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Sample records for suprachiasmatic nucleus scn

  1. 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

  2. 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

  3. 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,

  4. Functional network inference of the suprachiasmatic nucleus

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    Abel, John H.; Meeker, Kirsten; Granados-Fuentes, Daniel; St. John, Peter C.; Wang, Thomas J.; Bales, Benjamin B.; Doyle, Francis J.; Herzog, Erik D.; Petzold, Linda R.

    2016-04-04

    In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data from individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure.

  5. 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

  6. Cardiovascular control by the suprachiasmatic nucleus: neural and neuroendocrine mechanisms in human and rat

    NARCIS (Netherlands)

    Scheer, Frank A.; Kalsbeek, Andries; Buijs, Ruud M.

    2003-01-01

    The risk for cardiovascular incidents is highest in the early morning, which seems partially due to endogenous factors. Endogenous circadian rhythms in mammalian physiology and behavior are regulated by the suprachiasmatic nucleus (SCN). Recently, anatomical evidence has been provided that SCN

  7. 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

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

    Science.gov (United States)

    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.

  9. The suprachiasmatic nucleus: age-related decline in biological rhythms.

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    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system.

  10. 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

  11. 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

  12. Grafted fetal suprachiasmatic nucleus cells survive much better in tissue pieces than in suspension

    NARCIS (Netherlands)

    Boer, G. J.; Griffioen, H. A.; Saeed, P.

    1992-01-01

    A comparison was made between the survival of fetal suprachiasmatic nucleus (SCN) grafted either in tissue pieces or as tissue suspension. Donor tissue was obtained from day 15, 16 or 17 Wistar fetuses, and stereotaxically placed in the dorsal thalamus of the brain of vasopressin(VP)-deficient

  13. 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

  14. Combined Pharmacological and Genetic Manipulations Unlock Unprecedented Temporal Elasticity and Reveal Phase-Specific Modulation of the Molecular Circadian Clock of the Mouse Suprachiasmatic Nucleus

    OpenAIRE

    Patton, Andrew P.; Chesham, Johanna E.; Hastings, Michael H.

    2016-01-01

    The suprachiasmatic nucleus (SCN) is the master circadian oscillator encoding time-of-day information. SCN timekeeping is sustained by a cell-autonomous transcriptional–translational feedback loop, whereby expression of the Period and Cryptochrome genes is negatively regulated by their protein products. This loop in turn drives circadian oscillations in gene expression that direct SCN electrical activity and thence behavior. The robustness of SCN timekeeping is further enhanced by interneuron...

  15. The Suprachiasmatic Nucleus of the Dromedary Camel (Camelus dromedarius: Cytoarchitecture and Neurochemical Anatomy

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    Khalid El Allali

    2017-11-01

    Full Text Available In mammals, biological rhythms are driven by a master circadian clock located in the suprachiasmatic nucleus (SCN of the hypothalamus. Recently, we have demonstrated that in the camel, the daily cycle of environmental temperature is able to entrain the master clock. This raises several questions about the structure and function of the SCN in this species. The current work is the first neuroanatomical investigation of the camel SCN. We carried out a cartography and cytoarchitectural study of the nucleus and then studied its cell types and chemical neuroanatomy. Relevant neuropeptides involved in the circadian system were investigated, including arginine-vasopressin (AVP, vasoactive intestinal polypeptide (VIP, met-enkephalin (Met-Enk, neuropeptide Y (NPY, as well as oxytocin (OT. The neurotransmitter serotonin (5-HT and the enzymes tyrosine hydroxylase (TH and aromatic L-amino acid decarboxylase (AADC were also studied. The camel SCN is a large and elongated nucleus, extending rostrocaudally for 9.55 ± 0.10 mm. Based on histological and immunofluorescence findings, we subdivided the camel SCN into rostral/preoptic (rSCN, middle/main body (mSCN and caudal/retrochiasmatic (cSCN divisions. Among mammals, the rSCN is unusual and appears as an assembly of neurons that protrudes from the main mass of the hypothalamus. The mSCN exhibits the triangular shape described in rodents, while the cSCN is located in the retrochiasmatic area. As expected, VIP-immunoreactive (ir neurons were observed in the ventral part of mSCN. AVP-ir neurons were located in the rSCN and mSCN. Results also showed the presence of OT-ir and TH-ir neurons which seem to be a peculiarity of the camel SCN. OT-ir neurons were either scattered or gathered in one isolated cluster, while TH-ir neurons constituted two defined populations, dorsal parvicellular and ventral magnocellular neurons, respectively. TH colocalized with VIP in some rSCN neurons. Moreover, a high density of Met

  16. Distribution of AVP and Ca2+-dependent PKC-isozymes in the suprachiasmatic nucleus of the mouse and rabbit

    NARCIS (Netherlands)

    Zee, Eddy A. van der; Bult, Abel

    1995-01-01

    The suprachiasmatic nucleus (SCN) is the circadian pacemaker in mammals and contains a network of arginine-vasopressin-immunoreactive (AVP-ir) neurons. AVP-recipient cells contain the V1a class of receptors linked to phosphoinositol turnover and protein kinase C (PKC). The present study describes

  17. 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

  18. 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.

  19. Intracellular calcium spikes in rat suprachiasmatic nucleus neurons induced by BAPTA-based calcium dyes.

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    Jin Hee Hong

    Full Text Available BACKGROUND: Circadian rhythms in spontaneous action potential (AP firing frequencies and in cytosolic free calcium concentrations have been reported for mammalian circadian pacemaker neurons located within the hypothalamic suprachiasmatic nucleus (SCN. Also reported is the existence of "Ca(2+ spikes" (i.e., [Ca(2+](c transients having a bandwidth of 10 approximately 100 seconds in SCN neurons, but it is unclear if these SCN Ca(2+ spikes are related to the slow circadian rhythms. METHODOLOGY/PRINCIPAL FINDINGS: We addressed this issue based on a Ca(2+ indicator dye (fluo-4 and a protein Ca(2+ sensor (yellow cameleon. Using fluo-4 AM dye, we found spontaneous Ca(2+ spikes in 18% of rat SCN cells in acute brain slices, but the Ca(2+ spiking frequencies showed no day/night variation. We repeated the same experiments with rat (and mouse SCN slice cultures that expressed yellow cameleon genes for a number of different circadian phases and, surprisingly, spontaneous Ca(2+ spike was barely observed (<3%. When fluo-4 AM or BAPTA-AM was loaded in addition to the cameleon-expressing SCN cultures, however, the number of cells exhibiting Ca(2+ spikes was increased to 13 approximately 14%. CONCLUSIONS/SIGNIFICANCE: Despite our extensive set of experiments, no evidence of a circadian rhythm was found in the spontaneous Ca(2+ spiking activity of SCN. Furthermore, our study strongly suggests that the spontaneous Ca(2+ spiking activity is caused by the Ca(2+ chelating effect of the BAPTA-based fluo-4 dye. Therefore, this induced activity seems irrelevant to the intrinsic circadian rhythm of [Ca(2+](c in SCN neurons. The problems with BAPTA based dyes are widely known and our study provides a clear case for concern, in particular, for SCN Ca(2+ spikes. On the other hand, our study neither invalidates the use of these dyes as a whole, nor undermines the potential role of SCN Ca(2+ spikes in the function of SCN.

  20. Calcium Circadian Rhythmicity in the Suprachiasmatic Nucleus: Cell Autonomy and Network Modulation.

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    Noguchi, Takako; Leise, Tanya L; Kingsbury, Nathaniel J; Diemer, Tanja; Wang, Lexie L; Henson, Michael A; Welsh, David K

    2017-01-01

    Circadian rhythms of mammalian physiology and behavior are coordinated by the suprachiasmatic nucleus (SCN) in the hypothalamus. Within SCN neurons, various aspects of cell physiology exhibit circadian oscillations, including circadian clock gene expression, levels of intracellular Ca 2+ ([Ca 2+ ] i ), and neuronal firing rate. [Ca 2+ ] i oscillates in SCN neurons even in the absence of neuronal firing. To determine the causal relationship between circadian clock gene expression and [Ca 2+ ] i rhythms in the SCN, as well as the SCN neuronal network dependence of [Ca 2+ ] i rhythms, we introduced GCaMP3, a genetically encoded fluorescent Ca 2+ indicator, into SCN neurons from PER2::LUC knock-in reporter mice. Then, PER2 and [Ca 2+ ] i were imaged in SCN dispersed and organotypic slice cultures. In dispersed cells, PER2 and [Ca 2+ ] i both exhibited cell autonomous circadian rhythms, but [Ca 2+ ] i rhythms were typically weaker than PER2 rhythms. This result matches the predictions of a detailed mathematical model in which clock gene rhythms drive [Ca 2+ ] i rhythms. As predicted by the model, PER2 and [Ca 2+ ] i rhythms were both stronger in SCN slices than in dispersed cells and were weakened by blocking neuronal firing in slices but not in dispersed cells. The phase relationship between [Ca 2+ ] i and PER2 rhythms was more variable in cells within slices than in dispersed cells. Both PER2 and [Ca 2+ ] i rhythms were abolished in SCN cells deficient in the essential clock gene Bmal1 . These results suggest that the circadian rhythm of [Ca 2+ ] i in SCN neurons is cell autonomous and dependent on clock gene rhythms, but reinforced and modulated by a synchronized SCN neuronal network.

  1. Topological specificity and hierarchical network of the circadian calcium rhythm in the suprachiasmatic nucleus.

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    Enoki, Ryosuke; Kuroda, Shigeru; Ono, Daisuke; Hasan, Mazahir T; Ueda, Tetsuo; Honma, Sato; Honma, Ken-ichi

    2012-12-26

    The circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) is a hierarchical multioscillator system in which neuronal networks play crucial roles in expressing coherent rhythms in physiology and behavior. However, our understanding of the neuronal network is still incomplete. Intracellular calcium mediates the input signals, such as phase-resetting stimuli, to the core molecular loop involving clock genes for circadian rhythm generation and the output signals from the loop to various cellular functions, including changes in neurotransmitter release. Using a unique large-scale calcium imaging method with genetically encoded calcium sensors, we visualized intracellular calcium from the entire surface of SCN slice in culture including the regions where autonomous clock gene expression was undetectable. We found circadian calcium rhythms at a single-cell level in the SCN, which were topologically specific with a larger amplitude and more delayed phase in the ventral region than the dorsal. The robustness of the rhythm was reduced but persisted even after blocking the neuronal firing with tetrodotoxin (TTX). Notably, TTX dissociated the circadian calcium rhythms between the dorsal and ventral SCN. In contrast, a blocker of gap junctions, carbenoxolone, had only a minor effect on the calcium rhythms at both the single-cell and network levels. These results reveal the topological specificity of the circadian calcium rhythm in the SCN and the presence of coupled regional pacemakers in the dorsal and ventral regions. Neuronal firings are not necessary for the persistence of the calcium rhythms but indispensable for the hierarchical organization of rhythmicity in the SCN.

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

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    Jack Kent

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

  3. 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

    of the mammalian SCN, but its role in circadian timing is not known. In the present study, CCK was demonstrated in a distinct population of neurons located in the shell region of the SCN and in a few cells in the core region. The CCK neurons did not express vasopressin or vasoactive intestinal peptide. However......The suprachiasmatic nucleus (SCN) is the principal pacemaker driving circadian rhythms of physiology and behaviour. Neurons within the SCN express both classical and neuropeptide transmitters which regulate clock functions. Cholecyctokinin (CCK) is a potent neurotransmitter expressed in neurons......, 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...

  4. Distribution of N-methyl D-aspartate (NMDA) receptor mRNAs in the rat suprachiasmatic nucleus

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    Mikkelsen, J.D.; Larsen, Philip J.; Ebling, Francis J.P.

    1993-01-01

    Anatomi, neurobiologi, glutamate receptor, circadian rhythms, suprachiasmatic nucleus, in situ hybridization, rat......Anatomi, neurobiologi, glutamate receptor, circadian rhythms, suprachiasmatic nucleus, in situ hybridization, rat...

  5. Circadian waves of cytosolic calcium concentration and long-range network connections in rat suprachiasmatic nucleus.

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    Hong, Jin Hee; Jeong, Byeongha; Min, Cheol Hong; Lee, Kyoung J

    2012-05-01

    The suprachiasmatic nucleus (SCN) is the master clock in mammals governing the daily physiological and behavioral rhythms. It is composed of thousands of clock cells with their own intrinsic periods varying over a wide range (20-28 h). Despite this heterogeneity, an intact SCN maintains a coherent 24 h periodic rhythm through some cell-to-cell coupling mechanisms. This study examined how the clock cells are connected to each other and how their phases are organized in space by monitoring the cytosolic free calcium ion concentration ([Ca(2+)](c)) of clock cells using the calcium-binding fluorescent protein, cameleon. Extensive analysis of 18 different organotypic slice cultures of the SCN showed that the SCN calcium dynamics is coordinated by phase-synchronizing networks of long-range neurites as well as by diffusively propagating phase waves. The networks appear quite extensive and far-reaching, and the clock cells connected by them exhibit heterogeneous responses in their amplitudes and periods of oscillation to tetrodotoxin treatments. Taken together, our study suggests that the network of long-range cellular connectivity has an important role for the SCN in achieving its phase and period coherence. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  6. The Role of the Suprachiasmatic Nucleus in Cardiac Autonomic Control during Sleep.

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    S D Joustra

    Full Text Available The suprachiasmatic nucleus (SCN may play an important role in central autonomic control, since its projections connect to (parasympathetic relay stations in the brainstem and spinal cord. The cardiac autonomic modifications during nighttime may therefore not only result from direct effects of the sleep-related changes in the central autonomic network, but also from endogenous circadian factors as directed by the SCN. To explore the influence of the SCN on autonomic fluctuations during nighttime, we studied heart rate and its variability (HRV in a clinical model of SCN damage.Fifteen patients in follow-up after surgical treatment for nonfunctioning pituitary macroadenoma (NFMA compressing the optic chiasm (8 females, 26-65 years old and fifteen age-matched healthy controls (5 females, 30-63 years underwent overnight ambulatory polysomnography. Eleven patients had hypopituitarism and received adequate replacement therapy. HRV was calculated for each 30-second epoch and corrected for sleep stage, arousals, and gender using mixed effect regression models.Compared to controls, patients spent more time awake after sleep onset and in NREM1-sleep, and less in REM-sleep. Heart rate, low (LF and high frequency (HF power components and the LF/HF ratio across sleep stages were not significantly different between groups.These findings suggest that the SCN does not play a dominant role in cardiac autonomic control during sleep.

  7. Neonatal exposure to monosodium glutamate induces morphological alterations in suprachiasmatic nucleus of adult rat.

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    Rojas-Castañeda, Julio César; Vigueras-Villaseñor, Rosa María; Chávez-Saldaña, Margarita; Rojas, Patricia; Gutiérrez-Pérez, Oscar; Rojas, Carolina; Arteaga-Silva, Marcela

    2016-02-01

    Neonatal exposure to monosodium glutamate (MSG) induces circadian disorders in several physiological and behavioural processes regulated by the suprachiasmatic nucleus (SCN). The objective of this study was to evaluate the effects of neonatal exposure to MSG on locomotor activity, and on morphology, cellular density and expression of proteins, as evaluated by optical density (OD), of vasopressin (VP)-, vasoactive intestinal polypeptide (VIP)- and glial fibrillary acidic protein (GFAP)-immunoreactive cells in the SCN. Male Wistar rats were used: the MSG group was subcutaneously treated from 3 to 10 days of age with 3.5 mg/g/day. Locomotor activity was evaluated at 90 days of age using 'open-field' test, and the brains were processed for immunohistochemical studies. MSG exposure induced a significant decrease in locomotor activity. VP- and VIP-immunoreactive neuronal densities showed a significant decrease, while the somatic OD showed an increase. Major axes and somatic area were significantly increased in VIP neurons. The cellular and optical densities of GFAP-immunoreactive sections of SCN were significantly increased. These results demonstrated that newborn exposure to MSG induced morphological alterations in SCN cells, an alteration that could be the basis for behavioural disorders observed in the animals. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  8. Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity

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    Morin, Lawrence P.; Blanchard, Jane H.; Provencio, Ignacio

    2003-01-01

    The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain. Copyright 2003 Wiley-Liss, Inc.

  9. 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.

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

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    Chiara Tesoriero

    2018-02-01

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

  11. 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...

  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

    The suprachiasmatic nucleus (SCN) is the principal pacemaker driving circadian rhythms of physiology and behaviour. Neurons within the SCN express both classical and neuropeptide transmitters which regulate clock functions. Cholecyctokinin (CCK) is a potent neurotransmitter expressed in neurons......, 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......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...

  13. 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.

  14. Retinohypothalamic Tract Synapses in the Rat Suprachiasmatic Nucleus Demonstrate Short-Term Synaptic Plasticity

    Science.gov (United States)

    Moldavan, Mykhaylo G.

    2010-01-01

    The master circadian pacemaker located in the suprachiasmatic nucleus (SCN) is entrained by light intensity–dependent signals transmitted via the retinohypothalamic tract (RHT). Short-term plasticity at glutamatergic RHT–SCN synapses was studied using stimulus frequencies that simulated the firing of light sensitive retinal ganglion cells. The evoked excitatory postsynaptic current (eEPSC) was recorded from SCN neurons located in hypothalamic brain slices. The eEPSC amplitude was stable during 0.08 Hz stimulation and exhibited frequency-dependent short-term synaptic depression (SD) during 0.5 to 100 Hz stimulus trains in 95 of 99 (96%) recorded neurons. During SD the steady-state eEPSC amplitude decreased, whereas the cumulative charge transfer increased in a frequency-dependent manner and saturated at 20 Hz. SD was similar during subjective day and night and decreased with increasing temperature. Paired-pulse stimulation (PPS) and voltage-dependent Ca2+ channel (VDCC) blockers were used to characterize a presynaptic release mechanism. Facilitation was present in 30% and depression in 70% of studied neurons during PPS. Synaptic transmission was reduced by blocking both N- and P/Q-type presynaptic VDCCs, but only the N-type channel blocker significantly relieved SD. Aniracetam inhibited AMPA receptor desensitization but did not alter SD. Thus we concluded that SD is the principal form of short-term plasticity at RHT synapses, which presynaptically and frequency-dependently attenuates light-induced glutamatergic RHT synaptic transmission protecting SCN neurons against excessive excitation. PMID:20220078

  15. Bmal1 is an essential regulator for circadian cytosolic Ca²⁺ rhythms in suprachiasmatic nucleus neurons.

    Science.gov (United States)

    Ikeda, Masayuki; Ikeda, Masaaki

    2014-09-03

    The hypothalamic suprachiasmatic nucleus (SCN) plays a pivotal role in the mammalian circadian clock system. Bmal1 is a clock gene that drives transcriptional-translational feedback loops (TTFLs) for itself and other genes, and is expressed in nearly all SCN neurons. Despite strong evidence that Bmal1-null mutant mice display arrhythmic behavior under constant darkness, the function of Bmal1 in neuronal activity is unknown. Recently, periodic changes in the levels of intracellular signaling messengers, such as cytosolic Ca(2+) and cAMP, were suggested to regulate TTFLs. However, the opposite aspect of how clock gene TTFLs regulate cytosolic signaling remains unclear. To investigate intracellular Ca(2+) dynamics under Bmal1 perturbations, we cotransfected some SCN neurons with yellow cameleon together with wild-type or dominant-negative Bmal1 using a gene-gun applied for mouse organotypic cultures. Immunofluorescence staining for a tag protein linked to BMAL1 showed nuclear expression of wild-type BMAL1 and its degradation within 1 week after transfection in SCN neurons. However, dominant-negative BMAL1 did not translocate into the nucleus and the cytosolic signals persisted beyond 1 week. Consistently, circadian Ca(2+) rhythms in SCN neurons were inhibited for longer periods by dominant-negative Bmal1 overexpression. Furthermore, SCN neurons transfected with a Bmal1 shRNA lengthened, whereas those overexpressing wild-type Bmal1 shortened, the periods of Ca(2+) rhythms, with a significant reduction in their amplitude. BMAL1 expression was intact in the majority of neighboring neurons in organotypic cultures. Therefore, we conclude that proper intrinsic Bmal1 expression, but not passive signaling via cell-to-cell interactions, is the determinant of circadian Ca(2+) rhythms in SCN neurons. Copyright © 2014 the authors 0270-6474/14/3412029-10$15.00/0.

  16. Effect of network architecture on synchronization and entrainment properties of the circadian oscillations in the suprachiasmatic nucleus.

    Science.gov (United States)

    Hafner, Marc; Koeppl, Heinz; Gonze, Didier

    2012-01-01

    In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus constitutes the central circadian pacemaker. The SCN receives light signals from the retina and controls peripheral circadian clocks (located in the cortex, the pineal gland, the liver, the kidney, the heart, etc.). This hierarchical organization of the circadian system ensures the proper timing of physiological processes. In each SCN neuron, interconnected transcriptional and translational feedback loops enable the circadian expression of the clock genes. Although all the neurons have the same genotype, the oscillations of individual cells are highly heterogeneous in dispersed cell culture: many cells present damped oscillations and the period of the oscillations varies from cell to cell. In addition, the neurotransmitters that ensure the intercellular coupling, and thereby the synchronization of the cellular rhythms, differ between the two main regions of the SCN. In this work, a mathematical model that accounts for this heterogeneous organization of the SCN is presented and used to study the implication of the SCN network topology on synchronization and entrainment properties. The results show that oscillations with larger amplitude can be obtained with scale-free networks, in contrast to random and local connections. Networks with the small-world property such as the scale-free networks used in this work can adapt faster to a delay or advance in the light/dark cycle (jet lag). Interestingly a certain level of cellular heterogeneity is not detrimental to synchronization performances, but on the contrary helps resynchronization after jet lag. When coupling two networks with different topologies that mimic the two regions of the SCN, efficient filtering of pulse-like perturbations in the entrainment pattern is observed. These results suggest that the complex and heterogeneous architecture of the SCN decreases the sensitivity of the network to short entrainment perturbations while, at the same time

  17. Expression profiles and functional annotation analysis of mRNAs in suprachiasmatic nucleus of Clock mutant mice.

    Science.gov (United States)

    Wang, Yanli; Lv, Ke; Zhao, Mei; Liang, Fengji; Chen, Hailong; Ji, Guohua; Wang, Tingmei; Zhang, Yongliang; Cao, Hongqing; Li, Yinghui; Qu, Lina

    2018-03-20

    The core circadian clock gene, Clock, is a positive component of the transcription/translation feedback loop in the master pacemaker suprachiasmatic nucleus (SCN) in mammals. The robust daytime peak of some clock genes in the wild-type SCN is absent in Clock mutant mice. However, very little is known about the impact of Clock mutation on the expression of other functional genes in SCN. Here, we performed cDNA microarray and found 799 differentially expressed genes (DEGs) at zeitgeber time 2 (ZT2) and 1289 DEGs at ZT14 in SCN of Clock △19/△19 mutant mice. KEGG pathway analysis showed that the changed mRNAs were highly associated with hedgehog signaling pathway, retinol metabolism, allograft rejection, drug metabolism, hematopoietic cell lineage and neuroactive ligand-receptor interaction. The top 14 and 71 hub genes were identified from the protein-protein interaction (PPI) network at ZT2 and ZT14, respectively. The sub-networks revealed hub genes were involved in olfactory transduction and neuroactive ligand-receptor interaction pathways. These results demonstrate the Clock △19/△19 mutation alters the expression of various genes involved in a wide spectrum of biological function in mouse SCN, which are helpful for better understanding the function of Clock and potential regulatory mechanisms. Copyright © 2017. Published by Elsevier B.V.

