that Per1(-/-) and Per2(-/-) mice had robust negative masking responses to light. In addition, the locomotor activity of Per1(-/-)/Per2(-/-) mice appeared to be rhythmic in the light-dark (LD) cycle, and the phase of activity onset was advanced (but varied among individual mice) relative to lights off. This rhythm persisted for 1 to 2 days in constant darkness in some Per1(-/-)/Per2(-/-) mice. Furthermore, Per1(-/-)/Per2(-/-) mice exhibited robust negative masking responses to light. Negative masking was phase dependent in wild-type mice such that maximal suppression was induced by light pulses at zeitgeber time 14 (ZT14) and gradually weaker suppression occurred during light pulses at ZT16 and ZT18. By measuring the phase shifts induced by the masking protocol (light pulses were administered to mice maintained in the LD cycle), we found that the phase responsiveness of Per mutant mice was altered compared to wild-types. Together, our data suggest that negative masking responses to light are robust in Per mutant mice and that the Per1(-/-)/Per2(-/-) SCN may be a light-driven, weak/damping oscillator.

  1. Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas.

    Science.gov (United States)

    Müller, Mareike Hildegard; Rödel, Franz; Rüb, Udo; Korf, Horst-Werner

    2015-02-01

    The circadian clock of man and mammals shows a hierarchic organization. The master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral oscillators distributed throughout the body. Rhythm generation depends on molecular clockworks based on transcriptional/translational interaction of clock genes. Numerous studies have shown that the clockwork in peripheral oscillators is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the absence of signals from the SCN. The aim of the present study is to analyze the effects of irradiation with X-rays on the clockwork of liver, adrenal and pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from transgenic mPer2(luc) mice which express luciferase under the control of the promoter of an important clock gene, Per2, and allow to study the dynamics of the molecular clockwork by bioluminometry. The preparations were cultured in a membrane-based liquid-air interface culturing system and irradiated with X-rays at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days in vitro. Oscillations persist after irradiation with X-rays. However, a dose of 50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h and in the OAEC by 6 h. Our study shows that X-rays affect the molecular clockwork in liver, pancreas and adrenal leading to phase advances. Our results confirm and extend previous studies showing a phase-advancing effect of X-rays at the level of the whole animal and single cells.

  2. Rapid Adjustment of Circadian Clocks to Simulated Travel to Time Zones across the Globe.

    Science.gov (United States)

    Harrison, Elizabeth M; Gorman, Michael R

    2015-12-01

    Daily rhythms in mammalian physiology and behavior are generated by a central pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN), the timing of which is set by light from the environment. When the ambient light-dark cycle is shifted, as occurs with travel across time zones, the SCN and its output rhythms must reset or re-entrain their phases to match the new schedule-a sluggish process requiring about 1 day per hour shift. Using a global assay of circadian resetting to 6 equidistant time-zone meridians, we document this characteristically slow and distance-dependent resetting of Syrian hamsters under typical laboratory lighting conditions, which mimic summer day lengths. The circadian pacemaker, however, is additionally entrainable with respect to its waveform (i.e., the shape of the 24-h oscillation) allowing for tracking of seasonally varying day lengths. We here demonstrate an unprecedented, light exposure-based acceleration in phase resetting following 2 manipulations of circadian waveform. Adaptation of circadian waveforms to long winter nights (8 h light, 16 h dark) doubled the shift response in the first 3 days after the shift. Moreover, a bifurcated waveform induced by exposure to a novel 24-h light-dark-light-dark cycle permitted nearly instant resetting to phase shifts from 4 to 12 h in magnitude, representing a 71% reduction in the mismatch between the activity rhythm and the new photocycle. Thus, a marked enhancement of phase shifting can be induced via nonpharmacological, noninvasive manipulation of the circadian pacemaker waveform in a model species for mammalian circadian rhythmicity. Given the evidence of conserved flexibility in the human pacemaker waveform, these findings raise the promise of flexible resetting applicable to circadian disruption in shift workers, frequent time-zone travelers, and any individual forced to adjust to challenging schedules. © 2015 The Author(s).

  3. EphA4 is Involved in Sleep Regulation but Not in the Electrophysiological Response to Sleep Deprivation.

    Science.gov (United States)

    Freyburger, Marlène; Pierre, Audrey; Paquette, Gabrielle; Bélanger-Nelson, Erika; Bedont, Joseph; Gaudreault, Pierre-Olivier; Drolet, Guy; Laforest, Sylvie; Blackshaw, Seth; Cermakian, Nicolas; Doucet, Guy; Mongrain, Valérie

    2016-03-01

    Optimal sleep is ensured by the interaction of circadian and homeostatic processes. Although synaptic plasticity seems to contribute to both processes, the specific players involved are not well understood. The EphA4 tyrosine kinase receptor is a cell adhesion protein regulating synaptic plasticity. We investigated the role of EphA4 in sleep regulation using electrocorticography in mice lacking EphA4 and gene expression measurements. EphA4 knockout (KO) mice, Clock(Δ19/Δ19) mutant mice and littermates, C57BL/6J and CD-1 mice, and Sprague-Dawley rats were studied under a 12 h light: 12 h dark cycle, under undisturbed conditions or 6 h sleep deprivation (SLD), and submitted to a 48 h electrophysiological recording and/or brain sampling at different time of day. EphA4 KO mice showed less rapid eye movement sleep (REMS), enhanced duration of individual bouts of wakefulness and nonrapid eye movement sleep (NREMS) during the light period, and a blunted daily rhythm of NREMS sigma activity. The NREMS delta activity response to SLD was unchanged in EphA4 KO mice. However, SLD increased EphA4 expression in the thalamic/hypothalamic region in C57BL/6J mice. We further show the presence of E-boxes in the promoter region of EphA4, a lower expression of EphA4 in Clock mutant mice, a rhythmic expression of EphA4 ligands in several brain areas, expression of EphA4 in the suprachiasmatic nuclei of the hypothalamus (SCN), and finally an unchanged number of cells expressing Vip, Grp and Avp in the SCN of EphA4 KO mice. Our results suggest that EphA4 is involved in circadian sleep regulation. © 2016 Associated Professional Sleep Societies, LLC.

  4. Pseudomagic nuclei

    International Nuclear Information System (INIS)

    Scharff-Goldhaber, G.

    1979-01-01

    It was shown previously that, below a critical angular momentum, yrast bands of nonmagic nuclei are well described by the two-parameter variable moment of inertia model. Some striking exceptions to this rule are found in nuclei which have the same mass number as doubly magic nuclei but possess either one (or two) proton pairs beyond a magic number and one (or two) neutron hole pairs, or vice versa. Yrast bands in these pseudomagic nuclei resemble those in magic nuclei. 17 references

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

    Science.gov (United States)

    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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. 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.

  10. 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.

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

    Science.gov (United States)

    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.

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  16. Neural correlates of food anticipatory activity in mice subjected to once- or twice-daily feeding periods.

    Science.gov (United States)

    Rastogi, Ashutosh; Mintz, Eric M

    2017-10-01

    In rodents, restricted food access to a limited period each day at a predictable time results in the appearance of food anticipatory activity (FAA). Two shorter periods of food access each day can result in two FAA bouts. In this study, we examine FAA under 12:12 and 18:6 photoperiods in mice (Mus musculus) with one or two food access periods per day and measure the activation of the suprachiasmatic, dorsomedial and arcuate nuclei by assaying Fos protein expression, while making use of tissue-type plasminogen activator knockout mice to assess the role of neural plasticity in adaptation to restricted feeding cycles. Long days were utilised to allow for temporal separation of two restricted feeding periods during the light phase. Mice fed twice per day generally divided FAA into two distinct bouts, with mice lacking tissue-type plasminogen activator showing reduced FAA. Increases in Fos expression in response to one restricted feeding period per day were seen in the dorsomedial and arcuate nuclei in both 12:12 and 18:6 conditions, with an increase seen in the SCN in only the 12:12 condition. These increases were eliminated or reduced in the two feeding time conditions (done in 18:6 only). Both activity patterns and Fos expression differed for single restricted feeding times between 18:6 and 12:12 photoperiods. Fos activation was lower during RF in 18:6 than 12:12 across all three brain regions, a pattern not reflective of changes in FAA. These data suggest that involvement of these regions in FAA may be influenced by photoperiodic context. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. 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

  18. The mechanism of total disintegration of heavy nuclei by fast hadrons and nuclei

    International Nuclear Information System (INIS)

    Strugalska-Gola, E.; Strugalski, Z.

    1997-01-01

    The mechanism of the total disintegration of atomic nuclei by fast hadrons and nuclei is considered. The passage of energetic hadrons through layers of intranuclear matter, accompanied by emission of fast nucleons with kinetic energies from about 20 up to about 500 MeV from definite local small regions in the nuclei around projectile courses in them, allows one to explain simply the occurrence of the total destruction of nuclei involved in the collisions. Light nuclei may be totally disintegrated by fast hadrons and nuclei; heavier nuclei may be totally disintegrated only in central collisions of nuclei with similar mass numbers

  19. 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.

  20. 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 ...

  1. 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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Exotic nuclei

    International Nuclear Information System (INIS)

    Villari, A.C.C.

    1990-01-01

    The actual tendencies to study exotic nuclei; applications of exotic nuclei beams in material study and medicine; recent results obtained by GANIL and Berkeley Laboratories of measurements of binding energy and radii of light nuclei; the future experiences to be carry out in several international laboratories and; proposal of studies in Brazil using Pelletron-USP accelerator and the LINAC superconductor accelerator, in construction in the same laboratory, are presented. (M.C.K.)

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

    Science.gov (United States)

    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.

  6. Nuclei transmutation by collisions with fast hadrons and nuclei

    International Nuclear Information System (INIS)

    Strugalski, Z.; Strugalska-Gola, E.; Drzymala, A.

    1998-01-01

    Atomic nuclei change their mass- and charge-numbers if bombarded by fast hadrons and nuclei; the transmutation appears as a complicated process. It proceeds in a definite way - through a few stages or phases. Adequate identification of the nucleons and light nuclear fragments emitted and evaporated in a hadron-nucleus or nucleus-nucleus collisions and in the collision-induced intranuclear reactions allows one to estimate quantitatively the nuclei transmutations in the various stages (phases) of the process

  7. 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

  8. Pair correlations in nuclei

    International Nuclear Information System (INIS)

    Shimizu, Yoshifumi

    2009-01-01

    Except for the closed shell nuclei, almost all nuclei are in the superconducting state at their ground states. This well-known pair correlation in nuclei causes various interesting phenomena. It is especially to be noted that the pair correlation becomes weak in the excited states of nuclei with high angular momentum, which leads to the pair phase transition to the normal state in the high spin limit. On the other hand, the pair correlation becomes stronger in the nuclei with lower nucleon density than in those with normal density. In the region of neutron halo or skin state of unstable nuclei, this phenomenon is expected to be further enhanced to be observed compared to the ground state of stable nuclei. An overview of those interesting aspects caused via the pair correlation is presented here in the sections titled 'pair correlations in ground states', pair correlations in high spin states' and 'pair correlations in unstable nuclei' focusing on the high spin state. (S. Funahashi)

  9. From heavy nuclei to super-heavy nuclei

    International Nuclear Information System (INIS)

    Theisen, Ch.

    2003-01-01

    The existence of super-heavy nuclei has been predicted nearly fifty years ago. Due to the strong coulomb repulsion, the stabilisation of these nuclei is possible only through shell effects. The reasons for this fragile stability, as well as the theoretical predictions concerning the position of the island of stability are presented in the first part of this lecture. In the second part, experiments and experimental techniques which have been used to synthesize or search for super-heavy elements are described. Spectroscopic studies performed in very heavy elements are presented in the following section. We close this lecture with techniques that are currently being developed in order to reach the superheavy island and to study the structure of very-heavy nuclei. (author)

  10. Studies of exotic nuclei

    International Nuclear Information System (INIS)

    Angelique, J.C.; Orr, N.A.

    1997-01-01

    The study of the nuclei far off stability valley is of much interest for testing the nuclear models established for the stable nuclei but also for astrophysics to understand the nucleosynthesis. Experiments aim to measure the mass and lifetime, to build the decay schemes and also to study the structure and the properties of these nuclei. The radioactive beam group focused its research on light neutron-rich nuclei having a halo neutron structure. Mass measurements in N ∼ Z nuclei namely in A ∼ 60-80 proton-rich nuclei, important for understanding the rp process, are mentioned, as well as in nuclei in the 100 Sn region. In the newly obtained 26 O and 28 O nuclei the lifetimes, the probabilities of emission of one for more neutrons were determined. The data analysis has permitted to determine also for the first time the lifetimes of 27,29 F and 30 Ne. Studies of nuclei in the 100 Sn region, near the proton drip line in the ground and isomeric states are now under way. The spectroscopy (energy levels, gamma emissions, etc.) of the neutron-rich nuclei produced by the 36 S fragmentation has been carried out in 31 Ne, 17 B and 29 F. Studies by Coulomb excitation of the 2 + excited states and associated probability B (E2) in O, Ne, Ni and Zn are now analysed

  11. 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...

  12. The asymptotic hadron spectrum, anti-nuclei, hyper-nuclei and quark phase

    International Nuclear Information System (INIS)

    Glendenning, N.K.

    1978-01-01

    The only hope of determining the hadronic spectrum in the high mass region is through a study of matter produced in very high energy nuclear collisions. Along the way, exotic nuclei, i.e., anti-nuclei and hyper-nuclei may be produced in appreciable numbers, and the detection of a quark phase may be possible. (orig.) [de

  13. 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.

  14. Level structures in Yb nuclei far from stable nuclei

    International Nuclear Information System (INIS)

    Hashizume, Akira

    1982-01-01

    Applying n-γ, γ-γ coincidence techniques, the excited levels in 158 Yb and in 157 Yb nuclei were studied. Stress is placed ona neutron detection technique to assign (HI,xn) reactions which produce the nuclei far from β stability line. (author)

  15. Masking Responses to Light in Period Mutant Mice

    Science.gov (United States)

    Pendergast, Julie S.; Yamazaki, Shin

    2013-01-01

    Masking is an acute effect of an external signal on an overt rhythm and is distinct from the process of entrainment. In the current study, we investigated the phase dependence and molecular mechanisms regulating masking effects of light pulses on spontaneous locomotor activity in mice. The circadian genes, Period1 (Per1) and Per2, are necessary components of the timekeeping machinery and entrainment by light appears to involve the induction of the expression of Per1 and Per2 mRNAs in the suprachiasmatic nuclei (SCN). We assessed the roles of the Per genes in regulating masking by assessing the effects of light pulses on nocturnal locomotor activity in C57BL/6J Per mutant mice. We found that Per1−/− and Per2−/− mice had robust negative masking responses to light. In addition, the locomotor activity of Per1−/−/Per2−/− mice appeared to be rhythmic in the light-dark (LD) cycle, and the phase of activity onset was advanced (but varied among individual mice) relative to lights off. This rhythm persisted for 1 to 2 days in constant darkness in some Per1−/−/Per2−/− mice. Furthermore, Per1−/−/Per2−/− mice exhibited robust negative masking responses to light. Negative masking was phase dependent in wild-type mice such that maximal suppression was induced by light pulses at zeitgeber time 14 (ZT14) and gradually weaker suppression occurred during light pulses at ZT16 and ZT18. By measuring the phase shifts induced by the masking protocol (light pulses were administered to mice maintained in the LD cycle), we found that the phase responsiveness of Per mutant mice was altered compared to wild-types. Together, our data suggest that negative masking responses to light are robust in Per mutant mice and that the Per1−/−/Per2−/− SCN may be a light-driven, weak/damping oscillator. PMID:21793695

  16. [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

  17. 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.

  18. 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)

  19. K-bar-mesic nuclei

    International Nuclear Information System (INIS)

    Dote, Akinobu; Akaishi, Yoshinori; Yamazaki, Toshimitsu

    2005-01-01

    New nuclei 'K-bar-Mesic Nuclei' having the strangeness are described. At first it is shown that the strongly attractive nature of K-bar N interaction is reasoned inductively from consideration of the relation between Kaonic hydrogen atom and Λ (1405) which is an excited state of hyperon Λ. The K-bar N interactions are reviewed and summarized into three categories: 1. Phenomenological approach with density dependent K-bar N interaction (DD), relativistic mean field (RMF) approach, and hybrid of them (RMF+DD). 2. Boson exchange model. 3. Chiral SU(3) theory. The investigation of some light K-bar-nuclei by Akaishi and Yamazaki using phenomenological K-bar N interaction is explained in detail. Studies by antisymmetrized molecular dynamics (AMD) approach are also presented. From these theoretical researches, the following feature of K-bar-mesic nuclei are revealed: 1) Ground state is discrete and bound by 100 MeV or more. 2) Density is very high in side the K-bar-mesic nuclei. 3) Strange structures develop which are not seen in ordinary nuclei. Finally some recent experiments to explore K-bar-mesic nuclei are reviewed. (S. Funahashi)

  20. 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

  1. Experience-independent development of the hamster circadian visual system.

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. 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

  4. 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.

  5. 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.)

  6. Gamow-Teller decay of T = 1 nuclei to odd-odd N = Z nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Lisetskiy, A F [National Superconducting Cyclotron Laboratory, MSU, East Lansing, MI 48824 (United States); Gelberg, A [Institute for Nuclear Physics, University of Cologne, 50937 Cologne (Germany); Institute of Physical and Chemical Reasearch (RIKEN), Wako, 351-0198 (Japan); Brentano, P von [Institute for Nuclear Physics, University of Cologne, 50937 Cologne (Germany)

    2005-01-01

    Transition strengths of Gamow-Teller decay of T{sub z} = {+-}1 nuclei to N = Z odd-odd nuclei have been calculated in a two-nucleon approximation for spherical and deformed nuclei. The results obtained for the latter are quite close to the values obtained by full-space shell-model calculations and to the experiment.

  7. Pairing correlations in nuclei

    International Nuclear Information System (INIS)

    Baba, C.V.K.

    1988-01-01

    There are many similarities between the properties of nucleons in nuclei and electrons in metals. In addition to the properties explainable in terms of independent particle motion, there are many important co-operative effects suggesting correlated motion. Pairing correlation which leads to superconductivity in metals and several important properties in nuclei , is an exmple of such correlations. An attempt has been made to review the effects of pairing correlations in nuclei. Recent indications of reduction in pairing correlations at high angular momenta is discussed. A comparision between pairing correlations in the cases of nuclei and electrons in metals is attempted. (author). 20 refs., 10 figs

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. Nuclei and quantum worlds

    International Nuclear Information System (INIS)

    Chomaz, Ph.

    2000-01-01

    This document gathers the slides and their commentaries that have been presented at the conference 'physics and fundamental questions' by P. Chomaz. The author reviews the different quantum aspects of nuclei: tunnel effect, symmetries, magic numbers, wave functions, size, shapes and deformations. The author shows that nuclei are quantum objects of great complexity, their structures are not yet well understood and the study of exotic nuclei will continue bringing valuable information

  12. 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...

  13. 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...

  14. Superdeformed nuclei

    International Nuclear Information System (INIS)

    Janssens, R.V.F.; Khoo, T.L.

    1991-01-01

    Superdeformation was first proposed some twenty years ago to explain the fission isomers observed in some actinide nuclei. It was later realized that superdeformed shapes can occur at high angular momentum in lighter nuclei. The interest in the mechanisms responsible for these exotic shapes has increased enormously with the discovery of a superdeformed band of nineteen discrete lines in 152 Dy (8). At about the same time, evidence for highly deformed nuclei (axis ratio 3:2) was also reported near 132 Ce(9). Striking properties emerged from the first experiments, such as the essentially constant energy spacing between transitions (picket-fence spectra), the unexpectedly strong population of superdeformed bands at high spins, and the apparent lack of a link between the superdeformed states and the yrast levels. These findings were reviewed by Nolan and Twin. The present article follows upon their work and discusses the wealth of information that has since become available. This includes the discovery of a new island of superdeformation near A = 190, the detailed spectroscopy of ground and excited bands in the superdeformed well near A = 150 and A = 190, the surprising occurrence of superdeformed bands with identical transition energies in nuclei differing by one or two mass units, and the improved understanding of mechanisms responsible for the feeding into and the decay out of the superdeformed states

  15. Structure of neutron-rich nuclei

    International Nuclear Information System (INIS)

    Nazarewicz, W.

    2000-01-01

    Complete text of publication follows. The uncharted regions of the (N,Z) plane contain information that can answer many questions of fundamental importance for science: How many protons and neutrons can be clustered together by the strong interaction to form a bound nucleus? What are the proton and neutron magic numbers of the exotic nuclei? What are the properties of very short-lived exotic nuclei with extreme neutron-to-proton ratios? What is the effective nucleon-nucleon interaction in a nucleus that has a very large neutron excess? Nuclear life far from stability is different from that around the stability line; the promised access to completely new combinations of proton and neutron numbers offers prospects for new structural phenomena. The main objective of this talk is to discuss some of the challenges and opportunities of research with exotic nuclei. The covered topics will include: Theoretical challenges; Skins and halos in heavy nuclei; Shape coexistence in exotic nuclei; Beta-decays of neutron-rich nuclei. (author)

  16. Spectrin-like proteins in plant nuclei

    NARCIS (Netherlands)

    Ruijter, de N.C.A.; Ketelaar, T.; Blumenthal, S.S.D.; Emons, A.M.C.; Schel, J.H.N.

    2000-01-01

    We analysed the presence and localization of spectrin-like proteins in nuclei of various plant tissues, using several anti-erythrocyte spectrin antibodies on isolated pea nuclei and nuclei in cells. Western blots of extracted purified pea nuclei show a cross-reactive pair of bands at 220–240 kDa,

  17. Energetic Nuclei, Superdensity and Biomedicine

    Science.gov (United States)

    Baldin, A. M.

    1977-01-01

    High-energy, relativistic nuclei were first observed in cosmic rays. Studing these nuclei has provided an opportunity for analyzing the composition of cosmic rays and for experimentally verifying principles governing the behavior of nuclear matter at high and super-high temperatures. Medical research using accelerated nuclei is suggested.…

  18. Problem of ''deformed'' superheavy nuclei

    International Nuclear Information System (INIS)

    Sobiczewski, A.; Patyk, Z.; Muntian, I.

    2000-08-01

    Problem of experimental confirmation of deformed shapes of superheavy nuclei situated in the neighbourhood of 270 Hs is discussed. Measurement of the energy E 2+ of the lowest 2+ state in even-even species of these nuclei is considered as a method for this confirmation. The energy is calculated in the cranking approximation for heavy and superheavy nuclei. The branching ratio p 2+ /p 0+ between α decay of a nucleus to this lowest 2+ state and to the ground state 0+ of its daughter is also calculated for these nuclei. The results indicate that a measurement of the energy E 2+ for some superheavy nuclei by electron or α spectroscopy is a promising method for the confirmation of their deformed shapes. (orig.)

  19. Critical-point nuclei

    International Nuclear Information System (INIS)

    Clark, R.M.

    2004-01-01

    It has been suggested that a change of nuclear shape may be described in terms of a phase transition and that specific nuclei may lie close to the critical point of the transition. Analytical descriptions of such critical-point nuclei have been introduced recently and they are described briefly. The results of extensive searches for possible examples of critical-point behavior are presented. Alternative pictures, such as describing bands in the candidate nuclei using simple ΔK = 0 and ΔK = 2 rotational-coupling models, are discussed, and the limitations of the different approaches highlighted. A possible critical-point description of the transition from a vibrational to rotational pairing phase is suggested

  20. Cluster structures in light nuclei

    International Nuclear Information System (INIS)

    Horiuchi, H.

    2000-01-01

    Complete text of publication follows. Clustering in neutron-rich nuclei is discussed. To understand the novel features (1,2,3) of the clustering in neutron-rich nuclei, the basic features of the clustering in stable nuclei (4) are briefly reviewed. In neutron-rich nuclei, the requirement of the stability of clusters is questioned and the threshold rule is no more obeyed. Examples of clustering in Be and B isotopes (4,5) are discussed in some detail. Possible existence of novel type of clustering near neutron dripline is suggested (1). (author)

  1. Inelastic collisions of neon-22 nuclei with nuclei in photoemulsion at 90 GeV/c momentum

    International Nuclear Information System (INIS)

    Vokalova, A.; Krasnov, S.A.; Tolstov, K.D.

    1985-01-01

    The experimental data obtained according to the analysis of 4303 inelastic interactions of the relativistic neon-22 nuclei with the nuclei in photoemulsion are presented. The multiplicities and angular distributions are shown as the functions of the disintegration degree of the colliding nuclei. It is shown that the same number of interacting nucleons of the projectile neon and carbon nuclei are connected with the different impact parameters with the target nucleus

  2. Interactions of 10.6 GeV/n gold nuclei with light and heavy target nuclei in nuclear emulsion

    International Nuclear Information System (INIS)

    Cherry, M.L.; Denes-Jones, P.

    1994-03-01

    We have investigated the particle production and fragmentation of nuclei participating in the interactions of 10.6 GeV/n gold nuclei in nuclear emulsions. A new criteria has been developed to distinguish between the interactions of these gold nuclei with the light (H, C, N, O) and heavy (Ag, Br) target nuclei in the emulsion. This has allowed separate analyzes of the multiplicity and pseudo-rapidity distributions of the singly charged particles emitted in Au-(H, C, N, O) and Au-(Ag, Br) interactions, as well as of the models of breakup of the projectile and target nuclei. The pseudo-rapidity distributions show strong forward asymmetries, particularly for the interactions with the light nuclei. Heavy target nuclei produce a more severe breakup of the projectile gold nucleus than do the lighter targets. A negative correlation between the number of fragments emitted from the target nuclei and the degree of centrality of the collisions has been observed, which can be attributed to the total destruction of the relatively light target nuclei by these very heavy projectile nuclei. (author). 14 refs, 11 figs, 1 tab

  3. Quarks in Few Body Nuclei

    Directory of Open Access Journals (Sweden)

    Holt Roy J.

    2016-01-01

    Full Text Available Electron scattering at very high Bjorken x from hadrons provides an excellent test of models, has an important role in high energy physics, and from nuclei, provides a window into short range correlations. Light nuclei have a key role because of the relatively well-known nuclear structure. The development of a novel tritium target for Jefferson Lab has led to renewed interest in the mass three system. For example, deep inelastic scattering experiments in the light nuclei provide a powerful means to determine the neutron structure function. The isospin dependence of electron scattering from mass-3 nuclei provide information on short range correlations in nuclei. The program using the new tritium target will be presented along with a summary of other experiments aimed at revealing the large-x structure of the nucleon.

  4. Complete destruction of heavy nuclei by hadrons and nuclei

    International Nuclear Information System (INIS)

    Tolstov, K.D.

    1980-01-01

    The total disintegration is considered of Ag and Pb nuclei and 4 He, 12 C nuclei With a momentum of 4.5 GeV/c per nucleon. It is shown that nucleons are mainly emitted, and there is no residual nUcleus the mass of which is comparable to that of the primary nucleus. The probability of total nucleus disintegration is considered as a function of projectile energy and the mass. The multiplicity, energy and emission angle of particles are considerred as well. It is shown that the density of nuclear matter in the overlap zone of colliding nuclei exceeds the usual one by a factor of approximately 4. A comparison is made with interaction models. A conclusion is drawn of the collective interaction mechanism (perhaps, of the shock wave type) of particle ejection from the target nucleus at the first stage of interaction and of explosive decay of the residual nucleus at the next one

  5. 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.

  6. Systems Chronotherapeutics

    OpenAIRE

    Ballesta, Annabelle; Innominato, Pasquale F.; Dallmann, Robert; Rand, David A.; L?vi, Francis A.

    2017-01-01

    Chronotherapeutics aim at treating illnesses according to the endogenous biologic rhythms, which moderate xenobiotic metabolism and cellular drug response. The molecular clocks present in individual cells involve approximately fifteen clock genes interconnected in regulatory feedback loops. They are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker, which also adjusts the circadian rhythms to environmental cycles. As a result, many mechanisms of diseases and drug effects are...

  7. High-spin excitations of atomic nuclei

    International Nuclear Information System (INIS)

    Xu Furong; National Laboratory of Heavy Ion Physics, Lanzhou; Chinese Academy of Sciences, Beijing

    2004-01-01

    The authors used the cranking shell model to investigate the high-spin motions and structures of atomic nuclei. The authors focus the collective rotations of the A∼50, 80 and 110 nuclei. The A∼50 calculations show complicated g spectroscopy, which can have significant vibration effects. The A≅80 N≅Z nuclei show rich shape coexistence with prolate and oblate rotational bands. The A≅110 nuclei near the r-process path can have well-deformed oblate shapes that become yrast and more stable with increasing rotational frequency. As another important investigation, the authors used the configuration-constrained adiabatic method to calculate the multi-quasiparticle high-K states in the A∼130, 180 and superheavy regions. The calculations show significant shape polarizations due to quasi-particle excitations for soft nuclei, which should be considered in the investigations of high-K states. The authors predicted some important high-K isomers, e.g., the 8 - isomers in the unstable nuclei of 140 Dy and 188 Pb, which have been confirmed in experiments. In superheavy nuclei, our calculations show systematic existence of high-K states. The high-K excitations can increase the productions of synthesis and the survival probabilities of superheavy nuclei. (authors)

  8. 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

  9. The shape of nuclei

    International Nuclear Information System (INIS)

    Mackintosh, R.S.

    1977-01-01

    For the class of nuclei which are 'strongly deformed' it is possible to introduce the idea of an empirically measurable static nuclear shape. The limitations of this concept as applied to nuclei (fundamentally quantum-mechanical objects) are discussed. These are basically the limitations of the rotational model which must be introduced in order to define and measure nuclear shape. A unified discussion of the ways in which the shape has been parametrized is given with emphasis on the fact that different parametrizations correspond to different nuclear structures. Accounts of the various theoretical procedures for calculating nuclear shapes and of the interaction between nuclear shapes and nuclear spectroscopy are given. A coherent account of a large subset of nuclei (strongly deformed nuclei) can be given by means of a model in which the concept of nuclear shape plays a central role. (author)

  10. Structure of Warm Nuclei

    International Nuclear Information System (INIS)

    Aaberg, S.; Uhrenholt, H.

    2009-01-01

    We study the structure of nuclei in the energy region between the ground state and the neutron separation energy, here called warm nuclei. The onset of chaos in the nucleus as excitation energy is increased is briefly reviewed. Chaos implies fluctuations of energies and wave functions qualitatively the same for all chaotic nuclei. On the other hand, large structure effects are seen, e.g. in the level-density function at same excitation energies. A microscopic model for the level density is reviewed and we discuss effects on structure of the total level-density function, parity enhancement, and the spin distribution function. Comparisons to data are performed at the neutron separation energy for all observed nuclei, and structure of the level-density function for a few measured cases. The role of structure effects in the level-density function for fission dynamics is exemplified.

  11. Dynamic polarisation of nuclei

    International Nuclear Information System (INIS)

    Borghini, M.; Abragam, A.

    1961-01-01

    In magnetic fields of about 13000 gauss, at a temperature of 1.5 deg. K, in samples of about 2 mm 3 , we have obtained by the 'solid effect' (application of a magnetic field at an appropriate frequency around 35000 MHz), nuclear polarizations /I of a few percent: 19 per cent for hydrogen nuclei in single crystals of La 2 Mg 3 (NO 3 ) 12 , 24H 2 O; 5 per cent for hydrogen nuclei in polystyrene; 6 per cent for fluorine nuclei in single crystals of LiF. (author) [fr

  12. Diffraction scattering and disintegration of 3He nuclei by atomic nuclei

    International Nuclear Information System (INIS)

    Koval'chuk, V.I.

    2006-01-01

    Within diffraction model framework a method of cross sections calculation for scattering and disintegration of weakly-bounded two-clustered nuclei by nuclei when both of its clusters are changed has been proposed. The experimental elastic scattering cross sections of 3 He by 40 Ca, 90 Zr and coincidence spectra of disintegration products from 28 Si( 3 He,dp) have been described

  13. 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.

  14. Neutron rich nuclei

    International Nuclear Information System (INIS)

    Foucher, R.

    1979-01-01

    If some β - emitters are particularly interesting to study in light, medium, and heavy nuclei, another (and also) difficult problem is to know systematically the properties of these neutron rich nuclei far from the stability line. A review of some of their characteristics is presented. How far is it possible to be objective in the interpretation of data is questioned and implications are discussed

  15. Baryon resonances in nuclei

    International Nuclear Information System (INIS)

    Arenhoevel, H.

    1977-01-01

    The field of baryon resonances in nuclei is reviewed. Theoretical developments and experimental evidence as well are discussed. Special emphasis is laid on electromagnetic processes for the two nucleon system. Some aspects of real isobars in nuclei are touched upon. (orig.) [de

  16. 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...

  17. Isolation of Nuclei and Nucleoli.

    Science.gov (United States)

    Pendle, Alison F; Shaw, Peter J

    2017-01-01

    Here we describe methods for producing nuclei from Arabidopsis suspension cultures or root tips of Arabidopsis, wheat, or pea. These methods could be adapted for other species and cell types. The resulting nuclei can be further purified for use in biochemical or proteomic studies, or can be used for microscopy. We also describe how the nuclei can be used to obtain a preparation of nucleoli.

  18. 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.

  19. 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

  20. Nucleons in nuclei, however

    International Nuclear Information System (INIS)

    Grange, P.; Mathiot, J.F.; Roy-Stephan, M.; Frascaria, R.; Gales, S.

    1990-01-01

    The topics presented at the 1989 Joliot-Curie Lectures are reported. Two main subjects were retained: a simplified description of the N-body motion of particles in the quasi-particle configuration; study of the dynamics of nuclear components which are not described by nucleons in their ground state. The following themes were presented: quasiparticles and the Green functions, relativistic aspects of the quasiparticle concept, the dimensions of nucleons in the nuclei and the EMC effect, quarks and gluons in the nuclei, the delta in the nuclei, the strangeness, quasiparticles far from the Fermi sea, diffusion of electrons, stellar evolution and nucleosynthesis [fr

  1. 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

  2. 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.

  3. Reflection asymmetric shapes in nuclei

    International Nuclear Information System (INIS)

    Ahmad, I.; Carpenter, M.P.; Emling, H.

    1989-01-01

    Experimental data show that there is no even-even nucleus with a reflection asymmetric shape in its ground state. Maximum octupole- octupole correlations occur in nuclei in the mass 224 (N∼134, Z∼88) region. Parity doublets, which are the characteristic signature of octupole deformation, have been observed in several odd mass Ra, Ac and Pa nuclei. Intertwined negative and positive parity levels have been observed in several even-even Ra and Th nuclei above spin ∼8ℎ. In both cases, the opposite parity states are connected by fast El transitions. In some medium-mass nuclei intertwined negative and positive parity levels have also been observed above spin ∼7ℎ. The nuclei which exhibit octupole deformation in this mass region are 144 Ba, 146 Ba and 146 Ce; 142 Ba, 148 Ce, 150 Ce and 142 Xe do not show these characteristics. No case of parity doublet has been observed in the mass 144 region. 32 refs., 16 figs., 1 tab

  4. Precision measurement of the mass difference between light nuclei and anti-nuclei

    CERN Document Server

    Adam, Jaroslav; Aggarwal, Madan Mohan; Aglieri Rinella, Gianluca; Agnello, Michelangelo; Agrawal, Neelima; Ahammed, Zubayer; Ahmed, Ijaz; Ahn, Sang Un; Aimo, Ilaria; Aiola, Salvatore; Ajaz, Muhammad; Akindinov, Alexander; Alam, Sk Noor; Aleksandrov, Dmitry; Alessandro, Bruno; Alexandre, Didier; Alfaro Molina, Jose Ruben; Alici, Andrea; Alkin, Anton; Alme, Johan; Alt, Torsten; Altinpinar, Sedat; Altsybeev, Igor; Alves Garcia Prado, Caio; Andrei, Cristian; Andronic, Anton; Anguelov, Venelin; Anielski, Jonas; Anticic, Tome; Antinori, Federico; Antonioli, Pietro; Aphecetche, Laurent Bernard; Appelshaeuser, Harald; Arcelli, Silvia; Armesto Perez, Nestor; Arnaldi, Roberta; Aronsson, Tomas; Arsene, Ionut Cristian; Arslandok, Mesut; Augustinus, Andre; Averbeck, Ralf Peter; Azmi, Mohd Danish; Bach, Matthias Jakob; Badala, Angela; Baek, Yong Wook; Bagnasco, Stefano; Bailhache, Raphaelle Marie; Bala, Renu; Baldisseri, Alberto; Ball, Markus; Baltasar Dos Santos Pedrosa, Fernando; Baral, Rama Chandra; Barbano, Anastasia Maria; Barbera, Roberto; Barile, Francesco; Barnafoldi, Gergely Gabor; Barnby, Lee Stuart; Ramillien Barret, Valerie; Bartalini, Paolo; Bartke, Jerzy Gustaw; Bartsch, Esther; Basile, Maurizio; Bastid, Nicole; Basu, Sumit; Bathen, Bastian; Batigne, Guillaume; Batista Camejo, Arianna; Batyunya, Boris; Batzing, Paul Christoph; Bearden, Ian Gardner; Beck, Hans; Bedda, Cristina; Behera, Nirbhay Kumar; Belikov, Iouri; Bellini, Francesca; Bello Martinez, Hector; Bellwied, Rene; Belmont Iii, Ronald John; Belmont Moreno, Ernesto; Belyaev, Vladimir; Bencedi, Gyula; Beole, Stefania; Berceanu, Ionela; Bercuci, Alexandru; Berdnikov, Yaroslav; Berenyi, Daniel; Bertens, Redmer Alexander; Berzano, Dario; Betev, Latchezar; Bhasin, Anju; Bhat, Inayat Rasool; Bhati, Ashok Kumar; Bhattacharjee, Buddhadeb; Bhom, Jihyun; Bianchi, Livio; Bianchi, Nicola; Bianchin, Chiara; Bielcik, Jaroslav; Bielcikova, Jana; Bilandzic, Ante; Biswas, Saikat; Bjelogrlic, Sandro; Blanco, Fernando; Blau, Dmitry; 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De Cuveland, Jan; De Falco, Alessandro; De Gruttola, Daniele; De Marco, Nora; De Pasquale, Salvatore; Deisting, Alexander; Deloff, Andrzej; Denes, Ervin Sandor; D'Erasmo, Ginevra; Di Bari, Domenico; Di Mauro, Antonio; Di Nezza, Pasquale; Diaz Corchero, Miguel Angel; Dietel, Thomas; Dillenseger, Pascal; Divia, Roberto; Djuvsland, Oeystein; Dobrin, Alexandru Florin; Dobrowolski, Tadeusz Antoni; Domenicis Gimenez, Diogenes; Donigus, Benjamin; Dordic, Olja; Dubey, Anand Kumar; Dubla, Andrea; Ducroux, Laurent; Dupieux, Pascal; Ehlers Iii, Raymond James; Elia, Domenico; Engel, Heiko; Erazmus, Barbara Ewa; Erhardt, Filip; Eschweiler, Dominic; Espagnon, Bruno; Estienne, Magali Danielle; Esumi, Shinichi; Evans, David; Evdokimov, Sergey; Eyyubova, Gyulnara; Fabbietti, Laura; Fabris, Daniela; Faivre, Julien; Fantoni, Alessandra; Fasel, Markus; Feldkamp, Linus; Felea, Daniel; Feliciello, Alessandro; Feofilov, Grigorii; Ferencei, Jozef; Fernandez Tellez, Arturo; Gonzalez Ferreiro, Elena; Ferretti, Alessandro; Festanti, Andrea; Figiel, Jan; Araujo Silva Figueredo, Marcel; Filchagin, Sergey; Finogeev, Dmitry; Fionda, Fiorella; Fiore, Enrichetta Maria; Fleck, Martin Gabriel; Floris, Michele; Foertsch, Siegfried Valentin; Foka, Panagiota; Fokin, Sergey; Fragiacomo, Enrico; Francescon, Andrea; Frankenfeld, Ulrich Michael; Fuchs, Ulrich; Furget, Christophe; Furs, Artur; Fusco Girard, Mario; Gaardhoeje, Jens Joergen; Gagliardi, Martino; Gago Medina, Alberto Martin; Gallio, Mauro; Gangadharan, Dhevan Raja; Ganoti, Paraskevi; Gao, Chaosong; Garabatos Cuadrado, Jose; Garcia-Solis, Edmundo Javier; Gargiulo, Corrado; Gasik, Piotr Jan; Germain, Marie; Gheata, Andrei George; Gheata, Mihaela; Ghosh, Premomoy; Ghosh, Sanjay Kumar; Gianotti, Paola; Giubellino, Paolo; Giubilato, Piero; Gladysz-Dziadus, Ewa; Glassel, Peter; Gomez Ramirez, Andres; Gonzalez Zamora, Pedro; Gorbunov, Sergey; Gorlich, Lidia Maria; Gotovac, Sven; Grabski, Varlen; Graczykowski, Lukasz Kamil; Grelli, Alessandro; Grigoras, Alina Gabriela; Grigoras, Costin; Grigoryev, Vladislav; Grigoryan, Ara; Grigoryan, Smbat; Grynyov, Borys; Grion, Nevio; Grosse-Oetringhaus, Jan Fiete; Grossiord, Jean-Yves; Grosso, Raffaele; Guber, Fedor; Guernane, Rachid; Guerzoni, Barbara; Gulbrandsen, Kristjan Herlache; Gulkanyan, Hrant; Gunji, Taku; Gupta, Anik; Gupta, Ramni; Haake, Rudiger; Haaland, Oystein Senneset; Hadjidakis, Cynthia Marie; Haiduc, Maria; Hamagaki, Hideki; Hamar, Gergoe; Hanratty, Luke David; Hansen, Alexander; Harris, John William; Hartmann, Helvi; Harton, Austin Vincent; Hatzifotiadou, Despina; Hayashi, Shinichi; Heckel, Stefan Thomas; Heide, Markus Ansgar; Helstrup, Haavard; Herghelegiu, Andrei Ionut; Herrera Corral, Gerardo Antonio; Hess, Benjamin Andreas; Hetland, Kristin Fanebust; Hilden, Timo Eero; Hillemanns, Hartmut; Hippolyte, Boris; Hristov, Peter Zahariev; Huang, Meidana; Humanic, Thomas; Hussain, Nur; Hussain, Tahir; Hutter, Dirk; Hwang, Dae Sung; Ilkaev, Radiy; Ilkiv, Iryna; Inaba, Motoi; Ionita, Costin; Ippolitov, Mikhail; Irfan, Muhammad; Ivanov, Marian; Ivanov, Vladimir; Izucheev, Vladimir; Jacobs, Peter Martin; Jahnke, Cristiane; Jang, Haeng Jin; Janik, Malgorzata Anna; Pahula Hewage, Sandun; Jena, Chitrasen; Jena, Satyajit; Jimenez Bustamante, Raul Tonatiuh; Jones, Peter Graham; Jung, Hyungtaik; Jusko, Anton; Kalinak, Peter; Kalweit, Alexander Philipp; Kamin, Jason Adrian; Kang, Ju Hwan; Kaplin, Vladimir; Kar, Somnath; Karasu Uysal, Ayben; Karavichev, Oleg; Karavicheva, Tatiana; Karpechev, Evgeny; Kebschull, Udo Wolfgang; Keidel, Ralf; Keijdener, Darius Laurens; Keil, Markus; Khan, Kamal; Khan, Mohammed Mohisin; Khan, Palash; Khan, Shuaib Ahmad; Khanzadeev, Alexei; Kharlov, Yury; Kileng, Bjarte; Kim, Beomkyu; Kim, Do Won; Kim, Dong Jo; Kim, Hyeonjoong; Kim, Jinsook; Kim, Mimae; Kim, Minwoo; Kim, Se Yong; Kim, Taesoo; Kirsch, Stefan; Kisel, Ivan; Kiselev, Sergey; Kisiel, Adam Ryszard; Kiss, Gabor; Klay, Jennifer Lynn; Klein, Carsten; Klein, Jochen; Klein-Boesing, Christian; Kluge, Alexander; Knichel, Michael Linus; Knospe, Anders Garritt; Kobayashi, Taiyo; Kobdaj, Chinorat; Kofarago, Monika; Kohler, Markus Konrad; Kollegger, Thorsten; Kolozhvari, Anatoly; Kondratev, Valerii; Kondratyeva, Natalia; Kondratyuk, Evgeny; Konevskikh, Artem; Kouzinopoulos, Charalampos; Kovalenko, Vladimir; Kowalski, Marek; Kox, Serge; Koyithatta Meethaleveedu, Greeshma; Kral, Jiri; Kralik, Ivan; Kravcakova, Adela; Krelina, Michal; Kretz, Matthias; Krivda, Marian; Krizek, Filip; Kryshen, Evgeny; Krzewicki, Mikolaj; Kubera, Andrew Michael; Kucera, Vit; Kucheryaev, Yury; Kugathasan, Thanushan; Kuhn, Christian Claude; Kuijer, Paulus Gerardus; Kulakov, Igor; Kumar, Jitendra; Lokesh, Kumar; Kurashvili, Podist; Kurepin, Alexander; Kurepin, Alexey; Kuryakin, Alexey; Kushpil, Svetlana; Kweon, Min Jung; Kwon, Youngil; La Pointe, Sarah Louise; La Rocca, Paola; Lagana Fernandes, Caio; Lakomov, Igor; Langoy, Rune; Lara Martinez, Camilo Ernesto; Lardeux, Antoine Xavier; Lattuca, Alessandra; Laudi, Elisa; Lea, Ramona; Leardini, Lucia; 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Scioli, Gilda; Scomparin, Enrico; Scott, Rebecca Michelle; Seeder, Karin Soraya; Seger, Janet Elizabeth; Sekiguchi, Yuko; Selyuzhenkov, Ilya; Senosi, Kgotlaesele; Seo, Jeewon; Serradilla Rodriguez, Eulogio; Sevcenco, Adrian; Shabanov, Arseniy; Shabetai, Alexandre; Shadura, Oksana; Shahoyan, Ruben; Shangaraev, Artem; Sharma, Ankita; Sharma, Natasha; Shigaki, Kenta; Shtejer Diaz, Katherin; Sibiryak, Yury; Siddhanta, Sabyasachi; Sielewicz, Krzysztof Marek; Siemiarczuk, Teodor; Silvermyr, David Olle Rickard; Silvestre, Catherine Micaela; Simatovic, Goran; Simonetti, Giuseppe; Singaraju, Rama Narayana; Singh, Ranbir; Singha, Subhash; Singhal, Vikas; Sinha, Bikash; Sarkar - Sinha, Tinku; Sitar, Branislav; Sitta, Mario; Skaali, Bernhard; Slupecki, Maciej; Smirnov, Nikolai; Snellings, Raimond; Snellman, Tomas Wilhelm; Soegaard, Carsten; Soltz, Ron Ariel; Song, Jihye; Song, Myunggeun; Song, Zixuan; Soramel, Francesca; Sorensen, Soren Pontoppidan; Spacek, Michal; Spiriti, Eleuterio; Sputowska, Iwona Anna; Spyropoulou-Stassinaki, Martha; Srivastava, Brijesh Kumar; Stachel, Johanna; Stan, Ionel; Stefanek, Grzegorz; Steinpreis, Matthew Donald; Stenlund, Evert Anders; Steyn, Gideon Francois; Stiller, Johannes Hendrik; Stocco, Diego; Strmen, Peter; Alarcon Do Passo Suaide, Alexandre; Sugitate, Toru; Suire, Christophe Pierre; Suleymanov, Mais Kazim Oglu; Sultanov, Rishat; Sumbera, Michal; Symons, Timothy; Szabo, Alexander; Szanto De Toledo, Alejandro; Szarka, Imrich; Szczepankiewicz, Adam; Szymanski, Maciej Pawel; Takahashi, Jun; Tanaka, Naoto; Tangaro, Marco-Antonio; Tapia Takaki, Daniel Jesus; Tarantola Peloni, Attilio; Tariq, Mohammad; Tarzila, Madalina-Gabriela; Tauro, Arturo; Tejeda Munoz, Guillermo; Telesca, Adriana; Terasaki, Kohei; Terrevoli, Cristina; Teyssier, Boris; Thaeder, Jochen Mathias; Thomas, Deepa; Tieulent, Raphael Noel; Timmins, Anthony Robert; Toia, Alberica; Trogolo, Stefano; Trubnikov, Victor; Trzaska, Wladyslaw Henryk; Tsuji, Tomoya; Tumkin, Alexandr; Turrisi, Rosario; Tveter, Trine Spedstad; Ullaland, Kjetil; Uras, Antonio; Usai, Gianluca; Utrobicic, Antonija; Vajzer, Michal; Vala, Martin; Valencia Palomo, Lizardo; Vallero, Sara; Van Der Maarel, Jasper; Van Hoorne, Jacobus Willem; Van Leeuwen, Marco; Vanat, Tomas; Vande Vyvre, Pierre; Varga, Dezso; Diozcora Vargas Trevino, Aurora; Vargyas, Marton; Varma, Raghava; Vasileiou, Maria; Vasiliev, Andrey; Vauthier, Astrid; Vechernin, Vladimir; Veen, Annelies Marianne; Veldhoen, Misha; Velure, Arild; Venaruzzo, Massimo; Vercellin, Ermanno; Vergara Limon, Sergio; Vernet, Renaud; Verweij, Marta; Vickovic, Linda; Viesti, Giuseppe; Viinikainen, Jussi Samuli; Vilakazi, Zabulon; Villalobos Baillie, Orlando; Vinogradov, Alexander; Vinogradov, Leonid; Vinogradov, Yury; Virgili, Tiziano; Vislavicius, Vytautas; Viyogi, Yogendra; Vodopyanov, Alexander; Volkl, Martin Andreas; Voloshin, Kirill; Voloshin, Sergey; Volpe, Giacomo; Von Haller, Barthelemy; Vorobyev, Ivan; Vranic, Danilo; Vrlakova, Janka; Vulpescu, Bogdan; Vyushin, Alexey; Wagner, Boris; Wagner, Jan; Wang, Hongkai; Wang, Mengliang; Wang, Yifei; Watanabe, Daisuke; Weber, Michael; Weber, Steffen Georg; Wessels, Johannes Peter; Westerhoff, Uwe; Wiechula, Jens; Wikne, Jon; Wilde, Martin Rudolf; Wilk, Grzegorz Andrzej; Wilkinson, Jeremy John; Williams, Crispin; Windelband, Bernd Stefan; Winn, Michael Andreas; Yaldo, Chris G; Yamaguchi, Yorito; Yang, Hongyan; Yang, Ping; Yano, Satoshi; Yasnopolskiy, Stanislav; Yin, Zhongbao; Yokoyama, Hiroki; Yoo, In-Kwon; Yurchenko, Volodymyr; Yushmanov, Igor; Zaborowska, Anna; Zaccolo, Valentina; Zaman, Ali; Zampolli, Chiara; Correia Zanoli, Henrique Jose; Zaporozhets, Sergey; Zarochentsev, Andrey; Zavada, Petr; Zavyalov, Nikolay; Zbroszczyk, Hanna Paulina; Zgura, Sorin Ion; Zhalov, Mikhail; Zhang, Haitao; Zhang, Xiaoming; Zhang, Yonghong; Zhao, Chengxin; Zhigareva, Natalia; Zhou, Daicui; Zhou, You; Zhou, Zhuo; Zhu, Hongsheng; Zhu, Jianhui; Zhu, Xiangrong; Zichichi, Antonino; Zimmermann, Alice; Zimmermann, Markus Bernhard; Zinovjev, Gennady; Zyzak, Maksym