  18. The Circadian Clock Gene Period1 Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus.

    Science.gov (United States)

    Kudo, Takashi; Block, Gene D; Colwell, Christopher S

    2015-01-01

    The neural activity patterns of suprachiasmatic nucleus (SCN) neurons are dynamically regulated throughout the circadian cycle with highest levels of spontaneous action potentials during the day. These rhythms in electrical activity are critical for the function of the circadian timing system and yet the mechanisms by which the molecular clockwork drives changes in the membrane are not well understood. In this study, we sought to examine how the clock gene Period1 (Per1) regulates the electrical activity in the mouse SCN by transiently and selectively decreasing levels of PER1 through use of an antisense oligodeoxynucleotide. We found that this treatment effectively reduced SCN neural activity. Direct current injection to restore the normal membrane potential partially, but not completely, returned firing rate to normal levels. The antisense treatment also reduced baseline [Ca(2+)]i levels as measured by Fura2 imaging technique. Whole cell patch clamp recording techniques were used to examine which specific potassium currents were altered by the treatment. These recordings revealed that the large conductance [Ca(2+)]i-activated potassium currents were reduced in antisense-treated neurons and that blocking this current mimicked the effects of the anti-sense on SCN firing rate. These results indicate that the circadian clock gene Per1 alters firing rate in SCN neurons and raise the possibility that the large conductance [Ca(2+)]i-activated channel is one of the targets. © The Author(s) 2015.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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)

  1. Identification of PAC1 receptor isoform mRNAs by real-time PCR in rat suprachiasmatic nucleus.

    Science.gov (United States)

    Ajpru, Supaporn; McArthur, Angela J; Piggins, Hugh D; Sugden, David

    2002-09-30

    The pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in the photic resetting of the rodent circadian clock in the suprachiasmatic nucleus (SCN). PACAP can exert its effects via VPAC1, VPAC2 and PAC1 G-protein coupled receptors. PAC1 and VPAC2, but not VPAC1, mRNA is expressed in rat SCN. A variety of PAC1 receptor splice variants have been described showing differences in ligand binding affinity and selectivity, G-protein coupling and ability to activate signal transduction pathways. The present experiments used PCR with isoform specific primers to determine which PAC1 variants are expressed in rat SCN. The PAC1(null) isoform and a variant containing a single 28-amino acid insert in the third intracellular (IC3) loop (hop1/2) were detected. No other IC3 variants (hip, hip-hop), N-terminal variants (PAC1(short), PAC1(very short) and PAC1(3a)) or the variant differing in transmembrane II and IV (PAC1TM4) were detected in SCN obtained at any time of day. A quantitative real-time PCR assay was established which measured combined expression of the PAC1(null/hop) variants in rat SCN during a 12:12-h light:dark (L:D) cycle. There was no significant variation of PAC1 mRNA expression (PAC1(null)+PAC1(hop)) with time of day. Nor was there a significant difference in the proportion of these two variants with time of day. These results indicate that the phase-dependency of the actions of PACAP on SCN firing and circadian behaviour are not mediated by changes in the level of expression of PAC1 receptor mRNA, nor by phase-dependent expression of PAC1 receptor variants with altered ligand binding, G-protein coupling or signalling characteristics. Copyright 2002 Elsevier Science B.V.

  2. Mitochondrial calcium signaling mediates rhythmic extracellular ATP accumulation in suprachiasmatic nucleus astrocytes.

    Science.gov (United States)

    Burkeen, Jeff F; Womac, Alisa D; Earnest, David J; Zoran, Mark J

    2011-06-08

    The master circadian pacemaker located within the suprachiasmatic nuclei (SCN) controls neural and neuroendocrine rhythms in the mammalian brain. Astrocytes are abundant in the SCN, and this cell type displays circadian rhythms in clock gene expression and extracellular accumulation of ATP. Still, the intracellular signaling pathways that link the SCN clockworks to circadian rhythms in extracellular ATP accumulation remain unclear. Because ATP release from astrocytes is a calcium-dependent process, we investigated the relationship between intracellular Ca(2+) and ATP accumulation and have demonstrated that intracellular Ca(2+) levels fluctuate in an antiphase relationship with rhythmic ATP accumulation in rat SCN2.2 cell cultures. Furthermore, mitochondrial Ca(2+) levels were rhythmic and maximal in precise antiphase with the peak in cytosolic Ca(2+). In contrast, our finding that peak mitochondrial Ca(2+) occurred during maximal extracellular ATP accumulation suggests a link between these cellular rhythms. Inhibition of the mitochondrial Ca(2+) uniporter disrupted the rhythmic production and extracellular accumulation of ATP. ATP, calcium, and the biological clock affect cell division and have been implicated in cell death processes. Nonetheless, rhythmic extracellular ATP accumulation was not disrupted by cell cycle arrest and was not correlated with caspase activity in SCN2.2 cell cultures. Together, these results demonstrate that mitochondrial Ca(2+) mediates SCN2.2 rhythms in extracellular ATP accumulation and suggest a role for circadian gliotransmission in SCN clock function.

  3. Cellular Neurophysiology of the Rat Suprachiasmatic Nucleus: Electrical Properties, Neurotransmission, and Mechanisms of Synchronization

    Science.gov (United States)

    1994-07-29

    activity in rabbit mino -atrial node. Journal of Physiology 308, 331-351. CAHILL. (.M. & MFtNAKER. M. (1987). Kynurenic acid blocks suprachiasmatic nucleus...E. (1987) The Retina: An Approachable Part of* the Brain. Harvard University Press. Cambridge. MA. 35. Drucker-Colin R., Aguilar -Roblero R., Garcia

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

    Science.gov (United States)

    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.

  5. 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.

  6. Facilitation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor transmission in the suprachiasmatic nucleus by aniracetam enhances photic responses of the biological clock in rodents.

    Science.gov (United States)

    Moriya, Takahiro; Ikeda, Masayuki; Teshima, Koji; Hara, Reiko; Kuriyama, Koji; Yoshioka, Tohru; Allen, Charles N; Shibata, Shigenobu

    2003-05-01

    This study was designed to test whether the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-facilitating drug, aniracetam, could potentiate photic responses of the biological clock in the suprachiasmatic nucleus (SCN) of rodents. Using the whole-cell patch technique, we first demonstrated that AMPA currents elicited by either local AMPA application or optic chiasm stimulation were augmented by aniracetam in the neurons of the SCN. The AMPA application-elicited increase of intracellular Ca2+ concentration in SCN slices was also enhanced by aniracetam treatment. The systemic injection of aniracetam dose-dependently (10-100 mg/kg) potentiated the phase delay in behavioral rhythm induced by brief light exposure of low intensity (3 lux) but not high intensity (10 or 60 lux) during early subjective night. Under the blockade of NMDA receptors by (+) MK801, aniracetam failed to potentiate a light (3 lux)-induced phase delay in behavioral rhythm. Aniracetam increased the photic induction of c-Fos protein in the SCN that was elicited by low intensity light exposure (3 lux). These results suggest that AMPA receptor-mediated responses facilitated by aniracetam can explain enhanced photic responses of the biological clock in the SCN of rodents.

  7. 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.

  8. Phase preference for the display of activity is associated with the phase of extra-suprachiasmatic nucleus oscillators within and between species.

    Science.gov (United States)

    Ramanathan, C; Stowie, A; Smale, L; Nunez, A A

    2010-10-27

    Many features of the suprachiasmatic nucleus (SCN) are the same in diurnal and nocturnal animals, suggesting that differences in phase preference are determined by mechanisms downstream from the SCN. Here, we examined this hypothesis by characterizing rhythmic expression of Period 1 (PER1) and Period 2 (PER2) in several extra-SCN areas in the brains of a diurnal murid rodent, Arvicanthis niloticus (grass rats). In the shell of the nucleus accumbens, dorsal striatum, piriform cortex, and CA1 of the hippocampus, both PER1 and PER2 were rhythmic, with peak expression occurring at ZT10. PER1 in the dentate gyrus also peaked at ZT10, but PER2 was arrhythmic in this region. In general, these patterns are 180 degrees out of phase with those reported for nocturnal species. In a second study, we examined inter-individual differences in the multioscillator system of grass rats. Here, we housed grass rats in cages with running wheels, under which conditions some individuals spontaneously adopt a day active (DA) and others a night active (NA) phase preference. In the majority of the extra-SCN regions sampled, the patterns of PER1 and PER2 expression of NA grass rats resembled those of nocturnal species, while those of DA grass rats were similar to the ones seen in grass without access to running wheels. In contrast, the rhythmic expression of both PER proteins was identical in the SCN and ventral subparaventricular zone (vSPZ) of DA and NA animals. Differences in the phase of oscillators downstream from the SCN, and perhaps the vSPZ, appear to determine the phase preference of particular species, as well as that of members of a diurnal species that show voluntary phase reversals. The latter observation has important implications for the understanding of health problems associated with human shift work. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Irena Svobodova

    2018-03-01

    Full Text Available The circadian rhythms in physiological and behavioral functions are driven by a pacemaker located in the suprachiasmatic nucleus (SCN. The rhythms continue in constant darkness and depend on cell-cell communication between neurons and glia. The SCN astrocytes generate also a circadian rhythm in extracellular adenosine 5′-triphosphate (ATP accumulation, but molecular mechanisms that regulate ATP release are poorly understood. Here, we tested the hypothesis that ATP is released via the plasma membrane purinergic P2X7 receptors (P2X7Rs and P2Y receptors (P2YRs which have been previously shown to be expressed in the SCN tissue at transcriptional level. We have investigated this hypothesis using SCN organotypic cultures, primary cultures of SCN astrocytes, ATP bioluminescent assays, immunohistochemistry, patch-clamping, and calcium imaging. We found that extracellular ATP accumulation in organotypic cultures followed a circadian rhythm, with a peak between 24:00 and 04:00 h, and the trough at ~12:00 h. ATP rhythm was inhibited by application of AZ10606120, A438079, and BBG, specific blockers of P2X7R, and potentiated by GW791343, a positive allosteric modulator of this receptor. Double-immunohistochemical staining revealed high expression of the P2X7R protein in astrocytes of SCN slices. PPADS, a non-specific P2 antagonist, and MRS2179, specific P2Y1R antagonist, also abolished ATP rhythm, whereas the specific P2X4R blocker 5-BDBD was not effective. The pannexin-1 hemichannel blocker carbenoxolone displayed a partial inhibitory effect. The P2Y1R agonist MRS2365, and the P2Y2R agonist MRS2768 potentiated ATP release in organotypic cultures and increase intracellular Ca2+ level in cultured astrocytes. Thus, SCN utilizes multiple purinergic receptor systems and pannexin-1 hemichannels to release ATP.

  10. Combined Pharmacological and Genetic Manipulations Unlock Unprecedented Temporal Elasticity and Reveal Phase-Specific Modulation of the Molecular Circadian Clock of the Mouse Suprachiasmatic Nucleus.

    Science.gov (United States)

    Patton, Andrew P; Chesham, Johanna E; Hastings, Michael H

    2016-09-07

    The suprachiasmatic nucleus (SCN) is the master circadian oscillator encoding time-of-day information. SCN timekeeping is sustained by a cell-autonomous transcriptional-translational feedback loop, whereby expression of the Period and Cryptochrome genes is negatively regulated by their protein products. This loop in turn drives circadian oscillations in gene expression that direct SCN electrical activity and thence behavior. The robustness of SCN timekeeping is further enhanced by interneuronal, circuit-level coupling. The aim of this study was to combine pharmacological and genetic manipulations to push the SCN clockwork toward its limits and, by doing so, probe cell-autonomous and emergent, circuit-level properties. Circadian oscillation of mouse SCN organotypic slice cultures was monitored as PER2::LUC bioluminescence. SCN of three genetic backgrounds-wild-type, short-period CK1ε(Tau/Tau) mutant, and long-period Fbxl3(Afh/Afh) mutant-all responded reversibly to pharmacological manipulation with period-altering compounds: picrotoxin, PF-670462 (4-[1-Cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-pyrimidinamine dihydrochloride), and KNK437 (N-Formyl-3,4-methylenedioxy-benzylidine-gamma-butyrolactam). This revealed a remarkably wide operating range of sustained periods extending across 25 h, from ≤17 h to >42 h. Moreover, this range was maintained at network and single-cell levels. Development of a new technique for formal analysis of circadian waveform, first derivative analysis (FDA), revealed internal phase patterning to the circadian oscillation at these extreme periods and differential phase sensitivity of the SCN to genetic and pharmacological manipulations. For example, FDA of the CK1ε(Tau/Tau) mutant SCN treated with the CK1ε-specific inhibitor PF-4800567 (3-[(3-Chlorophenoxy)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride) revealed that period acceleration in the mutant is due to inappropriately phased

  11. Sustained activation of GABAA receptors in the suprachiasmatic nucleus mediates light-induced phase delays of the circadian clock: a novel function of ionotropic receptors.

    Science.gov (United States)

    Hummer, Daniel L; Ehlen, J Christopher; Larkin, Tony E; McNeill, John K; Pamplin, John R; Walker, Colton A; Walker, Phillip V; Dhanraj, Daryl R; Albers, H Elliott

    2015-07-01

    The suprachiasmatic nucleus (SCN) contains a circadian clock that generates endogenous rhythmicity and entrains that rhythmicity with the day-night cycle. The neurochemical events that transduce photic input within the SCN and mediate entrainment by resetting the molecular clock have yet to be defined. Because GABA is contained in nearly all SCN neurons we tested the hypothesis that GABA serves as this signal in studies employing Syrian hamsters (Mesocricetus auratus). Activation of GABAA receptors was found to be necessary and sufficient for light to induce phase delays of the clock. Remarkably, the sustained activation of GABAA receptors for more than three consecutive hours was necessary to phase-delay the clock. The duration of GABAA receptor activation required to induce phase delays would not have been predicted by either the prevalent theory of circadian entrainment or by expectations regarding the duration of ionotropic receptor activation necessary to produce functional responses. Taken together, these data identify a novel neurochemical mechanism essential for phase-delaying the 'master' circadian clock within the SCN as well as identifying an unprecedented action of an amino acid neurotransmitter involving the sustained activation of ionotropic receptors. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. 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.

  13. Concurrent decrease of vasopressin and protein kinase C-alpha immunoreactivity during the light phase in the vole suprachiasmatic nucleus

    NARCIS (Netherlands)

    Jansen, K; Van der Zee, EA; Gerkema, MP

    1998-01-01

    Vasopressin (AVP) is a major neuropeptide in the suprachiasmatic nucleus, the mammalian hypothalamic circadian pacemaker. Protein kinase C alpha is a putatively coupled intracellular messenger. Mean numbers of AVP- and protein kinase C alpha- immunoreactive neurons were determined in the

  14. Histamine resets the circadian clock in the suprachiasmatic nucleus through the H1R-CaV 1.3-RyR pathway in the mouse.

    Science.gov (United States)

    Kim, Yoon Sik; Kim, Young-Beom; Kim, Woong Bin; Yoon, Bo-Eun; Shen, Feng-Yan; Lee, Seung Won; Soong, Tuck-Wah; Han, Hee-Chul; Colwell, Christopher S; Lee, C Justin; Kim, Yang In

    2015-10-01

    Histamine, a neurotransmitter/neuromodulator implicated in the control of arousal state, exerts a potent phase-shifting effect on the circadian clock in the rodent suprachiasmatic nucleus (SCN). In this study, the mechanisms by which histamine resets the circadian clock in the mouse SCN were investigated. As a first step, Ca(2+) -imaging techniques were used to demonstrate that histamine increases intracellular Ca(2+) concentration ([Ca(2+) ]i ) in acutely dissociated SCN neurons and that this increase is blocked by the H1 histamine receptor (H1R) antagonist pyrilamine, the removal of extracellular Ca(2+) and the L-type Ca(2+) channel blocker nimodipine. The histamine-induced Ca(2+) transient is reduced, but not blocked, by application of the ryanodine receptor (RyR) blocker dantrolene. Immunohistochemical techniques indicated that CaV 1.3 L-type Ca(2+) channels are expressed mainly in the somata of SCN cells along with the H1R, whereas CaV 1.2 channels are located primarily in the processes. Finally, extracellular single-unit recordings demonstrated that the histamine-elicited phase delay of the circadian neural activity rhythm recorded from SCN slices is blocked by pyrilamine, nimodipine and the knockout of CaV 1.3 channel. Again, application of dantrolene reduced but did not block the histamine-induced phase delays. Collectively, these results indicate that, to reset the circadian clock, histamine increases [Ca(2+) ]i in SCN neurons by activating CaV 1.3 channels through H1R, and secondarily by causing Ca(2+) -induced Ca(2+) release from RyR-mediated internal stores. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. 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 - Neurology Impact factor: 1.971, year: 2005

  16. Photoperiodic modulation of the hepatic clock by the suprachiasmatic nucleus and feeding regime in mice

    Czech Academy of Sciences Publication Activity Database

    Parkanová, Daniela; Nováková, Marta; Sosniyenko, Serhiy; Sumová, Alena

    2012-01-01

    Roč. 35, č. 9 (2012), s. 1446-1457 ISSN 0953-816X R&D Projects: GA ČR(CZ) GA305/09/0321; GA ČR(CZ) GAP303/11/0668 EU Projects: European Commission(XE) 18741 - EUCLOCK Institutional research plan: CEZ:AV0Z50110509 Keywords : suprachiasmatic nucleus * photoperiod * circadian clock * clock gene * mice Subject RIV: FH - Neurology Impact factor: 3.753, year: 2012

  17. 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

  18. Novel description of ionic currents recorded with the action potential clamp technique: application to excitatory currents in suprachiasmatic nucleus neurons.

    Science.gov (United States)

    Clay, John R

    2015-07-01

    The traditional method of recording ionic currents in neurons has been with voltage-clamp steps. Other waveforms such as action potentials (APs) can be used. The AP clamp method reveals contributions of ionic currents that underlie excitability during an AP (Bean BP. Nat Rev Neurosci 8: 451-465, 2007). A novel usage of the method is described in this report. An experimental recording of an AP from the literature is digitized and applied computationally to models of ionic currents. These results are compared with experimental AP-clamp recordings for model verification or, if need be, alterations to the model. The method is applied to the tetrodotoxin-sensitive sodium ion current, INa, and the calcium ion current, ICa, from suprachiasmatic nucleus (SCN) neurons (Jackson AC, Yao GL, Bean BP. J Neurosci 24: 7985-7998, 2004). The latter group reported voltage-step and AP-clamp results for both components. A model of INa is constructed from their voltage-step results. The AP clamp computational methodology applied to that model compares favorably with experiment, other than a modest discrepancy close to the peak of the AP that has not yet been resolved. A model of ICa was constructed from both voltage-step and AP-clamp results of this component. The model employs the Goldman-Hodgkin-Katz equation for the current-voltage relation rather than the traditional linear dependence of this aspect of the model on the Ca(2+) driving force. The long-term goal of this work is a mathematical model of the SCN AP. The method is general. It can be applied to any excitable cell.

  19. Differential regulation of fos family genes in the ventrolateral and dorsomedial subdivisions of the rat suprachiasmatic nucleus.

    Science.gov (United States)

    Schwartz, W J; Carpino, A; de la Iglesia, H O; Baler, R; Klein, D C; Nakabeppu, Y; Aronin, N

    2000-01-01

    Extensive studies have established that light regulates c-fos gene expression in the suprachiasmatic nucleus, the site of an endogenous circadian clock, but relatively little is known about the expression of genes structurally related to c-fos, including fra-1, fra-2 and fosB. We analysed the photic and temporal regulation of these genes at the messenger RNA and immunoreactive protein levels in rat suprachiasmatic nucleus, and we found different expression patterns after photic stimulation and depending on location in the ventrolateral or dorsomedial subdivisions. In the ventrolateral suprachiasmatic nucleus, c-fos, fra-2 and fosB expression was stimulated after a subjective-night (but not subjective-day) light pulse. Expression of the fra-2 gene was prolonged following photic stimulation, with elevated messenger RNA and protein levels that appeared unchanged for at least a few hours beyond the c-fos peak. Unlike c-fos and fra-2, the fosB gene appeared to be expressed constitutively in the ventrolateral suprachiasmatic nucleus throughout the circadian cycle; immunohistochemical analysis suggested that delta FosB was the protein product accounting for this constitutive expression, while FosB was induced by the subjective-night light pulse. In the dorsomedial suprachiasmatic nucleus, c-fos and fra-2 expression exhibited an endogenous circadian rhythm, with higher levels during the early subjective day, although the relative abundance was much lower than that measured after light pulses in the ventrolateral suprachiasmatic nucleus. Double-label immunohistochemistry suggested that some of the dorsomedial cells responsible for the circadian expression of c-Fos also synthesized arginine vasopressin. No evidence of suprachiasmatic nucleus fra-1 expression was found. In summary, fos family genes exhibit differences in their specific expression patterns in the suprachiasmatic nucleus, including their photic and circadian regulation in separate cell populations in the

  20. 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.

  1. 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

  2. Phase preference for the display of activity is associated with the phase of extra-SCN oscillators within and between species

    OpenAIRE

    Ramanathan, Chidambaram; Stowie, Adam; Smale, Laura; Nunez, Antonio A.

    2010-01-01

    Many features of the suprachiasmatic nucleus (SCN) are the same in diurnal and nocturnal animals, suggesting that differences in phase preference are determined by mechanisms downstream from the SCN. Here, we examined this hypothesis by characterizing rhythmic expression of PER1 and PER2 in several extra-SCN areas in the brains of a diurnal murid rodent, Arvicanthis niloticus (grass rats). In the shell of the nucleus accumbens, dorsal striatum, piriform cortex, and CA1 of the hippocampus, bot...

  3. The neuronal transition probability (NTP model for the dynamic progression of non-REM sleep EEG: the role of the suprachiasmatic nucleus.

    Directory of Open Access Journals (Sweden)

    Helli Merica

    Full Text Available 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 activity we show that the SCN has the information required to provide a threshold-triggered flip-flop for TIMING the towards-and-away alternations, information provided by sleep-relevant feedback to the SCN. NTP then determines the PATTERN of spectral power within each dynamic-state. NTP was fitted to individual NREM episodes 1-4, using data from 30 healthy subjects aged 20-30 years, and the quality of fit for each NREM measured. We show that the model fits well all NREM episodes and the best-fit probability-set is found to be effectively the same in fitting all subject data. The significant model-data agreement, the constant probability parameter and the proposed role of the SCN add considerable strength to the model. With it we link for the first time findings at cellular level and detailed time-course data at EEG level, to give a coherent picture of NREM dynamics over the entire night and over hierarchic brain levels all the way from the SCN

  4. 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

  5. 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...

  6. Neuropeptide Y-mediated long-term depression of excitatory activity in suprachiasmatic nucleus neurons.

    Science.gov (United States)

    van den Pol, A N; Obrietan, K; Chen, G; Belousov, A B

    1996-09-15

    A brief exposure to light can shift the phase of mammalian circadian rhythms by 1 hr or more. Neuropeptide Y (NPY) administration to the hypothalamic suprachiasmatic nucleus, the circadian clock in the brain, also causes a phase shift in circadian rhythms. After a phase shift, the neural clock responds differently to light, suggesting that learning has occurred in neural circuits related to clock function. Thus, certain stimuli can produce effects that last for an extended period, but possible mechanisms of this long-term effect have not been previously examined at the cellular level. Here, we report that NPY caused a long-term depression in both electrical activity and intracellular calcium levels of neurons, as studied with whole-cell patch-clamp recording and Fura-2 digital imaging. In contrast to the immediate (1 sec) recovery after relief from glutamate receptor blockade, a brief single application of NPY (100 nM) depressed cytosolic Ca2+ for > 1 hr. The mechanism of this long-term calcium depression, a form of cellular learning, is dependent on the simultaneous release of glutamate and activation of NPY receptors, because both the extended response to NPY and any aftereffect were blocked by coapplication of glutamate receptor antagonists. Postsynaptic actions of NPY, mediated by both Y1- and Y2-like receptors, were short term and recovered rapidly. The primary site of long-term NPY actions may be on presynaptic glutamatergic axons, because the frequency of miniature excitatory postsynaptic currents in the presence of tetrodotoxin was reduced by transient exposure to NPY in both cultures and slices.

  7. Restricted feeding regime affects clock gene expression profiles in the suprachiasmatic nucleus of rats exposed to constant light

    Czech Academy of Sciences Publication Activity Database

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

    2011-01-01

    Roč. 197, - (2011), s. 65-71 ISSN 0306-4522 R&D Projects: GA ČR(CZ) GA305/09/0321; GA ČR(CZ) GAP303/11/0668; GA MŠk(CZ) LC554 Grant - others:GA ČR(CZ) GD309/08/H079 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian system * suprachiasmatic nucleus * restricted feeding * constant light Subject RIV: FH - Neurology Impact factor: 3.380, year: 2011

  8. Effects of SCN lesions on circadian blood pressure rhythm in normotensive and transgenic hypertensive rats

    NARCIS (Netherlands)

    Witte, K.; Schnecko, A.; Buijs, R. M.; van der Vliet, J.; Scalbert, E.; Delagrange, P.; Guardiola-Lemaître, B.; Lemmer, B.