    2015-08-17

    The measurement of the mass differences for systems bound by the strong force has reached a very high precision with protons and anti-protons. The extension of such measurement from (anti-)baryons to (anti-)nuclei allows one to probe any difference in the interactions between nucleons and anti-nucleons encoded in the (anti-)nuclei masses. This force is a remnant of the underlying strong interaction among quarks and gluons and can be described by effective theories, but cannot yet be directly derived from quantum chromodynamics. Here we report a measurement of the difference between the ratios of the mass and charge of deuterons (d) and anti-deuterons ($\\bar{d}$), and $^{3}{\\rm He}$ and $^3\\overline{\\rm He}$ nuclei carried out with the ALICE (A Large Ion Collider Experiment) detector in Pb-Pb collisions at a centre-of-mass energy per nucleon pair of 2.76 TeV. Our direct measurement of the mass-over-charge differences confirm CPT invariance to an unprecedented precision in the sector of light nuclei. This funda...

  5. 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.

  6. Barriers in the energy of deformed nuclei

    Directory of Open Access Journals (Sweden)

    V. Yu. Denisov

    2014-06-01

    Full Text Available Interaction energy between two nuclei considering to their deformations is studied. Coulomb and nuclear in-teraction energies, as well as the deformation energies of both nuclei, are taken into account at evaluation of the interaction energy. It is shown that the barrier related to the interaction energy of two nuclei depends on the de-formations and the height of the minimal barrier is evaluated. It is obtained that the heavier nucleus-nucleus sys-tems have large deformation values at the lowest barrier. The difference between the barrier between spherical nuclei and the lowest barrier between deformed nuclei increases with the mass and the charge of the interacting nuclei.

  7. Healthy clocks, healthy body, healthy mind

    OpenAIRE

    Reddy, Akhilesh B.; O’Neill, John S.

    2010-01-01

    Circadian rhythms permeate mammalian biology. They are manifested in the temporal organisation of behavioural, physiological, cellular and neuronal processes. Whereas it has been shown recently that these ?24-hour cycles are intrinsic to the cell and persist in vitro, internal synchrony in mammals is largely governed by the hypothalamic suprachiasmatic nuclei that facilitate anticipation of, and adaptation to, the solar cycle. Our timekeeping mechanism is deeply embedded in cell function and ...

  8. Structure of Light Neutron-rich Nuclei

    International Nuclear Information System (INIS)

    Dlouhy, Zdenek

    2007-01-01

    In this contribution we searched for irregularities in various separation energies in the frame of mass measurement of neutron-rich nuclei at GANIL. On this basis we can summarize that the new doubly magic nuclei are 8 He, 22 O and 24 O. They are characterized by extra stability and, except 24 O, they cannot accept and bind additional neutrons. However, if we add to these nuclei a proton we obtain 9 Li and 25 F which are the core for two-neutron halo nucleus 11 Li and enables that fluorine can bound even 6 more neutrons, respectively. In that aspect the doubly magic nuclei in the neutron-rich region can form the basis either for neutron halo or very neutron-rich nuclei. (Author)

  9. 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

  10. Light Hygiene: Time to make preventive use of insights--old and new--into the nexus of the drug light, melatonin, clocks, chronodisruption and public health.

    Science.gov (United States)

    Erren, Thomas C; Reiter, Russel J

    2009-10-01

    Light is, clearly, a key to life on Earth and light, equally clearly, determines biological rhythmicity in organisms. Light does the latter by setting internal or endogenous clocks which allow a multitude of species, including man, to adjust their lives to changing external or environmental conditions. Critical changes over time occur from day to night and throughout the year. In this paper, we sum up how visible light provides electromagnetic information about environmental "time" via the ocular interface of newly discovered photoreceptive cells to a master clock in our brain, viz the suprachiasmatic nuclei [SCN], and how the SCN translate this input, with melatonin as a key biologic intermediary, into endogenous or biological time. We summarize experimental and epidemiological evidence suggesting how chronodisruption, a relevant disturbance of the temporal organization or order of physiology, endocrinology, metabolism and behaviour, is probably detrimental for human beings. On the basis of our synthesis, and in line with suggestions by other researchers voiced decades ago, light must, functionally, be considered as a drug equivalent. In this vein, the very timing, quality (wavelength), quantity (dose) and side effects, including chronodisruption, of light exposures can be critically important for health and disease in man. As a promising means to foster public health, we advocate an appropriate balance of exposures to the key Zeitgeber light in terms of "light hygiene", implying strong and appropriate rather than weak and confusing temporal information. This focus on "light hygiene", and thus on the key Zeitgeber light, does not mean to ignore that there are multiple entrainment pathways for our circadian clocks. Indeed, when dealing with light, chronodisruption and a multitude of adverse health effects, we ultimately need to consider Zeitgeber cues, and their possible interplay, beyond light alone. Confusions of the temporal programmes in humans can also stem

  11. Cosmology and unstable nuclei

    International Nuclear Information System (INIS)

    Schramm, D.N.

    1995-01-01

    Primordial nucleosynthesis has established itself as one of the three pillars of Big Bang cosmology. Many of the Big Bang Nucleosynthesis reactions involve unstable nuclei. Hence there is a tight relationship hetween the subject of this conference and cosmology. The prime role of unstable nuclei in cosmology is related to lithium synthesis and the lack of cosmological synthesis of Be and B. These nuclei will thus be focused upon. Nucleosynthesis involves comparing calculated abundances with observed abundances. In general, abundance determinations are dominated by systematic rather than statistical errors, and work on bounding systematics is crucial. The quark-hadron inspired inhomogeneous calculations now unanimously agree that only relatively small variations in Ω b are possible vis-a-vis the homogeneous model; hence the robustness of Ω b ∼0.05 is now apparent. (These calculations depend critically on unstable nuclei.) The above argues that the bulk of the baryons in the universe are not producing visible light. A comparison with the ROSAT cluster data is also shown to be consistent with the standard BBN model. Ω b ∼1 seems to be definitely excluded, so if Ω TOTAL =1, as some recent observations may hint, then non-baryonic dark matter is required. The implications of the recently reported halo microlensing events are discussed. In summary, it is argued that the physics of unstable nuclei affects the fundamental dark matter argument. ((orig.))

  12. 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

  13. Vibrational-rotational model of odd-odd nuclei

    International Nuclear Information System (INIS)

    Afanas'ev, A.V.; Guseva, T.V.; Tamberg, Yu.Ya.

    1988-01-01

    The rotational vibrational (RV) model of odd nuclei is generalized to odd-odd nuclei. The hamiltonian, wave functions and matrix elements of the RV-model of odd-odd nuclei are obtained. The expressions obtained for matrix elements of the RV-model of odd-odd nuclei can be used to study the role of vibrational additions in low-lying two-particle states of odd-odd deformed nuclei. Such calculations permit to study more correctly the residual neutron-proton interaction of valent nucleons with respect to collectivization effects

  14. Nuclei with exotic constituents

    International Nuclear Information System (INIS)

    Yamazaki, Toshimitsu.

    1990-08-01

    We discuss various interesting features in the behavior of exotic constituents of nuclei such as hyperons and mesons, in particular, with emphases on the aspect of exotic halos which are formed in general by short-range repulsion and long-range attraction. Specifically, Λ and Σ hypernuclei and pionic nuclei are discussed. (author)

  15. The colours of Hubble Sc galaxy nuclei

    International Nuclear Information System (INIS)

    Iskudaryan, S.G.

    1975-01-01

    The colorimetric data on the nuclei of the Sc galaxies are given. Comparison of the following parameters: color of a nucleus, integral color of a galaxy, Byurakan class, and spectral type of normal spirals gives the possibility to conclude: (1) The colors of the nuclei of the Sc galaxies have a high dispersion in its values. In all Byurakan classes the galaxies with intensely red and blue nuclei occur; (2) Some Sc galaxies exhibit a discrepancy between the spectral and morphological types. The results of colorimetry of nuclei indicate that almost all such Sc galaxies have intensely red nuclei which, naturally, provide for these late spectral types. It can be assumed that the intensely red color of the nuclei of such Sc galaxies is a result of a new type of activity of these nuclei; and (3) some Sc galaxies show the characteristics of the Markarian objects

  16. 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.

  17. Nuclei in high forms

    International Nuclear Information System (INIS)

    Szymanski, Z.; Berger, J.F.; Heenen, P.H.; Heyde, K.; Haas, B.; Janssens, R.; Paya, D.; Gogny, D.; Huber, G.; Bjoernholm, S.; Brack, M.

    1991-01-01

    The purpose of 1991 Joliot-Curie Summer School is to review the most advances in the understanding of the nuclei physics after the considerable progress in gamma spectroscopy. It covers the following topics: Highly and super-deformed nuclei, nuclear structures, mean-field approach and beyond, fission isomers, nuclear excitations with long lifetime and metal clusters

  18. Exotic nuclei: another aspect of nuclear structure

    International Nuclear Information System (INIS)

    Dobaczewski, J.; Blumenfeld, Y.; Flocard, H.; Garcia Borge, M.J.; Nowacki, F.; Rombouts, S.; Theisen, Ch.; Marques, F.M.; Lacroix, D.; Dessagne, P.; Gaeggeler, H.

    2002-01-01

    This document gathers the lectures made at the Joliot Curie international summer school in 2002 whose theme that year was exotic nuclei. There were 11 contributions whose titles are: 1) interactions, symmetry breaking and effective fields from quarks to nuclei; 2) status and perspectives for the study of exotic nuclei: experimental aspects; 3) the pairing interaction and the N = Z nuclei; 4) borders of stability region and exotic decays; 5) shell structure of nuclei: from stability to decay; 6) variational approach of system with a few nucleons; 7) from heavy to super-heavy nuclei; 8) halos, molecules and multi-neutrons; 9) macroscopic approaches for fusion reactions; 10) beta decay: a tool for spectroscopy; 11) the gas phase chemistry of super-heavy elements

  19. Exotic nuclei and radioactive beams

    International Nuclear Information System (INIS)

    Chomaz, P.

    1996-01-01

    The Nuclei called exotic are all the nuclei that it is necessary to recreate in laboratory to study them. Their life time is too short -in relation to earth age- for it remains enough on earth. The researchers are going to have at their s disposal at GANIL (Caen) with the S.P.I.R.A.L. project, exotic nuclei beams and will study new kinds of nuclear reactions to better understand the atom nucleus. (N.C.). 2 refs., 9 figs

  20. Isotope shifts in unstable nuclei

    International Nuclear Information System (INIS)

    Rebel, H.

    1980-05-01

    Current experimental investigations of isotope shifts in atomic spectra of unstable nuclei and the resulting information about size and shape of nuclei far off stability are discussed with reference to some representative examples. (orig.)

  1. Dynamic polarization of radioactive nuclei

    International Nuclear Information System (INIS)

    Kiselev, Yu.F.; Lyuboshits, V.L.; )

    2001-01-01

    Radioactive nuclei, embedded into a frozen polarized proton target, atr proposed to polarize by means of some dynamic polarization methods. Angular distributions of γ-quanta emitted ny 22 Na(3 + ) in the cascade β-γ-radiation are calculated. It is shown that this distribution does not depend on the spin temperature sing at the Boltzmann distribution of populations among the Zeeman magnetic substates, whereas the tensor polarization of quadrupole nuclei, placed in the electric field of the crystal, causes the considerable sing dependence. The new method promises wide opportunities for the magnetic structure investigations as well as for the study of spin-spin interaction dynamics of rare nuclei in dielectrics. Physical-technical advantages and disadvantages of the given method are discussed for the polarization of heavy nuclei in the on-line implantation mode [ru

  2. Eta mesons in nuclei

    International Nuclear Information System (INIS)

    Liu, L.C.

    1987-01-01

    The possibility of producing eta-mesic nuclei by the use of pions is discussed. If these nuclei are observed experimentally, then the binding energies of the eta in this new nuclear matter can be used to extract accurately the eta-N-N* coupling constant in a nucleus. The framework for these calculations is the coupled channel isobar model

  3. [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

  4. Some morphometric and radio-isotopic studies of the early post-natal development of the hypothalamus of the normal and androgenized rat

    International Nuclear Information System (INIS)

    Martyn, C.N.

    1979-01-01

    Female rats given a single injection of testosterone propionate (TP) in the first few days of post-natal life exhibit post-pubertally, persistent vaginal oestrous, sterility, disordered secretion of gonadotrophins and modified patterns of sexual behaviour. The effects of TP on the incorporation of 14 C-uridine in the CNS of 5 and 61/2 day old litter mate triads consisting of male, female and TP treated female rats were investigated. Low resolution autoradiographs of serial sections of brain were prepared and analysed. A sexual dimorphism in cell nuclear size was found in the suprachiasmatic, arcuate and paraventricular nuclei of the hypothalamus. TP treatment resulted in an increase in nuclear size towards the male pattern in the latter two areas. A decrease in cell nuclear size was found in the ventromedial and suprachiasmatic nuclei. Neither sex differences nor changes following TP injection were detected in rate of incorporation of 14 C-uridine in any areas of the brain, although a significant (p<0.02) reduction in uridine incorporation in the adrenal of the female animal 24 hours after TP injection was demonstrated. The results suggested an immediate direct action of TP on the hypothalamus and peripheral tissues of the neonatal rat. (author)

  5. Multifragmentation of hot nuclei

    International Nuclear Information System (INIS)

    Tamain, B.

    1990-10-01

    It is difficult to deposit a large amount (∼ 1 Gev) of excitation energy into a nucleus. And if one wants to deposit large excitation energy values, the best way consists of shooting a given target nucleus with several nucleons, which can be achieved by using intermediate energy (10-100 MeV/nucleon) heavy ions. Such very excited objects were named hot nuclei. The study of hot nuclei has been undertaken only for 7 years because intermediate energy heavy ion facilities were not available before. The game is then to determine the decay properties of such nuclei, their limits of existence. Their study is connected with general properties of nuclear matter: namely its equation of state. Of special interest, is the onset of a new decay mechanism: multifragmentation, which is the non-sequential disassembly of a hot nucleus into several light nuclei (often called intermediate-mass fragments or IMF) or particles. This paper, shows how this mechanism can reflect fundamental properties of nuclear matter, but also how its experimental signature is difficult to establish. Multifragmentation has also been studied by using very energetic projectiles (protons and heavy ions) in the relativistic or ultra-relativistic region. The multifragmentation question of hot nuclei is far from being solved. One knows that IMF production increases when the excitation energy brought into a system is strongly increased, but very little is known about the mechanisms involved and a clear onset for multifragmentation is not established

  6. nuclei

    Directory of Open Access Journals (Sweden)

    Minkov N.