    1998-01-01

    Transgenic hypertensive TGR(mREN2)27 (TGR) rats, carrying an additional mouse renin gene, have been found to show inverse circadian blood pressure profiles compared to normotensive Sprague-Dawley rats. In order to evaluate the contributions of the suprachiasmatic nucleus (SCN) and the neurohormone

  9. 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.

  10. Chronic ethanol consumption disrupts the core molecular clock and diurnal rhythms of metabolic genes in the liver without affecting the suprachiasmatic nucleus.

    Directory of Open Access Journals (Sweden)

    Ashley N Filiano

    Full Text Available Chronic ethanol consumption disrupts several metabolic pathways including β-oxidation and lipid biosynthesis, facilitating the development of alcoholic fatty liver disease. Many of these same metabolic pathways are directly regulated by cell autonomous circadian clocks, and recent studies suggest that disruption of daily rhythms in metabolism contributes to multiple common cardiometabolic diseases (including non-alcoholic fatty liver disease. However, it is not known whether ethanol disrupts the core molecular clock in the liver, nor whether this, in turn, alters rhythms in lipid metabolism. Herein, we tested the hypothesis that chronic ethanol consumption disrupts the molecular circadian clock in the liver and potentially changes the diurnal expression patterns of lipid metabolism genes. Consistent with previous studies, male C57BL/6J mice fed an ethanol-containing diet exhibited higher levels of liver triglycerides compared to control mice, indicating hepatic steatosis. Further, the diurnal oscillations of core clock genes (Bmal1, Clock, Cry1, Cry2, Per1, and Per2 and clock-controlled genes (Dbp, Hlf, Nocturnin, Npas2, Rev-erbα, and Tef were altered in livers from ethanol-fed mice. In contrast, ethanol had only minor effects on the expression of core clock genes in the suprachiasmatic nucleus (SCN. These results were confirmed in Per2(Luciferase knock-in mice, in which ethanol induced a phase advance in PER2::LUC bioluminescence oscillations in liver, but not SCN. Further, there was greater variability in the phase of PER2::LUC oscillations in livers from ethanol-fed mice. Ethanol consumption also affected the diurnal oscillations of metabolic genes, including Adh1, Cpt1a, Cyp2e1, Pck1, Pdk4, Ppargc1a, Ppargc1b and Srebp1c, in the livers of C57BL/6J mice. In summary, chronic ethanol consumption alters the function of the circadian clock in liver. Importantly, these results suggest that chronic ethanol consumption, at levels sufficient to

  11. Study of SCN Neurochemistry using In Vivo Microdialysis in the Conscious Brain: Correlation with Circadian Activity Rhythms.

    Science.gov (United States)

    1992-12-29

    Hydroxyindole -acetic acid In vivo brain microdialysis was used to characterize the daily pattern of 5 -hy- Suprachiasmatic nucleus droxyindole-acetic acid...principal serotonin metabolite, 5 - hydroxyindole - SCN is comprised of cells that exhibit a self-generating acetic acid ( 5 -HIAA), in the SCN. The...significance of pacemaker activity [3, 4] and is richly innervated by amino the 5 -HIAA rhythm is not certain, however, because acid, peptidergic and

  12. 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

  13. 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)...

  14. Sensitivity of housekeeping genes in the suprachiasmatic nucleus of the mouse brain to diet and the daily light-dark cycle.

    Science.gov (United States)

    Cleal, Jane K; Shepherd, James N; Shearer, Jasmine L; Bruce, Kimberley D; Cagampang, Felino R

    2014-08-05

    The endogenous timing system within the suprachiasmatic nuclei (SCN) of the hypothalamus drives the cyclic expression of the clock molecules across the 24h day-night cycle controlling downstream molecular pathways and physiological processes. The developing fetal clock system is sensitive to the environment and physiology of the pregnant mother and as such disruption of this system could lead to altered physiology in the offspring. Characterizing the gene profiles of the endogenous molecular clock system by quantitative reverse transcription polymerase chain reaction is dependent on normalization by appropriate housekeeping genes (HKGs). However, many HKGs commonly used as internal controls, although stably expressed under control conditions, can vary significantly in their expression under certain experimental conditions. Here we analyzed the expression of 10 classic HKG across the 24h light-dark cycle in the SCN of mouse offspring exposed to normal chow or a high fat diet during early development and in postnatal life. We found that the HKGs glyceraldehyde-3-phosphate dehydrogenase, beta actin and adenosine triphosphate synthase subunit to be the most stably expressed genes in the SCN regardless of diet or time within the 24h light-dark cycle, and are therefore suitable to be used as internal controls. However SCN samples collected during the light and dark periods did show differences in expression and as such the timing of collection should be considered when carrying out gene expression studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. 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.

  16. 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

  17. Flank-marking behavior and the neural distribution of vasopressin innervation in golden hamsters with suprachiasmatic lesions.

    Science.gov (United States)

    Delville, Y; De Vries, G J; Schwartz, W J; Ferris, C F

    1998-12-01

    In golden hamsters, microinjections of arginine-vasopressin (AVP) within the anterior hypothalamus trigger a stereotyped scent-marking behavior, flank marking. Our experiment was carried out to test the contribution of AVP neurons within the suprachiasmatic nucleus (SCN) in the control of this behavior. Our results suggest that the SCN does not contribute to flank-marking behavior. Whereas SCN lesions disrupted circadian rhythms of wheel running, the same lesions did not disrupt flank-marking. The results also suggest that neurons located outside the SCN contribute significantly to the vasopressinergic innervation of the brain and the expression of AVP-dependent behaviors, such as flank-marking behavior. Although AVP-immunoreactive fibers were severely (ca. 95%) depleted from several forebrain areas in SCN-lesioned hamsters, the effect of the lesions was much more limited within the forebrain areas involved in flank-marking behavior as well as within the midbrain and hindbrain.

  18. Continuous illumination through larval development suppresses dopamine synthesis in the suprachiasmatic nucleus, causing activation of α-MSH synthesis in the pituitary and abnormal metamorphic skin pigmentation in flounder.

    Science.gov (United States)

    Itoh, Kae; Washio, Youhei; Fujinami, Yuichiro; Shimizu, Daisuke; Uji, Susumu; Yokoi, Hayato; Suzuki, Tohru

    2012-04-01

    In order to better understand the endocrine aberrations related to abnormal metamorphic pigmentation that appear in flounder larvae reared in tanks, this study examined the effects of continuous 24-h illumination (LL) through larval development on the expression of tyrosine hydroxylase-1 (th1), proopiomelanocortin (pomc), α-melanophore-stimulating hormone (α-MSH) and melanin concentrating hormone (MCH), which are known to participate in the control of background adaptation of body color. We observed two conspicuous deviations in the endocrine system under LL when compared with natural light conditions (LD). First, LL severely suppressed th1 expression in the dopaminergic neurons in the anterior diencephalon, including the suprachiasmatic nucleus (SCN). Second, pomc and α-MSH expression in the pars intermedia melanotrophs was enhanced by LL. Skin color was paler under LL than LD before metamorphic pigmentation, and abnormal metamorphic pigmentation occurred at a higher ratio in LL. We therefore hypothesize that continuous LL inhibited dopamine synthesis in the SCN, which resulted in up-regulation of pomc mRNA expression in the melanotrophs. In spite of the up-regulation of pomc in the melanotrophs, larval skin was adjusted to be pale by MCH which was not affected by LL. Accumulation of α-MSH in the melanotrophs is caused by uncoupling of α-MSH synthesis and secretion due to inhibitory role of MCH on α-MSH secretion, which results in abnormal metamorphic pigmentation by affecting differentiation of adult-type melanophores. Our data demonstrate that continuous illumination at the post-embryonic stage has negative effects on the neuroendocrine system and pituitary in flounder. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Biological Rhythms Workshop IB: neurophysiology of SCN pacemaker function.

    Science.gov (United States)

    Kuhlman, S J

    2007-01-01

    Pacemakers are functional units capable of generating oscillations that synchronize downstream rhythms. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is a circadian pacemaker composed of individual neurons that intrinsically express a near 24-hour rhythm in gene expression. Rhythmic gene expression is tightly coupled to a rhythm in spontaneous firing rate via intrinsic daily regulation of potassium current. Recent progress in the field indicates that SCN pacemaking is a specialized property that emerges from intrinsic features of single cells, structural connectivity among cells, and activity dynamics within the SCN. The focus of this chapter is on how Nature built a functional pacemaker from many individual oscillators that is capable of coordinating the daily timing of essential brain and physiological processes.

  20. 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

  1. 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

  2. Development of SCN connectivity and the circadian control of arousal: a diminishing role for humoral factors?

    Directory of Open Access Journals (Sweden)

    Andrew J Gall

    Full Text Available The suprachiasmatic nucleus (SCN is part of a wake-promoting circuit comprising the dorsomedial hypothalamus (DMH and locus coeruleus (LC. Although widely considered a "master clock," the SCN of adult rats is also sensitive to feedback regarding an animal's behavioral state. Interestingly, in rats at postnatal day (P2, repeated arousing stimulation does not increase neural activation in the SCN, despite doing so in the LC and DMH. Here we show that, by P8, the SCN is activated by arousing stimulation and that selective destruction of LC terminals with DSP-4 blocks this activational effect. We next show that bidirectional projections among the SCN, DMH, and LC are nearly absent at P2 but present at P8. Despite the relative lack of SCN connectivity with downstream structures at P2, day-night differences in sleep-wake activity are observed, suggesting that the SCN modulates behavior at this age via humoral factors. To test this hypothesis, we lesioned the SCN at P1 and recorded sleep-wake behavior at P2: Day-night differences in sleep and wake were eliminated. We next performed precollicular transections at P2 and P8 that isolate the SCN and DMH from the brainstem and found that day-night differences in sleep-wake behavior were retained at P2 but eliminated at P8. Finally, the SCN or DMH was lesioned at P8: When recorded at P21, rats with either lesion exhibited similarly fragmented wake bouts and no evidence of circadian modulation of wakefulness. These results suggest an age-related decline in the SCN's humoral influence on sleep-wake behavior that coincides with the emergence of bidirectional connectivity among the SCN, DMH, and LC.

  3. 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

  4. The expression of NR2B subunit of NMDA receptor in the suprachiasmatic nucleus of Wistar rats and its role in glutamate-induced CREB and ERK1/2 phosphorylation

    Czech Academy of Sciences Publication Activity Database

    Bendová, Zdeňka; Sládek, Martin; Svobodová, Irena

    2012-01-01

    Roč. 61, č. 1 (2012), s. 43-47 ISSN 0197-0186 R&D Projects: GA ČR GAP303/10/1227 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : circadian clock * NMDA receptor * NR2B subunit * rat * suprachiasmatic nucleus Subject RIV: FH - Neurology Impact factor: 2.659, year: 2012

  5. 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

    , 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......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...

  6. 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

  7. 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.

  8. 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

  9. 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

  10. Photic stimulation of the suprachiasmatic nucleus via the non-visual optic system. A gene expression study in the blind Crx (-/-) mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Møller, Morten

    2014-01-01

    photoreceptors. At zeitgeber time 16, the Crx (-/-) and wild-type mice were exposed to 1 h of light. This resulted in a strong up-regulation of the immediate early genes Nr4a1, Erg, and Rrad in the SCN of both genotypes. Light stimulation during the subjective night resulted in a strong up-regulation of c...... to light during the subjective night is an immediate expression of several early response genes in the SCN. We show, by quantitative real-time polymerase chain reaction, that the amount of melanopsin mRNA in the retinal ganglion cells is preserved in the blind Crx (-/-) mouse with degenerated classic......-fos in both genotypes with a significantly higher up-regulation in the blind Crx (-/-) mouse. Expression of Grp and Vip, the genes for two classic peptides located in the SCN, was not influenced by light stimulation. The data strongly indicate the involvement of the melanopsin-based non-visual optic system...

  11. 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.

  12. Prenatal administration of letrozole reduces SDN and SCN volume and cell number independent of partner preference in the male rat.

    Science.gov (United States)

    Olvera-Hernández, Sandra; Tapia-Rodríguez, Miguel; Swaab, Dick F; Fernández-Guasti, Alonso

    2017-03-15

    During development, the exposure to testosterone, and its conversion to estradiol by an enzyme complex termed aromatase, appears to be essential in adult male rats for the expression of typical male sexual behavior and female-sex preference. Some hypothalamic areas are the supposed neural bases of sexual preference/orientation; for example, male-oriented rams have a reduced volume of the sexually dimorphic nucleus (oSDN), while in homosexual men this nucleus does not differ from that of heterosexual men. In contrast, homosexual men showed a larger number of vasopressinergic cells in the suprachiasmatic nucleus (SCN). Interestingly, male rats perinatally treated with an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), also showed bisexual preference and an increased number of vasopressinergic neurons in the SCN. However, this steroidal aromatase inhibitor has affinity for all three steroid receptors. Recently, we reported that the prenatal administration of the selective aromatase inhibitor, letrozole, produced a subpopulation of males with same-sex preference. The aim of this study was to compare the volume and number of cells of the SDN and SCN (the latter nucleus was immunohistochemically stained for vasopressin) between males treated with letrozole with same-sex preference, males treated with letrozole with female preference and control males with female preference. Results showed that all males prenatally treated with letrozole have a reduced volume and estimated cell number in the SDN and SCN, independent of their partner preference. These results indicate that the changes in these brain areas are not related to sexual preference, but rather to the effects of letrozole. The divergent results may be explained by species differences as well as by the critical windows during which the aromatase inhibitor was administered. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Histamine 1 receptor-Gβγ-cAMP/PKA-CFTR pathway mediates the histamine-induced resetting of the suprachiasmatic circadian clock.

    Science.gov (United States)

    Kim, Yoon Sik; Kim, Young-Beom; Kim, Woong Bin; Lee, Seung Won; Oh, Seog Bae; Han, Hee-Chul; Lee, C Justin; Colwell, Christopher S; Kim, Yang In

    2016-05-06

    Recent evidence indicates that histamine, acting on histamine 1 receptor (H1R), resets the circadian clock in the mouse suprachiasmatic nucleus (SCN) by increasing intracellular Ca(2+) concentration ([Ca(2+)]i) through the activation of CaV1.3 L-type Ca(2+) channels and Ca(2+)-induced Ca(2+) release from ryanodine receptor-mediated internal stores. In the current study, we explored the underlying mechanisms with various techniques including Ca(2+)- and Cl(-)-imaging and extracellular single-unit recording. Our hypothesis was that histamine causes Cl(-) efflux through cystic fibrosis transmembrane conductance regulator (CFTR) to elicit membrane depolarization needed for the activation of CaV1.3 Ca(2+) channels in SCN neurons. We found that histamine elicited Cl(-) efflux and increased [Ca(2+)]i in dissociated mouse SCN cells. Both of these events were suppressed by bumetanide [Na(+)-K(+)-2Cl(-) cotransporter isotype 1 (NKCC1) blocker], CFTRinh-172 (CFTR inhibitor), gallein (Gβγ protein inhibitor) and H89 [protein kinase A (PKA) inhibitor]. By itself, H1R activation with 2-pyridylethylamine increased the level of cAMP in the SCN and this regulation was prevented by gallein. Finally, histamine-evoked phase shifts of the circadian neural activity rhythm in the mouse SCN slice were blocked by bumetanide, CFTRinh-172, gallein or H89 and were not observed in NKCC1 or CFTR KO mice. Taken together, these results indicate that histamine recruits the H1R-Gβγ-cAMP/PKA pathway in the SCN neurons to activate CaV1.3 channels through CFTR-mediated Cl(-) efflux and ultimately to phase-shift the circadian clock. This pathway and NKCC1 may well be potential targets for agents designed to treat problems resulting from the disturbance of the circadian system.

  14. Melatonin Signal Transduction Pathways Require E-Box-Mediated Transcription of Per1 and Per2 to Reset the SCN Clock at Dusk.

    Directory of Open Access Journals (Sweden)

    Patty C Kandalepas

    Full Text Available Melatonin is released from the pineal gland into the circulatory system at night in the absence of light, acting as "hormone of darkness" to the brain and body. Melatonin also can regulate circadian phasing of the suprachiasmatic nucleus (SCN. During the day-to-night transition, melatonin exposure advances intrinsic SCN neural activity rhythms via the melatonin type-2 (MT2 receptor and downstream activation of protein kinase C (PKC. The effects of melatonin on SCN phasing have not been linked to daily changes in the expression of core genes that constitute the molecular framework of the circadian clock. Using real-time RT-PCR, we found that melatonin induces an increase in the expression of two clock genes, Period 1 (Per1 and Period 2 (Per2. This effect occurs at CT 10, when melatonin advances SCN phase, but not at CT 6, when it does not. Using anti-sense oligodeoxynucleotides (α ODNs to Per 1 and Per 2, as well as to E-box enhancer sequences in the promoters of these genes, we show that their specific induction is necessary for the phase-altering effects of melatonin on SCN neural activity rhythms in the rat. These effects of melatonin on Per1 and Per2 were mediated by PKC. This is unlike day-active non-photic signals that reset the SCN clock by non-PCK signal transduction mechanisms and by decreasing Per1 expression. Rather, this finding extends roles for Per1 and Per2, which are critical to photic phase-resetting, to a nonphotic zeitgeber, melatonin, and suggest that the regulation of these clock gene transcripts is required for clock resetting by diverse regulatory cues.

  15. Circadian Tick-Talking Across the Neuroendocrine System and Suprachiasmatic Nuclei Circuits: The Enigmatic Communication Between the Molecular and Electrical Membrane Clocks.

    Science.gov (United States)

    Belle, M D C

    2015-07-01

    As with many processes in nature, appropriate timing in biological systems is of paramount importance. In the neuroendocrine system, the efficacy of hormonal influence on major bodily functions, such as reproduction, metabolism and growth, relies on timely communication within and across many of the brain's homeostatic systems. The activity of these circuits is tightly orchestrated with the animal's internal physiological demands and external solar cycle by a master circadian clock. In mammals, this master clock is located in the hypothalamic suprachiasmatic nucleus (SCN), where the ensemble activity of thousands of clock neurones generates and communicates circadian time cues to the rest of the brain and body. Many regions of the brain, including areas with neuroendocrine function, also contain local daily clocks that can provide feedback signals to the SCN. Although much is known about the molecular processes underpinning endogenous circadian rhythm generation in SCN neurones and, to a lesser extent, extra-SCN cells, the electrical membrane clock that acts in partnership with the molecular clockwork to communicate circadian timing across the brain is poorly understood. The present review focuses on some circadian aspects of reproductive neuroendocrinology and processes involved in circadian rhythm communication in the SCN, aiming to identify key gaps in our knowledge of cross-talk between our daily master clock and neuroendocrine function. The intention is to highlight our surprisingly limited understanding of their interaction in the hope that this will stimulate future work in these areas. © 2015 The Author. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of The British Society for Neuroendocrinology.

  16. Delayed Cryptochrome Degradation Asymmetrically Alters the Daily Rhythm in Suprachiasmatic Clock Neuron Excitability.

    Science.gov (United States)

    Wegner, Sven; Belle, Mino D C; Hughes, Alun T L; Diekman, Casey O; Piggins, Hugh D

    2017-08-16

    Suprachiasmatic nuclei (SCN) neurons contain an intracellular molecular circadian clock and the Cryptochromes (CRY1/2), key transcriptional repressors of this molecular apparatus, are subject to post-translational modification through ubiquitination and targeting for proteosomal degradation by the ubiquitin E3 ligase complex. Loss-of-function point mutations in a component of this ligase complex, Fbxl3, delay CRY1/2 degradation, reduce circadian rhythm strength, and lengthen the circadian period by ∼2.5 h. The molecular clock drives circadian changes in the membrane properties of SCN neurons, but it is unclear how alterations in CRY1/2 stability affect SCN neurophysiology. Here we use male and female Afterhours mice which carry the circadian period lengthening loss-of-function Fbxl3 Afh mutation and perform patch-clamp recordings from SCN brain slices across the projected day/night cycle. We find that the daily rhythm in membrane excitability in the ventral SCN (vSCN) was enhanced in amplitude and delayed in timing in Fbxl3 Afh/Afh mice. At night, vSCN cells from Fbxl3 Afh/Afh mice were more hyperpolarized, receiving more GABAergic input than their Fbxl3 +/+ counterparts. Unexpectedly, the progression to daytime hyperexcited states was slowed by Afh mutation, whereas the decline to hypoexcited states was accelerated. In long-term bioluminescence recordings, GABA A receptor blockade desynchronized the Fbxl3 +/+ but not the Fbxl3 Afh/Afh vSCN neuronal network. Further, a neurochemical mimic of the light input pathway evoked larger shifts in molecular clock rhythms in Fbxl3 Afh/Afh compared with Fbxl3 +/+ SCN slices. These results reveal unanticipated consequences of delaying CRY degradation, indicating that the Afh mutation prolongs nighttime hyperpolarized states of vSCN cells through increased GABAergic synaptic transmission. SIGNIFICANCE STATEMENT The intracellular molecular clock drives changes in SCN neuronal excitability, but it is unclear how mutations

  17. Clock-dependent and system-driven oscillators interact in the suprachiasmatic nuclei to pace mammalian circadian rhythms.

    Directory of Open Access Journals (Sweden)

    Karine Abitbol

    Full Text Available Circadian clocks drive biological rhythms with a period of approximately 24 hours and keep in time with the outside world through daily resetting by environmental cues. While this external entrainment has been extensively investigated in the suprachiasmatic nuclei (SCN, the role of internal systemic rhythms, including daily fluctuations in core temperature or circulating hormones remains debated. Here, we show that lactating mice, which exhibit dampened systemic rhythms, possess normal molecular clockwork but impaired rhythms in both heat shock response gene expression and electrophysiological output in their SCN. This suggests that body rhythms regulate SCN activity downstream of the clock. Mathematical modeling predicts that systemic feedback upon the SCN functions as an internal oscillator that accounts for in vivo and ex vivo observations. Thus we are able to propose a new bottom-up hierarchical organization of circadian timekeeping in mammals, based on the interaction in the SCN between clock-dependent and system-driven oscillators.

  18. SCN2A encephalopathy

    Science.gov (United States)

    Howell, Katherine B.; McMahon, Jacinta M.; Carvill, Gemma L.; Tambunan, Dimira; Mackay, Mark T.; Rodriguez-Casero, Victoria; Webster, Richard; Clark, Damian; Freeman, Jeremy L.; Calvert, Sophie; Olson, Heather E.; Mandelstam, Simone; Poduri, Annapurna; Mefford, Heather C.; Harvey, A. Simon

    2015-01-01

    Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy. Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping. Results: Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1–4 in 8, week 2–6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one. Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile–onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control. PMID:26291284

  19. 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

  20. Maternal Control of the Fetal and Neonatal Rat Suprachiasmatic Nucleus

    Czech Academy of Sciences Publication Activity Database

    El-Hennamy, Rehab; Matějů, Kristýna; Bendová, Zdena; Sosniyenko, Serhiy; Sumová, Alena

    2008-01-01

    Roč. 23, č. 5 (2008), s. 435-444 ISSN 0748-7304 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA309/05/0350; GA ČR GA309/08/0503 Grant - others:GA ČR(CZ) GD309/08/H079; EUCLOCK(XE) LSH-2004-115-4-018741 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian system * ontogenesis * maternal entrainment Subject RIV: FH - Neurology Impact factor: 4.211, year: 2008

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

    Directory of Open Access Journals (Sweden)

    Hugues Dardente

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

  2. The opioid fentanyl affects light input, electrical activity and Per gene expression in the hamster suprachiasmatic nuclei.

    Science.gov (United States)

    Vansteensel, Mariska J; Magnone, Maria Chiara; van Oosterhout, Floor; Baeriswyl, Stéphanie; Albrecht, Urs; Albus, Henk; Dahan, Albert; Meijer, Johanna H

    2005-06-01

    The suprachiasmatic nuclei (SCN) contain a major circadian pacemaker, which is regulated by photic and nonphotic stimuli. Although enkephalins are present in the SCN, their role in phase regulation of the pacemaker is largely unknown. The opioid agonist fentanyl, a homologue of morphine, is an addictive drug that induces phase shifts of circadian rhythms in hamsters. We observed that these phase shifts are blocked by naloxone, which is a critical test for true opioid receptor involvement, and conclude that opioid receptors are the sole mediators of the actions of fentanyl on the circadian timing system. A strong interaction between opioids and light input was shown by the ability of fentanyl and light to completely block each other's phase shifts of behavioural activity rhythms. Neuronal ensemble recordings in vitro provide first evidence that SCN cells show direct responses to fentanyl and react with a suppression of firing rate. Moreover, we show that fentanyl induces a strong attenuation of light-induced Syrian hamster Period 1 (shPer1) gene expression during the night. During the subjective day, we found no evidence for a role of shPer1 in mediation of fentanyl-induced phase shifts. Based on the present results, however, we cannot exclude the involvement of shPer2. Our data indicate that opioids can strongly modify the photic responsiveness of the circadian pacemaker and may do so via direct effects on SCN electrical activity and regulation of Per genes. This suggests that the pathways regulating addictive behaviour and the circadian clock intersect.

  3. A common genetic variant within SCN10A modulates cardiac SCN5A expression

    NARCIS (Netherlands)

    van den Boogaard, Malou; Smemo, Scott; Burnicka-Turek, Ozanna; Arnolds, David E.; van de Werken, Harmen J. G.; Klous, Petra; McKean, David; Muehlschlegel, Jochen D.; Moosmann, Julia; Toka, Okan; Yang, Xinan H.; Koopmann, Tamara T.; Adriaens, Michiel E.; Bezzina, Connie R.; de Laat, Wouter; Seidman, Christine; Seidman, J. G.; Christoffels, Vincent M.; Nobrega, Marcelo A.; Barnett, Phil; Moskowitz, Ivan P.

    2014-01-01

    Variants in SCN10A, which encodes a voltage-gated sodium channel, are associated with alterations of cardiac conduction parameters and the cardiac rhythm disorder Brugada syndrome; however, it is unclear how SCN10A variants promote dysfunctional cardiac conduction. Here we showed by high-resolution

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

    Science.gov (United States)

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

    2015-09-01

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

  5. 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

  6. Role of common and rare variants in SCN10A

    DEFF Research Database (Denmark)

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

    2015-01-01

    , CASQ2, TKT, TBX3, and TBX5) in 156 Caucasian SCN5A mutation-negative BrS patients (80% male; mean age 48) with symptoms (64%) and/or a family history of sudden death (47%) or BrS (18%). Forty-nine variants were identified: 18 were rare (MAF ..., were predicted as pathogenic using multiple bioinformatics tools. Allele frequencies were compared with the Exome Sequencing and UK10K Projects. SKAT methods tested rare variation in SCN10A finding no statistically significant difference between cases and controls. Co-segregation analysis was possible.......8 were performed for SCN10A common variants V1073, A1073, and rare variants of interest: A200V and I671V. V1073, A200V and I671V, demonstrated significant reductions in peak INa compared with ancestral allele A1073 (rs6795970). CONCLUSION: Rare variants in the screened QRS-associated genes (including SCN...

  7. 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.

  8. SCN Neurochemistry using In Vivo, Microdialysis in the Conscious Brain

    Science.gov (United States)

    1993-12-27

    related to the the activities of serotonergic and excitatory amino acid activities in the SCN. Specifically, it was found that 1) serotonin inhibits...pacemaker activity. These involved direct application of a reversible inhibitor of glial cell metabolism ( fluorocitrate ) to the SCN via a microdialysis...extraneuronal concentration of the excitatory amino acid (EAA), glutamate. The present experiments were undertaken to extend these findings by characterizing the

  9. Daily rhythms in glucose metabolism: suprachiasmatic nucleus output to peripheral tissue

    NARCIS (Netherlands)

    La Fleur, S. E.

    2003-01-01

    The body has developed several control mechanisms to maintain plasma glucose concentrations within strict boundaries. Within those physiological boundaries, a clear daily rhythm in plasma glucose concentrations is present; this rhythm depends on the biological clock, which is located in the

  10. Neuroglobin expression in the rat suprachiasmatic nucleus: colocalization, innervation, and response to light

    DEFF Research Database (Denmark)

    Hundahl, C A; Hannibal, J; Fahrenkrug, J

    2010-01-01

    protect neurons-remains largely elusive. We have previously described the localization of Ngb in the rat brain and found it to be expressed in areas primarily involved in sleep/wake, circadian, and food regulation. The present study was undertaken, using immunohistochemistry, to characterize......-containing cells received input from neuropeptide Y (NPY)-containing nerve fibers of the geniticulo-hypothalamic tract (GHT), whereas no direct input from the eye or the midbrain raphe system was demonstrated. The results indicate that the Ngb could be involved in both photic and nonphotic entrainment via input...

  11. Encoding le quattro stagioni within the mammalian brain: photoperiodic orchestration through the suprachiasmatic nucleus

    Czech Academy of Sciences Publication Activity Database

    Schwartz, W. J.; de la Iglesia, H. O.; Zlomanczuk, P.; Illnerová, Helena

    2001-01-01

    Roč. 16, č. 4 (2001), s. 302-311 ISSN 0748-7304 R&D Projects: GA ČR GA309/00/1655 Grant - others:NIH(US) R011NS24542 Institutional research plan: CEZ:AV0Z5011922 Keywords : cfos * circadian * clock genes Subject RIV: EA - Cell Biology Impact factor: 2.695, year: 2001

  12. African trypanosomiasis in the rat alters melatonin secretion and melatonin receptor binding in the suprachiasmatic nucleus

    DEFF Research Database (Denmark)

    Kristensson, Krister; Claustrat, Bruno; Mhlanga, Jama D.M.

    1998-01-01

    Neurobiology, cytokines, circadian rhythm, infection, nervous system, pineal gland, trypanosoma brucei......Neurobiology, cytokines, circadian rhythm, infection, nervous system, pineal gland, trypanosoma brucei...

  13. Output pathways of the mammalian suprachiasmatic nucleus: coding circadian time by transmitter selection and specific targeting

    NARCIS (Netherlands)

    Kalsbeek, Andries; Buijs, Ruud M.

    2002-01-01

    Every day, we experience profound changes in our mental and physical condition as body and brain alternate between states of high activity during the waking day and rest during night-time steep. The fundamental evolutionary adaptation to these profound daily changes in our physiological state is an

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

    NARCIS (Netherlands)

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

    2006-01-01

    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,

  15. Primary erythermalgia as a sodium channelopathy: screening for SCN9A mutations: exclusion of a causal role of SCN10A and SCN11A.

    NARCIS (Netherlands)

    Drenth, J.P.H.; Morsche, R.H.M. te; Mansour, S.; Mortimer, P.S.

    2008-01-01

    OBJECTIVES: To elucidate the rate of missense mutations in the SCN9A gene (which encodes sodium channel Na(v)1.7) (OMIM 603415) among patients with primary erythermalgia and to examine the possibility that other sodium channels can cause the disease. DESIGN: Case series. SETTING: Department of

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. Pineal clock gene oscillation is disturbed in Alzheimer's disease, due to functional disconnection from the "master clock".

    NARCIS (Netherlands)

    Wu, Y.-H.; Fischer, D.F.; Kalsbeek, A.; Garidou-Boof, M.-L.; Vliet, J. van der; Heijningen, C. van; Liu, R.-Y.; Zhou, J.-N.; Swaab, D.F.

    2006-01-01

    The suprachiasmatic nucleus (SCN) is the "master clock" of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer's disease

  2. Pineal clock gene oscillation is disturbed in Alzheimer's disease, due to functional disconnection from the "master clock"

    NARCIS (Netherlands)

    Wu, Ying-Hui; Fischer, David F.; Kalsbeek, Andries; Garidou-Boof, Marie-Laure; van der Vliet, Jan; van Heijningen, Caroline; Liu, Rong-Yu; Zhou, Jiang-Ning; Swaab, Dick F.

    2006-01-01

    The suprachiasmatic nucleus (SCN) is the "master clock" of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer's disease

  3. Compression of the optic chiasm is associated with permanent shorter sleep duration in patients with pituitary insufficiency

    NARCIS (Netherlands)

    Borgers, Anke J.; Romeijn, Nico; van Someren, Eus; Fliers, Eric; Alkemade, Anneke; Bisschop, Peter H.

    2011-01-01

    Patients with pituitary insufficiency often experience some degree of impaired sleep. Sleep-wake rhythm is regulated to a large extent by the suprachiasmatic nucleus (SCN). Because the SCN is located just superior to the optic chiasm, we hypothesized that a history of compression of the optic chiasm

  4. Compression of the optic chiasm is associated with permanent shorter sleep duration in patients with pituitary insufficiency.

    NARCIS (Netherlands)

    Borgers, A.J.F.; Romeijn, N.; Someren, E. van; Fliers, E.A.; Alkemade, A.; Bisschop, P.H.

    2011-01-01

    OBJECTIVE: Patients with pituitary insufficiency often experience some degree of impaired sleep. Sleep-wake rhythm is regulated to a large extent by the suprachiasmatic nucleus (SCN). Because the SCN is located just superior to the optic chiasm, we hypothesized that a history of compression of the

  5. Sleep deprivation and its impact on circadian rhythms and glucose metabolism

    NARCIS (Netherlands)

    Jha, P.K.

    2016-01-01

    The mammalian master pacemaker is located in the hypothalamic suprachiasmatic nucleus (SCN). The SCN generates rhythms of behavioural and metabolic processes throughout the body via both endocrine and neuronal outputs. For example, daily rhythms of sleep-wake, fasting-feeding, plasma glucose,

  6. 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

  7. NO and SCN -intercalated layered double hydroxides: structure and ...

    Indian Academy of Sciences (India)

    2018-02-05

    Feb 5, 2018 ... Nitrite ion; thiocyanate ion; layered double hydroxide; structure refinement. 1. Introduction. The layered .... the synthesis. The [Zn−Al−NO2] and [Zn–Al–SCN] LDHs were synthe- sized by coprecipitation at constant pH = 8 and temperature of 60 ... were obtained by the difference Fourier method embedded in.

  8. 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...

  9. Improved CuSCN–ZnO diode performance with spray deposited CuSCN

    Energy Technology Data Exchange (ETDEWEB)

    Hatch, S.M., E-mail: s.c.dunn@qmul.ac.uk; Briscoe, J.; Dunn, S.

    2013-03-01

    P-type copper(I) thiocyanate (β-CuSCN) was deposited using a pneumatic micro-spray gun from a saturated solution in propyl sulphide. An as-produced 6 μm CuSCN film exhibited a hole mobility of 70 cm {sup 2}/V·s and conductivity of 0.02 S·m{sup −1}. A zinc oxide (ZnO) nanorod array was filled with CuSCN, demonstrating the capability of the process for filling nanostructured materials. This produced a diode with a n-type ZnO and p-type CuSCN junction. The best performing diodes exhibited rectifications of 3550 at ± 3 V. The electronic characteristics exhibited by the diode were attributed to a compact grain structure of the β-CuSCN giving increased carrier mobility and an absence of cracks preventing electrical shorts between electrode contacts that are typically associated with β-CuSCN films. - Highlights: ► CuSCN depositions using impregnation and a spray technique are compared. ► ZnO nanorod–CuSCN diodes were fabricated to demonstrate device performance. ► Hall mobility measurements show good conductivity of CuSCN films. ► Spray deposition improved film morphology and reduced device production time. ► Device rectifications are higher than previously reported for ZnO–CuSCN diodes.

  10. 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 .

  11. 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.

  12. In Vivo Initiation of Clock Gene Expression Rhythmicity in Fetal Rat Suprachiasmatic Nuclei

    Czech Academy of Sciences Publication Activity Database

    Houdek, Pavel; Sumová, Alena

    2014-01-01

    Roč. 9, č. 9 (2014), e107360 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP303/12/1108 Institutional support: RVO:67985823 Keywords : circadian * suprachiasmatic nuclei * ontogenesis * clock gene * entrainment * rat Subject RIV: FH - Neurology Impact factor: 3.234, year: 2014

  13. 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...

  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...

  15. Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy

    NARCIS (Netherlands)

    Berghuis, Bianca; de Kovel, Carolien G F; van Iterson, Loretta; Lamberts, Robert J.; Sander, Josemir W.; Lindhout, Dick; Koeleman, Bobby P. C.

    Background: De novo SCN8A missense mutations have been identified as a rare dominant cause of epileptic encephalopathy. We described a person with epileptic encephalopathy associated with a mosaic deletion of the SCN8A gene. Methods: Array comparative genome hybridization was used to identify

  16. 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

  17. 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.

  18. Remarkable Phenytoin Sensitivity in 4 Children with SCN8A-related Epilepsy : A Molecular Neuropharmacological Approach

    NARCIS (Netherlands)

    Boerma, Ragna S.; Braun, Kees P.; van de Broek, Maarten P. H.; van Berkestijn, Frederique M. C.; Swinkels, Marielle E.; Hagebeuk, Eveline O.; Lindhout, Dick; van Kempen, Marjan; Boon, Maartje; Nicolai, Joost; de Kovel, Carolien G.; Brilstra, Eva H.; Koeleman, Bobby P. C.

    Mutations in SCN8A are associated with epilepsy and intellectual disability. SCN8A encodes for sodium channel Nav1.6, which is located in the brain. Gain-of-function missense mutations in SCN8A are thought to lead to increased firing of excitatory neurons containing Nav1.6, and therefore to lead to

  19. Biological rhythms in the human life cycle and their relationship to functional changes in the suprachiasmatic nucleus

    NARCIS (Netherlands)

    Swaab, D. F.; van Someren, E. J.; Zhou, J. N.; Hofman, M. A.

    1996-01-01

    Biological rhythms play a prominent role in the human life cycle. The endogenous rhythms are entrained by the environment and have an astronomical counterpart which is obvious for daily, monthly, and yearly rhythms, and may possibly also be present in weekly rhythms. Circadian rhythms are present

  20. Diurnal changes of arginine vasopressin-enhanced green fluorescent protein fusion transgene expression in the rat suprachiasmatic nucleus

    Czech Academy of Sciences Publication Activity Database

    Maruyama, T.; Ohbuchi, T.; Fujihara, H.; Shibata, M.; Mori, K.; Murphy, D.; Dayanithi, Govindan; Ueta, Y.

    2010-01-01

    Roč. 31, č. 11 (2010), s. 2089-2093 ISSN 0196-9781 Institutional research plan: CEZ:AV0Z50390703 Keywords : hypothalamus * GFP * period gene Subject RIV: FH - Neurology Impact factor: 2.654, year: 2010

  1. Adenoviral vector-mediated gene transfer and neurotransplantation : possibilities and limitations in grafting of the fetal rat suprachiasmatic nucleus

    NARCIS (Netherlands)

    van Esseveldt, K E; Liu, R.; Hermens, W.T.J.M.C.; Verhaagen, J; Boer, G J

    Several studies have reported on the use of primary neural cells transduced by adenoviral vectors as donor cells in neurotransplantation. In the present investigation, we examined whether adenoviral vector-mediated gene transfer could be used to introduce and express a foreign gene in solid neural

  2. Perspective of ultrarelativistic nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Specht, H.J.

    1985-01-01

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

  3. Distinctive electro-clinical features of epilepsy in severe early onset SCN8A encephalopathy

    DEFF Research Database (Denmark)

    Gardella, E.; Larsen, Jan; Wolff, M.

    2015-01-01

    Rationale: SCN8A mutations have been recently associated with early infantile epileptic encephalopathy with a broad phenotypic spectrum. We aim to further delineate the interictal and ictal video-EEG features of a peculiar clinical subgroup of patients affected by early onset SCN8A-related enceph......Rationale: SCN8A mutations have been recently associated with early infantile epileptic encephalopathy with a broad phenotypic spectrum. We aim to further delineate the interictal and ictal video-EEG features of a peculiar clinical subgroup of patients affected by early onset SCN8A....../9 patients (follow-up 10-25 months); all seizure types have been documented. Patients had both focal and generalized seizures (FS,GS), the latter consisting of GTCS, pseudo-absences, spasms and myoclonus. FS were usually prolonged (3-5 min), with prominent hypomotor and vegetative semiology, evolving...

  4. An R1632C variant in the SCN5A gene causing Brugada syndrome.

    Science.gov (United States)

    García-Molina, Esperanza; Sabater-Molina, María; Muñoz, Carmen; Ruiz-Espejo, Francisco; Gimeno, Juan R

    2016-06-01

    Brugada syndrome (BS) is an electrical disease, inherited in an autosomal dominant manner. BS is caused by mutations in up to 13 different genes. SCN5A is the gene most frequently mutated in BS, although this presents an incomplete penetrance. The present case study investigated the SCN5A gene in a family exhibiting BS. Direct sequencing of the SCN5A gene was performed to identify mutations and a familial investigation was performed. A novel variant was identified in the voltage‑sensing domain of the SCN5A protein. This familial investigation revealed one novel asymptomatic carrier in the family. Genetic investigations are useful to classify individuals who require more frequent clinical monitoring and to stratify the risk of developing the disease.

  5. 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.

  6. Multiple arrhythmic syndromes in a newborn, owing to a novel mutation in SCN5A

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Schmitt, Nicole; Grubb, Søren

    2011-01-01

    Mutations in the SCN5A gene have been linked to Brugada syndrome (BrS), conduction disease, Long QT syndrome (LQT3), atrial fibrillation (AF), and to pre- and neonatal ventricular arrhythmias.......Mutations in the SCN5A gene have been linked to Brugada syndrome (BrS), conduction disease, Long QT syndrome (LQT3), atrial fibrillation (AF), and to pre- and neonatal ventricular arrhythmias....

  7. Onuf's nucleus X

    DEFF Research Database (Denmark)

    Schrøder, H D

    1981-01-01

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

  8. Daily and circadian rhythms of neurotransmitters and related compounds in the hypothalamic suprachiasmatic nuclei of a diurnal vertebrate.

    Science.gov (United States)

    Magnone, Maria Chiara; Bertolucci, Cristiano; Piazza, Francesca; Foà, Augusto

    2003-05-23

    By using immunocytochemistry we tested whether neurotransmitters, and enzymes specific to neurotransmitters synthesis are rhythmically expressed in the suprachiasmatic nuclei of the hypothalamus of Ruin lizards Podarcis sicula either kept in light-dark cycles or constant darkness. Within the suprachiasmatic nuclei, prominent 24 h rhythms under 12:12 light-dark cycles were found for vasoactive intestinal polypeptide (VIP) and for tyrosine hydroxylase (TH). Peaks of both VIP and TH fell in the light phase of the cycle. Rhythmic expression of TH persisted under constant temperature and darkness, demonstrating the existence of circadian rhythms of TH in the suprachiasmatic nuclei. No rhythmic expression of neurotransmitters and related compounds was found in the periventricular nuclei, the supraoptic nuclei, and the rest of the hypothalamus. Our data are the first demonstration of rhythmic expression of neurotransmitters and related compounds in the suprachiasmatic nuclei of a non-mammalian vertebrate. The demonstration of a diurnal peak of VIP in a diurnal reptile-vs. nocturnal peak of VIP typical of nocturnal mammals-provides new information for comparative studies on the circadian physiology of the suprachiasmatic nuclei across vertebrate classes and their adaptation strategies to different temporal niches.

  9. Ab initio investigation of the SCN{sup -} chemisorption of single-walled boron nitride nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Soltani, Alireza, E-mail: alireza.soltani46@yahoo.com [Young Researchers Club, Gorgan Branch, Islamic Azad University, Gorgan (Iran, Islamic Republic of); Ahmadian, Nasim [Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr (Iran, Islamic Republic of); Kanani, Yaser [Department of Chemistry, Gorgan Branch, Islamic Azad University, Gorgan (Iran, Islamic Republic of); Dehnokhalaji, Aliakbar; Mighani, Hossein [Department of Chemistry, Faculty of Science, Golestan University, Gorgan (Iran, Islamic Republic of)

    2012-10-01

    Highlights: Black-Right-Pointing-Pointer We explored the adsorption behavior of the SCN{sup -} on outer surface BNNTs via DFT. Black-Right-Pointing-Pointer We reported the NBO charge distribution of SCN{sup -} on BNNTs surface. Black-Right-Pointing-Pointer Chemisorptions are observed for SCN{sup -} on Al- and Ga-doped BNNTs. Black-Right-Pointing-Pointer Notable changes are observed in the electronic properties of BNNT after doping. - Abstract: The thiocyanate anion (SCN{sup -}) adsorption capacity of zigzag single-walled boron nitride nanotubes (SWBNNTs) is studied via first-principles theory. Binding energy corresponding to the most stable configuration of SCN{sup -}/BNNT is found to be -148.42 kJ mol{sup -1}, which is typical for the chemisorptions. Our results indicate that both aluminum and gallium doping can significantly enhance the adsorption energy of SCN{sup -}/BNNTs complexes. Our electronic results reveal that there is a significant orbital hybridization between two species in adsorption process being an evidence of strong interaction. Thus, we arrive at the prediction that the BNNTs nanocage can be implemented as suitable sensor for practical applications.

  10. Mutation analysis of CACNA1S and SCN4A in patients with hypokalemic periodic paralysis.

    Science.gov (United States)

    Wang, Xiao-Ying; Ren, Bing-Wen; Yong, Zeng-Hua; Xu, Hong-Yan; Fu, Qiu-Xia; Yao, He-Bin

    2015-10-01

    Mutations in CACNA1S (calcium channel, voltage‑dependent, L type, alpha 1S subunit) and SCN4A (sodium channel, voltage‑gated, type IV, alpha subunit) are associated with hypokalemic periodic paralysis (HPP). The aim of the current study was to investigate CACNA1S and SCN4A mutations in patients with HPP. Mutations in CACNA1S and SCN4A were detected in three familial hypokalemic periodic paralysis (FHPP) pedigrees and in two thyrotoxic hypokalemic periodic paralysis (THPP) pedigrees using polymerase chain reaction, DNA sequencing and sequence alignment with GenBank data. A single base mutation from cytosine to guanine at site 1582 was identified in exon 11 of CACNA1S in one FHPP pedigree, resulting in an arginine to glycine (R528G) substitution. A single base mutation from thymine to cytosine at site 2012 was identified in exon 12 of SCN4A in one THPP pedigree, resulting in a phenylalanine to serine (F671S) substitution. No mutations in CACNA1S or SCN4A were identified in the remaining three pedigrees. The present study indicated that CACNA1S and SCN4A mutations are relatively rare in patients with HPP, and further studies are required to determine whether these mutation‑associated substitutions are representative of patients with HPP.

  11. 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....

  12. Influence of annealing on microstructural and photoelectrochemical characteristics of CuSCN thin films via electrochemical process

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Mao-Chia [Institute of Materials Science and Engineering, National Central University, Jhongli 32001, Taiwan (China); Wang, TsingHai [Department of Biomedical Engineering and Environment Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Tseng, Yao-Tien [Institute of Materials Science and Engineering, National Central University, Jhongli 32001, Taiwan (China); Wu, Ching-Chen [Green Energy and Environment Research Laboratories, Industrial Technology Research Institute, Hsinchu 310, Taiwan (China); Lin, Jing-Chie, E-mail: jclin4046@gmail.com [Institute of Materials Science and Engineering, National Central University, Jhongli 32001, Taiwan (China); Department of Mechanical Engineering, National Central University, Jhongli 32001, Taiwan (China); Hsu, Wan-Yi [Department of Mechanical Engineering, National Central University, Jhongli 32001, Taiwan (China); Chang, Wen-Sheng [Green Energy and Environment Research Laboratories, Industrial Technology Research Institute, Hsinchu 310, Taiwan (China); Chen, I-Chen [Institute of Materials Science and Engineering, National Central University, Jhongli 32001, Taiwan (China); Peng, Kun-Cheng [Department of Materials Engineering, Mingchi University of Technology, New Taipei City 24301, Taiwan (China)

    2015-02-15

    Highlights: • CuSCN films were synthesized by electrochemical process. • The parameter of CuSCN films was annealing temperature. • The photoelectrochemical characteristics of CuSCN films were investigated. - Abstract: Thin films of p-type β-CuSCN were deposited on indium-tin oxide glass substrates via electrochemical process. Various annealing temperatures (200, 300 and 400 °C) were taken into consideration. The influence of annealing temperature on structural, optical, electrical and photoelectrochemical characteristics of β-CuSCN thin films were investigated. Results from X-ray diffraction indicated as-obtained β-CuSCN thin film was in a hexagonal close pack crystal structure. We found that the crystallographic orientation changed and the optical energy band gap slightly increased with increasing annealing temperatures. These properties made CuSCN films annealed at 400 °C a better photoelectrochemical performance with photocurrent density of about −0.39 mA/cm{sup 2} at −0.5 V vs. SCE. This value is about 5 times higher than the as-deposited CuSCN film. Observed higher photocurrent density is likely due to the intrinsic of a higher charge carrier concentration, and a lower resistance within CuSCN crystal and at CuSCN/electrolyte interface.