    2016-01-01

    Full Text Available We study the effects of quadrupole-octupole deformations on the energy and magnetic properties of high-K isomeric states in even-even heavy and superheavy nuclei. The neutron two-quasiparticle (2qp isomeric energies and magnetic dipole moments are calculated within a deformed shell model with the Bardeen-Cooper- Schrieffer (BCS pairing interaction over a wide range of quadrupole and octupole deformations. We found that in most cases the magnetic moments exhibit a pronounced sensitivity to the octupole deformation, while the 2qp energies indicate regions of nuclei in which the presence of high-K isomeric states may be associated with the presence of octupole softness or even with octupole deformation. In the present work we also examine the influence of the BCS pairing strength on the energy of the blocked isomer configuration. We show that the formation of 2qp energy minima in the space of quadrupole-octupole and eventually higher multipolarity deformations is a subtle effect depending on nuclear pairing correlations.

  7. Are there multiquark bags in nuclei

    International Nuclear Information System (INIS)

    Kondratyuk, L.A.; Scmatkov, M.Zh.

    1983-01-01

    Arguments are presented favouring the idea that multiquark bags do eXist in nuclei. Such hypothesis makes possible to reveal the relationship among three different scopes of phenomena: deep inelastic scattering of leptons by nUclei, large q 2 (where q 2 is a square of momentum transfer) behaviour of the form factors of light nuclei and yield of cumulative proton.s

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Electron scattering for exotic nuclei

    International Nuclear Information System (INIS)

    Suda, T.

    2013-01-01

    An electron scattering facility is under construction in RIKEN RI Beam Factory, Japan, which is dedicated to the structure studies of short-lived nuclei. This is the world's first and currently only facility of its type. The construction is nearly completed, and the first electron scattering experiment off short-lived nuclei will be carried out in the beginning of next year. The charge density distributions of short-lived nuclei will be precisely determined by elastic electron scattering for the first time. Physics pursued at this facility including future perspectives are explained

  12. The decay of hot nuclei

    International Nuclear Information System (INIS)

    Moretto, L.G.; Wozniak, G.J.

    1988-11-01

    The formation of hot compound nuclei in intermediate-energy heavy ion reactions is discussed. The statistical decay of such compound nuclei is responsible for the abundant emission of complex fragments and high energy gamma rays. 43 refs., 23 figs

  13. Thermodynamics of pairing phase transition in nuclei

    International Nuclear Information System (INIS)

    Karim, Afaque; Ahmad, Shakeb

    2014-01-01

    The pairing gaps, pairing energy, heat capacity and entropy are calculated within BCS (Bardeen- Cooper-Schrieffer) based quasi particle approach, including thermal fluctuations on pairing field within pairing model for all nuclei (light, medium, heavy and super heavy nuclei). Quasi particles approach in BCS theory was introduced and reformulated to study various properties. For thermodynamic behavior of nuclei at finite temperatures, the anomalous averages of creation and annihilation operators are introduced. It is solved self consistently at finite temperatures to obtain BCS Hamiltonian. After doing unitary transformation, we obtained the Hamiltonian in the diagonal form. Thus, one gets temperature dependence gap parameter and pairing energy for nuclei. Moreover, the energy at finite temperatures is the sum of the condensation energy and the thermal energy of fermionic quasi particles. With the help of BCS Hamiltonian, specific heat, entropy and free energy are calculated for different nuclei. In this paper the gap parameter occupation number and pairing energy as a function of temperature which is important for all the light, medium, heavy and super heavy nuclei is calculated. Moreover, the various thermo dynamical quantities like specific heat, entropy and free energy is also obtained for different nuclei. Thus, the thermodynamics of pairing phase transition in nuclei is studied

  14. On the distribution of quarks in nuclei

    International Nuclear Information System (INIS)

    Baldin, A.M.; Panebrattsev, V.S.; Stavinskij, V.S.

    1984-01-01

    On the basis of the data on cumulative proton, deuteron and nuclear fragment production in hadr on-nucleon reactions and deep inelastic muon-nucleon scattering quark distributions in light, intemediate and heavy nuclei have been investigated. Conditions of limiting fragmentation of hadrons and nuclei in the studied processes have been investigated to obtain quark-parton structure functions (Gs 2 ) of the studied hadrons or nuclei. Invariant differential cross sections of π + , π - , K + meson production on aluminium, deuterium and lead nuclei and their dependence on scale variable at the transverse momentum value Psub(T) approximately 0 have been obtained. Properties of structure functions G 2 and behaviour of different nuclei differential cross sections of limiting fragmentation have been investigated. It is concluded that considered regularities testify to the presence of multiquark states in nuclei, different by its structure from nUcleons

  15. Collisions with nuclei

    International Nuclear Information System (INIS)

    Gulamov, K.G.

    1987-01-01

    It is well known that interactions of high energy particles with nuclei, owing to possible intranuclear rescatterings, may provide information about the space-time behaviour of the production process. Therefore the main goals of these investigations are related with the attempts to study the space-time process of hadronization of coloured quarks and gluons produced at the initial stage of an interaction to white final state particles and to clarify the influence of composite quark-gluon structure of both the projectile and target on features of the production mechanisms. Since in both the initial and final states of these reactions the authors have strongly interacting multiparticle systems, it is of importance to study the collective properties of these systems. The questions to the point are: what is the degree of collectivization of particles newly produced in collisions with nuclei and what is the influence of the collective nature of a nucleus itself on the production mechanisms, in particular, what are the manifestations of possible multinucleon (multiquark) configurations in nuclei? It is obvious that the reductability of, say, hadron-nucleus (hA) interaction to hadron-nucleon (hN) collisions is directly related to the above problems. Due to time limitations the author discusses here only a few aspects of low p/sub t/ hA interactions which in his opinion are of importance for better understanding of general regularities of collisions with nuclei and for further investigations of the above problems

  16. Spectroscopy of heavy fissionable nuclei

    Indian Academy of Sciences (India)

    2015-08-05

    Aug 5, 2015 ... Nuclei in the actinide chain and beyond are prone to fission owing to ... mass nuclei are typically more difficult, because the intensity is .... j15/2 neutron alignments in a region where shell stablization effects are crucial.

  17. 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.

  18. From heavy nuclei to super-heavy nuclei; Des noyaux lourds aux super-lourds

    Energy Technology Data Exchange (ETDEWEB)

    Theisen, Ch

    2003-01-01

    The existence of super-heavy nuclei has been predicted nearly fifty years ago. Due to the strong coulomb repulsion, the stabilisation of these nuclei is possible only through shell effects. The reasons for this fragile stability, as well as the theoretical predictions concerning the position of the island of stability are presented in the first part of this lecture. In the second part, experiments and experimental techniques which have been used to synthesize or search for super-heavy elements are described. Spectroscopic studies performed in very heavy elements are presented in the following section. We close this lecture with techniques that are currently being developed in order to reach the superheavy island and to study the structure of very-heavy nuclei. (author)

  19. Colliding nuclei

    International Nuclear Information System (INIS)

    Balian, Roger; Remaud, Bernard; Suraud, E.; Durand, Dominique; Tamain, Bernard; Gobbi, A.; Cugnon, J.; Drapier, Olivier; Govaerts, Jan; Prieels, Rene

    1995-09-01

    This 14. international school Joliot-Curie of nuclear physic deals with nuclei in collision at high energy. Nine lectures are included in the proceedings of this summer school: 1 - From statistical mechanics outside equilibrium to transport equations (Balian, R.); 2 - Modeling of heavy ions reactions (Remaud, B.); 3 - Kinetic equations in heavy ions physics (Suraud, E.); 4 - Colliding nuclei near the Fermi energy (Durand, D.; Tamain, B.); 5 - From the Fermi to the relativistic energy domain: which observable? For which physics? (Gobbi, A.); 6 - Collisions at relativistic and ultra relativistic energies, Theoretical aspects (Cugnon, J.); 7 - Quark-gluon plasma: experimental signatures (Drapier, O.); 8 - Electroweak interaction: a window on physics beyond the standard model (Govaerts, J.); 9 - Symmetry tests in β nuclear process: polarization techniques (Prieels, R.)

  20. Symmetry and Phase Transitions in Nuclei

    International Nuclear Information System (INIS)

    Iachello, F.

    2009-01-01

    Phase transitions in nuclei have received considerable attention in recent years, especially after the discovery that, contrary to expectations, systems at the critical point of a phase transition display a simple structure. In this talk, quantum phase transitions (QPT), i.e. phase transitions that occur as a function of a coupling constant that appears in the quantum Hamiltonian, H, describing the system, will be reviewed and experimental evidence for their occurrence in nuclei will be presented. The phase transitions discussed in the talk will be shape phase transitions. Different shapes have different symmetries, classified by the dynamic symmetries of the Interacting Boson Model, U(5), SU(3) and SO(6). Very recently, the concept of Quantum Phase Transitions has been extended to Excited State Quantum Phase Transitions (ESQPT). This extension will be discussed and some evidence for incipient ESQPT in nuclei will be presented. Systems at the critical point of a phase transition are called 'critical systems'. Approximate analytic formulas for energy spectra and other properties of 'critical nuclei', in particular for nuclei at the critical point of the second order U(5)-SO(6) transition, called E(5), and along the line of first order U(5)-SU(3) transitions, called X(5), will be presented. Experimental evidence for 'critical nuclei' will be also shown. Finally, the microscopic derivation of shape phase transitions in nuclei within the framework of density functional methods will be briefly discussed.(author)

  1. 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.

  2. Deformation and shape coexistence in medium mass nuclei

    International Nuclear Information System (INIS)

    Meyer, R.A.

    1985-01-01

    Emerging evidence for deformed structures in medium mass nuclei is reviewed. Included in this review are both nuclei that are ground state symmetric rotors and vibrational nuclei where there are deformed structures at excited energies (shape coexistence). For the first time, Nilsson configurations in odd-odd nuclei within the region of deformation are identified. Shape coexistence in nuclei that abut the medium mass region of deformation is also examined. Recent establishment of a four-particle, four-hole intruder band in the double subshell closure nucleus 96 Zr 56 is presented and its relation to the nuclear vibron model is discussed. Special attention is given to the N=59 nuclei where new data have led to the reanalysis of 97 Sr and 99 Zr and the presence of the [404 9/2] hole intruder state as isomers in these nuclei. The low energy levels of the N=59 nuclei from Z=38 to 50 are compared with recent quadrupole-phonon model calculations that can describe their transition from near-rotational to single closed shell nuclei. The odd-odd N=59 nuclei are discussed in the context of coexisting shape isomers based on the (p[303 5/2]n[404 9/2])2 - configuration. Ongoing in-beam (t,p conversion-electron) multiparameter measurements that have led to the determination of monopole matrix elements for even-even 42 Mo nuclei are presented, and these are compared with initial estimates using IBA-2 calculations that allow mixing of normal and cross subshell excitations. Lastly, evidence for the neutron-proton 3 S 1 force's influence on the level structure of these nuclei is discussed within the context of recent quadrupole-phonon model calculations. (Auth.)

  3. Strength of Coriolis Coupling in actinide nuclei

    International Nuclear Information System (INIS)

    Peker, L.K.; Rasmussen, J.O.; Hamilton, J.H.

    1982-01-01

    Coriolis Coupling V/sub cor/ plays an important role in deformed nuclei. V/sub cor/ is proportional to h 2 /J[j (j + 1) -Ω (Ω + 1)]/sup 1/2/ and therefore is particularly significant in the nuclei with large j and low Ω Nilsson levels close to Fermi surface: n(i/sub 13/2/) in A = 150 to 170 rare-earth nuclei and p(i/sub 13/2/) and n(j/sub 15/2/) in A greater than or equal to 224 actinide nuclei. Because of larger j (n(j/sub 15/2/) versus n(i/sub 13/2/)) and smaller deformations (β approx. = 0.22 versus β 0.28) it was reasonable to expect that in actinide nuclei Coriolis effects are stronger than in the rare earth nuclei. Recently it was realized that the strength of observed Coriolis effects depends not only on the genuine Coriolis Coupling but also on the interplay between Coriolis ad pairing forces which leads to an interference between the wave functions of two mixing rotational bands. As a consequence the effective interaction V/sub eff/ of both bands is an oscillating function of the degree of shell filling (or chemical potential lambda F). It was shown that in the rare earth nuclei this interference strongly influenced conclusions about the trends in the Coriolis coupling strength and explained many of the observed band-mixing features (the sharpness of back banding curves, details of the blocking effect etc.). From theoretical analysis it was concluded that in the majority of actinide nuclei the effective interaction V/sub eff/ is strong, and therefore the Coriolis band-mixing have to be very strong. In this paper we would like to demonstrate that contrary to these predictions experimental data suggest that Coriolis band mixing in studied actinide nuclei is relatively weak and possibly significantly weaker than in rare earth nuclei

  4. Monopole transitions in hot nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Sujkowski, Z. [Soltan Inst. for Nuclear Studies, Otwock-Swierk (Poland)

    1994-12-31

    Monopole transitions can be a signature of shape changing in a hot, pulsating nucleus (the low energy E0 mode) and/or a measure of the compressibility of finite nuclei (GMR, the breathing mode). Experimental information pertaining to GMR is reviewed. Recipes for deducing the incompressibility modules for infinite nuclear matter from data on GMR are discussed. Astrophysical implications are outlined. The first attempts at locating the GMR strength in moderately hot nuclei are described. Prospects for improving the experimental techniques to make an observation of this strength in selected nuclei unambiguous are discussed. (author). 46 refs, 8 figs.

  5. Monopole transitions in hot nuclei

    International Nuclear Information System (INIS)

    Sujkowski, Z.

    1994-01-01

    Monopole transitions can be a signature of shape changing in a hot, pulsating nucleus (the low energy E0 mode) and/or a measure of the compressibility of finite nuclei (GMR, the breathing mode). Experimental information pertaining to GMR is reviewed. Recipes for deducing the incompressibility modules for infinite nuclear matter from data on GMR are discussed. Astrophysical implications are outlined. The first attempts at locating the GMR strength in moderately hot nuclei are described. Prospects for improving the experimental techniques to make an observation of this strength in selected nuclei unambiguous are discussed. (author). 46 refs, 8 figs

  6. Cavitation inception from bubble nuclei

    DEFF Research Database (Denmark)

    Mørch, Knud Aage

    2015-01-01

    , and experimental investigations of bubbles and cavitation inception have been presented. These results suggest that cavitation nuclei in equilibrium are gaseous voids in the water, stabilized by a skin which allows diffusion balance between gas inside the void and gas in solution in the surrounding liquid....... The cavitation nuclei may be free gas bubbles in the bulk of water, or interfacial gaseous voids located on the surface of particles in the water, or on bounding walls. The tensile strength of these nuclei depends not only on the water quality but also on the pressure-time history of the water. A recent model...

  7. 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

  8. Electron-microscope study of cloud and fog nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Ogiwara, S; Okita, T

    1952-01-01

    Droplets of clouds on a mountain and of fog in an urban area were captured and the form, nature and size of their nuclei were studied by means of an electron-microscope and by a chamber of constant humidity. These nuclei have similar form and nature to the hygroscopic particles in haze and to the artificially produced combustion particles. No sea-salt nuclei were found in our observations, therefore, sea-spray appears to be an insignificant source of condensation nuclei. It was found that both the cloud and the fog nuclei originated in combustion products which were the mixture of hygroscopic and non-hygroscopic substances, and that the greater part of the nuclei did not contain pure sulfuric acid.

  9. Quarks in nuclei

    International Nuclear Information System (INIS)

    Rho, M.; CEA Centre d'Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette

    1983-01-01

    Some features of quark degrees of freedom in nuclei are discussed in the light of recent developments in QCD. The principal aim of this talk is to propose, and give a tentative support to, the motion that one can study through nuclear matter different facets of the vacuum structure implied by quantum chromodynamics (QCD). This will be done using the recent (exciting) results obtained in particle physics, in particular lattice gauge calculations. Relevance of this aspect of problem to quark degrees of freedom as well as meson degrees of freedom in nuclei will be discussed. (orig.)

  10. The dynamics of the nuclei-nuclei interactions at very high energies

    International Nuclear Information System (INIS)

    Blaizot, J.P.

    1988-01-01

    The lectures on the dynamics of nuclei-nuclei interactions at very high energies, presented in the Summer School on Nuclear Physics and Particle Physics (1988), are shown. The equation of state of the hadronic matter is analyzed, by means of simple models, and some orders of magnitude can be asserted. The main characteristics of the high energy hadronic interactions are recalled. The basis of the dynamics of the relativistic fluids are given. Applications of this dynamics in the description of the space-time evolution of a plasma, generated by heavy ions collision, are carried out [fr

  11. Electric monopole transitions from low energy excitations in nuclei

    CERN Document Server

    Wood, J L; De Coster, C; Heyde, Kris L G

    1999-01-01

    Electric monopole (E0) properties are studied across the entire nuclear mass surface. Besides an introductory discussion of various model results (shell model, geometric vibrational and rotational models, algebraic models), we point out that many of the largest E0 transition strengths, $\\rho^2$(E0), are associated with shape mixing. We discuss in detail the manifestation of E0 transitions and present extensive data for~: single-closed shell nuclei, vibrational nuclei, well-deformed nuclei, nuclei that exhibit sudden ground-state changes, and nuclei that exhibit shape coexistence and intruder states. We also give attention to light nuclei, odd-A nuclei, and illustrate a suggested relation between $\\rho^2$(E0) and isotopic shifts.

  12. Implications of Circadian Rhythm in Dopamine and Mood Regulation.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  14. Symmetry energy, unstable nuclei and neutron star crusts

    Energy Technology Data Exchange (ETDEWEB)

    Iida, Kei [Kochi University, Department of Natural Science, Kochi (Japan); RIKEN Nishina Center, Saitama (Japan); Oyamatsu, Kazuhiro [RIKEN Nishina Center, Saitama (Japan); Aichi Shukutoku University, Department of Human Informatics, Aichi (Japan)

    2014-02-15

    The phenomenological approach to inhomogeneous nuclear matter is useful to describe fundamental properties of atomic nuclei and neutron star crusts in terms of the equation of state of uniform nuclear matter. We review a series of researches that we have developed by following this approach. We start with more than 200 equations of state that are consistent with empirical masses and charge radii of stable nuclei and then apply them to describe matter radii and masses of unstable nuclei, proton elastic scattering and total reaction cross sections off unstable nuclei, and nuclei in neutron star crusts including nuclear pasta. We finally discuss the possibility of constraining the density dependence of the symmetry energy from experiments on unstable nuclei and even observations of quasi-periodic oscillations in giant flares of soft gamma-ray repeaters. (orig.)

  15. Cluster structure in Cf nuclei

    International Nuclear Information System (INIS)

    Singh, Shailesh K.; Biswal, S.K.; Bhuyan, M.; Patra, S.K.; Gupta, R.K.

    2014-01-01

    Due to the availability of advance experimental facilities, it is possible to probe the nuclei upto their nucleon level very precisely and analyzed the internal structure which will help us to resolve some mysterious problem of the decay of nuclei. Recently, the relativistic nuclear collision, confirmed the α cluster type structure in the 12 C which is the mile stone for the cluster structure in nuclei. The clustering phenomena in light and intermediate elements in nuclear chart is very interesting. There is a lot of work done by our group in the clustering behaviour of the nuclei. In this paper, the various prospectus of clustering in the isotopes of Cf nucleus including fission state is discussed. Here, 242 Cf isotope for the analysis, which is experimentally known is taken. The relativistic mean field model with well established NL3 parameter set is taken. For getting the exact ground state configuration of the isotopes, the calculation for minimizing the potential energy surface is performed by constraint method. The clustering structure of other Cf isotopes is discussed

  16. Critical and shape-unstable nuclei

    CERN Document Server

    Cailliau, M; Husson, J P; Letessier, J; Mang, H J

    1973-01-01

    The authors' experimental work on the decay of neutron deficient mercury osmium nuclei, some other studies at ISOLDE (CERN) and their first theoretical analysis show that the nuclei around /sup 186/Pt (Z=78, N=108) are at the limit of spherical, oblate, prolate nuclei, have (the even one) their first 0/sup +/ excited states at very low energy; quasi- rotational bands are associated to these states. The energy of this O/sup +/ state in /sup 186-/Pt deviate from the Kumar value: angular shape instability is not enough to explain this result. The authors look at radial shape and pairing fluctuations. The position of the 4p-4n state must also be known. (0 refs).

  17. Protonic decay of oriented nuclei

    International Nuclear Information System (INIS)

    Kadmensky, S.G.

    2002-01-01

    On the basis of the multiparticle theory of protonic decay, the angular distributions of protons emitted by oriented spherical and deformed nuclei in the laboratory frame and in the internal coordinate frame of deformed parent nuclei are constructed with allowance for symmetry with respect to time inversion. It is shown that, because of the deep-subbarrier character of protonic decay, the adiabatic approximation is not applicable to describing the angular distributions of protons emitted by oriented deformed nuclei and that the angular distribution of protons in the laboratory frame does not coincide with that in the internal coordinate frame. It is demonstrated that these angular distributions coincide only if the adiabatic and the semiclassical approximation are simultaneously valid

  18. Coulomb energy differences in mirror nuclei

    International Nuclear Information System (INIS)

    Lenzi, Silvia M

    2006-01-01

    By comparing the excitation energies of analogue states in mirror nuclei, several nuclear structure properties can be studied as a function of the angular momentum up to high spin states. They can be described in the shell model framework by including electromagnetic and nuclear isospin-non-conserving interactions. Calculations for the mirror energy differences in nuclei of the f 7/2 shell are described and compared with recent experimental data. These studies are extended to mirror nuclei in the upper sd and fp shells

  19. Is there chirality in atomic nuclei?

    International Nuclear Information System (INIS)

    Meng Jie

    2009-01-01

    Static chiral symmetries are common in nature, for example, the macroscopic spirals of snail shells, the microscopic handedness of certain molecules, and human hands. The concept of chirality in atomic nuclei was first proposed in 1997, and since then many efforts have been made to understand chiral symmetry and its spontaneous breaking in atomic nuclei. Recent theoretical and experimental progress in the verification of chirality in atomic nuclei will be reviewed, together with a discussion of the problems that await to be solved in the future. (authors)

  20. Study of the experimental data of multifragmentation of gold and krypton nuclei on interactions with photoemulsion nuclei at high energies

    International Nuclear Information System (INIS)

    Saleh, Z.A.; Abdel-Hafez, A.