  13. Hadron-nucleus collisions

    International Nuclear Information System (INIS)

    Strugalski, Z.

    1981-01-01

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

  14. Association between SCN1A polymorphism and carbamazepine-resistant epilepsy

    Science.gov (United States)

    Abe, Tomohide; Seo, Takayuki; Ishitsu, Takateru; Nakagawa, Takehiro; Hori, Masaharu; Nakagawa, Kazuko

    2008-01-01

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The SCN1Agene encodes the α subunit of the neuronal voltage-gated sodium channel, which is a target for carbamazepine and other antiepileptic drugs (AEDs). Recent studies have demonstrated that a common polymorphism of SCN1A IVS5-91 G > A was associated with carbamazepine and phenytoin use in daily practice. However, it has not been determined whether the polymorphism affects carbamazepine or other AED responsiveness. WHAT THIS STUDY ADDS This study demonstrated a significant association between the SCN1A IVS5-91 AA genotype and carbamazepine-resistant epilepsy, while the AA genotype did not affect carbamazepine use. AIMS To establish whether the SCN1A IVS5-91 G > A polymorphism of the SCN1A gene, which encodes the neuronal sodium channel α subunit, affects responsivenss to the antiepileptic drugs (AEDS) carbamazepine and/or phenytoin. METHODS SCN1A IVS5-91 G > A polymorphism was genotyped in 228 Japanese epileptic patients treated with AEDs. The association between AED responsiveness and the polymorphism was estimated by logistic regression analysis, adjusting for clinical factors affecting the outcome of AED therapy. RESULTS The frequency of the AA genotype was significantly higher in carbamazepine-resistant patients (odds ratio, 2.7; 95% confidence interval (CI), 1.1, 7.1) and was insignificantly higher in AED-resistant patients. CONCLUSIONS This is the first report demonstrating an association between the SCN1A polymorphism and carbamazepine-resistant epilepsy. PMID:18489610

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

    OpenAIRE

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

    2016-01-01

    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 set by our biological clock, such as shift work, jet lag, sleep deprivation, or simply eating at the wrong time of the day, may have deleterious effects on health. This infringement, also known as ...

  16. Molecular components of the mammalian circadian clock

    OpenAIRE

    Buhr, Ethan D.; Takahashi, Joseph S.

    2013-01-01

    Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. This is achieved by ocular photoreception relaying signals to the suprachiasmatic nucleus (SCN) in the hypothalamus. Signals from the SCN cause the synchronization of independent circadian clocks throughout the body to appropriate phases. Signals that can entrain these peripheral clocks include humoral signals, metabolic factors, and body temperature. At the level of individual tissu...

  17. Review Article Clockworks in the Central and Peripheral Organs: from Clock-related Genes to the Physiological and Pathological Rhythms

    OpenAIRE

    Moriya, Takahiro; Shinohara, Kazuyuki

    2003-01-01

    Daily rhythms such as sleep-wake, feeding, and the core body temperature, persist with a period of approximately 24 hr even in the absence of environmental time cues, suggesting the existence of an endogenous time-keeping system, the circadian clock. In mammals, the circadian clock is located in the suprachiasmatic nucleus of the hypothalamus (SCN). Recently, a number of studies have revealed that circadian oscillations in the SCN are driven by the intracellular transcriptional and post-trans...

  18. 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...

  19. SCN8A mutations in Chinese patients with early onset epileptic encephalopathy and benign infantile seizures.

    Science.gov (United States)

    Wang, Jiaping; Gao, Hua; Bao, Xinhua; Zhang, Qingping; Li, Jiarui; Wei, Liping; Wu, Xiru; Chen, Yan; Yu, Shujie

    2017-09-18

    SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. This study aimed to broaden the phenotypic-spectrum of disease related with SCN8A mutations. To identify the pathogenic gene of a Chinese family, in which six members suffered from epilepsy, whole-exome sequencing was performed. In addition, target next-generation sequencing (NGS) was performed on 178 sporadic patients, who had epilepsy of unknown etiology within 6 months after birth. A detailed clinical history was obtained. A heterozygous missense mutation of SCN8A was identified in the Chinese family. Six de novo mutations of SCN8A were detected in 6 sporadic patients with epilepsy. In the family, six members developed seizures within a few years after birth. Five of them had milder clinical performance, that they had normal cognition and developmental milestones, and seizure-free was achieved by mono-therapy. The other one affected member presented with refractory epilepsy and developmental regression. She died from sudden unexpected death in epilepsy (SUDEP) at 17-year-old. Clinical features of six sporadic patients with SCN8A mutations were diverse, ranging from severe epileptic encephalopathy to benign epilepsy with normal cognition. Seizures started at the mean age of 3.9 months (from 2 months to 6 months). Seizure-free was achieved in four of them by mono- or multi-antiepileptic drugs. Five of them demonstrated mild or severe psychomotor retardation, whereas the other one was normal in development and intelligence. Our findings extend the spectrum of SCN8A mutations and the clinical features of patients with SCN8A mutations. The majority of SCN8A mutations were de novo, inherited mutations from the heterozygous parents can also occur. The phenotypic spectrum of SCN8A mutation varied largely. Most affected patients manifested as refractory epilepsy and severe intellectual disability, only a small number of patients presented with milder clinical patterns

  20. K+-nucleus interaction

    International Nuclear Information System (INIS)

    Gibbs, W.R.

    1984-01-01

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

  1. Fine Mapping of the SCN Resistance Locus rhg1-b from PI 88788

    Directory of Open Access Journals (Sweden)

    Myungsik Kim

    2010-09-01

    Full Text Available Soybean cyst nematode (SCN ( Ichinohe is the most economically damaging soybean [ (L. Merr.] pest in the USA and genetic resistance is a key component for its control. Although SCN resistance is quantitative, the locus on chromosome 18 (formerly known as Linkage Group G confers a high level of resistance. The objective of this study was to fine-map the allele that is derived from plant introduction (PI 88788. F and F plants and F lines from crosses between SCN resistant and susceptible genotypes were tested with genetic markers to identify recombination events close to . Lines developed from these recombinant plants were then tested for resistance to the SCN isolate PA3, which originally had an HG type 0 phenotype, and with genetic markers. Analysis of lines carrying key recombination events positioned between the simple sequence repeat (SSR markers BARCSOYSSR_18_0090 and BARCSOYSSR_18_0094. This places to a 67-kb region of the ‘Williams 82’ genome sequence. The receptor-like kinase gene that has been previously identified as a candidate for the ‘Peking’-derived SCN resistant gene is adjacent to, but outside of, the interval defined in the present study.

  2. 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.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  4. Insulin-FOXO3 signaling modulates circadian rhythms via regulation of clock transcription

    NARCIS (Netherlands)

    Chaves, I.; van der Horst, G.T.J.; Schellevis, R.; Nijman, R.M.; Groot Koerkamp, M.; Holstege, F.C.P.; Smidt, M.P.; Hoekman, M.F.M.

    2014-01-01

    Circadian rhythms are responsive to external and internal cues, light and metabolism being among the most important. In mammals, the light signal is sensed by the retina and transmitted to the suprachiasmatic nucleus (SCN) master clock [1], where it is integrated into the molecular oscillator via

  5. Interval timing in mice does not rely upon the circadian pacemaker

    NARCIS (Netherlands)

    Lewis, PA; Miall, RC; Daan, S

    2003-01-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus is a precise timekeeper that controls and synchronizes the circadian period of countless physiological and behavioural functions and entrains them to the 24 h light/dark cycle. We examined the possibility that it is also indirectly involved in

  6. 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…

  7. Nutrition and the circadian timing system

    NARCIS (Netherlands)

    Stenvers, Dirk Jan; Jonkers, Cora F.; Fliers, Eric; Bisschop, Peter H. L. T.; Kalsbeek, Andries

    2012-01-01

    Life on earth has evolved under the daily rhythm of light and dark. Consequently, most creatures experience a daily rhythm in food availability. In this review, we first introduce the mammalian circadian timing system, consisting of a central clock in the suprachiasmatic nucleus (SCN) and peripheral

  8. Living by the clock: the circadian pacemaker in older people.

    NARCIS (Netherlands)

    Hofman, M.A.; Swaab, D.F.

    2006-01-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus is considered to be a critical component of a neural oscillator system implicated in the timing of a wide variety of biological processes. The circadian cycles established by this biological clock occur throughout nature and have a period of

  9. The biological clock tunes the organs of the body: timing by hormones and the autonomic nervous system

    NARCIS (Netherlands)

    Buijs, R. M.; van Eden, C. G.; Goncharuk, V. D.; Kalsbeek, A.

    2003-01-01

    The biological clock, the suprachiasmatic nucleus (SCN), is essential for our daily well-being. it prepares us for the upcoming period of activity by an anticipatory rise in heart rate, glucose and cortisol. At the same time the 'hormone of the darkness', melatonin, decreases. Thus, the time-of-day

  10. Living by the clock: the circadian pacemaker in older people

    NARCIS (Netherlands)

    Hofman, Michel A.; Swaab, Dick F.

    2006-01-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus is considered to be a critical component of a neural oscillator system implicated in the timing of a wide variety of biological processes. The circadian cycles established by this biological clock occur throughout nature and have a period of

  11. The biological clock: the bodyguard of temporal homeostasis

    NARCIS (Netherlands)

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

    2004-01-01

    In order for any organism to function properly, it is crucial that it be table to control the timing of its biological functions. An internal biological clock, located, in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), therefore carefully guards this temporal homeostasis by

  12. 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

  13. 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...

  14. 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

  15. 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

  16. Coexistence of CLCN1 and SCN4A mutations in one family suffering from myotonia.

    Science.gov (United States)

    Maggi, Lorenzo; Ravaglia, Sabrina; Farinato, Alessandro; Brugnoni, Raffaella; Altamura, Concetta; Imbrici, Paola; Camerino, Diana Conte; Padovani, Alessandro; Mantegazza, Renato; Bernasconi, Pia; Desaphy, Jean-François; Filosto, Massimiliano

    2017-12-01

    Non-dystrophic myotonias are characterized by clinical overlap making it challenging to establish genotype-phenotype correlations. We report clinical and electrophysiological findings in a girl and her father concomitantly harbouring single heterozygous mutations in SCN4A and CLCN1 genes. Functional characterization of N1297S hNav1.4 mutant was performed by patch clamp. The patients displayed a mild phenotype, mostly resembling a sodium channel myotonia. The CLCN1 c.501C>G (p.F167L) mutation has been already described in recessive pedigrees, whereas the SCN4A c.3890A>G (p.N1297S) variation is novel. Patch clamp experiments showed impairment of fast and slow inactivation of the mutated Nav1.4 sodium channel. The present findings suggest that analysis of both SCN4A and CLCN1 genes should be considered in myotonic patients with atypical clinical and neurophysiological features.

  17. 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

  18. Infantile Epileptic Encephalopathy Associated With SCN2A Mutation Responsive to Oral Mexiletine.

    Science.gov (United States)

    Foster, Laura A; Johnson, Maria R; MacDonald, John T; Karachunski, Peter I; Henry, Thomas R; Nascene, David R; Moran, Brian P; Raymond, Gerald V

    2017-01-01

    Genetic alterations are significant causes of epilepsy syndromes; especially early-onset epileptic encephalopathies and voltage-gated sodium channelopathies are among the best described. Mutations in the SCN2A subunit of voltage-gated sodium channels have been associated with benign familial neonatal-infantile seizures, generalized epilepsy febrile seizures plus, and an early-onset infantile epileptic encephalopathy. We describe two infants with medically refractory seizures due to a de novo SCN2A mutation. The first child responded to intravenous lidocaine with significant reduction in seizure frequency and was successfully transitioned to enteral mexiletine. Mexiletine was subsequently used in a second infant with reduction in seizure frequency. Class 1b antiarrhythmic agents, lidocaine and mexiletine, may be useful in infants with medically refractory early infantile epileptic encephalopathy secondary to mutations in SCN2A. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The phenotypic spectrum of SCN8A encephalopathy

    DEFF Research Database (Denmark)

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

    2015-01-01

    of the SCN8A gene in 683 patients with a range of epileptic encephalopathies. In addition, we ascertained cases with SCN8A mutations from other centers. A detailed clinical history was obtained together with a review of EEG and imaging data. RESULTS: Seventeen patients with de novo heterozygous mutations...... refractory to antiepileptic therapy. Development was normal in 12 patients and slowed after seizure onset, often with regression; 5 patients had delayed development from birth. All patients developed intellectual disability, ranging from mild to severe. Motor manifestations were prominent including hypotonia...

  20. H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters.

    Science.gov (United States)

    Matsumura, Hiroya; Nakano, Yukiko; Ochi, Hidenori; Onohara, Yuko; Sairaku, Akinori; Tokuyama, Takehito; Tomomori, Shunsuke; Motoda, Chikaaki; Amioka, Michitaka; Hironobe, Naoya; Toshishige, Masaaki; Takahashi, Shinya; Imai, Katsuhiko; Sueda, Taijiro; Chayama, Kazuaki; Kihara, Yasuki

    2017-12-04

    A common SCN5A polymorphism H558R (c.1673 A > G, rs1805124) improves sodium channel activity in mutated channels and known to be a genetic modifier of Brugada syndrome patients (BrS). We investigated clinical manifestations and underlying mechanisms of H558R in BrS. We genotyped H558R in 100 BrS (mean age 45 ± 14 years; 91 men) and 1875 controls (mean age 54 ± 18 years; 1546 men). We compared clinical parameters in BrS with and without H558R (H558R+ vs. H558R- group, N = 9 vs. 91). We also obtained right atrial sections from 30 patients during aortic aneurysm operations and compared SCN5A expression and methylation with or without H558R. H558R was less frequent in BrS than controls (9.0% vs. 19.2%, P = 0.028). The VF occurrence ratio was significantly lower (0% vs. 29.7%, P = 0.03) and spontaneous type 1 ECG was less observed in H558R+ than H558R- group (33.3% vs. 74.7%, P = 0.01). The SCN5A expression level was significantly higher and the methylation rate was significantly lower in sections with H558R (N = 10) than those without (0.98 ± 0.14 vs. 0.83 ± 0.19, P = 0.04; 0.7 ± 0.2% vs. 1.6 ± 0.1%, P = 0.004, respectively). In BrS with heterozygous H558R, the A allele mRNA expression was 1.38 fold higher than G allele expression. The SCN5A polymorphism H558R may be a modifier that protects against VF occurrence in BrS. The H558R decreased the SCN5A promoter methylation and increased the expression level in cardiac tissue. An allelic expression imbalance in BrS with a heterozygous H558R may also contribute to the protective effects in heterozygous mutations.

  1. Embryonic type Na+ channel β-subunit, SCN3B masks the disease phenotype of Brugada syndrome.

    Science.gov (United States)

    Okata, Shinichiro; Yuasa, Shinsuke; Suzuki, Tomoyuki; Ito, Shogo; Makita, Naomasa; Yoshida, Tetsu; Li, Min; Kurokawa, Junko; Seki, Tomohisa; Egashira, Toru; Aizawa, Yoshiyasu; Kodaira, Masaki; Motoda, Chikaaki; Yozu, Gakuto; Shimojima, Masaya; Hayashiji, Nozomi; Hashimoto, Hisayuki; Kuroda, Yusuke; Tanaka, Atsushi; Murata, Mitsushige; Aiba, Takeshi; Shimizu, Wataru; Horie, Minoru; Kamiya, Kaichiro; Furukawa, Tetsushi; Fukuda, Keiichi

    2016-09-28

    SCN5A is abundant in heart and has a major role in I Na . Loss-of-function mutation in SCN5A results in Brugada syndrome (BrS), which causes sudden death in adults. It remains unclear why disease phenotype does not manifest in the young even though mutated SCN5A is expressed in the young. The aim of the present study is to elucidate the timing of the disease manifestation in BrS. A gain-of-function mutation in SCN5A also results in Long QT syndrome type 3 (LQTS3), leading to sudden death in the young. Induced pluripotent stem cells (iPSCs) were generated from a patient with a mixed phenotype of LQTS3 and BrS with the E1784K SCN5A mutation. Here we show that electrophysiological analysis revealed that LQTS3/BrS iPSC-derived cardiomyocytes recapitulate the phenotype of LQTS3 but not BrS. Each β-subunit of the sodium channel is differentially expressed in embryonic and adult hearts. SCN3B is highly expressed in embryonic hearts and iPSC-derived cardiomyocytes. A heterologous expression system revealed that I Na of mutated SCN5A is decreased and SCN3B augmented I Na of mutated SCN5A. Knockdown of SCN3B in LQTS3/BrS iPSC-derived cardiomyocytes successfully unmasked the phenotype of BrS. Isogenic control of LQTS3/BrS (corrected-LQTS3/BrS) iPSC-derived cardiomyocytes gained the normal electrophysiological properties.

  2. Differences in sino-atrial and atrio-ventricular function with age and sex attributable to the Scn5a+/- mutation in a murine cardiac model.

    Science.gov (United States)

    Jeevaratnam, K; Zhang, Y; Guzadhur, L; Duehmke, R M; Lei, M; Grace, A A; Huang, C L-H

    2010-09-01

    To investigate the interacting effects of age and sex on electrocardiographic (ECG) features of Scn5a(+/-) mice modelling Brugada syndrome. Recordings were performed on anaesthetized wild-type (WT) and Scn5a(+/-) mice and differences attributable to these risk factors statistically stratified. Scn5a(+/-) exerted sex-dependent effects upon sino-atrial function that only became apparent with age. RR intervals were greater in old male than in old female Scn5a(+/-). Atrio-ventricular (AV) conduction was slower in young female mice, whether WT and Scn5a(+/-), than the corresponding young male WT and Scn5a(+/-). However, PR intervals lengthened with age in male but not in female Scn5a(+/-) giving the greatest PR intervals in old male Scn5a(+/-) compared with either old male WT or young male Scn5a(+/-) mice. In contrast, PR intervals were similar in old female Scn5a(+/-) and in old female WT. QTc was prolonged in Scn5a(+/-) compared with WT, and female Scn5a(+/-) compared with female WT. Age-dependent alterations in durations of ventricular repolarization relative to WT affected male but not female Scn5a(+/-). Thus, T-wave durations were greater in old male Scn5a(+/-) compared with old male WT, but indistinguishable between old female Scn5a(+/-) and old female WT. Finally, analysis for combined interactions of genotype, age and sex demonstrated no effects on P wave and QRS durations and QTc intervals. We demonstrate for the first time that age, sex and genotype exert both independent and interacting ECG effects. The latter suggest alterations in cardiac pacemaker function, atrio-ventricular conduction and ventricular repolarization greatest in ageing male Scn5a(+/-).

  3. Novel SCN5A mutation associated with idiopathic ventricular fibrillation due to subclinical Brugada syndrome

    Directory of Open Access Journals (Sweden)

    Juan Jiménez-Jáimez

    2011-12-01

    Full Text Available Idiopathic ventricular fibrillation can be caused by subclinical channelopathies such as Brugada syndrome. Our objective is to study the clinical behaviour of a new SCN5A mutation found in a woman with idiopathic ventricular fibrillation. A 53-year-old woman presented with multiple episodes of ventricular fibrillation, a structurally normal heart and normal baseline electrocardiogram. Genetic testing included KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 and identified a mutation in SCN5A (D1816fs/g98747-98748insT. We studied 15 immediate family members by means of electrocardiogram, echocardiogram, flecainide challenge test and genetic study. Eight subjects had the mutation. The flecainide challenge test was positive for Brugada syndrome in two subjects in the case group and none in the control group. The PR and QRS intervals on the baseline electrocardiogram were longer in the case group. The left atrial volume indexed to body surface was higher in the case group, likely due to the fact that two patients with the mutation had atrial fibrillation and none had it in the control group. The D1816fs/g98747-98748insT mutation in SCN5A may be associated with idiopathic ventricular fibrillation and Brugada syndrome with a broad phenotypic spectrum and incomplete penetrance. Genetic testing may be useful to identify the etiology of idiopathic ventricular fibrillation in patients with a negative thorough clinical evaluation.

  4. Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis

    Science.gov (United States)

    Corrochano, Silvia; Männikkö, Roope; Joyce, Peter I.; McGoldrick, Philip; Lassi, Glenda; Raja Rayan, Dipa L.; Blanco, Gonzalo; Quinn, Colin; Liavas, Andrianos; Lionikas, Arimantas; Amior, Neta; Dick, James; Healy, Estelle G.; Stewart, Michelle; Carter, Sarah; Hutchinson, Marie; Bentley, Liz; Fratta, Pietro; Cortese, Andrea; Cox, Roger; Brown, Steve D. M.; Tucci, Valter; Wackerhage, Henning; Amato, Anthony A.; Greensmith, Linda; Koltzenburg, Martin; Hanna, Michael G.; Acevedo-Arozena, Abraham

    2014-01-01

    Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathies, including non-dystrophic myotonias and periodic paralysis. The effects of many of these mutations on channel function have been characterized both in vitro and in vivo. However, little is known about the consequences of SCN4A mutations downstream from their impact on the electrophysiology of the Nav1.4 channel. Here we report the discovery of a novel SCN4A mutation (c.1762A>G; p.I588V) in a patient with myotonia and periodic paralysis, located within the S1 segment of the second domain of the Nav1.4 channel. Using N-ethyl-N-nitrosourea mutagenesis, we generated and characterized a mouse model (named draggen), carrying the equivalent point mutation (c.1744A>G; p.I582V) to that found in the patient with periodic paralysis and myotonia. Draggen mice have myotonia and suffer from intermittent hind-limb immobility attacks. In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms. We discovered metabolic alterations leading to lean mice, as well as abnormal AMP-activated protein kinase activation, which were associated with the immobility attacks and may provide a novel potential therapeutic target. PMID:25348630

  5. The SCN9A channel and plasma membrane depolarization promote cellular senescence through Rb pathway.

    Science.gov (United States)

    Warnier, Marine; Flaman, Jean-Michel; Chouabe, Christophe; Wiel, Clotilde; Gras, Baptiste; Griveau, Audrey; Blanc, Elena; Foy, Jean-Philippe; Mathot, Pauline; Saintigny, Pierre; Van Coppenolle, Fabien; Vindrieux, David; Martin, Nadine; Bernard, David

    2018-02-15

    Oncogenic signals lead to premature senescence in normal human cells causing a proliferation arrest and the elimination of these defective cells by immune cells. Oncogene-induced senescence (OIS) prevents aberrant cell division and tumor initiation. In order to identify new regulators of OIS, we performed a loss-of-function genetic screen and identified that the loss of SCN9A allowed cells to escape from OIS. The expression of this sodium channel increased in senescent cells during OIS. This upregulation was mediated by NF-κB transcription factors, which are well-known regulators of senescence. Importantly, the induction of SCN9A by an oncogenic signal or by p53 activation led to plasma membrane depolarization, which in turn, was able to induce premature senescence. Computational and experimental analyses revealed that SCN9A and plasma membrane depolarization mediated the repression of mitotic genes through a calcium/Rb/E2F pathway to promote senescence. Taken together, our work delineates a new pathway, which involves the NF-κB transcription factor, SCN9A expression, plasma membrane depolarization, increased calcium, the Rb/E2F pathway and mitotic gene repression in the regulation of senescence. This work thus provides new insight into the involvement of ion channels and plasma membrane potential in the control of senescence. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  6. 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

  7. Multifocal Ectopic Purkinje-Related Premature Contractions A New SCN5A-Related Cardiac Channelopathy

    NARCIS (Netherlands)

    Laurent, Gabriel; Saal, Samuel; Amarouch, Mohamed Yassine; Béziau, Delphine M.; Marsman, Roos F. J.; Faivre, Laurence; Barc, Julien; Dina, Christian; Bertaux, Geraldine; Barthez, Olivier; Thauvin-Robinet, Christel; Charron, Philippe; Fressart, Véronique; Maltret, Alice; Villain, Elisabeth; Baron, Estelle; Mérot, Jean; Turpault, Rodolphe; Coudière, Yves; Charpentier, Flavien; Schott, Jean-Jacques; Loussouarn, Gildas; Wilde, Arthur A. M.; Wolf, Jean-Eric; Baró, Isabelle; Kyndt, Florence; Probst, Vincent

    2012-01-01

    Objectives The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease. Background Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited

  8. 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...

  9. SCN2A mutation in a Chinese boy with infantile spasm - response to Modified Atkins Diet.

    Science.gov (United States)

    Wong, Virginia C N; Fung, C W; Kwong, Anna K Y

    2015-08-01

    Mutation of SCN2A, encoding for voltage-gated sodium channel type II alpha subunit, has been demonstrated in various epilepsy phenotypes, ranging from benign to severe epileptic disorders and recently this had been reported for cases with infantile spasm (IS). We study a 6 years-old Chinese boy with severe developmental delay who had infantile spasm since 15 months. He later had severe intellectual disability and autistic features. He failed to respond to most anticonvulsants. Modified Atkins Diet was introduced at 4 years of age and he showed a seizure remission for 12 months with only 1 anticonvulsants. To clarify the unknown etiology, mutations were screened for genes associated with brain development or synaptic function. A heterozygous mutation (c.3631G>A; p.E1211K) was identified in exon 21 of SCN2A gene. This mutation has been reported previously only in a Japanese patient with IS. This is the first case of SCN2A mutation identified in Chinese. Similarity of our case and one Japanese case of infantile spasm indicated that this E1211K mutation is important as possible etiology of IS. Trial of Modified Atkins Diet for other cases of infantile spasm with similar SCN2A mutations is worthwhile pursuing. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  10. Unusual association of SCN2A epileptic encephalopathy with severe cortical dysplasia detected by prenatal MRI.

    Science.gov (United States)

    Bernardo, Silvia; Marchionni, Enrica; Prudente, Sabrina; De Liso, Paola; Spalice, Alberto; Giancotti, Antonella; Manganaro, Lucia; Pizzuti, Antonio

    2017-05-01

    We present an atypical association of SCN2A epileptic encephalopathy with severe cortical dysplasia. SCN2A mutations are associated with epileptic syndromes from benign to extremely severe in absence of such macroscopic brain findings. Prenatal MRI (Magnetic Resonance Imaging) in a 32 weeks fetus, with US (Ultrasonography) diagnosis of isolated ventriculomegaly showed CNS (Central Nervous System) dysplasia characterized by lack of differentiation between cortical and subcortical layers, pachygyria and corpus callosum dysgenesis. Postnatal MRI confirmed the prenatal findings. On day 6 the baby presented a focal status epilepticus, partially controlled by phenobarbital, phenytoin, and levetiracetam. After three weeks a moderate improvement in seizure control has been achieved with carbamazepine. Exome sequencing detected a de novo heterozygous mutation in the SCN2A gene, encoding the α II -subunit of a sodium channel. The patient findings expand the phenotype spectrum of SCN2A mutations to epileptic encephalopathies with macroscopic brain developmental features. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  11. SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures.

    Science.gov (United States)

    Howell, Katherine B; McMahon, Jacinta M; Carvill, Gemma L; Tambunan, Dimira; Mackay, Mark T; Rodriguez-Casero, Victoria; Webster, Richard; Clark, Damian; Freeman, Jeremy L; Calvert, Sophie; Olson, Heather E; Mandelstam, Simone; Poduri, Annapurna; Mefford, Heather C; Harvey, A Simon; Scheffer, Ingrid E

    2015-09-15

    De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy. Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping. Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one. Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control. © 2015 American Academy of Neurology.

  12. 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

    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...... 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...

  13. Statistical simulation of hadron-nucleus and light nucleus-nucleus interaction. Intranuclear cascade model

    International Nuclear Information System (INIS)

    Lobov, G.A.; Stepanov, N.V.; Sibirtsev, A.A.; Trebukhovskij, Yu.V.

    1983-01-01

    A new version of the program of statistical simulation of hadron-nucleus and light nucleus-nucleus interaction is elaborated. The cascade part of the program is described. The comparison of model predictions with the proton-nucleus interaction experiments is performed. A satisfactory calculations-experiment agreement is obtained

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

    International Nuclear Information System (INIS)

    Sato, H.; Okuhara, Y.

    1985-07-01

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

  15. Anomalously high thermoelectric power factor in epitaxial ScN thin films

    International Nuclear Information System (INIS)

    Kerdsongpanya, Sit; Zukauskaite, Agne; Jensen, Jens; Birch, Jens; Lu Jun; Hultman, Lars; Wingqvist, Gunilla; Eklund, Per; Van Nong, Ngo; Pryds, Nini

    2011-01-01

    Thermoelectric properties of ScN thin films grown by reactive magnetron sputtering on Al 2 O 3 (0001) wafers are reported. X-ray diffraction and elastic recoil detection analyses show that the composition of the films is close to stoichiometry with trace amounts (∼1 at. % in total) of C, O, and F. We found that the ScN thin-film exhibits a rather low electrical resistivity of ∼2.94 μΩm, while its Seebeck coefficient is approximately ∼-86 μV/K at 800 K, yielding a power factor of ∼2.5 x 10 -3 W/mK 2 . This value is anomalously high for common transition-metal nitrides.

  16. Recurrent and non-recurrent mutations of SCN8A in epileptic encephalopathy

    Directory of Open Access Journals (Sweden)

    Jacy L Wagnon

    2015-05-01

    Full Text Available Mutations of the voltage-gated sodium channel SCN8A have been identified in approximately 1% of nearly 1,000 children with early-infantile epileptic encephalopathies (EIEE who have been tested by DNA sequencing. EIEE caused by mutation of SCN8A is designated EIEE13 (OMIM #614558. Affected children have seizure onset before 18 months of age as well as developmental and cognitive disabilities, movement disorders, and a high incidence of sudden death (SUDEP. EIEE13 is caused by de novo missense mutations of evolutionarily conserved residues in the Nav1.6 channel protein. One-third of the mutations are recurrent, and many occur at CpG dinucleotides. In this review we discuss the effect of pathogenic mutations on the structure of the channel protein, the rate of recurrent mutation, and changes in channel function underlying this devastating disorder.

  17. Multifragmentation in peripheral nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Trautmann, W.; Adloff, J.C.; Bouissou, P.; Hubele, J.; Imme, G.; Iori, I.; Kreutz, P.; Leray, S.; Lindenstruth, V.; Liu, Z.; Lynen, U.; Meijer, R.J.; Milkau, U.; Moroni, A.; Mueller, W.F.J.; Ngo, C.; Ogilvie, C.A.; Pochodzalla, J.; Raciti, G.; Rudolf, G.; Schuettauf, A.; Stuttge, L.

    1993-10-01

    The complete fragmentation of highly excited nuclear systems into fragments of intermediate mass is observed in heavy-ion reactions at relativistic bombarding energies in the range of several hundreds of MeV per nucleon. Similar features are found for peripheral collisions between heavy nuclei and for more central collisions between a heavy and a light nucleus. The partition space explored in multifragment decays is well described by the statistical multifragmentation models. The expansion before breakup is confirmed by the analysis of the measured fragment energies of ternary events in their own rest frame. Collective radial flow is confined to rather small values in these peripheral-type reactions. Many conceptually different models seem to be capable of reproducing the charge correlations measured for the multifragment decays. (orig.)

  18. 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.

  19. Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis.

    Science.gov (United States)

    Corrochano, Silvia; Männikkö, Roope; Joyce, Peter I; McGoldrick, Philip; Wettstein, Jessica; Lassi, Glenda; Raja Rayan, Dipa L; Blanco, Gonzalo; Quinn, Colin; Liavas, Andrianos; Lionikas, Arimantas; Amior, Neta; Dick, James; Healy, Estelle G; Stewart, Michelle; Carter, Sarah; Hutchinson, Marie; Bentley, Liz; Fratta, Pietro; Cortese, Andrea; Cox, Roger; Brown, Steve D M; Tucci, Valter; Wackerhage, Henning; Amato, Anthony A; Greensmith, Linda; Koltzenburg, Martin; Hanna, Michael G; Acevedo-Arozena, Abraham

    2014-12-01

    Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathies, including non-dystrophic myotonias and periodic paralysis. The effects of many of these mutations on channel function have been characterized both in vitro and in vivo. However, little is known about the consequences of SCN4A mutations downstream from their impact on the electrophysiology of the Nav1.4 channel. Here we report the discovery of a novel SCN4A mutation (c.1762A>G; p.I588V) in a patient with myotonia and periodic paralysis, located within the S1 segment of the second domain of the Nav1.4 channel. Using N-ethyl-N-nitrosourea mutagenesis, we generated and characterized a mouse model (named draggen), carrying the equivalent point mutation (c.1744A>G; p.I582V) to that found in the patient with periodic paralysis and myotonia. Draggen mice have myotonia and suffer from intermittent hind-limb immobility attacks. In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms. We discovered metabolic alterations leading to lean mice, as well as abnormal AMP-activated protein kinase activation, which were associated with the immobility attacks and may provide a novel potential therapeutic target. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

  20. 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.

  1. 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.

  2. Anomalously high thermoelectric power factor in epitaxial ScN thin films

    DEFF Research Database (Denmark)

    Kerdsongpanya, Sit; Van Nong, Ngo; Pryds, Nini

    2011-01-01

    found that the ScN thin-film exhibits a rather low electrical resistivity of ∼2.94 μΩm, while its Seebeck coefficient is approximately ∼−86 μV/K at 800 K, yielding a power factor of ∼2.5 × 10−3 W/mK2. This value is anomalously high for common transition-metal nitrides. © 2011 American Institute...

  3. SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism.

    Science.gov (United States)

    Sundaram, Senthil K; Chugani, Harry T; Tiwari, Vijay N; Huq, A H M M

    2013-07-01

    Genetic mutations play a crucial role in the etiology of cryptogenic infantile spasms, but the cause is still unknown in a significant proportion of patients. Whole exome sequencing technology shows great promise in identifying genetic causes of infantile spasms. In this study whole exome sequencing was performed with 2-deoxy-2-((18)F)fluoro-d-glucose positron emission tomography scan of an infant boy with infantile spasms. Exome sequencing was also performed in the parents to identify any de novo mutations. The positron emission tomography scan showed a pattern of bilateral symmetric temporal lobe glucose hypometabolism. A total of 8171 nonsynonymous variants were identified in the child. Despite the large number of nonsynonymous variants, there was only a single de novo missense mutation in SCN2A in the child (NCBI hg19 assembly, position: Chr2:166234116, K1422E). Subsequent Sanger sequencing confirmed the de novo status of this variant. This mutation has never been reported in 6500 individuals of the exome variant server database. Similarly, this variant is not reported in the Online Mendelian Inheritance in Man Database or the Human Gene Mutation Database. It has previously been shown that SCN2A mutations are associated with hippocampal hyperexcitability. Therefore, this study indicates that infantile spasms and bitemporal hypometabolism in this patient might have been caused by hippocampal hyperexcitability due to SCN2A mutation. The simultaneous presence of an SCN2A mutation and bitemporal hypometabolism in this patient with infantile spasms suggests a plausible hippocampal origin. However, additional mechanistic and clinical studies are required to validate this link. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy.

    Science.gov (United States)

    de Kovel, Carolien G F; Meisler, Miriam H; Brilstra, Eva H; van Berkestijn, Frederique M C; van 't Slot, Ruben; van Lieshout, Stef; Nijman, Isaac J; O'Brien, Janelle E; Hammer, Michael F; Estacion, Mark; Waxman, Stephen G; Dib-Hajj, Sulayman D; Koeleman, Bobby P C

    2014-11-01

    Recently, de novo SCN8A missense mutations have been identified as a rare dominant cause of epileptic encephalopathies (EIEE13). Functional studies on the first described case demonstrated gain-of-function effects of the mutation. We describe a novel de novo mutation of SCN8A in a patient with epileptic encephalopathy, and functional characterization of the mutant protein. Whole exome sequencing was used to discover the variant. We generated a mutant cDNA, transfected HEK293 cells, and performed Western blotting to assess protein stability. To study channel functional properties, patch-clamp experiments were carried out in transfected neuronal ND7/23 cells. The proband exhibited seizure onset at 6 months of age, diffuse brain atrophy, and more profound developmental impairment than the original case. The mutation p.Arg233Gly in the voltage sensing transmembrane segment D1S4 was present in the proband and absent in both parents. This mutation results in a temperature-sensitive reduction in protein expression as well as reduced sodium current amplitude and density and a relative increased response to a slow ramp stimulus, though this did not result in an absolute increased current at physiological temperatures. The new de novo SCN8A mutation is clearly deleterious, resulting in an unstable protein with reduced channel activity. This differs from the gain-of-function attributes of the first SCN8A mutation in epileptic encephalopathy, pointing to heterogeneity of mechanisms. Since Nav1.6 is expressed in both excitatory and inhibitory neurons, a differential effect of a loss-of-function of Nav1.6 Arg223Gly on inhibitory interneurons may underlie the epilepsy phenotype in this patient. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Antiproton-nucleus interaction

    International Nuclear Information System (INIS)

    Gibbs, W.R.

    1984-01-01

    Several facets of antinucleon-nucleus interactions are explored. The topics treated are: coherent interactions, production of unusual states and particles in the nuclear medium, and the creation of extreme states of matter by antimatter annihilation. It is found that temperatures of the magnitude necessary to achieve the predicted quark-gluon phase transition are obtained. 20 references

  6. Multiple arrhythmic syndromes in a newborn, owing to a novel mutation in SCN5A

    Science.gov (United States)

    Calloe, Kirstine; Schmitt, Nicole; Grubb, Soren; Pfeiffer, Ryan; David, Jens-Peter; Kanter, Ronald; Cordeiro, Jonathan M.; Antzelevitch, Charles

    2011-01-01

    Background Mutations in the SCN5A gene have been linked to Brugada syndrome (BrS), conduction disease, Long QT syndrome (LQT3), atrial fibrillation (AF), and to pre- and neonatal ventricular arrhythmias. Objective The objective of this study is to characterize a novel mutation in Nav1.5 found in a newborn with fetal chaotic atrial tachycardia, postpartum intraventricular conduction delay, and QT interval prolongation. Methods Genomic DNA was isolated and all exons and intron borders of 15 ion-channel genes were sequenced, revealing a novel missense mutation (Q270K) in SCN5A. Nav1.5 wild type (WT) and Q270K were expressed in CHO-K1 with and without the Navβ1 subunit. Results Patch-clamp analysis showed ~40% reduction in peak sodium channel current (INa) density for Q270K compared with WT. Fast and slow decay of INa were significantly slower in Q270K. Steady-state activation and inactivation of Q270K channels were shifted to positive potentials, and window current was increased. The tetrodotoxin-sensitive late INa was increased almost 3-fold compared with WT channels. Ranolazine reduced late INa in WT and Q270K channels, while exerting minimal effects on peak INa. Conclusion The Q270K mutation in SCN5A reduces peak INa while augmenting late INa, and may thus underlie the development of atrial tachycardia, intraventricular conduction delay, and QT interval prolongation in an infant. PMID:21895525

  7. Copper(I) thiocyanate (CuSCN) as a hole-transport material for large-area opto/electronics

    Science.gov (United States)

    Wijeyasinghe, Nilushi; Anthopoulos, Thomas D.

    2015-10-01

    Recent advances in large-area optoelectronics research have demonstrated the tremendous potential of copper(I) thiocyanate (CuSCN) as a universal hole-transport interlayer material for numerous applications, including transparent thin-film transistors, high-efficiency organic and hybrid organic-inorganic photovoltaic cells, and organic light-emitting diodes. CuSCN combines intrinsic hole-transport (p-type) characteristics with a large bandgap (>3.5 eV) which facilitates optical transparency across the visible to near infrared part of the electromagnetic spectrum. Furthermore, CuSCN is readily available from commercial sources while it is inexpensive and can be processed at low-temperatures using solution-based techniques. This unique combination of desirable characteristics makes CuSCN a promising material for application in emerging large-area optoelectronics. In this review article, we outline some important properties of CuSCN and examine its use in the fabrication of potentially low-cost optoelectronic devices. The merits of using CuSCN in numerous emerging applications as an alternative to conventional hole-transport materials are also discussed.

  8. Study of Relativistic Nucleus - Nucleus Collisions

    CERN Multimedia

    2002-01-01

    The aim of the experiment is to survey the reaction mechanisms involved in the collision of 60~GeV/nucleon and 200~GeV/nucleon light ions ($^{16}$0 and $^{32}$S provided by a new GSI-LBL injector) with different nuclei, to determine the stopping power of nuclear matter and to search for evidence of the formation of quark matter by comparison to hadron-nucleus reactions at the same incident energies. \\\\ The experimental set-up consists of a 2 m Streamer Chamber in the Vertex Magnet used to detect all the charged particles emerging from the interaction as well as the neutral strange particles that decay inside the chamber. The high energy of the forward-going particles are detected by four sets of calorimeters. A highly segmented Photon Position Detector (PPD) backed up by a 240 segment Ring Calorimeter will cover one unit of rapidity around mid-rapidity. An Intermediate Calorimeter will cover the rest of the forward phase space except for the region around beam rapidity, where a Veto Calorimeter will detect be...

  9. SCN4A variants and Brugada syndrome: phenotypic and genotypic overlap between cardiac and skeletal muscle sodium channelopathies.

    Science.gov (United States)

    Bissay, Véronique; Van Malderen, Sophie C H; Keymolen, Kathelijn; Lissens, Willy; Peeters, Uschi; Daneels, Dorien; Jansen, Anna C; Pappaert, Gudrun; Brugada, Pedro; De Keyser, Jacques; Van Dooren, Sonia

    2016-03-01

    SCN5A mutations involving the α-subunit of the cardiac voltage-gated muscle sodium channel (NaV1.5) result in different cardiac channelopathies with an autosomal-dominant inheritance such as Brugada syndrome. On the other hand, mutations in SCN4A encoding the α-subunit of the skeletal voltage-gated sodium channel (NaV1.4) cause non-dystrophic myotonia and/or periodic paralysis. In this study, we investigated whether cardiac arrhythmias or channelopathies such as Brugada syndrome can be part of the clinical phenotype associated with SCN4A variants and whether patients with Brugada syndrome present with non-dystrophic myotonia or periodic paralysis and related gene mutations. We therefore screened seven families with different SCN4A variants and non-dystrophic myotonia phenotypes for Brugada syndrome and performed a neurological, neurophysiological and genetic work-up in 107 Brugada families. In the families with an SCN4A-associated non-dystrophic myotonia, three patients had a clinical diagnosis of Brugada syndrome, whereas we found a remarkably high prevalence of myotonic features involving different genes in the families with Brugada syndrome. One Brugada family carried an SCN4A variant that is predicted to probably affect function, one family suffered from a not genetically confirmed non-dystrophic myotonia, one family was diagnosed with myotonic dystrophy (DMPK gene) and one family had a Thomsen disease myotonia congenita (CLCN1 variant that affects function). Our findings and data suggest a possible involvement of SCN4A variants in the pathophysiological mechanism underlying the development of a spontaneous or drug-induced type 1 electrocardiographic pattern and the occurrence of malignant arrhythmias in some patients with Brugada syndrome.

  10. Leukocyte nucleus segmentation and nucleus lobe counting.

    Science.gov (United States)

    Chan, Yung-Kuan; Tsai, Meng-Hsiun; Huang, Der-Chen; Zheng, Zong-Han; Hung, Kun-Ding

    2010-11-12

    Leukocytes play an important role in the human immune system. The family of leukocytes is comprised of lymphocytes, monocytes, eosinophils, basophils, and neutrophils. Any infection or acute stress may increase or decrease the number of leukocytes. An increased percentage of neutrophils may be caused by an acute infection, while an increased percentage of lymphocytes can be caused by a chronic bacterial infection. It is important to realize an abnormal variation in the leukocytes. The five types of leukocytes can be distinguished by their cytoplasmic granules, staining properties of the granules, size of cell, the proportion of the nuclear to the cytoplasmic material, and the type of nucleolar lobes. The number of lobes increased when leukemia, chronic nephritis, liver disease, cancer, sepsis, and vitamin B12 or folate deficiency occurred. Clinical neutrophil hypersegmentation has been widely used as an indicator of B12 or folate deficiency.Biomedical technologists can currently recognize abnormal leukocytes using human eyes. However, the quality and efficiency of diagnosis may be compromised due to the limitations of the biomedical technologists' eyesight, strength, and medical knowledge. Therefore, the development of an automatic leukocyte recognition system is feasible and necessary. It is essential to extract the leukocyte region from a blood smear image in order to develop an automatic leukocyte recognition system. The number of lobes increased when leukemia, chronic nephritis, liver disease, cancer, sepsis, and vitamin B12 or folate deficiency occurred. Clinical neutrophil hypersegmentation has been widely used as an indicator of B12 or folate deficiency. The purpose of this paper is to contribute an automatic leukocyte nuclei image segmentation method for such recognition technology. The other goal of this paper is to develop the method of counting the number of lobes in a cell nucleus. The experimental results demonstrated impressive segmentation accuracy

  11. 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.

  12. Stress and strain effects on the electronic structure and optical properties of ScN monolayer

    Science.gov (United States)

    Tamleh, Shirin; Rezaei, Ghasem; Jalilian, Jaafar

    2018-02-01

    Based on the density functional theory, electronic and optical properties of a monolayer scandium nitride structure have been studied under different strain conditions. Our results indicate that both biaxial compressive and tensile strain effects lead to change the band gap of this structure with different rates. Also, optical absorption spectrum peaks experience an obvious red and blue shifts with the exerting of tensile and compressive strains, respectively. Our results express that ScN monolayer can be the promising candidate for the future nano-base electrical and optical devices.

  13. Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A

    DEFF Research Database (Denmark)

    Tfelt-Hansen, J; Jespersen, T; Hofman-Bang, J

    2009-01-01

    -cell patch clamp experiments using human embryonic kidney 293 cells transfected with the mutated SCN5A, no current could be recorded. Hence, the results suggest that the patient suffered from haploinsufficiency of Na(v)1.5, and that this mutation was the cause of his Brugada syndrome.......The aim of the present study was to identify the molecular mechanism behind ventricular tachycardia in a patient with Brugada syndrome. Arrhythmias in patients with Brugada syndrome often occur during sleep. However, a 28-year-old man with no previously documented arrhythmia or syncope who...

  14. SCN1Bb R214Q found in 3 patients: 1 with Brugada syndrome and 2 with lone atrial fibrillation

    DEFF Research Database (Denmark)

    Olesen, Morten S; Holst, Anders G; Haunsø, Stig

    2012-01-01

    BACKGROUND: SCN1Bb encodes the ß-subunit of the sodium channel. A mutation in SCN1Bb R214Q has recently been shown both to increase the Kv4.3 current and to decrease the sodium current. The variant was suggested to increase the susceptibility to Brugada syndrome (BrS). OBJECTIVE: To sequence...... a population of BrS and early-onset lone atrial fibrillation (AF) patients for the R214Q mutation in the SCN1Bb gene. METHODS: The coding sequence and splice junctions of SCN1Bb were bidirectionally sequenced by using Big Dye chemistry in 192 early-onset lone AF patients and 22 BrS patients. RESULTS: Three......) and has not previously been reported in conjunction to AF. CONCLUSION: Three patients of 192 young lone AF and 22 BrS patients carried the nonsynonymous R214Q mutations in SCN1Bb, thereby indicating that this variant increases the susceptibility to both BrS and AF....

  15. The imaginary part of the nucleus - nucleus optical potential

    International Nuclear Information System (INIS)

    Phatak, S.C.; Sinha, B.

    1978-01-01

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

  16. Higgs-Boson Production in Nucleus-Nucleus Collisions

    Science.gov (United States)

    Norbury, John W.