    2002-01-01

    Results from EMU-01/12 collaboration for the experimental data on multifragmentation of gold residual nuclei created in the interactions with photoemulsion nuclei at the energy of 10.7 GeV/nucleon are presented together with the experimental data on multifragmentation of krypton created on the interactions with photoemulsion nuclei at energy of 0.9 GeV/nucleon. The data are analyzed in the frame of the statistical model of multifragmentation. It is obvious that there are two regimes for nuclear multifragmentation: the former is when less than one-half of nucleons of projectile nucleus are knocked out, the later is when more than one-half of nucleons are knocked out. Residual nuclei with masses close to each other created at different reactions are fragmented practically simultaneously when more than one-half of nucleons of original nuclei are knocked out. These results give an indication that projectiles other than Gold and Krypton may give the same characterization on interaction with emulsion nuclei at high energies

  1. Spectroscopy of very heavy nuclei with a view to study super-heavy nuclei

    International Nuclear Information System (INIS)

    Khalfallah, F.

    2007-08-01

    Within the recent years, the spectroscopic study of single particle orbitals of very heavy elements (VHE) has become possible with the development of increasingly efficient experimental setups. This allows us, through nuclear deformation, to access with these deformed nuclei to orbitals situated around the Fermi level in the spherical superheavy elements (SHE) and learn more about the nuclear structure of these nuclei. The aim of this work is the spectroscopic studies of heavy and very heavy elements. Because of the experimental difficulties associated with the fusion reactions in the VHE region, a detailed optimization studies is essential. Simulation of energy loss and angular straggling of these nuclei due to the interaction in the target and to neutron's evaporation was carried out and allowed us to optimize the angular acceptance of the separators according to the target thickness. An extensive survey and exploration in the VHE region was also conducted on the basis of cross section's systematics in the literature and simulations carried out using the statistical code Hivap. In this framework, the possible extension of the range of validity of a set of Hivap parameters was investigated. This work has enabled us to prepare a list of experiments of interest for the production of very heavy nuclei. In this thesis, our work was concentrated on the spectroscopy of the nuclei No 256 et Rf 256 for which two experimental proposals were accepted. The octupole deformations predicted in the actinides region is studied in another part of this thesis, a part witch is dedicated to the gamma spectroscopy of Pa 223 . The data from a new experiment carried out using the Jurogam-Ritu-Great setup are analysed and compared to previous results. They confirm the octupole deformed shape in this nucleus. (author)

  2. Hot nuclei and fragmentation

    International Nuclear Information System (INIS)

    Guerreau, D.

    1993-01-01

    A review is made of the present status concerning the production of nuclei above 5 MeV temperature. Considerable progress has been made recently on the understanding of the formation and the fate of such hot nuclei. It appears that the nucleus seems more stable against temperature than predicted by static calculations. However, the occurrence of multifragment production at high excitation energies is now well established. The various experimental features of the fragmentation process are discussed. (author) 59 refs., 12 figs

  3. Early programming of astrocyte organization in the mouse suprachiasmatic nuclei by light

    Czech Academy of Sciences Publication Activity Database

    Canal, M. M.; Mohammed, N. M.; Rodríguez Arellano, Jose Julio

    2009-01-01

    Roč. 26, č. 8 (2009), s. 1545-1558 ISSN 0742-0528 Institutional research plan: CEZ:AV0Z50390512 Keywords : Development * GFAP * Circadian rhythm Subject RIV: FH - Neurology Impact factor: 3.987, year: 2009

  4. 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)...

  5. Major new sources of biological ice nuclei

    Science.gov (United States)

    Moffett, B. F.; Hill, T.; Henderson-Begg, S. K.

    2009-12-01

    Almost all research on biological ice nucleation has focussed on a limited number of bacteria. Here we characterise several major new sources of biogenic ice nuclei. These include mosses, hornworts, liverworts and cyanobacteria. Ice nucleation in the eukaryotic bryophytes appears to be ubiquitous. The temperature at which these organisms nucleate is that at which the difference in vapour pressure over ice and water is at or close to its maximum. At these temperatures (-8 to -18 degrees C) ice will grow at the expense of supercooled water. These organisms are dependent for their water on occult precipitation - fog, dew and cloudwater which by its nature is not collected in conventional rain gauges. Therefore we suggest that these organism produce ice nuclei as a water harvesting mechanism. Since the same mechanism would also drive the Bergeron-Findeisen process, and as moss is known to become airborne, these nuclei may have a role in the initiation of precipitation. The properties of these ice nuclei are very different from the well characterised bacterial nuclei. We will also present DNA sequence data showing that, although related, the proteins responsible are only very distantly related to the classical bacterial ice nuclei.

  6. Structure and clusters of light unstable nuclei

    International Nuclear Information System (INIS)

    En'yo, Yoshiko

    2010-01-01

    As it is known, cluster structures are often observed in light nuclei. In the recent evolution of unstable nuclear research (on nuclei having unbalanced number of neutron and proton) further new types of clusters are coming to be revealed. In this report, structures of light unstable nuclei and some of the theoretical models to describe them are reviewed. The following topics are picked up. 1. Cluster structure and theoretical models, 2. Cluster structure of unstable nuclei (low excited state). 3. Cluster structure of neutron excess beryllium isotopes. 4. Cluster gas like state in C isotope. 5. Dineutron structure of He isotopes. Numbers of strange nuclear structures of light nuclei are illustrated. Antisymmetrized molecular dynamics (AMD) is the recently developed theoretical framework which has been successfully used in heavy ion reactions and nuclear structure studies. Successful application of AMD to the isotopes of Be, B and C are illustrated. (S. Funahashi)

  7. Perturbative many-body approaches to finite nuclei

    International Nuclear Information System (INIS)

    Hjort-Jensen, M.; Engeland, T.; Holt, A.; Osnes, E.

    1992-06-01

    In this work the authors discuss various approaches to the effective interaction appropriate for finite nuclei. The methods reviewed are the folded-diagram method of Kuo and co-workers and the summation of the folded diagrams as advocated by Lee and Suzuki. Examples of applications to sd-shell nuclei from previous works are discussed together with hitherto unpublished results for nuclei in pf-shell. Since the method of Lee and Suzuki is found to yield the best converged results, this method is applied to calculate the effective interaction for nuclei in the pf-shell. For the calculation of the effective interaction, three recent versions of the Bonn meson-exchange potential model have been used. These versions are fitted to the same set of data and differ only in the strength of the tensor force. The importance of the latter for finite nuclei is discussed. 67 refs., 17 figs., 7 tabs

  8. A new spin-oriented nuclei facility: POLAREX

    Directory of Open Access Journals (Sweden)

    Etilé A.

    2014-03-01

    Full Text Available Using the On-Line Nuclear Orientation method, POLAREX (POLARization of EXotic nuclei is a new facility allowing to study the anisotropic decay of spin-oriented nuclei. Based on the combination of on-line implantation of radioactive nuclei with Low Temperature Nuclear Orientation technique and Nuclear Magnetic Resonance, POLAREX allows to measure nuclear electromagnetic moments and ground-state spins, in the aim to get information about the wave function composition of the nuclear state. Polarized nuclei can also be used to study fundamental interactions involving nuclear β-decay asymmetries. The POLAREX infrastructure will be installed at Accélérateur Linéaire auprés du Tandem d’Orsay in order to study neutron-rich nuclei, some of which have not been studied yet. Will be presented here, all the possibilities of this new facility and a non exhaustive scientific program.

  9. Formation and decay of hot nuclei

    International Nuclear Information System (INIS)

    Tamain, B.

    1992-09-01

    The mechanisms involved in hot nuclei formation and decay and their eventual connexion with fundamental properties of nuclear matter are discussed, i.e. its equation of state is considered. After a brief review of the reactions in which hot nuclei can be formed, the variables which are used to describe them, the corresponding theoretical descriptions and their limits when extreme states are reached are discussed. Experimental evidences for hot nuclei formation are presented, with the corresponding decay properties used as signatures. (R.P.) 64 refs.; 25 figs.; 2 tabs

  10. Elusive active galactic nuclei

    Science.gov (United States)

    Maiolino, R.; Comastri, A.; Gilli, R.; Nagar, N. M.; Bianchi, S.; Böker, T.; Colbert, E.; Krabbe, A.; Marconi, A.; Matt, G.; Salvati, M.

    2003-10-01

    A fraction of active galactic nuclei do not show the classical Seyfert-type signatures in their optical spectra, i.e. they are optically `elusive'. X-ray observations are an optimal tool to identify this class of objects. We combine new Chandra observations with archival X-ray data in order to obtain a first estimate of the fraction of elusive active galactic nuclei (AGN) in local galaxies and to constrain their nature. Our results suggest that elusive AGN have a local density comparable to or even higher than optically classified Seyfert nuclei. Most elusive AGN are heavily absorbed in the X-rays, with gas column densities exceeding 1024 cm-2, suggesting that their peculiar nature is associated with obscuration. It is likely that in elusive AGN the nuclear UV source is completely embedded and the ionizing photons cannot escape, which prevents the formation of a classical narrow-line region. Elusive AGN may contribute significantly to the 30-keV bump of the X-ray background.

  11. 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

  12. Nuclei quadrupole coupling constants in diatomic molecule

    International Nuclear Information System (INIS)

    Ivanov, A.I.; Rebane, T.K.

    1993-01-01

    An approximate relationship between the constants of quadrupole interaction of nuclei in a two-atom molecule is found. It enabled to establish proportionality of oscillatory-rotation corrections to these constants for both nuclei in the molecule. Similar results were obtained for the factors of electrical dipole-quadrupole screening of nuclei. Applicability of these relationships is proven by the example of lithium deuteride molecule. 4 refs., 1 tab

  13. Nuclei at the limits of particle stability

    International Nuclear Information System (INIS)

    Mueller, A.C.

    1993-01-01

    The properties and synthesis of nuclei at the limits of particle stability are reviewed. Nuclear reactions were induced and studied by means of the 'exotic' nuclear beams, i.e. beams of radioactive drip-line nuclei. The beams are mostly generated in heavy-ion projectile fragmentation. The cases of both neutron-rich and proton-rich nuclei are discussed. (K.A.) 270 refs.; 13 figs.; 1 tab

  14. Automated Segmentation of Nuclei in Breast Cancer Histopathology Images.

    Science.gov (United States)

    Paramanandam, Maqlin; O'Byrne, Michael; Ghosh, Bidisha; Mammen, Joy John; Manipadam, Marie Therese; Thamburaj, Robinson; Pakrashi, Vikram

    2016-01-01

    The process of Nuclei detection in high-grade breast cancer images is quite challenging in the case of image processing techniques due to certain heterogeneous characteristics of cancer nuclei such as enlarged and irregularly shaped nuclei, highly coarse chromatin marginalized to the nuclei periphery and visible nucleoli. Recent reviews state that existing techniques show appreciable segmentation accuracy on breast histopathology images whose nuclei are dispersed and regular in texture and shape; however, typical cancer nuclei are often clustered and have irregular texture and shape properties. This paper proposes a novel segmentation algorithm for detecting individual nuclei from Hematoxylin and Eosin (H&E) stained breast histopathology images. This detection framework estimates a nuclei saliency map using tensor voting followed by boundary extraction of the nuclei on the saliency map using a Loopy Back Propagation (LBP) algorithm on a Markov Random Field (MRF). The method was tested on both whole-slide images and frames of breast cancer histopathology images. Experimental results demonstrate high segmentation performance with efficient precision, recall and dice-coefficient rates, upon testing high-grade breast cancer images containing several thousand nuclei. In addition to the optimal performance on the highly complex images presented in this paper, this method also gave appreciable results in comparison with two recently published methods-Wienert et al. (2012) and Veta et al. (2013), which were tested using their own datasets.

  15. Automated Segmentation of Nuclei in Breast Cancer Histopathology Images.

    Directory of Open Access Journals (Sweden)

    Maqlin Paramanandam

    Full Text Available The process of Nuclei detection in high-grade breast cancer images is quite challenging in the case of image processing techniques due to certain heterogeneous characteristics of cancer nuclei such as enlarged and irregularly shaped nuclei, highly coarse chromatin marginalized to the nuclei periphery and visible nucleoli. Recent reviews state that existing techniques show appreciable segmentation accuracy on breast histopathology images whose nuclei are dispersed and regular in texture and shape; however, typical cancer nuclei are often clustered and have irregular texture and shape properties. This paper proposes a novel segmentation algorithm for detecting individual nuclei from Hematoxylin and Eosin (H&E stained breast histopathology images. This detection framework estimates a nuclei saliency map using tensor voting followed by boundary extraction of the nuclei on the saliency map using a Loopy Back Propagation (LBP algorithm on a Markov Random Field (MRF. The method was tested on both whole-slide images and frames of breast cancer histopathology images. Experimental results demonstrate high segmentation performance with efficient precision, recall and dice-coefficient rates, upon testing high-grade breast cancer images containing several thousand nuclei. In addition to the optimal performance on the highly complex images presented in this paper, this method also gave appreciable results in comparison with two recently published methods-Wienert et al. (2012 and Veta et al. (2013, which were tested using their own datasets.

  16. α decay chains in 271-294115 superheavy nuclei

    International Nuclear Information System (INIS)

    Santhosh, K. P.; Priyanka, B.; Joseph, Jayesh George; Sahadevan, Sabina

    2011-01-01

    α decay of 271-294 115 superheavy nuclei is studied using the Coulomb and proximity potential model for deformed nuclei (CPPMDN). The predicted α half-lives of 287 115 and 288 115 nuclei and their decay products are in good agreement with experimental values. Comparison of α and spontaneous fission half-lives predicts four-α chains and three-α chains, respectively, from 287 115 and 288 115 nuclei and are in agreement with experimental observation. Our study predicts two-α chains from 273,274,289 115, three-α chains from 275 115, and four-α chains consistently from 284,285,286 115 nuclei. These observations will be useful for further experimental investigation in this region.

  17. 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.

  18. 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

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  1. 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.

  2. Nuclear Computational Low Energy Initiative (NUCLEI)

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Sanjay K. [University of Washington

    2017-08-14

    This is the final report for University of Washington for the NUCLEI SciDAC-3. The NUCLEI -project, as defined by the scope of work, will develop, implement and run codes for large-scale computations of many topics in low-energy nuclear physics. Physics to be studied include the properties of nuclei and nuclear decays, nuclear structure and reactions, and the properties of nuclear matter. The computational techniques to be used include Quantum Monte Carlo, Configuration Interaction, Coupled Cluster, and Density Functional methods. The research program will emphasize areas of high interest to current and possible future DOE nuclear physics facilities, including ATLAS and FRIB (nuclear structure and reactions, and nuclear astrophysics), TJNAF (neutron distributions in nuclei, few body systems, and electroweak processes), NIF (thermonuclear reactions), MAJORANA and FNPB (neutrino-less double-beta decay and physics beyond the Standard Model), and LANSCE (fission studies).

  3. Laser method of free atom nuclei orientation

    International Nuclear Information System (INIS)

    Barabanov, A.L.

    1987-01-01

    Orientation process of free atom (atoms in beams) nuclei, scattering quanta of circularly polarized laser radiation is considered. A method for the evaluation of nuclei orientation parameters is developed. It is shown that in the process of pumping between the ground and first excited atomic states with electron shell spins J 1 and J 2 , so that J 2 = J 1 + 1, a complete orientation of nuclei can be attained

  4. Possible existence of backbending in actinide nuclei

    International Nuclear Information System (INIS)

    Dudek, J.; Nazarewicz, W.; Szymanski, Z.

    1982-01-01

    The possibilities for the backbending effect to occur in actinide nuclei are studied using the pairing-self-consistent independent quasiparticle method. The Hamiltonian used is that of the deformed Woods-Saxon potential plus monopole pairing term. The results of the calculations explain why there is no backbending in most actinide nuclei and simultaneously suggest that in some light neutron deficient nuclei around Th and 22 Ra a backbending effect may occur

  5. Collisions between complex atomic nuclei

    International Nuclear Information System (INIS)

    Vaagen, J. S.

    1977-08-01

    The use of heavy ion accelerators in the study of nuclear structure and states is reviewed. The reactions discussed are the quasielastic reactions in which small amounts of energy and few particles are exchanged between the colliding nuclei. The development of heavy ion accelerators is also discussed, as well as detection equipment. Exotic phenomena, principally the possible existence of superheavy nuclei, are also treated. (JIW)

  6. Bound states of Θ+ in nuclei

    International Nuclear Information System (INIS)

    Oset, E.; Cabrera, D.; Li, Q.B.; Magas, V.K.; Vicente Vacas, M.J.

    2005-01-01

    We study the binding energy and the width of the Θ + in nuclei, associated to the KN and KπN components. The first one leads to negligible contributions while the second one leads to a sizeable attraction, enough to bind the Θ + in nuclei. Pauli blocking and binding effects on the KN decay reduce considerably the Θ + decay width in nuclei and medium effects associated to the KπN component also lead to a very small width, as a consequence of which one finds separation between the bound levels considerably larger than the width of the states

  7. Chaos in nuclei: Theory and experiment

    Science.gov (United States)

    Muñoz, L.; Molina, R. A.; Gómez, J. M. G.

    2018-05-01

    During the last three decades the quest for chaos in nuclei has been quite intensive, both with theoretical calculations using nuclear models and with detailed analyses of experimental data. In this paper we outline the concept and characteristics of quantum chaos in two different approaches, the random matrix theory fluctuations and the time series fluctuations. Then we discuss the theoretical and experimental evidence of chaos in nuclei. Theoretical calculations, especially shell-model calculations, have shown a strongly chaotic behavior of bound states in regions of high level density. The analysis of experimental data has shown a strongly chaotic behavior of nuclear resonances just above the one-nucleon emission threshold. For bound states, combining experimental data of a large number of nuclei, a tendency towards chaotic motion is observed in spherical nuclei, while deformed nuclei exhibit a more regular behavior associated to the collective motion. On the other hand, it had never been possible to observe chaos in the experimental bound energy levels of any single nucleus. However, the complete experimental spectrum of the first 151 states up to excitation energies of 6.20 MeV in the 208Pb nucleus have been recently identified and the analysis of its spectral fluctuations clearly shows the existence of chaotic motion.

  8. Particles and nuclei, letters

    International Nuclear Information System (INIS)

    2001-01-01

    The present collection of letters from JINR, Dubna, contains seven separate records on physics from extra dimensions, new physics in the new millennium with GENIUS: double beta decay, dark matter, solar neutrinos, the (μ - , e + ) conversion in nuclei mediated by light Majorana neutrinos, exotic muon-to-positron conversion in nuclei: partial transition sum evaluation by using shell model, solar neutrino problem accounting for self consistent magnetohydrodynamics solution for solar magnetic fields, first neutrino observations from the Sudbury neutrino observatory and status report on BOREXINO and results of the muon-background measurements at CERN

  9. Particles and nuclei, letters

    International Nuclear Information System (INIS)

    2002-01-01

    The present collection of letters from JINR, Dubna, contains seven separate records on kinematic separation and mass analysis of heavy recoiling nuclei, dynamical effects prior to heavy ion fusion, VACTIV-DELPHI graphical dialog based program for the analysis of gamma-ray spectra, irradiation of nuclear emulsions in relativistic beams of 6 He and 3 H nuclei, optical and structural investigations of PLZT x/65/35 (x = 4, 8 %) ferroelectric ceramics irradiated by a high-current pulsed electron beam, the oscillating charge and first evidence for neutrinoless double beta decay

  10. Weak interactions with nuclei

    International Nuclear Information System (INIS)

    Walecka, J.D.

    1983-01-01

    Nuclei provide systems where the strong, electomagnetic, and weak interactions are all present. The current picture of the strong interactions is based on quarks and quantum chromodynamics (QCD). The symmetry structure of this theory is SU(3)/sub C/ x SU(2)/sub W/ x U(1)/sub W/. The electroweak interactions in nuclei can be used to probe this structure. Semileptonic weak interactions are considered. The processes under consideration include beta decay, neutrino scattering and weak neutral-current interactions. The starting point in the analysis is the effective Lagrangian of the Standard Model

  11. 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...

  12. 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.

  13. Reentrainment of radioactive nuclei from filters

    International Nuclear Information System (INIS)

    Dincklage, R.-D. von

    1982-01-01

    The possible relevance of atomic phenomena for the reentrainment of radioactive nuclei is discussed. The considerations are based on the coulombic fragmentation mechanism. Nuclei of potential interest in reprocessing technology are identified. Future experiments have been shown to be of definite need in this field. (author)

  14. On the occurrence of nuclei in mature sieve elements.

    Science.gov (United States)

    Event, R F; Davis, J D; Tucker, C M; Alfieri, F J

    1970-12-01

    The secondary phloem of 3 species of the Taxodiaceae and 13 species of woody dicotyledons was examined for the occurrence of nuclei in mature sieve elements. Nuclei were found in all mature sieve cells of Metasequoia glyptostroboides, Sequoia sempervirens and Taxodium distichum, and in some mature sieve-tube members in 12 of the 13 species of woody dicotyledons. Except for nuclei of sieve cells undergoing cessation of function, the nuclei in mature sieve cells of M. glyptostroboides, S. sempervirens and T. distichum were normal in appearance. The occurrence and morphology of nuclei in mature sieve-tube members of the woody dicotyledons were quite variable. Only 3 species, Robinia pseudoacacia, Ulmus americana and Vitis riparia, contained some mature sieve elements with apparently normal nuclei.