    1992-01-01

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

  17. Global features of nucleus-nucleus collisions in ultrarelativistic domain

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  18. Heterobimetallic thiocyanato-bridged coordination polymers based on [Hg(SCN)4]2-: Synthesis, crystal structure, magnetic properties and ESR studies

    International Nuclear Information System (INIS)

    Jian Fangfang; Xiao Hailian; Liu Faqian

    2006-01-01

    Three new M/Hg bimetallic thiocyanato-bridged coordination polymers; [Hg(SCN) 4 Ni(Im) 3 ] ∞ 1, [Hg(SCN) 4 Mn(Im) 2 ] ∞ 2, and [Hg(SCN) 4 Cu(Me-Im) 2 Hg(SCN) 4 Cu(Me-Im) 4 ] ∞ 3, (Im=imidazole, Me-Im=N-methyl-imidazole), have been synthesized and characterized by means of elemental analysis, ESR, and single-crystal X-ray. X-ray diffraction analysis reveals that these three complexes all form 3D network structure, and their structures all contain a thiocyanato-bridged Hg...Hg chain (M=Mn, Ni, Cu) in which the metal and mercury centers exhibit different coordination environments. In complex 1, the [Hg(SCN) 4 ] 2- anion connects three [Ni(Im) 3 ] 2+ using three SCN ligands giving rise to a 3D structure, and in complex 2, four SCN ligands bridge [Hg(SCN) 4 ] 2- and [Mn(Im) 2 ] 2+ to form a 3D structure. The structure of 3 contains two copper atoms with distinct coordination environment; one is coordinated by four N-methyl-imidazole ligands and two axially elongated SCN groups, and another by four SCN groups (two elongated) and two N-methyl-imidazole ligands. The magnetic property of complex 1 has been investigated. The spin state structure in hetermetallic NiHgNi systems of complex 1 is irregular. The ESR spectra results of complex 3 demonstrate Cu 2+ ion lie on octahedral environment. -- Graphical abstract: Three new M/Hg bimetallic thiocyanato-bridged coordination polymers; [Hg(SCN) 4 Ni(Im) 3 ] ∞ 1, [Hg(SCN) 4 Mn(Im) 2 ] ∞ 2, and [Hg(SCN) 4 Cu(Me-Im) 2 Hg(SCN) 4 Cu(Me-Im) 4 ] ∞ 3, (Im=imidazole, Me-Im=N-methyl-imidazole), have been synthesized and characterized by single-crystal X-ray. All coordination polymers possess 3-D structures, and consist of organic base neutral ligands (imidazole and N-methyl-imidazole) and SCN -1 anions. Their structural difference is mainly caused by the role of the organic base and metal ions. The complex 1 shows the irregular spin state structure

  19. Development of the light sensitivity of the clock genes Period1 and Period2, and immediate-early gene c-fos within the rat suprachiasmatic nucleus

    Czech Academy of Sciences Publication Activity Database

    Matějů, Kristýna; Bendová, Zdena; El-Hennamy, Rehab; Sládek, Martin; Sosniyenko, Serhiy; Sumová, Alena

    2009-01-01

    Roč. 29, č. 3 (2009), s. 490-501 ISSN 0953-816X 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 : circadian clock * ontogenesis * photic entrainment Subject RIV: FH - Neuro logy Impact factor: 3.418, year: 2009

  20. 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.

  1. Altered gene expression profile in a mouse model of SCN8A encephalopathy.

    Science.gov (United States)

    Sprissler, Ryan S; Wagnon, Jacy L; Bunton-Stasyshyn, Rosie K; Meisler, Miriam H; Hammer, Michael F

    2017-02-01

    SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Na v 1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures. The abundance of 50 transcripts increased more than 3-fold and 15 transcripts decreased more than 3-fold after seizures. The elevated transcripts included two anti-convulsant neuropeptides and more than a dozen genes involved in reactive astrocytosis and response to neuronal damage. There was no change in the level of transcripts encoding other voltage-gated sodium, potassium or calcium channels. Reactive astrocytosis was observed in the hippocampus of mutant mice after seizures. There is considerable overlap between the genes affected in this genetic model of epilepsy and those altered by chemically induced seizures, traumatic brain injury, ischemia, and inflammation. The data support the view that gain-of-function mutations of SCN8A lead to pathogenic alterations in brain function contributing to encephalopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. SCN8A Epileptic Encephalopathy: Detection of Fetal Seizures Guides Multidisciplinary Approach to Diagnosis and Treatment.

    Science.gov (United States)

    McNally, Melanie A; Johnson, Julia; Huisman, Thierry A; Poretti, Andrea; Baranano, Kristin W; Baschat, Ahmet A; Stafstrom, Carl E

    2016-11-01

    SCN8A mutations are rare and cause a phenotypically heterogeneous early onset epilepsy known as early infantile epileptic encephalopathy type 13 (EIEE13, OMIM #614558). There are currently no clear genotype-phenotype correlations to help guide patient counseling and management. We describe a patient with EIEE13 (de novo heterozygous pathogenic mutation in SCN8A - p.Ile240Val (ATT>GTT)) who presented prenatally with maternally reported intermittent, rhythmic movements that, when observed on ultrasound, were concerning for fetal seizures. Ultrasound also revealed abnormal developmental states. With maternal administration of levetiracetam, the rhythmic fetal movements stopped. After birth, the patient developed treatment-refractory multi-focal epilepsy confirmed by electroencephalogram. Neuroimaging revealed restricted diffusion in the superior cerebellar peduncles, a finding not reported previously in EIEE13. This is the first report of EIEE13 associated with clinical prenatal-onset seizures. Ultrasonography can be useful for identifying fetal seizures, which may be treatable in utero. Ideally, the clinical approach to fetal seizures should involve a multidisciplinary team spanning the pre- and postnatal course to expedite early diagnosis and optimize management, as illustrated by this patient. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body.

    Science.gov (United States)

    Evans, Jennifer A; Suen, Ting-Chung; Callif, Ben L; Mitchell, Andrew S; Castanon-Cervantes, Oscar; Baker, Kimberly M; Kloehn, Ian; Baba, Kenkichi; Teubner, Brett J W; Ehlen, J Christopher; Paul, Ketema N; Bartness, Timothy J; Tosini, Gianluca; Leise, Tanya; Davidson, Alec J

    2015-06-23

    Daily rhythms in mammals are programmed by a master clock in the suprachiasmatic nucleus (SCN). The SCN contains two main compartments (shell and core), but the role of each region in system-level coordination remains ill defined. Herein, we use a functional assay to investigate how downstream tissues interpret region-specific outputs by using in vivo exposure to long day photoperiods to temporally dissociate the SCN. We then analyze resulting changes in the rhythms of clocks located throughout the brain and body to examine whether they maintain phase synchrony with the SCN shell or core. Nearly all of the 17 tissues examined in the brain and body maintain phase synchrony with the SCN shell, but not the SCN core, which indicates that downstream oscillators are set by cues controlled specifically by the SCN shell. Interestingly, we also found that SCN dissociation diminished the amplitude of rhythms in core clock gene and protein expression in brain tissues by 50-75 %, which suggests that light-driven changes in the functional organization of the SCN markedly influence the strength of rhythms in downstream tissues. Overall, our results reveal that body clocks receive time-of-day cues specifically from the SCN shell, which may be an adaptive design principle that serves to maintain system-level phase relationships in a changing environment. Further, we demonstrate that lighting conditions alter the amplitude of the molecular clock in downstream tissues, which uncovers a new form of plasticity that may contribute to seasonal changes in physiology and behavior.

  4. 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.

  5. 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.

  6. Mutation status of gene CACNA1S and SCN4A in the hypokalemic periodic paralysis pedigree in Chinese population

    Directory of Open Access Journals (Sweden)

    Kun WU

    2013-04-01

    Full Text Available Objective  To investigate the mutation status of gene CACNA1S and SCN4A in hypokalemic periodic paralysis (HPP pedigree of Chinese population, and compare the status with that in Caucasian populations as reported in previous literature. Methods  To define the gene mutation status, the genes CACNA1S and SCN4A were sequenced by PCR and DNA sequencing technology in two familial HPP pedigrees, one hyperthyroid HPP pedigree and four sporadic HPP patients, the findings were then compared with the reference sequences in gene library. A total of nine relevant reports concerning the gene CACNA1S and SCN4A mutation of HPP pedigree published from Jan. 1999 to Dec. 2012 were retrieved from PubMed database. Results  All the probands were suffering from paroxysmal muscle weakness with hypokalemia. As a typical symptom of HPP, muscle weakness often involved the extremities. Auxiliary examination confirmed serum hypopotassemia, electrocardiogram (ECG showed hypokalemic change, and electromyography (EMG showed shortened motor potential duration and low amplitude. All the findings mentioned above were in accordance with clinical diagnosis of HPP. Gene analysis indicated that no mutation of CACNA1S and SCN4A was found in the probands, the family members of the three HPP pedigrees and the four patients of sporadic HPP. The previous literature presented that mutation rate of gene CACN1AS and SCN4A was much higher in Caucasian HPP patients than in Chinese population. Conclusion  The mutation rate of gene CACN1AS and SCN4A is lower in Chinese HPP patients than in Caucasian patients with significant difference.

  7. 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.

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  9. Antiproton-nucleus scattering

    International Nuclear Information System (INIS)

    Shastry, C.S.

    1988-01-01

    The operation of low energy antiproton ring at CERN has initiated antiproton-nucleus(antip - A) collision experiments. These give information on antiproton-nucleon(antiproton - N) interaction in the nuclei, structure of antiprotonic atoms, antiprotonic bound states in the nucleus, strange particle production etc. Considerable data on antiproton - A scattering cross sections at several incident energies for targets like 12 C, 16 O, 18 Ca etc. have become available. Both elastic and inelastic antiproton-A cross sections show diffractive oscillatory behaviour. As a result, it is possible to qualitatively understand antiproton-A cross sections by treating the target as a black sphere with diffused surface. Phenomenological optical potentials including those generated by the model independent Fourier-Bessel method show that the potential is highly absorptive; imaginary part dominates and has longer range than real part and the latter decreases with energy. Spin-orbit term is less important. Some of these can be understood in terms of meson exchange antiproton-N potentials. The large imaginary part is due to the availability of additional channels initiated by antiproton annihilation. Optical potentials show several ambiguities including the Igo ambiguity. More fundamental approaches to the potential based on antiproton-N t matrix and folding models have been attempted. A comparison of heavy ion scatering and antiproton-A scattering is made. It is shown that semi-classical WKB method is applicable for antiproton-A scattering. Some recent work on antiproton-p potentials, antiprotonic states and strange particle production is discussed. (author). 28 refs., 10 figs., 7 tables

  10. Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry.

    Science.gov (United States)

    Yamagata, Kenichiro; Horie, Minoru; Aiba, Takeshi; Ogawa, Satoshi; Aizawa, Yoshifusa; Ohe, Tohru; Yamagishi, Masakazu; Makita, Naomasa; Sakurada, Harumizu; Tanaka, Toshihiro; Shimizu, Akihiko; Hagiwara, Nobuhisa; Kishi, Ryoji; Nakano, Yukiko; Takagi, Masahiko; Makiyama, Takeru; Ohno, Seiko; Fukuda, Keiichi; Watanabe, Hiroshi; Morita, Hiroshi; Hayashi, Kenshi; Kusano, Kengo; Kamakura, Shiro; Yasuda, Satoshi; Ogawa, Hisao; Miyamoto, Yoshihiro; Kapplinger, Jamie D; Ackerman, Michael J; Shimizu, Wataru

    2017-06-06

    The genotype-phenotype correlation of SCN5A mutations as a predictor of cardiac events in Brugada syndrome remains controversial. We aimed to establish a registry limited to probands, with a long follow-up period, so that the genotype-phenotype correlation of SCN5A mutations in Brugada syndrome can be examined without patient selection bias. This multicenter registry enrolled 415 probands (n=403; men, 97%; age, 46±14 years) diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations. During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/y. In comparison with probands without mutations ( SCN5A (-), n=355), probands with SCN5A mutations ( SCN5A (+), n=60) experienced their first cardiac event at a younger age (34 versus 42 years, P =0.013), had a higher positive rate of late potentials (89% versus 73%, P =0.016), exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events ( P =0.017 by log-rank). Multivariate analysis indicated that only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events ( SCN5A (+) versus SCN5A (-): hazard ratio, 2.0 and P =0.045; history of aborted cardiac arrest versus no such history: hazard ratio, 6.5 and P syndrome patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events. © 2017 American Heart Association, Inc.

  11. Turning dilemmas into opportunities: a UNU/SCN capacity development network in public nutrition in Central and Eastern Europe

    NARCIS (Netherlands)

    Pavlovic, M.; Pepping, F.; Demes, M.; Biro, L.; Szabolcs, P.; Dimitrovska, Z.; Duleva, V.; Parvan, C.; Hadziomeragic, A.F.; Glibetic, M.; Oshaug, A.

    2009-01-01

    Capacity development in nutrition is a process whereby individuals, groups, institutions, organizations and societies enhance their abilities to identify and meet challenges in a sustainable manner. To address these issues, in 2001 the UN System Standing Committee on Nutrition (SCN) established a

  12. 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...

  13. 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

  14. Mutation Analysis of KCNQ1, KCNH2 and SCN5A Genes in Taiwanese Long QT Syndrome Patients.

    Science.gov (United States)

    Chang, Ya-Sian; Yang, Yi-Wen; Lin, Yen-Nien; Lin, Kuo-Hung; Chang, Kuan-Cheng; Chang, Jan-Gowth

    2015-01-01

    Long QT syndrome (LQTS) is a genetic cardiac disease. Gene mutation affects the structure or function of ion channels that are associated with a high risk of sudden death. The goal of this study was to determine the frequency of KCNQ1, KCNH2, and SCN5A mutations in LQTS in a Taiwanese population. Genomic DNA was extracted from peripheral blood samples obtained from 5 patients with LQTS and the family members of 3 LQTS patients. High resolution melting (HRM) analysis and direct DNA sequencing were used to characterize the KCNQ1, KCNH2, and SCN5A genetic variations. HRM analysis was successfully optimized for 14 of the 16 exons of the KCNQ1, 5 of the 15 exons of the KCNH2, and 23 of the 27 exons of the SCN5A. HRM and direct DNA sequencing was applied to the cohort of 5 cases and some of their family. The genetic testing revealed two pathogenic mutations (p.T309I in KCNQ1 and p.R744fs in KCNH2) and all of the mutational frequencies in KCNQ1 and KCNH2 were 20%. In the two patients who carry the pathogenic mutation presenting with recurrent syncope due to ventricular fibrillation, an implantable cardioverter defibrillator was implanted. We also discovered 11 polymorphisms in KCNQ1, 3 in KCNH2, and 5 in SCN5A. Two-fifths of cases (40%) presented with one of the three major LQTS-causing gene mutations.

  15. Redetermination of the crystal structure of K2Hg(SCN4

    Directory of Open Access Journals (Sweden)

    Jascha Bandemehr

    2017-07-01

    Full Text Available Single crystals of K2Hg(SCN4 [dipotassium tetrathiocyanatomercurate(II] were grown from aqueous solutions of potassium thiocyanate and mercury(II thiocyanate and studied by single-crystal X-ray diffraction. In comparison with the previously reported structure model [Zvonkova (1952. Zh. Fiz. Khim. 26, 1798–1803], all atoms in the crystal structure were located, with lattice parameters and fractional coordinates determined to a much higher precision. In the (crystal structure, the HgII atom is located on a twofold rotation axis and is coordinated in the form of a distorted tetrahedron by four S atoms of the thiocyanate anions. The K+ cation shows a coordination number of eight.

  16. 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.

  17. Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia.

    Science.gov (United States)

    Schwarz, N; Hahn, A; Bast, T; Müller, S; Löffler, H; Maljevic, S; Gaily, E; Prehl, I; Biskup, S; Joensuu, T; Lehesjoki, A-E; Neubauer, B A; Lerche, H; Hedrich, U B S

    2016-02-01

    Mutations in SCN2A cause epilepsy syndromes of variable severity including neonatal-infantile seizures. In one case, we previously described additional childhood-onset episodic ataxia. Here, we corroborate and detail the latter phenotype in three further cases. We describe the clinical characteristics, identify the causative SCN2A mutations and determine their functional consequences using whole-cell patch-clamping in mammalian cells. In total, four probands presented with neonatal-onset seizures remitting after five to 13 months. In early childhood, they started to experience repeated episodes of ataxia, accompanied in part by headache or back pain lasting minutes to several hours. In two of the new cases, we detected the novel mutation p.Arg1882Gly. While this mutation occurred de novo in both patients, one of them carries an additional known variant on the same SCN2A allele, inherited from the unaffected father (p.Gly1522Ala). Whereas p.Arg1882Gly alone shifted the activation curve by -4 mV, the combination of both variants did not affect activation, but caused a depolarizing shift of voltage-dependent inactivation, and a significant increase in Na(+) current density and protein production. p.Gly1522Ala alone did not change channel gating. The third new proband carries the same de novo SCN2A gain-of-function mutation as our first published case (p.Ala263Val). Our findings broaden the clinical spectrum observed with SCN2A gain-of-function mutations, showing that fairly different biophysical mechanisms can cause a convergent clinical phenotype of neonatal seizures and later onset episodic ataxia.

  18. Diabatic interaction potential for nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Noerenberg, W.; Lukasiak, A.

    1984-01-01

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

  19. The subthalamic nucleus, Part I

    NARCIS (Netherlands)

    Marani, Enrico; Heida, Tjitske; Lakke, Egbert A.J.F.; Usunoff, Kamen G.

    2008-01-01

    Part I. Development, cytology, topography and connections. This monograph on the subthalamic nucleus accentuates in Part I the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections. The light and electron microscopical cytology

  20. K+ nucleus total cross sections

    International Nuclear Information System (INIS)

    Sawafta, R.

    1990-01-01

    The scattering of K + mesons from nuclei has attracted considerable interest in the last few years. The K + holds a very special position as the weakest of all strongly interaction probes. The average cross section is not larger than about 10 mb at lab momenta below 800 MeV/c, corresponding to a mean free path in the nucleus larger than 5 fm. Thus the K + is capable of probing the entire volume of the nucleus. Single scattering of the K + with a nucleon in the nucleus dominates the nuclear scattering, and only small and calculable higher order corrections are needed. The nucleon is a dynamical entity and its internal structure can, in principle, be altered by its surrounding nuclear environment. This work reports an experiment in which the K + is used to compare the nucleon in the nucleus with a free nucleon

  1. Circadian behaviour in neuroglobin deficient mice

    DEFF Research Database (Denmark)

    Hundahl, Christian A; Fahrenkrug, Jan; Hay-Schmidt, Anders

    2012-01-01

    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......-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....

  2. Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey

    DEFF Research Database (Denmark)

    Hannibal, J; Kankipati, L; Strang, C E

    2014-01-01

    Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are entrained to the environmental light/dark cycle via intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin and the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP......-expressing cells characterized as inner and outer stratifying melanopsin RGCs. Two macaque monkeys were anesthetized and received a unilateral intravitreal injection of CtB. Bilateral retinal projections containing colocalized CtB and PACAP immunostaining were identified in the SCN, the lateral geniculate complex...

  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

    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.

  4. Red light emission from ZnO:Eu{sup 3+}|CuSCN hetero-junction under cathodic polarization

    Energy Technology Data Exchange (ETDEWEB)

    Sirimanne, P.M., E-mail: psirimane@hotmail.com [Department of Science and Technology, Uwa Wellassa University, Badulla (Sri Lanka); Minoura, H. [Environmental and Renewable Energy Systems Division, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan)

    2015-09-15

    Eu{sup 3+} ions were bonded to ZnO ceramic via organic ligand. Surface bonded Eu{sup 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{sup 3+} ions. A hetero-junction was prepared by depositing copper-thiocyanate on Eu{sup 3+} ions bonded ZnO ceramic. Red light emission was observed from surface bonded Eu{sup 3+} ions in ZnO:Eu{sup 3+}|CuSCN hetero-junction under reverse bias. - Highlights: • Europium doped ZnO ceramic exhibits photo-luminescence. • Semiconductor hetro-junction was prepared. • ZnO:Eu{sup 3+}|CuSCN hetero-junction emits red light under reverse bias.

  5. 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.

  6. 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.

  7. Crystal structure of K[Hg(SCN3] – a redetermination

    Directory of Open Access Journals (Sweden)

    Matthias Weil

    2014-09-01

    Full Text Available The crystal structure of the room-temperature modification of K[Hg(SCN3], potassium trithiocyanatomercurate(II, was redetermined based on modern CCD data. In comparison with the previous report [Zhdanov & Sanadze (1952. Zh. Fiz. Khim. 26, 469–478], reliability factors, standard deviations of lattice parameters and atomic coordinates, as well as anisotropic displacement parameters, were revealed for all atoms. The higher precision and accuracy of the model is, for example, reflected by the Hg—S bond lengths of 2.3954 (11, 2.4481 (8 and 2.7653 (6 Å in comparison with values of 2.24, 2.43 and 2.77 Å. All atoms in the crystal structure are located on mirror planes. The Hg2+ cation is surrounded by four S atoms in a seesaw shape [S—Hg—S angles range from 94.65 (2 to 154.06 (3°]. The HgS4 polyhedra share a common S atom, building up chains extending parallel to [010]. All S atoms of the resulting 1∞[HgS2/1S2/2] chains are also part of SCN− anions that link these chains with the K+ cations into a three-dimensional network. The K—N bond lengths of the distorted KN7 polyhedra lie between 2.926 (2 and 3.051 (3 Å.

  8. 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

  9. The first pseudo-ternary thiocyanate containing two alkali metals. Synthesis and single-crystal structure of LiK2[SCN]3

    International Nuclear Information System (INIS)

    Reckeweg, Olaf; DiSalvo, Francis J.

    2016-01-01

    A procedure was empirically developed to prepare the compound LiK 2 [SCN] 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 2 [SCN] 3 adopts the orthorhombic space group Pna2 1 (no. 33, Z = 4) with the cell parameters a = 1209.32(9), b = 950.85(9), and c = 849.95(6) pm.

  10. Dysfunction of the Scn8a Voltage-gated Sodium Channel Alters Sleep Architecture, Reduces Diurnal Corticosterone Levels, and Enhances Spatial Memory

    OpenAIRE

    Papale, Ligia Assumpção [UNIFESP; Paul, Ketema N.; Sawyer, Nikki T.; Manns, Joseph R.; Tufik, Sergio [UNIFESP; Escayg, Andrew

    2010-01-01

    Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of transient depolarizing currents and play a critical role in the electrical signaling between neurons. A null mutation in the VGSC gene SCN8A, which encodes the transmembrane protein Na(v)1.6, was identified previously in a human family. Heterozygous mutation carriers displayed a range of phenotypes, including ataxia, cognitive deficits, and emotional instability. A possible role for SCN8A was also prop...

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

    KAUST Repository

    Pattanasattayavong, Pichaya

    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.

  12. 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.

  13. Fabrication and characterization of ZnO nano wires/Cd Se/CuSCN eta-solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Tena-Zaera, R.; Ryan, M.A.; Abou, Katty; Hodes, G.; Bastide, St.; Levy-Clement, C. [LCMTR, Institut des sciences chimiques Seine-Amont, CNRS, 94 - Thiais (France); Tena-Zaera, R. [Valancia Univ., Dept. Fisica Aplicada i Electromagnetisme (Spain); Ryan, M.A. [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA (United States); Hodes, G. [Weizmann Institute of Science, Dept. of Materials and Interfaces, Rehovot (Israel)

    2006-05-15

    ZnO/CdSe/CuSCN extremely thin absorber (eta)-solar cells based on ZnO nano-wires have been successfully realized using easily accessible electrochemical and solution deposition techniques. An n-type ZnO film consisting of free-standing single crystal nano-wires several microns high and 100-200 nm in diameter was-deposited on a conducting glass (SnO{sub 2}:F) substrate covered by a thin spray pyrolysis ZnO electronic blocking layer. A 30-40-nm-thin layer of CdSe absorber was electrodeposited, coating the ZnO nano-wires. The voids between the ZnO/CdSe nano-wires were filled with p-type CuSCN; the entire assembly formed a p-i-n junction. The ZnO/CdSe nano-wire layer exhibited a high light-trapping effect, with an effective absorbance of {approx}89% and effective reflectance of {approx}8% in the 400-800 nm region of the solar spectrum (AM1.5). The effects of an annealing process on the CdSe grain size and on the energy conversion efficiency of the eta-solar cell have been analyzed. The obtained efficiencies, for cells with annealed CdSe (1.5-2.3%) show that the ZnO/CdSe/CuSCN nano-heterostructure is an interesting option for developing new solar cell devices. (authors)

  14. Fabrication and characterization of ZnO nano wires/Cd Se/CuSCN eta-solar cell

    International Nuclear Information System (INIS)

    Tena-Zaera, R.; Ryan, M.A.; Abou, Katty; Hodes, G.; Bastide, St.; Levy-Clement, C.; Tena-Zaera, R.; Ryan, M.A.; Hodes, G.