  15. Nuclear-physical investigations with oriented nuclei and polarized neutrons

    International Nuclear Information System (INIS)

    Alfimenkov, V.P.; Pikel'ner, L.B.; Sharapov, Eh.I.

    1980-01-01

    Several experiments with oriented nuclei and polarized neutrons are considered, as well as some methods of polarization of neutrons and nuclei. Experiments on the study of spin dependence of neutron cross sections for fissionable and nonfissionable nuclei interaction of polarized neutrons with polarized nuclei as well as measurement of magnetic momenta of compound-states of rare-earth nuclei. Described are some investigations with thermal neutrons: study on spin dependence of neutron scattering length with nuclei and gamma radiation of neutron radiation capture. Difficulties of production of high-intensive polarized neutron beams and construction of oriented targets are noted. Neutron polarization by transmission of them through a polarized proton target is the most universal method (out of existing methods) in the energy range under consideration [ru

  16. DNA Measurement of Overlapping Cell Nuclei in Thick Tissue Sections

    Directory of Open Access Journals (Sweden)

    Liang Ji

    1997-01-01

    Full Text Available The paper describes an improved image analysis procedure for measuring the DNA content of cell nuclei in thick sections of liver tissue by absorption densitometry. Whereas previous methods only permitted the analysis of isolated nuclei, the new technique enables both isolated and overlapping nuclei to be measured. A 3D segmentation procedure determines whether each object is an isolated nucleus or a pair of overlapping nuclei; in the latter case the combined optical density is redistributed to the individual nuclei. A selection procedure ensures that only complete nuclei are measured.

  17. 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.

  18. Single Particle Entropy in Heated Nuclei

    International Nuclear Information System (INIS)

    Guttormsen, M.; Chankova, R.; Hjorth-Jensen, M.; Rekstad, J.; Siem, S.; Sunde, A. C.; Syed, N. U. H.; Agvaanluvsan, U.; Schiller, A.; Voinov, A.

    2006-01-01

    The thermal motion of single particles represents the largest contribution to level density (or entropy) in atomic nuclei. The concept of single particle entropy is presented and shown to be an approximate extensive (additive) quantity for mid-shell nuclei. A few applications of single particle entropy are demonstrated

  19. Relativistic exotic nuclei as projectile beams. New perspectives of studies on the properties of nuclei

    International Nuclear Information System (INIS)

    Geissel, H.

    1997-03-01

    Examinations of the production cross-sections and the kinematics permitted refinement of model concepts of the peripheral reactions in exotic nuclei at energies from 100 to 1000 A MeV. Due to the strong selectivity and resolution achieved it was possible to discover a large number of novel isotopes at the fragment separator FRS, despite the relatively low projectile beam intensities of the SIS. The two twice magic nuclei found, Ni 78 and Sn 100, are particularly interesting, as they could not be measured so far with other experimental systems. Fission of relativistic uranium ions proved to be a particularly successful process yielding many medium-heavy, neutron-rich nuclei. Insight into the structure of light neutron halos could be improved. The superlarge spatial dimensions of the nuclear halos is discussed. (orig./CB) [de

  20. Understanding Nuclei in the upper sd - shell

    OpenAIRE

    Sarkar, M. Saha; Bisoi, Abhijit; Ray, Sudatta; Kshetri, Ritesh; Sarkar, S.

    2013-01-01

    Nuclei in the upper-$sd$ shell usually exhibit characteristics of spherical single particle excitations. In the recent years, employment of sophisticated techniques of gamma spectroscopy has led to observation of high spin states of several nuclei near A$\\simeq$ 40. In a few of them multiparticle, multihole rotational states coexist with states of single particle nature. We have studied a few nuclei in this mass region experimentally, using various campaigns of the Indian National Gamma Array...

  1. Shell-model Monte Carlo studies of nuclei

    International Nuclear Information System (INIS)

    Dean, D.J.

    1997-01-01

    The pair content and structure of nuclei near N = Z are described in the frwnework of shell-model Monte Carlo (SMMC) calculations. Results include the enhancement of J=0 T=1 proton-neutron pairing at N=Z nuclei, and the maxked difference of thermal properties between even-even and odd-odd N=Z nuclei. Additionally, a study of the rotational properties of the T=1 (ground state), and T=0 band mixing seen in 74 Rb is presented

  2. Particle-rotation coupling in atomic nuclei

    International Nuclear Information System (INIS)

    Almberger, J.

    1980-01-01

    Recently an increased interest in the rotational nuclei has been spurred by the new experimental high-spin activities and by the possibilities for lower spins to interpret an impressive amount of experimental data by some comparatively simple model calculations. The author discusses the particle modes of excitation for rotational nuclei in the pairing regime where some puzzles in the theoretical description remain to be resolved. A model comparison is made between the particle-rotor and cranking models which have different definitions of the collective rotation. The cranking model is found to imply a smaller value of the quasiparticle spin alignment than the particle-rotor model. Rotational spectra for both even and odd nuclei are investigated with the use of the many-BCS-quasiparticles plus rotor model. This model gives an accurate description of the ground and S-bands in many even-even rare-earth nuclei. However, the discrepancies for odd-A nuclei between theory and experiments point to the importance of additional physical components. Therefore the rotationally induced quadrupole pair field is considered. This field has an effect on the low spin states in odd-A nuclei, but is not sufficient to account for the experimental data. Another topic considered is the interaction matrix element in crossings for given spin between quasiparticle rotational bands. The matrix elements are found to oscillate as a function of the number of particles, thereby influencing the sharpness of the backbending. Finally the low-spin continuation of the S-band is studied and it is shown that such states can be populated selectively by means of one-particle pickup reactions involving high angular momentum transfer. (Auth.)

  3. Flavanol binding of nuclei from tree species.

    Science.gov (United States)

    Feucht, W; Treutter, D; Polster, J

    2004-01-01

    Light microscopy was used to examine the nuclei of five tree species with respect to the presence of flavanols. Flavanols develop a blue colouration in the presence of a special p-dimethylaminocinnamaldehyde (DMACA) reagent that enables those nuclei loaded with flavanols to be recognized. Staining of the nuclei was most pronounced in both Tsuga canadensis and Taxus baccata, variable in Metasequoia glyptostroboides, faint in Coffea arabica and minimal in Prunus avium. HPLC analysis showed that the five species contained substantial amounts of different flavanols such as catechin, epicatechin and proanthocyanidins. Quantitatively, total flavanols were quite different among the species. The nuclei themselves, as studied in Tsuga seed wings, were found to contain mainly catechin, much lower amounts of epicatechin and traces of proanthocyanidins. Blue-coloured nuclei located centrally in small cells were often found to maximally occupy up to 90% of a cell's radius, and the surrounding small rim of cytoplasm was visibly free of flavanols. A survey of 34 gymnosperm and angiosperm species indicated that the first group has much higher nuclear binding capacities for flavanols than the second group.

  4. Neutron rich nuclei around 132Sn

    International Nuclear Information System (INIS)

    Bhattacharya, Sarmishtha

    2016-01-01

    The neutron rich nuclei with few particles or holes in 132 Sn have various experimental and theoretical interest to understand the evolution of nuclear structure around the doubly magic shell closure Z=50 and N=82. Some of the exotic neutron rich nuclei in this mass region are situated near waiting points in the r-process path and are of special astrophysical interest. Neutron rich nuclei near 132 Sn have been studied using fission fragment spectroscopy. The lifetime of low lying isomeric states have been precisely measured and the beta decay from the ground and isomeric states have been characterized using gamma-ray spectroscopy

  5. Nuclei in a neutron star

    International Nuclear Information System (INIS)

    Oyamatsu, K.; Yamada, M.

    1994-01-01

    We report on the recent progress in understanding the matter in the crust of a neutron star. For nuclides in the outer crust, recently measured masses of neutron-rich nuclei enable us to determine more accurately the stable nuclide as a function of the matter density. In the inner crust, the compressible liquid-drop model predicts successive change of the nuclear shape, from sphere to cylinder, slab, cylindrical hole and spherical hole at densities just before the transition to uniform matter. In order to go beyond the liquiddrop model, we performed the Thomas-Fermi calculation paying special attention to the surface diffuseness, and have recently calculated the shell energies of the non-spherical nuclei. We have found from these studies that all these non-spherical nuclei exist stably in the above order even if we include the surface diffuseness and shell energies. (author)

  6. Systematics of light nuclei in a relativistic model

    International Nuclear Information System (INIS)

    Price, C.E.

    1988-01-01

    The results of relativistic mean field calculations for non-spherical nuclei are presented and discussed. The need for non-linear scalar meson self-couplings in order to describe the properties of s-d shell nuclei is emphasized along with the importance of self-consistency in calculations of magnetic moments of odd-mass nuclei. 16 refs., 3 figs., 2 tabs

  7. Stability and production of superheavy nuclei

    International Nuclear Information System (INIS)

    Moeller, P.; Los Alamos National Lab., NM; Nix, J.R.

    1997-01-01

    Beyond uranium heavy elements rapidly become increasingly unstable with respect to spontaneous fission as the proton number Z increases, because of the disruptive effect of the long-range Coulomb force. However, in the region just beyond Z = 100 magic proton and neutron numbers and the associated shell structure enhances nuclear stability sufficient to allow observation of additional nuclei. Some thirty years ago it was speculated that an island of spherical, relatively stable superheavy nuclei would exist near the next doubly magic proton-neutron combination beyond 208 Pb, that is, at proton number Z 114 and neutron number N = 184. Theory and experiment now show that there also exists a rock of stability in the vicinity of Z = 110 and N = 162 between the actinide region, which previously was the end of the peninsula of known elements, and the predicted island of spherical superheavy nuclei slightly southwest of the magic numbers Z = 114 and N = 184. The authors review here the stability properties of the heavy region of nuclei. Just as the decay properties of nuclei in the heavy region depend strongly on shell structure, this structure also dramatically affects the fusion entrance channel. The six most recently discovered new elements were all formed in cold-fusion reactions. They discuss here the effect of the doubly magic structure of the target in cold-fusion reactions on the fusion barrier and on dissipation

  8. Collective models of transition nuclei Pt. 2

    International Nuclear Information System (INIS)

    Dombradi, Zs.

    1982-01-01

    The models describing the even-odd and odd-odd transition nuclei (nuclei of moderate ground state deformation) are reviewed. The nuclear core is described by models of even-even nuclei, and the interaction of a single particle and the core is added. Different models of particle-core coupling (phenomenological models, collective models, nuclear field theory, interacting boson-fermion model, vibration nucleon cluster model) and their results are discussed. New developments like dynamical supersymmetry and new research trends are summarized. (D.Gy.)

  9. Particles and nuclei in PANIC

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1987-07-15

    PANIC is the triennal International Conference on Particles and Nuclei, and judging from the latest PANIC, held in Kyoto from 20-24 April there is no need for panic yet. Faced with two pictures – one of nuclei described in nucleon and meson terms, and another of nucleons containing quarks and gluons – physicists are intrigued to know what new insights from the quark level can tell us about nuclear physics, or vice versa.

  10. Particles and nuclei in PANIC

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    PANIC is the triennal International Conference on Particles and Nuclei, and judging from the latest PANIC, held in Kyoto from 20-24 April there is no need for panic yet. Faced with two pictures – one of nuclei described in nucleon and meson terms, and another of nucleons containing quarks and gluons – physicists are intrigued to know what new insights from the quark level can tell us about nuclear physics, or vice versa

  11. Understanding nuclei in the upper sd - shell

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, M. Saha; Bisoi, Abhijit; Ray, Sudatta [Nuclear Physics Division, Saha Institute of Nuclear Physics, Kolkata 700064 (India); Kshetri, Ritesh [Nuclear Physics Division, Saha Institute of Nuclear Physics, Kolkata 700064, India and Sidho-Kanho-Birsha University, Purulia - 723101 (India); Sarkar, S. [Indian Institute of Engineering Science and Technology, Shibpur, Howrah - 711103 (India)

    2014-08-14

    Nuclei in the upper-sd shell usually exhibit characteristics of spherical single particle excitations. In the recent years, employment of sophisticated techniques of gamma spectroscopy has led to observation of high spin states of several nuclei near A ≃ 40. In a few of them multiparticle, multihole rotational states coexist with states of single particle nature. We have studied a few nuclei in this mass region experimentally, using various campaigns of the Indian National Gamma Array setup. We have compared and combined our empirical observations with the large-scale shell model results to interpret the structure of these nuclei. Indication of population of states of large deformation has been found in our data. This gives us an opportunity to investigate the interplay of single particle and collective degrees of freedom in this mass region.

  12. 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...

  13. Quarks in nuclei

    International Nuclear Information System (INIS)

    Roberts, R.G.

    1984-11-01

    The paper concerns the behaviour of quarks in nuclei. Confinement size changes and dynamical rescaling; A dependence; low-x region; gluons and confinement size; and nucleons in a nucleus; are all discussed. (U.K.)

  14. 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.

  15. Microscopic Cluster Theory for Exotic Nuclei

    International Nuclear Information System (INIS)

    Tomaselli, M; Kuehl, T; Ursescu, D; Fritzsche, S

    2006-01-01

    For a better understanding of the dynamics of complex exotic nuclei it is of crucial importance to develop a practical microscopic theory easy to be applied to a wide range of masses. In this paper we propose to calculate the structure of neutron-rich nuclei within a dynamic model based on the EoM theory

  16. Mean-field models and exotic nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Bender, M; Buervenich, T; Maruhn, J A; Greiner, W [Inst. fuer Theoretische Physik, Univ. Frankfurt (Germany); Rutz, K [Inst. fuer Theoretische Physik, Univ. Frankfurt (Germany); [Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany); Reinhard, P G [Inst. fuer Theoretische Physik, Univ. Erlangen (Germany)

    1998-06-01

    We discuss two widely used nuclear mean-field models, the relativistic mean-field model and the (nonrelativistic) Skyrme-Hartree-Fock model, and their capability to describe exotic nuclei. Test cases are superheavy nuclei and neutron-rich Sn isotopes. New information in this regime helps to fix hitherto loosely determined aspects of the models. (orig.)

  17. Mean-field models and exotic nuclei

    International Nuclear Information System (INIS)

    Bender, M.; Buervenich, T.; Maruhn, J.A.; Greiner, W.; Rutz, K.; Reinhard, P.G.

    1998-01-01

    We discuss two widely used nuclear mean-field models, the relativistic mean-field model and the (nonrelativistic) Skyrme-Hartree-Fock model, and their capability to describe exotic nuclei. Test cases are superheavy nuclei and neutron-rich Sn isotopes. New information in this regime helps to fix hitherto loosely determined aspects of the models. (orig.)

  18. Structure functions of nucleons and nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Bentz, Wolfgang; Ito, Takuya [Department of Physics, Tokai University, Kanagawa (Japan); Cloet, Ian [Department of Physics, University of Washington, Seattle (United States); Thomas, Anthony [Jefferson Lab., Newport News, VA (United States); Yazaki, Koichi [RIKEN, Wako-shi, Saitama (Japan)

    2009-07-01

    We use an effective chiral quark theory to calculate the quark distributions and structure functions of nucleons and nuclei. The description of the single nucleon is based on the Faddeev framework, and nuclear systems are described in the mean field approximation. Particular amphasis is put on the prediction of the polarized EMC effect in nuclei, and on applications to deep inelastic neutrino-nucleus scattering. Concerning the polarized EMC effect, we discuss the quenching of the quark spin sum in nuclei and its implications for the spin dependent nuclear structure functions, and present results for several nuclei where an experimental observation is feasible. Concerning the case of deep inelastic neutrino-nucleus scattering, we estimate the effect of medium modifications of the quark distribution functions on the measured cross sections, and discuss an interesting resolution of the so called NuTeV anomaly. Finally, we discuss extensions of our model to describe fragmentation functions for semi-inclusive processes. The connection between our effective quark model description and the jet model of Field and Feynman is discussed.

  19. Interactions of 82Pb208 nuclei with energy 158 GeV per nucleon with photoemulsion nuclei

    International Nuclear Information System (INIS)

    Adamovich, M.I.; Andreeva, N.P.; Bubnov, V.I.; Gajtinov, A.Sh.; Kanygina, Eh.K.; Musaeva, A.K.; Sejtimbetov, A.M.; Skorobagatova, V.I.; Filippova, L.N.; Chasnikov, I.Ya.

    1999-01-01

    In this report there are experimental data on 82 Pb 208 nuclei (158 GeV) interaction with photoemulsion nuclei. The said data are compared to the similar ones for 79 Au 197 nuclei with less energy (10,7 A GeV). Stack of nuclear emulsion was irradiated with the beam of nuclei 82 Pb 208 at SPS of CERN. Events search was done along the primary nucleus trace. Pb nucleus average path length happened to be λ=(3,8±0,1) cm, this virtually coincides with the one calculated by Brandt and Peters formula (3,9 cm). Secondary particles were identified into s (storm), g (knock-on protons) and b- particles (target nucleus fragments), as well as into nucleus-bullet fragments with different charges (Z=1,2,≥3). This allowed obtaining event distribution by multiplicity of these particles (n s , n g , n b ) and fragments (n z=1,2,≥3 ), calculation of average values by multiplicity (see table), finding correlation of characteristics. >From the table it's clear that when the energy increases s > increases 2,5 times where as g > insignificantly decreases and b > doesn't change

  20. Atmospheric particles acting as ice forming nuclei in different size ranges and cloud condensation nuclei measurements

    International Nuclear Information System (INIS)

    Santachiara, G.; Di Matteo, L.; Belosi, F.; Prodi, F.

    2009-01-01

    Measurements of ice nuclei (I N) in different size classes of aerosol P M1, P M2.5, PM10, and total suspended particles (Tsp) were performed at a rural site (S.Pietro Capofiume, in the Po Valley, Italy). Simultaneous measurements of particle number concentrations were also made with a condensation nucleus counter (CN C-TSI), along with particle concentration in different size classes starting from diameter d > 0.3 μm (Optical Spectrometer Grimm, Mod.1.108). No correlation is observed between I N and the particle number concentration measured with the condensation nuclei counter, and there is only a weak correlation with the particle concentration measured using the optical counter, thus confirming the contribution of the accumulation and coarse aerosol fraction. A positive correlation is observed between supersaturation with respect to ice and water values and ice nuclei number concentration, and an exponential dependence of I N on temperature is found. In addition, cloud concentration nuclei (C CN) were measured. The present measurements reveal a diurnal trend, with lower values at about midday and higher ones during the night, a similar trend between C CN and the relative humidity, and opposite to the mixing layer height.

  1. Proton multiplicity distributions in high-energy hadron-nuclei collisions

    International Nuclear Information System (INIS)

    Strugalski, Z.

    1979-01-01

    The fast proton emission process is analyzed in high-energy hadron-nuclei collisions. The formula describing the proton multiplicity distributions is derived. It describes well enough the proton multiplicity distribution of pion-nuclei and proton-nuclei collisions at 200 and 400 GeV

  2. Quantum phase transitions in atomic nuclei

    International Nuclear Information System (INIS)

    Zamfir, N.V.

    2005-01-01

    Studies of quantum phase transitions in mesoscopic systems and applications to atomic nuclei are presented. Analysis in terms of the Interacting Boson Model shows that the main features persist even for moderate number of particles. Experimental evidence in rare-earth nuclei is discussed. New order and control parameters for systems with the same number of particles are proposed. (author)

  3. Study of nuclear level densities for exotic nuclei

    International Nuclear Information System (INIS)

    Nasrabadi, M. N.; Sepiani, M.

    2012-01-01

    Nuclear level density is one of the properties of nuclei with widespread applications in astrophysics and nuclear medicine. Since there has been little experimental and theoretical research on the study of nuclei which are far from stability line, studying nuclear level density for these nuclei is of crucial importance. Also, as nuclear level density is an important input for nuclear research codes, hence studying the methods for calculation of this parameter is essential. Besides introducing various methods and models for calculating nuclear level density for practical applications, we used exact spectra distribution (SPDM) for determining nuclear level density of two neutron and proton enriched exotic nuclei with the same mass number.

  4. Two-particle spatial correlations in superfluid nuclei

    International Nuclear Information System (INIS)

    Pillet, N.; Berger, J.-F.; Sandulescu, N.; Schuck, P.

    2010-01-01

    We discuss the effect of pairing on two-neutron space correlations in deformed nuclei. The spatial correlations are described by the pairing tensor in coordinate space calculated in the HFB approach. Calculations are done using the D1S Gogny force. We show that the pairing tensor has a rather small extension in the relative coordinate, a feature observed earlier in spherical nuclei. It is pointed out that in deformed nuclei the coherence length corresponding to the pairing tensor has a pattern similar to what we have found previously in spherical nuclei; that is, it is maximal in the interior of the nucleus and then it decreases rather rapidly in the surface region, where it reaches a minimal value of about 2 fm. This minimal value of the coherence length in the surface is essentially determined by the finite size properties of single-particle states in the vicinity of the chemical potential and has little to do with enhanced pairing correlations in the nuclear surface. It is shown that in nuclei the coherence length is not a good indicator of the intensity of pairing correlations. This feature is contrasted with the situation in infinite matter.

  5. Electron scattering and reactions from exotic nuclei

    International Nuclear Information System (INIS)

    Karataglidis, S.

    2017-01-01

    The SCRIT and FAIR/ELISe experiments are the first to attempt to measure directly electron scattering form factors from nuclei far from stability. This will give direct information for the (one-body) charge densities of those systems, about which there is little information available. The SCRIT experiment will be taking data for medium-mass exotic nuclei, while the electron-ion collider at ELISe, when constructed, will be able to measure form factors for a wide range of exotic nuclei, as available from the radioactive ion beams produced by the FAIR experiment. Other facilities are now being proposed, which will also consider electron scattering from exotic nuclei at higher energies, to study short-range correlations in exclusive reactions. This review will consider all available information concerning the current status (largely theoretical) of electron scattering from exotic nuclei and, where possible, complement such information with equivalent information concerning the neutron densities of those exotic systems, as obtained from intermediate energy proton scattering. The issue of long- and short-range correlations will be discussed, and whether extending such studies to the exotic sector will elicit new information. (orig.)

  6. Electron scattering and reactions from exotic nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Karataglidis, S. [University of Johannesburg, Department of Physics, Auckland Park (South Africa); University of Melbourne, School of Physics, Victoria (Australia)

    2017-04-15

    The SCRIT and FAIR/ELISe experiments are the first to attempt to measure directly electron scattering form factors from nuclei far from stability. This will give direct information for the (one-body) charge densities of those systems, about which there is little information available. The SCRIT experiment will be taking data for medium-mass exotic nuclei, while the electron-ion collider at ELISe, when constructed, will be able to measure form factors for a wide range of exotic nuclei, as available from the radioactive ion beams produced by the FAIR experiment. Other facilities are now being proposed, which will also consider electron scattering from exotic nuclei at higher energies, to study short-range correlations in exclusive reactions. This review will consider all available information concerning the current status (largely theoretical) of electron scattering from exotic nuclei and, where possible, complement such information with equivalent information concerning the neutron densities of those exotic systems, as obtained from intermediate energy proton scattering. The issue of long- and short-range correlations will be discussed, and whether extending such studies to the exotic sector will elicit new information. (orig.)

  7. Fundamental Physics with Electroweak Probes of Nuclei

    Science.gov (United States)

    Pastore, Saori

    2018-02-01

    The past decade has witnessed tremendous progress in the theoretical and computational tools that produce our understanding of nuclei. A number of microscopic calculations of nuclear electroweak structure and reactions have successfully explained the available experimental data, yielding a complex picture of the way nuclei interact with electroweak probes. This achievement is of great interest from the pure nuclear-physics point of view. But it is of much broader interest too, because the level of accuracy and confidence reached by these calculations opens up the concrete possibility of using nuclei to address open questions in other sub-fields of physics, such as, understanding the fundamental properties of neutrinos, or the particle nature of dark matter. In this talk, I will review recent progress in microscopic calculations of electroweak properties of light nuclei, including electromagnetic moments, form factors and transitions in between lowlying nuclear states along with preliminary studies for single- and double-beta decay rates. I will illustrate the key dynamical features required to explain the available experimental data, and, if time permits, present a novel framework to calculate neutrino-nucleus cross sections for A > 12 nuclei.

  8. Bubble nuclei in relativistic mean field theory

    International Nuclear Information System (INIS)

    Shukla, A.; Aberg, S.; Patra, S.K.

    2011-01-01

    Bubble nuclei are characterized by a depletion of their central density, i.e. the formation of the proton or neutron void and subsequently forming proton or neutron bubble nuclei. Possibility of the formation of bubble nuclei has been explored through different nuclear models and in different mass regions. Advancements in experimental nuclear physics has led our experimental access to many new shapes and structures, which were inaccessible hitherto. In the present paper, the possibility of observing nuclear bubble in oxygen isotopes, particularly for 22 O has been studied

  9. Hot nuclei: high temperatures, high angular momenta

    International Nuclear Information System (INIS)

    Guerreau, D.

    1991-01-01

    A review is made of the present status concerning the production of hot nuclei above 5 MeV temperature, concentrating mainly on the possible experimental evidences for the attainment of a critical temperature, on the existence of dynamical limitations to the energy deposition and on the experimental signatures for the formation of hot spinning nuclei. The data strongly suggest a nuclear disassembly in collisions involving very heavy ions at moderate incident velocities. Furthermore, hot nuclei seem to be quite stable against rotation on a short time scale. (author) 26 refs.; 12 figs

  10. Structures of exotic nuclei

    International Nuclear Information System (INIS)

    Hamilton, J.H.

    1987-01-01

    Discoveries of many different types of nuclear shape coexistence are being found at both low and high excitation energies throughout the periodic table, as documented in recent reviews. Many new types of shape coexistence have been observed at low excitation energies, for examples bands on more than four different overlapping and coexisting shapes are observed in 185 Au, and competing triaxial and prolate shapes in 71 Se and 176 Pt. Discrete states in super-deformed bands with deformations β 2 ∼ 0.4-0.6, coexisting with other shapes, have been seen to high spin up to 60ℎ in 152 Dy, 132 Ce and 135 Nd. Super-deformed nuclei with N and Z both around 38 and around Z = 38, N ≥ 60. These data led to the discovery of new shell gaps and magic numbers of 38 for N and Z and 60 for N but now for deformed shapes. Marked differences in structure are observed at spins of 6 to 20 in nuclei in this region, which differ by only two protons; for example, 68 Ge and 70 Se. The differences are thought to be related to the competing shell gaps in these nuclei

  11. Transitional nuclei near shell closures

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, G. [Variable Energy Cyclotron Centre, 1/AF Bidhan Nagar, Kolkata 700064 (India); Pai, H. [Variable Energy Cyclotron Centre, 1/AF Bidhan Nagar, Kolkata 700064, India and Present Address: Institut für Kernphysik, Technische Universität Darmstadt, Schlossgartenstrasse 9, 64289 Darmstadt (Germany)

    2014-08-14

    High spin states in Bismuth and Thallium nuclei near the Z = 82 shell closure and Cesium nuclei near the N = 82 shell closure in A = 190 and A = 130 regions, respectively, have been experimentally investigated using heavy-ion fusion evaporation reaction and by detecting the gamma rays using the Indian National Gamma Array (INGA). Interesting shape properties in these transitional nuclei have been observed. The results were compared with the neighboring nuclei in these two regions. The total Routhian surface (TRS) calculations have been performed for a better understanding of the observed properties. In mass region A = 190, a change in shape from spherical to deformed has been observd around neutron number N = 112 for the Bi (Z = 83) isotopes with proton number above the magic gap Z = 82, whereas, the shape of Tl (Z = 81) isotopes with proton number below the magic gap Z = 82 remains stable as a function of neutron number. An important transition from aplanar to planar configuration of angular momentum vectors leading to the occurance of nuclar chirality and magnetic rotation, respectively, has been proposed for the unique parity πh{sub 11/2}⊗νh{sub 11/2} configuration in Cs isotopes in the mass region A ∼ 130 around neutron number N = 79. These results are in commensurate with the TRS calculations.

  12. Pions scatter by nuclei

    International Nuclear Information System (INIS)

    Huefner, J.

    1975-01-01

    Are pions a good tool to study nuclei. If the emphasis of this question rests on ''tool'', the answer must be ''not yet.'' The reason: one does not even understand how a pion interacts with a nucleus. This is part of the many-body problem for strongly interacting particles and its study is a basic problem in physics. One must investigate questions like: Can one understand pion-nucleus interactions from pion-nucleon physics. How does a Δ-resonance look in nuclei. Once one has solved those basic problems, there will be spinoffs in medical, technical and nuclear areas. Then pions can be used as a tool to study nuclear properties

  13. Rotational motion in nuclei

    International Nuclear Information System (INIS)

    Bohr, A.

    1976-01-01

    Nuclear structure theories are reviewed concerned with nuclei rotational motion. The development of the deformed nucleus model facilitated a discovery of rotational spectra of nuclei. Comprehensive verification of the rotational scheme and a successful classification of corresponding spectra stimulated investigations of the rotational movement dynamics. Values of nuclear moments of inertia proved to fall between two marginal values corresponding to rotation of a solid and hydrodynamic pattern of an unrotating flow, respectively. The discovery of governing role of the deformation and a degree of a symmetry violence for determining rotational degrees of freedon is pointed out to pave the way for generalization of the rotational spectra

  14. Quasars, Seyfert galaxies and active galactic nuclei

    International Nuclear Information System (INIS)

    Osterbrock, D.E.

    1987-01-01

    This chapter is devoted to the spectroscopic methods for analyzing the observed plasma in the nuclei of quasars, Seyfert galazies, and active galactic nuclei. Both the narrow-line region and the broad-line region are discussed. Physical models are presented

  15. Role of neutrons in the fusion of nuclei

    International Nuclear Information System (INIS)

    Zagrebaev, V. I.; Samarin, V. V.

    2007-01-01

    The problem of a quantum-mechanical description of a near-barrier fusion of heavy nuclei under conditions of a strong coupling of their relative motion to neutron degrees of freedom is studied. New mutually complementing efficient models employing the multidimensional time-dependent Schroedinger equation and methods for numerically solving the problems in question within these models are proposed. This makes it possible to study the evolution of wave functions for outer neutrons and to calculate nucleon transfer probabilities and occupation numbers for quasimolecular states over the entire energy range, including that of deep-subbarrier energies. It is shown that the valence-neutron wave functions extend over the volumes of both colliding nuclei before their surfaces come into contact and even before these nuclei overcome the Coulomb barrier (collectivization of outer nucleons). This gives rise to a substantial neutron-transfer effect on the fusion of nuclei and, in particular, to a sizable increase in the probability of subbarrier fusion for specific combinations of nuclei

  16. Superheavy nuclei in the relativistic mean-field theory

    International Nuclear Information System (INIS)

    Lalazissis, G.A.; Ring, P.; Gambhir, Y.K.

    1996-01-01

    We have carried out a study of superheavy nuclei in the framework of the relativistic mean-field theory. Relativistic Hartree-Bogoliubov (RHB) calculations have been performed for nuclei with large proton and neutron numbers. A finite-range pairing force of Gogny type has been used in the RHB calculations. The ground-state properties of very heavy nuclei with atomic numbers Z=100-114 and neutron numbers N=154-190 have been obtained. The results show that in addition to N=184 the neutron numbers N=160 and N=166 exhibit an extra stability as compared to their neighbors. For the case of protons the atomic number Z=106 is shown to demonstrate a closed-shell behavior in the region of well deformed nuclei about N=160. The proton number Z=114 also indicates a shell closure. Indications for a doubly magic character at Z=106 and N=160 are observed. Implications of shell closures on a possible synthesis of superheavy nuclei are discussed. (orig.)

  17. Electro-magnetic properties of heavy nuclei

    International Nuclear Information System (INIS)

    Otsuka, Takaharu

    1989-01-01

    Two topics of electro-magnetic properties of heavy nuclei are discussed. The first topic is the M1 excitation from well-deformed heavy nuclei, and the other is the sudden increase of the isotope shift as a function of N in going away from the closed shell. These problems are considered in terms of the particle-number projected (Nilsson-) BCS calculation. (author)

  18. 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).

  19. Tests of the salt-nuclei hypothesis of rain formation

    Energy Technology Data Exchange (ETDEWEB)

    Woodcock, A H; Blanchard, D C

    1955-01-01

    Atmospheric chlorides in sea-salt nuclei and the chlorides dissolved in shower rainwaters were recently measured in Hawaii. A comparison of these measurements reveals the remarkable fact that the weight of chloride present in a certain number of nuclei in a cubic meter of clear air tends to be equal to the weight of chloride dissolved in an equal number of raindrops in a cubic meter of rainy air. This result is explained as an indication that the raindrops grow on the salt nuclei in some manner which prevents a marked change in the distribution of these nuclei during the drop-growth process. The data presented add new evidence in further support of the salt-nuclei raindrop hypothesis previously proposed by the first author.

  20. Superheavy nuclei: a relativistic mean field outlook

    International Nuclear Information System (INIS)

    Afanasjev, A.V.

    2006-01-01

    The analysis of quasi-particle spectra in the heaviest A∼250 nuclei with spectroscopic data provides an additional constraint for the choice of effective interaction for the description of superheavy nuclei. It strongly suggests that only the parametrizations which predict Z = 120 and N = 172 as shell closures are reliable for superheavy nuclei within the relativistic mean field theory. The influence of the central depression in the density distribution of spherical superheavy nuclei on the shell structure is studied. A large central depression produces large shell gaps at Z = 120 and N = 172. The shell gaps at Z = 126 and N = 184 are favoured by a flat density distribution in the central part of the nucleus. It is shown that approximate particle number projection (PNP) by means of the Lipkin-Nogami (LN) method removes pairing collapse seen at these gaps in the calculations without PNP

  1. 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

  2. Circadian behaviour in neuroglobin deficient mice.

    Directory of Open Access Journals (Sweden)

    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.

  3. Imaging of Nuclear Fragmentation in Nuclear Track Emulsion Relativistic Nuclei

    International Nuclear Information System (INIS)

    Zarubina, I.G. JINR

    2011-01-01

    The method of nuclear track emulsion provides a uniquely complete observation of multiple fragment systems produced in dissociation of relativistic nuclei. The most valuable events of coherent dissociation of nuclei in narrow jets of light and the lightest nuclei with a net charge as in the initial nucleus, occurring without the production of fragments of the target nuclei and mesons (the so-called w hite s tars), comprise a few percent among the observed interactions. The data on this phenomenon are fragmented, and the interpretation is not offered. The dissociation degree of light O, Ne, Mg and Si, and as well as heavy Au, Pb and U nuclei may reach a complete destruction to light and the lightest nuclei and nucleons, resulting in cluster systems of an unprecedented complexity. Studies with relativistic neutron-deficient nuclei have special advantages due to more complete observations. An extensive collection of macro videos of such interactions in nuclear track emulsion gathered by the Becquerel collaboration is presented

  4. Amygdala nuclei critical for emotional learning exhibit unique gene expression patterns.

    Science.gov (United States)

    Partin, Alexander C; Hosek, Matthew P; Luong, Jonathan A; Lella, Srihari K; Sharma, Sachein A R; Ploski, Jonathan E

    2013-09-01

    The amygdala is a heterogeneous, medial temporal lobe structure that has been implicated in the formation, expression and extinction of emotional memories. This structure is composed of numerous nuclei that vary in cytoarchitectonics and neural connections. In particular the lateral nucleus of the amygdala (LA), central nucleus of the amygdala (CeA), and the basal (B) nucleus contribute an essential role to emotional learning. However, to date it is still unclear to what extent these nuclei differ at the molecular level. Therefore we have performed whole genome gene expression analysis on these nuclei to gain a better understanding of the molecular differences and similarities among these nuclei. Specifically the LA, CeA and B nuclei were laser microdissected from the rat brain, and total RNA was isolated from these nuclei and subjected to RNA amplification. Amplified RNA was analyzed by whole genome microarray analysis which revealed that 129 genes are differentially expressed among these nuclei. Notably gene expression patterns differed between the CeA nucleus and the LA and B nuclei. However gene expression differences were not considerably different between the LA and B nuclei. Secondary confirmation of numerous genes was performed by in situ hybridization to validate the microarray findings, which also revealed that for many genes, expression differences among these nuclei were consistent with the embryological origins of these nuclei. Knowing the stable gene expression differences among these nuclei will provide novel avenues of investigation into how these nuclei contribute to emotional arousal and emotional learning, and potentially offer new genetic targets to manipulate emotional learning and memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Growth and Interaction of Colloid Nuclei

    Science.gov (United States)

    Lam, Michael-Angelo; Khusid, Boris; Meyer, William; Kondic, Lou

    2017-11-01

    We study evolution of colloid systems under zero-gravity conditions. In particular, we focus on the regime where there is a coexistence between a liquid and a solid state. Under zero gravity, the dominating process in the bulk of the fluid phase and the solid phase is diffusion. At the moving solid/liquid interface, osmotic pressure is balanced by surface tension, as well as balancing fluxes (conservation of mass) with the kinematics of nuclei growth (Wilson-Frenkel law). Due to the highly nonlinear boundary condition at the moving boundary, care has to be taken when performing numerical simulations. In this work, we present a nonlinear model for colloid nuclei growth. Numerical simulations using a finite volume method are compared with asymptotic analysis of the governing equation and experimental results for nuclei growth. Novel component in our numerical simulations is the inclusion of nonlinear (collective) diffusion terms that depend on the chemical potentials of the colloid in the solid and fluid phase. The results include growth and dissolution of a single colloidal nucleus, as well as evolution of multiple interacting nuclei. Supported by NASA Grant No. NNX16AQ79G.

  6. Determining the number of clusters for nuclei segmentation in breast cancer image

    Science.gov (United States)

    Fatichah, Chastine; Navastara, Dini Adni; Suciati, Nanik; Nuraini, Lubna

    2017-02-01

    Clustering is commonly technique for image segmentation, however determining an appropriate number of clusters is still challenging. Due to nuclei variation of size and shape in breast cancer image, an automatic determining number of clusters for segmenting the nuclei breast cancer is proposed. The phase of nuclei segmentation in breast cancer image are nuclei detection, touched nuclei detection, and touched nuclei separation. We use the Gram-Schmidt for nuclei cell detection, the geometry feature for touched nuclei detection, and combining of watershed and spatial k-Means clustering for separating the touched nuclei in breast cancer image. The spatial k-Means clustering is employed for separating the touched nuclei, however automatically determine the number of clusters is difficult due to the variation of size and shape of single cell breast cancer. To overcome this problem, first we apply watershed algorithm to separate the touched nuclei and then we calculate the distance among centroids in order to solve the over-segmentation. We merge two centroids that have the distance below threshold. And the new of number centroid as input to segment the nuclei cell using spatial k- Means algorithm. Experiment show that, the proposed scheme can improve the accuracy of nuclei cell counting.

  7. Exotic Nuclei Arena in JHP

    International Nuclear Information System (INIS)

    Nomura, T.

    1991-12-01

    The Exotic Nuclei Arena planned in Japanese Hadron Project aims to accelerate various unstable nuclei produced in 1-GeV proton-induced reactions up to 6.5 MeV/u by means of heavy-ion linacs. The present status of research and development for the Earena is briefly reported. The construction of the prototype facility to accelerate unstable beams up to 0.8 MeV/u is planned in 1992-94, in which the existing cyclotron in INS is used as the primary accelerator. (author)

  8. Spinodal decomposition of atomic nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Chomaz, P. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France); Colonna, M.; Guarnera, A. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France)]|[LNS, Catania (Italy)

    1996-12-31

    Multifragmentation of atomic nuclei is discussed. It is shown that this description of the dynamics of first order phase transitions in infinite and finite system is now partially achieved. An important conclusion is that in some specific cases well-defined collective motions were initiating the self-organisation of the unstable matter in fragments. In the case of finite systems the possible signals kept from this early fragmentation stage can inform on the possible occurrence of a liquid-gas phase transition in nuclei. (K.A.). 21 refs.

  9. Spinodal decomposition of atomic nuclei

    International Nuclear Information System (INIS)

    Chomaz, P.; Colonna, M.; Guarnera, A.

    1996-01-01

    Multifragmentation of atomic nuclei is discussed. It is shown that this description of the dynamics of first order phase transitions in infinite and finite system is now partially achieved. An important conclusion is that in some specific cases well-defined collective motions were initiating the self-organisation of the unstable matter in fragments. In the case of finite systems the possible signals kept from this early fragmentation stage can inform on the possible occurrence of a liquid-gas phase transition in nuclei. (K.A.)

  10. Structure of neutron-rich nuclei

    International Nuclear Information System (INIS)

    Nazarewicz, W.; Oak Ridge National Lab., TN; Warsaw Univ.

    1997-11-01

    One of the frontiers of today's nuclear science is the ''journey to the limits'': of atomic charge and nuclear mass, of neutron-to-proton ratio, and of angular momentum. The new data on exotic nuclei are expected to bring qualitatively new information about the fundamental properties of the nucleonic many-body system, the nature of the nuclear interaction, and nucleonic correlations at various energy-distance scales. In this talk, current developments in nuclear structure of neutron-rich nuclei are discussed from a theoretical perspective

  11. Relativistic mean field theory for unstable nuclei

    International Nuclear Information System (INIS)

    Toki, Hiroshi

    2000-01-01

    We discuss the properties of unstable nuclei in the framework of the relativistic mean field (RMF) theory. We take the RMF theory as a phenomenological theory with several parameters, whose form is constrained by the successful microscopic theory (RBHF), and whose values are extracted from the experimental values of unstable nuclei. We find the outcome with the newly obtained parameter sets (TM1 and TMA) is promising in comparison with various experimental data. We calculate systematically the ground state properties of even-even nuclei up to the drip lines; about 2000 nuclei. We find that the neutron magic shells (N=82, 128) at the standard magic numbers stay at the same numbers even far from the stability line and hence provide the feature of the r-process nuclei. However, many proton magic numbers disappear at the neutron numbers far away from the magic numbers due to the deformations. We discuss how to describe giant resonances for the case of the non-linear coupling terms for the sigma and omega mesons in the relativistic RPA. We mention also the importance of the relativistic effect on the spin observables as the Gamow-Teller strength and the longitudinal and transverse spin responses. (author)

  12. Nuclei far off the stability line

    International Nuclear Information System (INIS)

    Fenyes, T.

    1978-01-01

    Theoretical and experimental aspects of the formation of some ''exotic'' nuclei far off the stability line were reviewed in addition to the relevant results of research in this field. Results in beta- and gamma-ray spectroscopy, heavy-ion-spectroscopy, achievements in the fields of measuring the atomic mass, the moment, and the radius of the nuclei as well as some astronomical aspects were described. (Z.P.)

  13. Disintegration of comet nuclei

    International Nuclear Information System (INIS)

    Ksanfomality, Leonid V

    2012-01-01

    The breaking up of comets into separate pieces, each with its own tail, was seen many times by astronomers of the past. The phenomenon was in sharp contrast to the idea of the eternal and unchangeable celestial firmament and was commonly believed to be an omen of impending disaster, especially for comets with tails stretching across half the sky. It is only now that we have efficient enough space exploration tools to see comet nuclei and even - in the particular case of small comet Hartley-2 in 2010 - to watch their disintegration stage. There are also other suspected candidates for disintegration in the vast family of comet nuclei and other Solar System bodies. (physics of our days)

  14. Disintegration of comet nuclei

    Science.gov (United States)

    Ksanfomality, Leonid V.

    2012-02-01

    The breaking up of comets into separate pieces, each with its own tail, was seen many times by astronomers of the past. The phenomenon was in sharp contrast to the idea of the eternal and unchangeable celestial firmament and was commonly believed to be an omen of impending disaster, especially for comets with tails stretching across half the sky. It is only now that we have efficient enough space exploration tools to see comet nuclei and even - in the particular case of small comet Hartley-2 in 2010 - to watch their disintegration stage. There are also other suspected candidates for disintegration in the vast family of comet nuclei and other Solar System bodies.

  15. Electronuclear sum rules for the lightest nuclei

    International Nuclear Information System (INIS)

    Efros, V.D.

    1992-01-01

    It is shown that the model-independent longitudinal electronuclear sum rules for nuclei with A = 3 and A = 4 have an accuracy on the order of a percent in the traditional single-nucleon approximation with free nucleons for the nuclear charge-density operator. This makes it possible to test this approximation by using these sum rules. The longitudinal sum rules for A = 3 and A = 4 are calculated using the wave functions of these nuclei corresponding to a large set of realistic NN interactions. The values of the model-independent sum rules lie in the range of values calculated by this method. Model-independent expressions are obtained for the transverse sum rules for nuclei with A = 3 and A = 4. These sum rules are calculated using a large set of realistic wave functions of these nuclei. The contribution of the convection current and the changes in the results for different versions of realistic NN forces are given. 29 refs., 4 tabs

  16. Multifractal-based nuclei segmentation in fish images.

    Science.gov (United States)

    Reljin, Nikola; Slavkovic-Ilic, Marijeta; Tapia, Coya; Cihoric, Nikola; Stankovic, Srdjan

    2017-09-01

    The method for nuclei segmentation in fluorescence in-situ hybridization (FISH) images, based on the inverse multifractal analysis (IMFA) is proposed. From the blue channel of the FISH image in RGB format, the matrix of Holder exponents, with one-by-one correspondence with the image pixels, is determined first. The following semi-automatic procedure is proposed: initial nuclei segmentation is performed automatically from the matrix of Holder exponents by applying predefined hard thresholding; then the user evaluates the result and is able to refine the segmentation by changing the threshold, if necessary. After successful nuclei segmentation, the HER2 (human epidermal growth factor receptor 2) scoring can be determined in usual way: by counting red and green dots within segmented nuclei, and finding their ratio. The IMFA segmentation method is tested over 100 clinical cases, evaluated by skilled pathologist. Testing results show that the new method has advantages compared to already reported methods.

  17. Contact nuclei formation in aqueous dextrose solutions

    Science.gov (United States)

    Cerreta, Michael K.; Berglund, Kris A.

    1990-06-01

    A laser Raman microprobe was used in situ to observe the growth of alpha dextrose monohydrate on alpha anhydrous dextrose crystals. The Raman spectra indicate growth of the monohydrate below 28.1°C, but the presence of only the anhydrous form above 40.5°C. Contact nucleation experiments with parent anhydrous crystals yielded only monohydrate nuclei below 28.1°C, while contacts in solutions between 34.5 and 41.0°C produced both crystalline forms, and contacts in solutions above 43.5°C produced only anhydrous nuclei. The inability of the monohydrate to grow on anhydrous crystals in the same solution that forms the two crystalline phases with a single contact precludes a simple attrition mechanism of nuclei formation. For the same reason, the hypothetical mechanism involving parent crystal stabilization of pre-crystalline clusters, allowing the clusters to grow into nuclei, is also contradicted. A third, mechanism, which may be a combination of the two, is believed to apply.

  18. Spectroscopic Studies of Exotic Nuclei at ISOLDE

    CERN Multimedia

    2002-01-01

    Experiment IS50 is designed to: a) Investigate the full range of the @b strength function of heavy (A~$>$~48)~K nuclei b)~Study the decay of isomeric states in n-deficient bromine nuclei (A~=~72 and 70). The heavy K isotopes appeared to have complex decay schemes, including feeding by the @b-decay of levels having open neutron channels (Beta decay energy Q(@b) exceeds neutron binding energy S^n); in addition, a large fraction of the delayed transitions populate excited levels in the daughter nuclei. The allowed @b-decay selects states in the daughter nucleus with wave functions having a large overlap with the initial state. Hence, the @b strength functions, deduced from these deca reveal simple structures correlated to the particle-hole excitation energies in the Ca nuclei. These results are valuable for the application of the shell-model calculations far from stability. The delayed neutron spectra are measured with a large area curved scintillator in coincidence either with high resolution Ge(Li) detectors, ...

  19. Isospin invariant boson models for fp-shell nuclei

    International Nuclear Information System (INIS)

    Van Isacker, P.

    1994-01-01

    Isospin invariant boson models, IBM-3 and IBM-4, applicable in nuclei with neutrons and protons in the same valence shell, are reviewed. Some basic results related to these models are discussed: the mapping onto the shell model, the relation to Wigner's supermultiplet scheme, the boson-number and isospin dependence of parameters, etc. These results are examined for simple single-j shell situations (e.g. f 7/2 ) and their extension to the f p shell is investigated. Other extensions discussed here concern the treatment of odd-mass nuclei and the classification of particle-hole excitations in light nuclei. The possibility of a pseudo-SU(4) supermultiplet scheme in f p -shell nuclei is discussed. (author) 4 figs., 3 tabs., 23 refs

  20. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

    Directory of Open Access Journals (Sweden)

    Julian Lippert

    Full Text Available From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH in comparison to those of healthy controls (HC. Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG and Multiple Sleep Latency Test (MSLT. Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

  1. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

    Science.gov (United States)

    Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

    2014-01-01

    From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

  2. 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.

  3. Nuclei, hadrons, and elementary particles

    International Nuclear Information System (INIS)

    Bopp, F.W.

    1989-01-01

    This book is a short introduction to the physics of the nuclei, hadrons, and elementary particles for students of physics. Important facts and model imaginations on the structure, the decay, and the scattering of nuclei, the 'zoology' of the hadrons and basic facts of hadronic scattering processes, a short introduction to quantum electrodynamics and quantum chromodynamics and the most important processes of lepton and parton physics, as well as the current-current approach of weak interactions and the Glashow-Weinberg-Salam theory are presented. (orig.) With 153 figs., 10 tabs [de

  4. Are there superheavy atomic nuclei

    International Nuclear Information System (INIS)

    Herrmann, G.

    1982-04-01

    The author presents a populary introduction to the formation of nuclei with special regards to superheavy nuclei. After a general description of the methods of physics the atomic hypothesis is considered. Thereafter the structure of the nucleus is discussed, and the different isotopes are considered. Then radioactivity is described as an element transmutation. Thereafter the thermonuclear reactions in the sun are considered. Then the synthesis of elements using heavy ion reactions is described. In this connection the transuranium elements and the superheavy elements are considered. (orig./HSI) [de

  5. NEW EQUATIONS OF STATE BASED ON THE LIQUID DROP MODEL OF HEAVY NUCLEI AND QUANTUM APPROACH TO LIGHT NUCLEI FOR CORE-COLLAPSE SUPERNOVA SIMULATIONS

    International Nuclear Information System (INIS)

    Furusawa, Shun; Yamada, Shoichi; Sumiyoshi, Kohsuke; Suzuki, Hideyuki

    2013-01-01

    We construct new equations of state for baryons at subnuclear densities for the use in core-collapse simulations of massive stars. The abundance of various nuclei is obtained together with thermodynamic quantities. A model free energy is constructed, based on the relativistic mean field theory for nucleons and the mass formula for nuclei with the proton number up to ∼1000. The formulation is an extension of the previous model, in which we adopted the liquid drop model to all nuclei under the nuclear statistical equilibrium. We reformulate the new liquid drop model so that the temperature dependences of bulk energies could be taken into account. Furthermore, we extend the region in the nuclear chart, in which shell effects are included, by using theoretical mass data in addition to experimental ones. We also adopt a quantum-theoretical mass evaluation of light nuclei, which incorporates the Pauli- and self-energy shifts that are not included in the ordinary liquid drop model. The pasta phases for heavy nuclei are taken into account in the same way as in the previous model. We find that the abundances of heavy nuclei are modified by the shell effects of nuclei and temperature dependence of bulk energies. These changes may have an important effect on the rates of electron captures and coherent neutrino scatterings on nuclei in supernova cores. The abundances of light nuclei are also modified by the new mass evaluation, which may affect the heating and cooling rates of supernova cores and shocked envelopes

  6. New Equations of State Based on the Liquid Drop Model of Heavy Nuclei and Quantum Approach to Light Nuclei for Core-collapse Supernova Simulations

    Science.gov (United States)

    Furusawa, Shun; Sumiyoshi, Kohsuke; Yamada, Shoichi; Suzuki, Hideyuki

    2013-08-01

    We construct new equations of state for baryons at subnuclear densities for the use in core-collapse simulations of massive stars. The abundance of various nuclei is obtained together with thermodynamic quantities. A model free energy is constructed, based on the relativistic mean field theory for nucleons and the mass formula for nuclei with the proton number up to ~1000. The formulation is an extension of the previous model, in which we adopted the liquid drop model to all nuclei under the nuclear statistical equilibrium. We reformulate the new liquid drop model so that the temperature dependences of bulk energies could be taken into account. Furthermore, we extend the region in the nuclear chart, in which shell effects are included, by using theoretical mass data in addition to experimental ones. We also adopt a quantum-theoretical mass evaluation of light nuclei, which incorporates the Pauli- and self-energy shifts that are not included in the ordinary liquid drop model. The pasta phases for heavy nuclei are taken into account in the same way as in the previous model. We find that the abundances of heavy nuclei are modified by the shell effects of nuclei and temperature dependence of bulk energies. These changes may have an important effect on the rates of electron captures and coherent neutrino scatterings on nuclei in supernova cores. The abundances of light nuclei are also modified by the new mass evaluation, which may affect the heating and cooling rates of supernova cores and shocked envelopes.

  7. NEW EQUATIONS OF STATE BASED ON THE LIQUID DROP MODEL OF HEAVY NUCLEI AND QUANTUM APPROACH TO LIGHT NUCLEI FOR CORE-COLLAPSE SUPERNOVA SIMULATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Furusawa, Shun; Yamada, Shoichi [Advanced Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555 (Japan); Sumiyoshi, Kohsuke [Numazu College of Technology, Ooka 3600, Numazu, Shizuoka 410-8501 (Japan); Suzuki, Hideyuki, E-mail: furusawa@heap.phys.waseda.ac.jp [Faculty of Science and Technology, Tokyo University of Science, Yamazaki 2641, Noda, Chiba 278-8510 (Japan)

    2013-08-01

    We construct new equations of state for baryons at subnuclear densities for the use in core-collapse simulations of massive stars. The abundance of various nuclei is obtained together with thermodynamic quantities. A model free energy is constructed, based on the relativistic mean field theory for nucleons and the mass formula for nuclei with the proton number up to {approx}1000. The formulation is an extension of the previous model, in which we adopted the liquid drop model to all nuclei under the nuclear statistical equilibrium. We reformulate the new liquid drop model so that the temperature dependences of bulk energies could be taken into account. Furthermore, we extend the region in the nuclear chart, in which shell effects are included, by using theoretical mass data in addition to experimental ones. We also adopt a quantum-theoretical mass evaluation of light nuclei, which incorporates the Pauli- and self-energy shifts that are not included in the ordinary liquid drop model. The pasta phases for heavy nuclei are taken into account in the same way as in the previous model. We find that the abundances of heavy nuclei are modified by the shell effects of nuclei and temperature dependence of bulk energies. These changes may have an important effect on the rates of electron captures and coherent neutrino scatterings on nuclei in supernova cores. The abundances of light nuclei are also modified by the new mass evaluation, which may affect the heating and cooling rates of supernova cores and shocked envelopes.

  8. Probing the density tail of radioactive nuclei with antiprotons

    CERN Document Server

    Obertelli, Alexandre; Uesaka, Tomohiro; Corsi, Anna; Pollacco, Emmanuel; Flavigny, Freddy

    2017-01-01

    We propose an experiment to determine the proton and neutron content of the radial density tail in short-lived nuclei. The objectives are to (i) to evidence new proton and neutron halos, (ii) to understand the development of neutron skins in medium-mass nuclei, (iii) to provide a new observable that characterises the density tail of short-lived nuclei.

  9. The Role of Broken Cooper Pairs in Warm Nuclei

    International Nuclear Information System (INIS)

    Guttormsen, M.; Chankova, R.; Larsen, A.C.; Rekstad, J.; Siem, S.; Syed, N.U.H.; Agvaanluvsan, U.; Schiller, A.; Voinov, A.

    2007-01-01

    In order to understand warm nuclei and describe the underlying microscopic structure, entropy is measured for several even-even and odd-mass nuclei. Mid-shell nuclei show significant odd-even entropy differences interpreted as the single-particle entropy introduced by the valence nucleon. A method to extract critical temperatures for the pair breaking process is demonstrated. (author)

  10. 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.

  11. Nucleus fingerprinting for the unique identification of Feulgen-stained nuclei

    Science.gov (United States)

    Friedrich, David; Brozio, Matthias; Bell, André; Biesterfeld, Stefan; Böcking, Alfred; Aach, Til

    2012-03-01

    DNA Image Cytometry is a method for non-invasive cancer diagnosis which measures the DNA content of Feulgen-stained nuclei. DNA content is measured using a microscope system equipped with a digital camera as a densitometer and estimating the DNA content from the absorption of light when passing through the nuclei. However, a DNA Image Cytometry measurement is only valid if each nucleus is only measured once. To assist the user in preventing multiple measurements of the same nucleus, we have developed a unique digital identifier for the characterization of Feulgen-stained nuclei, the so called Nucleus Fingerprint. Only nuclei with a new fingerprint can be added to the measurement. This fingerprint is based on basic nucleus features, the contour of the nucleus and the spatial relationship to nuclei in the vicinity. Based on this characterization, a classifier for testing two nuclei for identity is presented. In a pairwise comparison of ~40000 pairs of mutually different nuclei, 99.5% were classified as different. In another 450 tests, the fingerprints of the same nucleus recorded a second time were in all cases judged identical. We therefore conclude that our Nucleus Fingerprint approach robustly prevents the repeated measurement of nuclei in DNA Image Cytometry.

  12. Hyperdeformed nuclei and the residual pseudo-SU(3) symmetry

    International Nuclear Information System (INIS)

    Dudek, J.; Werner, T.

    1988-01-01

    The author discusses superdeformed and hypothetical hyperdeformed nuclei. Quadrupole deformations characteristic of these types of nuclei are defined. Symmetry features are also discussed. The characteristic cycle dependence of shell structures as functions of the deformation gives rise to chains of the deformed shell closures. Such a chain structure applies to moderately-, super- and hyper-deformed nuclei as well. The resulting total energy calculations give a systematic variation of super- and hyperdeformations with, e.g., increasing N at fixed Z, thus predicting the way nuclei deviate from the simple a:b = 2:1 and a:b = 3:1 symmetries

  13. High energy particle interactions with nuclei

    International Nuclear Information System (INIS)

    Czyz, W.

    1978-01-01

    The recent interest in multiparticle production processes on nuclei was triggered by re-discovering their 'enigmatic simplicity' which has been known to cosmic ray physicists for over 20 years: the mean multiplicity and angular distributions of relativistic secondaries produced on nuclei do not differ markedly from what emerges from p-p collisions. The author considers how such reactions may provide a way of obtaining details of hadron structure. (Auth.)

  14. Proton radioactivity from proton-rich nuclei

    International Nuclear Information System (INIS)

    Guzman, F.; Goncalves, M.; Tavares, O.A.P.; Duarte, S.B.; Garcia, F.; Rodriguez, O.

    1999-03-01

    Half-lives for proton emission from proton-rich nuclei have been calculated by using the effective liquid drop model of heavy-particle decay of nuclei. It is shown that this model is able to offer results or spontaneous proton-emission half-life-values in excellent agreement with the existing experimental data. Predictions of half-life-values for other possible proton-emission cases are present for null orbital angular momentum. (author)

  15. Field-substance interaction and collective oscillation of nuclei

    International Nuclear Information System (INIS)

    Shermatov, E.N.; Choriev, M.

    2004-01-01

    Full text: In this work a mechanism of formation of collective excitation in a set of particles, including atomic nuclei, is proposed. According to [1] the energy density of cosmic vacuum significantly exceeds the energy density of an atomic nucleus. In [2] the process of formation of the physical vacuum in surrounding cosmic space was considered. We considered the behavior of a system of particles, which possesses transversal and longitudinal oscillation with frequency ω 0 in the physical or cosmic vacuum. The oscillating influence on the physical vacuum and surrounding particles on a single particle leads to inducing the spins with various directions and magnitudes. This process leads to the formation of oscillating response wave function (RWF) of particles. As a result of a phase coherency among RWF of particles an oscillating self-coordinated field in a set of particles is formed. As a result of realization of the phase coherency among harmonics of RWF of particles there occurs a deformation of the character of distribution of the energy structure of the self-coordinated field, which, finally, transforms into a resonant line. At this occurs a collapse of the RWF of particles there. In terms of these ideas we explained the observed regularities in the self-coordinated field in a set of particles, including the atomic nuclei. It was shown that the giant resonance in spectra of atomic nuclei is a result of manifestation of the self-coordinated field of atomic nuclei. As a result of realization of the phase coherency among harmonics of RWF of atomic nuclei there occurs a collapse of the RWF of particles, and the energy structure of the self-coordinated field of nuclei gains a resonant form, and it is manifested as the giant resonance. In deformable nuclei the RWF of particles possesses two oscillation modes, and that is why in the energy spectrum of the self-coordinated field of nuclei they are manifested as two maximum

  16. Control of Circadian Behavior by Transplanted Suprachiasmatic Nuclei and by the Tau Gene

    National Research Council Canada - National Science Library

    Menaker, Micahel

    1997-01-01

    The mammalian retina was found to contain an independent circadian oscillator which regulates the synthesis of melatonin and has effects, through a presently unknown pathway, on the circadian rhythm...

  17. Training nuclei detection algorithms with simple annotations

    Directory of Open Access Journals (Sweden)

    Henning Kost

    2017-01-01

    Full Text Available Background: Generating good training datasets is essential for machine learning-based nuclei detection methods. However, creating exhaustive nuclei contour annotations, to derive optimal training data from, is often infeasible. Methods: We compared different approaches for training nuclei detection methods solely based on nucleus center markers. Such markers contain less accurate information, especially with regard to nuclear boundaries, but can be produced much easier and in greater quantities. The approaches use different automated sample extraction methods to derive image positions and class labels from nucleus center markers. In addition, the approaches use different automated sample selection methods to improve the detection quality of the classification algorithm and reduce the run time of the training process. We evaluated the approaches based on a previously published generic nuclei detection algorithm and a set of Ki-67-stained breast cancer images. Results: A Voronoi tessellation-based sample extraction method produced the best performing training sets. However, subsampling of the extracted training samples was crucial. Even simple class balancing improved the detection quality considerably. The incorporation of active learning led to a further increase in detection quality. Conclusions: With appropriate sample extraction and selection methods, nuclei detection algorithms trained on the basis of simple center marker annotations can produce comparable quality to algorithms trained on conventionally created training sets.

  18. Exotic Nuclei and Yukawa's Forces

    International Nuclear Information System (INIS)

    Otsuka, Takaharu; Suzuki, Toshio; Utsuno, Yutaka

    2008-01-01

    In this plenary talk, we will overview the evolution of the shell structure in stable and exotic nuclei as a new paradigm of nuclear structure physics. This shell evolution is primarily due to the tensor force. The robust mechanism and some examples will be presented. Such examples include the disappearance of existing magic numbers and the appearance of new ones. The nuclear magic numbers have been believed, since Mayer and Jensen, to be constants as 2, 8, 20, 28, 50, ... This turned out to be changed, once we entered the regime of exotic nuclei. This shell evolution develops at many places on the nuclear chart in various forms. For example, superheavy magic numbers may be altered. Thus, we are led to a new paradigm as to how and where the nuclear shell evolves, and what consequences arise. The evolution of the shell affects weak process transitions, and plays a crucial role in deformation. The π and ρ mesons generate tensor forces, and are the fundamental elements of such intriguing phenomena. Thus, physics of exotic nuclei arises as a manifestation of Yukawa's forces

  19. Accretion disks in active galactic nuclei

    International Nuclear Information System (INIS)

    Shields, G.A.

    1989-01-01

    Active galactic nuclei (AGN) have taunted astrophysicists for a quarter century. How do these objects produce huge luminosities---in some cases, far outshining our galaxy---from a region perhaps no larger than the solar system? Accretion onto supermassive black holes has been widely considered the best buy in theories of AGN. Much work has gone into accretion disk theory, searches for black holes in galactic nuclei, and observational tests. These efforts have not proved the disk model, but there is progress. Evidence for black holes in the nuclei of nearby galaxies is provided by observations of stellar velocities, and radiation from the disk's hot surface may be observed in the ultraviolet (UV) and neighboring spectral bands. In the review, the author describe some of the recent work on accretion disks in AGN, with an emphasis on points of contact between theory and observation

  20. Effective forces in near-magic nuclei

    International Nuclear Information System (INIS)

    Artamonov, S.A.; Isakov, V.I.; Ogloblin, S.G.

    1984-01-01

    Characteristics of 146 Gd, 206 Hg, sup(206, 208)Tl, sup(206, 208, 210)Pb, sup(208, 210)Bi, 210 Po nuclei are calculated on the base of representations on universal effective interaction of finite range. Discrepancy with the experiment for 210 Bi nucleus disappears if the method of ''penalty'' functions is used for search of optimum parameters. New parameters of effective interaction common for all the considered two-quasi-particle nuclei are determined. Parameters of tensor forces undergo most noticeable danges as compared with other calculations. Descriptions of lowest levels not only 210 Bi but also 206 Tl as well as collective states of 208 Pb and a new magic nucleus 146 Gd are improved. The calculated probabilities of electric transitions between ground and one-phonon states in core nuclei also agree with the experiment