    2006-01-01

    ZnO/CdSe/CuSCN extremely thin absorber (eta)-solar cells based on ZnO nano-wires have been successfully realized using easily accessible electrochemical and solution deposition techniques. An n-type ZnO film consisting of free-standing single crystal nano-wires several microns high and 100-200 nm in diameter was-deposited on a conducting glass (SnO 2 :F) substrate covered by a thin spray pyrolysis ZnO electronic blocking layer. A 30-40-nm-thin layer of CdSe absorber was electrodeposited, coating the ZnO nano-wires. The voids between the ZnO/CdSe nano-wires were filled with p-type CuSCN; the entire assembly formed a p-i-n junction. The ZnO/CdSe nano-wire layer exhibited a high light-trapping effect, with an effective absorbance of ∼89% and effective reflectance of ∼8% in the 400-800 nm region of the solar spectrum (AM1.5). The effects of an annealing process on the CdSe grain size and on the energy conversion efficiency of the eta-solar cell have been analyzed. The obtained efficiencies, for cells with annealed CdSe (1.5-2.3%) show that the ZnO/CdSe/CuSCN nano-heterostructure is an interesting option for developing new solar cell devices. (authors)

  15. 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.

  16. 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

  17. Neutrino anomaly and -nucleus interactions

    Indian Academy of Sciences (India)

    neutrino nucleus interactions in the domain of low and intermediate energy. The nuclear physics inputs mainly enter through two types of processes. These are: A. The nuclear processes responsible for neutrino production in the calculation of solar and atmospheric neutrino fluxes. B. The nuclear processes in which ...

  18. The nucleus as a laboratory

    International Nuclear Information System (INIS)

    Blin-Stoyle, R.J.

    1979-01-01

    The nucleus is a complicated many-body structure whose properties when carefully studied can frequently give important information about the underlying elementary particle interactions. This article reviews progress in research of this kind over the last twenty-five years. (author)

  19. 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

  20. Higgs and Particle Production in Nucleus-Nucleus Collisions

    Science.gov (United States)

    Liu, Zhe

    We apply a diagrammatic approach to study Higgs boson, a color-neutral heavy particle, pro- duction in nucleus-nucleus collisions in the saturation framework without quantum evolution. We assume the strong coupling constant much smaller than one. Due to the heavy mass and colorless nature of Higgs particle, final state interactions are absent in our calculation. In order to treat the two nuclei dynamically symmetric, we use the Coulomb gauge which gives the appropriate light cone gauge for each nucleus. To further eliminate initial state interactions we choose specific prescriptions in the light cone propagators. We start the calculation from only two nucleons in each nucleus and then demonstrate how to generalize the calculation to higher orders diagrammatically. We simplify the diagrams by the Slavnov-Taylor-Ward identities. The resulting cross section is factorized into a product of two Weizsacker-Williams gluon distributions of the two nuclei when the transverse momentum of the produced scalar particle is around the saturation momentum. To our knowledge this is the first process where an exact analytic formula has been formed for a physical process, involving momenta on the order of the saturation momentum, in nucleus-nucleus collisions in the quasi-classical approximation. Since we have performed the calculation in an unconventional gauge choice, we further confirm our results in Feynman gauge where the Weizsacker-Williams gluon distribution is interpreted as a transverse momentum broadening of a hard gluons traversing a nuclear medium. The transverse momentum factorization manifests itself in light cone gauge but not so clearly in Feynman gauge. In saturation physics there are two different unintegrated gluon distributions usually encountered in the literature: the Weizsacker-Williams gluon distribution and the dipole gluon distribution. The first gluon distribution is constructed by solving classical Yang-Mills equation of motion in the Mc

  1. Olanzapine-induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin.

    Science.gov (United States)

    Romo-Nava, Francisco; Buijs, Frederik N; Valdés-Tovar, Marcela; Benítez-King, Gloria; Basualdo, MariCarmen; Perusquía, Mercedes; Heinze, Gerhard; Escobar, Carolina; Buijs, Ruud M

    2017-05-01

    Second generation antipsychotics (SGA) are associated with adverse cardiometabolic side effects contributing to premature mortality in patients. While mechanisms mediating these cardiometabolic side effects remain poorly understood, three independent studies recently demonstrated that melatonin was protective against cardiometabolic risk in SGA-treated patients. As one of the main target areas of circulating melatonin in the brain is the suprachiasmatic nucleus (SCN), we hypothesized that the SCN is involved in SGA-induced early cardiovascular effects in Wistar rats. We evaluated the acute effects of olanzapine and melatonin in the biological clock, paraventricular nucleus and autonomic nervous system using immunohistochemistry, invasive cardiovascular measurements, and Western blot. Olanzapine induced c-Fos immunoreactivity in the SCN followed by the paraventricular nucleus and dorsal motor nucleus of the vagus indicating a potent induction of parasympathetic tone. The involvement of a SCN-parasympathetic neuronal pathway after olanzapine administration was further documented using cholera toxin-B retrograde tracing and vasoactive intestinal peptide immunohistochemistry. Olanzapine-induced decrease in blood pressure and heart rate confirmed this. Melatonin abolished olanzapine-induced SCN c-Fos immunoreactivity, including the parasympathetic pathway and cardiovascular effects while brain areas associated with olanzapine beneficial effects including the striatum, ventral tegmental area, and nucleus accumbens remained activated. In the SCN, olanzapine phosphorylated the GSK-3β, a regulator of clock activity, which melatonin prevented. Bilateral lesions of the SCN prevented the effects of olanzapine on parasympathetic activity. Collectively, results demonstrate the SCN as a key region mediating the early effects of olanzapine on cardiovascular function and show melatonin has opposing and potentially protective effects warranting additional investigation. © 2017

  2. Color oscillations of nucleons in a nucleus

    International Nuclear Information System (INIS)

    Petrov, V.A.; Smirnov, A.Yu.

    1987-01-01

    Possibility of nucleus description as an object consisting of quarks and gluons is considered. A model of two-nucleon interaction in a nucleus is presented and analytical expressions for the nucleus nucleon ground state wave functions and also for nuclear nucleon structure functions are obtained. The carried out analysis shows that the suggested model permits to express the nucleus structure functions at quark level only by means of nucleon and Δ-isobaric degrees of freedom

  3. Aberrant Sodium Channel Currents and Hyperexcitability of Medial Entorhinal Cortex Neurons in a Mouse Model of SCN8A Encephalopathy.

    Science.gov (United States)

    Ottolini, Matteo; Barker, Bryan S; Gaykema, Ronald P; Meisler, Miriam H; Patel, Manoj K

    2017-08-09

    SCN8A encephalopathy, or early infantile epileptic encephalopathy 13 (EIEE13), is caused predominantly by de novo gain-of-function mutations in the voltage-gated Na channel Na v 1.6. Affected individuals suffer from refractory seizures, developmental delay, cognitive disability, and elevated risk of sudden unexpected death in epilepsy (SUDEP). A knock-in mouse model carrying the patient mutation p.Asn1768Asp (N1768D) reproduces many features of the disorder, including spontaneous seizures and SUDEP. We used the mouse model to examine the effects of the mutation on layer II stellate neurons of the medial entorhinal cortex (mEC), which transmit excitatory input to the hippocampus. Heterozygous ( Scn8a D/+ ), homozygous ( Scn8a D/D) ), and WT ( Scn8a +/+ ) littermates were compared at 3 weeks of age, the time of seizure onset for homozygous mice. Heterozygotes remain seizure free for another month. mEC layer II neurons of heterozygous and homozygous mice were hyperexcitable and generated long-lasting depolarizing potentials with bursts of action potentials after synaptic stimulation. Recording of Na currents revealed proexcitatory increases in persistent and resurgent currents and rightward shifts in inactivation parameters, leading to significant increases in the magnitude of window currents. The proexcitatory changes were more pronounced in homozygous mice than in heterozygotes, consistent with the earlier age of seizure onset in homozygotes. These studies demonstrate that the N1768D mutation increases the excitability of mEC layer II neurons by increasing persistent and resurgent Na currents and disrupting channel inactivation. The aberrant activities of mEC layer II neurons would provide excessive excitatory input to the hippocampus and contribute to hyperexcitability of hippocampal neurons in this model of SCN8A encephalopathy. SIGNIFICANCE STATEMENT SCN8A encephalopathy is a devastating neurological disorder that results from de novo mutations in the Na channel

  4. Comet Halley: nucleus and jets

    International Nuclear Information System (INIS)

    Sagdeev, R.Z.; Avanesov, G.A.; Barinov, I.V.

    1986-06-01

    The VEGA-1 and VEGA-2 spacecrafts made their closest approach to Comet Halley on 6 and 9 March, respectively. In this paper results of the onboard imaging experiment are discussed. The nucleus of the comet was clearly identifyable as an irregularly shaped object with overall dimensions of (16+-1)x(8+-1)x(8+-1) km. The nucleus rotates around its axis which is nearly perpendicular to the orbital plane, with a period of 53+-2 hours. Its albedo is only 0.04+-002. Most of the jet features observed during the second fly-by were spatially reconstructed. These sources form a quasi-linear structure on the surface. The dust above the surface is shown to be optically thin except certain specific dust jets. Brightness features on the surface are clearly seen. Correlating the data with other measurements it is concluded that the dirty snow-ball model probably has to be revised. (author)

  5. Hummingbird Comet Nucleus Analysis Mission

    Science.gov (United States)

    Kojiro, Daniel; Carle, Glenn C.; Lasher, Larry E.

    2000-01-01

    Hummingbird is a highly focused scientific mission, proposed to NASA s Discovery Program, designed to address the highest priority questions in cometary science-that of the chemical composition of the cometary nucleus. After rendezvous with the comet, Hummingbird would first methodically image and map the comet, then collect and analyze dust, ice and gases from the cometary atmosphere to enrich characterization of the comet and support landing site selection. Then, like its namesake, Hummingbird would carefully descend to a pre-selected surface site obtaining a high-resolution image, gather a surface material sample, acquire surface temperature and then immediately return to orbit for detailed chemical and elemental analyses followed by a high resolution post-sampling image of the site. Hummingbird s analytical laboratory contains instrumentation for a comprehensive molecular and elemental analysis of the cometary nucleus as well as an innovative surface sample acquisition device.

  6. 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.

  7. Effect of Rare Earth Elements (Er, Ho) on Semi-Metallic Materials (ScN) in an Applied Electric Field

    Science.gov (United States)

    Kim, Hyunjung; Park, Yeonjoon; King, Glen C.; Lee, Kunik; Choi, Sang H.

    2012-01-01

    The development of materials and fabrication technology for field-controlled spectrally active optics is essential for applications such as membrane optics, filters for LIDARs, windows for sensors, telescopes, spectroscopes, cameras and flat-panel displays. The dopants of rare earth elements, in a host of optical systems, create a number of absorption and emission band structures and can easily be incorporated into many high quality crystalline and amorphous hosts. In wide band-gap semiconductors like ScN, the existing deep levels can capture or emit the mobile charges, and can be ionized with the loss or capture of the carriers which are the fundamental basis of concept for smart optic materials. The band gap shrinkage or splitting with dopants supports the possibility of this concept. In the present work, a semi-metallic material (ScN) was doped with rare earth elements (Er, Ho) and tested under an applied electric field to characterize spectral and refractive index shifts by either Stark or Zeeman Effect. These effects can be verified using the UV-Vis spectroscopy, the Hall Effect measurement and the ellipsometric spectroscopy. The optical band gaps of ScN doped with Er and doped with Ho were experimentally estimated as 2.33eV and 2.24eV ( 0.2eV) respectively. This is less than that of undoped ScN (2.5 0.2eV). The red-shifted absorption onset is a direct evidence for the decrease of band gap energy (Eg), and the broadening of valence band states is attributable to the doping cases. A decrease in refractive index with an applied field was observed as a small shift in absorption coefficient using a variable angle spectroscopic ellipsometer. In the presence of an electric field, mobile carriers are redistributed within the space charge region (SCR) to produce this electro-refractive effect. The shift in refractive index is also affected by the density and location of deep potential wells within the SCR. In addition, the microstructure change was observed by a TEM

  8. 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.

  9. Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures

    Science.gov (United States)

    Peters, C.; Rosch, R. E.; Hughes, E.; Ruben, P. C.

    2016-09-01

    Dravet syndrome is the prototype of SCN1A-mutation associated epilepsies. It is characterised by prolonged seizures, typically provoked by fever. We describe the evaluation of an SCN1A mutation in a child with early-onset temperature-sensitive seizures. The patient carries a heterozygous missense variant (c3818C > T pAla1273Val) in the NaV1.1 brain sodium channel. We compared the functional effects of the variant vs. wild type NaV1.1 using patch clamp recordings from channels expressed in Chinese Hamster Ovary Cells at different temperatures (32, 37, and 40 °C). The variant channels produced a temperature-dependent destabilization of activation and fast inactivation. Implementing these empirical abnormalities in a computational model predicts a higher threshold for depolarization block in the variant, particularly at 40 °C, suggesting a failure to autoregulate at high-input states. These results reveal direct effects of abnormalities in NaV1.1 biophysical properties on neuronal dynamics. They illustrate the value of combining cellular measurements with computational models to integrate different observational scales (gene/channel to patient).

  10. 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.

  11. Applying the elastic model for various nucleus-nucleus fusion

    International Nuclear Information System (INIS)

    HASSAN, G.S.; RAGAB, H.S.; SEDDEEK, M.K.

    2000-01-01

    The Elastic Model of two free parameters m,d given by Scalia has been used for wider energy regions to fit the available experimental data for potential barriers and cross sections. In order to generalize Scalia's formula in both sub- and above-barrier regions, we calculated m, d for pairs rather than those given by Scalia and compared the calculated cross sections with the experimental data. This makes a generalization of the Elastic Model in describing fusion process. On the other hand, Scalia's range of interacting systems was 24 ≤ A ≤194 where A is the compound nucleus mass number. Our extension of that model includes an example of the pairs of A larger than his final limit aiming to make it as a general formula for any type of reactants: light, intermediate or heavy systems. A significant point is the comparison of Elastic Model calculations with the well known methods studying complete fusion and compound nucleus formation, namely with the resultants of using Proximity potential with either Sharp or Smooth cut-off approximations

  12. Pion production at 1800 in nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Chessin, S.A.

    1983-05-01

    A survey experiment of pion production at 180 0 in nucleus-nucleus collisions is presented. Beams of 1.05 GeV/A and 2.1 GeV/A protons, alphas, and carbon were used, as well as proton beams of 0.80 GeV, 3.5 GeV, and 4.89 GeV, and argon beams of 1.05 GeV/A and 1.83 GeV/A. This is the first such experiment to use the heavier beams. Targets used ranged from carbon to lead. An in-depth review of the literature, both experimental and theoretical, is also presented. The systematics of the data are discussed, and comparisons are made both with prior experiments and with the predictions of the models reviewed. The cross sections appear consistent with a simple single nucleon-nucleon collision picture, without the need for collective or other exotic effects. Suggestions for future work are made

  13. The nucleus-nucleus proximity potential and superheavy nuclei

    International Nuclear Information System (INIS)

    Myers, W.D.; Swiatecki, W.J.

    2000-01-01

    Using up-to-date values of nuclear radii and of the nuclear surface tension, the 1977 proximity treatment of nucleus-nucleus interaction is confronted with 113 measured fusion barriers. The ∼4% overestimate of theory with respect to experiment, seen in a similar comparison in 1981, is no longer present. The calculated proximity barriers, when applied to fusion reactions used to produce heavy elements with atomic number Z = 102-118, suggest that the unexpectedly large cross section observed in the reaction 86 Kr + 208 Pb r a rrow 293 118 + 1n may be due to the sinking of the Coulomb barrier below the level of the bombarding energy. Tests of this hypothesis are suggested. Some consequences of the appearance of such unshielded reactions for very heavy systems are discussed. An Appendix supplies very accurate analytic formulas for the universal nuclear proximity force and potential functions φand Φ. This does away with the need to consult the tables published in 1977

  14. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or ‘classical’ congenital myopathy

    Science.gov (United States)

    Zaharieva, Irina T.; Thor, Michael G.; Oates, Emily C.; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T.; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D’Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R.; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A.; Morgan, Jennifer E.; Laing, Nigel G.; Vallance, Hilary; Ruben, Peter; Hanna, Michael G.; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope

    2016-01-01

    See Cannon (doi:10.1093/brain/awv400) for a scientific commentary on this article. Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero- or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro

  15. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.

    Science.gov (United States)

    Zaharieva, Irina T; Thor, Michael G; Oates, Emily C; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D'Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A; Morgan, Jennifer E; Laing, Nigel G; Vallance, Hilary; Ruben, Peter; Hanna, Michael G; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope; Muntoni, Francesco

    2016-03-01

    Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero- or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro functional assessment in HEK293 cells of the impact of the identified SCN4A

  16. 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.

  17. 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.

  18. 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.

  19. Determination of Coil Inductances Cylindrical Iron Nucleus

    Directory of Open Access Journals (Sweden)

    Azeddine Mazouz

    2014-03-01

    Full Text Available The paper describes the investigation and development of a structure and performance characteristics of a coil iron nucleus cylindrical (C.I.N.C. The coil iron nucleus cylindrical is a nonlinear electro radio in which the moving of the nucleus in a sense or in other causes change in inductance and can reach extreme values at the superposition of nucleus and coil centers. The variation of the inductance and the degree of freedom of movement of the nucleus can lead to a device with electromechanical conversion The aim of this paper is the determination and visualization of self inductance and mutual of the (C.I.N.C based on geometric dimensions and the displacement of the nucleus.  

  20. Central Circadian Control of Female Reproductive Function

    Directory of Open Access Journals (Sweden)

    Brooke H Miller

    2014-01-01

    Full Text Available Over the past two decades, it has become clear just how much of our physiology is under the control of the suprachiasmatic nucleus (SCN and the cell-intrinsic molecular clock that ticks with a periodicity of approximately 24 hours. The SCN prepares our digestive system for meals, our adrenal axis for the stress of waking up in the morning, and the genes expressed in our muscles when we prepare to exercise, Long before molecular studies of genes such as Clock, Bmal1, and the Per homologs were possible, it was obvious that female reproductive function was under strict circadian control at every level of the hypothalamic-pituitary-gonadal (HPG axis, and in the establishment and successful maintenance of pregnancy. This review highlights our current understanding of the role that the SCN plays in regulating female reproductive physiology, with a special emphasis on the advances made possible through the use of circadian mutant mice.

  1. Circadian oscillators in the mouse brain

    DEFF Research Database (Denmark)

    Rath, Martin F; Rovsing, Louise; Møller, Morten

    2014-01-01

    The circadian timekeeper of the mammalian brain resides in the suprachiasmatic nucleus of the hypothalamus (SCN), and is characterized by rhythmic expression of a set of clock genes with specific 24-h daily profiles. An increasing amount of data suggests that additional circadian oscillators...... residing outside the SCN have the capacity to generate peripheral circadian rhythms. We have recently shown the presence of SCN-controlled oscillators in the neocortex and cerebellum of the rat. The function of these peripheral brain clocks is unknown, and elucidating this could involve mice...... and granular cell layers of the cerebellar cortex of the mouse brain. Among these, Per1, Per2, Cry1, Arntl, and Nr1d1 exhibit circadian rhythms suggesting that local running circadian oscillators reside within neurons of the mouse neocortex and cerebellar cortex. The temporal expression profiles of clock genes...

  2. Nucleus behavior in violent collisions

    International Nuclear Information System (INIS)

    Lefort, M.; Galin, J.; Guerreau, D.

    1985-01-01

    Thanks to new heavy ion beams (Argon, Krypton...) accelerated at Ganil and Sara to velocities of about 0.2 to 0.5 times the light one, very violent collisions, between complex nuclei can be made. During peripheral collisions, the projectile is strongly heated in '' wearing away'' the target and follows its way at high velocity in loosing nucleons. Resulting fragments can present themselves as nuclei very different from usual stable nuclei, often at existence limit. In more central collisions, the energy transferred is such that fusion of both leads to a new type of very hot nucleus near the immediate boiling. Another existence limit is reached by this way: where the bound nucleon system tend to become nucleon gas or a bulk of little fragments [fr

  3. 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.

  4. Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy

    NARCIS (Netherlands)

    Han, C.; Hoeijmakers, J.G.; Liu, S.; Gerrits, M.M.; te Morsche, R.H.; Lauria, G.; Dib-Hajj, S.D.; Drenth, J.P.H.; Faber, C.G.; Merkies, I.S.; Waxman, S.G.

    2012-01-01

    Patients with small fibre neuropathy typically manifest pain in distal extremities and severe autonomic dysfunction. However, occasionally patients present with minimal autonomic symptoms. The basis for this phenotypic difference is not understood. Sodium channel Na(v)1.7, encoded by the SCN9A gene,

  5. 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

  6. De novo SCN8A mutation identified by whole-exome sequencing in a boy with neonatal epileptic encephalopathy, multiple congenital anomalies, and movement disorders.

    Science.gov (United States)

    Vaher, Ulvi; Nõukas, Margit; Nikopensius, Tiit; Kals, Mart; Annilo, Tarmo; Nelis, Mari; Ounap, Katrin; Reimand, Tiia; Talvik, Inga; Ilves, Pilvi; Piirsoo, Andres; Seppet, Enn; Metspalu, Andres; Talvik, Tiina

    2014-12-01

    Epileptic encephalopathies represent a clinically and genetically heterogeneous group of disorders, majority of which are of unknown etiology. We used whole-exome sequencing of a parent-offspring trio to identify the cause of early infantile epileptic encephalopathy in a boy with neonatal seizures, movement disorders, and multiple congenital anomalies who died at the age of 17 months because of respiratory illness and identified a de novo heterozygous missense mutation (c.3979A>G; p.Ile1327Val) in SCN8A (voltage-gated sodium-channel type VIII alpha subunit) gene. The variant was confirmed in the proband with Sanger sequencing. Because the clinical phenotype associated with SCN8A mutations has previously been identified only in a few patients with or without epileptic seizures, these data together with our results suggest that mutations in SCN8A can lead to early infantile epileptic encephalopathy with a broad phenotypic spectrum. Additional investigations will be worthwhile to determine the prevalence and contribution of SCN8A mutations to epileptic encephalopathies. © The Author(s) 2013.

  7. 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.

  8. 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.

  9. 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.

  10. Action potentials: to the nucleus and beyond.

    Science.gov (United States)

    Saha, Ramendra N; Dudek, Serena M

    2008-04-01

    The neuronal nucleus is now widely accepted as playing a vital role in maintaining long-term changes in synaptic effectiveness. To act, however, the nucleus must be appropriately relayed with information regarding the latest round of synaptic plasticity. Several constraints of doing so in a neuron pertain to the often significant spatial distance of synapses from the nucleus and the number of synapses required for such a signal to reach functional levels in the nucleus. Largely based on the sensitivity of transcriptional responses to NMDA receptor antagonists, it has been postulated that the signals are physically relayed by biochemical messengers from the synapse to the nucleus. Alternatively, a second, less often considered but equally viable method of signal transduction may be initiated by action potentials generated proximal to the nucleus, wherefrom the signal can be relayed directly by calcium or indirectly by biochemical second messengers. We consider action potential-dependent signaling to the nucleus to have its own computational advantages over the synapse-to-nucleus signal for some functions. This minireview summarizes the logic and experimental support for these two modes of signaling and attempts to validate the action potential model as playing an important role in transcriptional regulation relating specifically to long-term synaptic plasticity.

  11. Do migrating cells need a nucleus?

    Science.gov (United States)

    Hawkins, Rhoda J

    2018-03-05

    How the nucleus affects cell polarity and migration is unclear. In this issue, Graham et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201706097) show that enucleated cells polarize and migrate in two but not three dimensions and propose that the nucleus is a necessary component of the molecular clutch regulating normal mechanical responses. © 2018 Hawkins.

  12. Actomyosin contractility rotates the cell nucleus

    Science.gov (United States)

    Kumar, Abhishek; Maitra, Ananyo; Sumit, Madhuresh; Ramaswamy, Sriram; Shivashankar, G. V.

    2014-01-01

    The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells. PMID:24445418

  13. Pedunculopontine nucleus cholinergic deficiency in cervical dystonia.

    Science.gov (United States)

    Mente, Karin; Edwards, Nancy A; Urbano, Demelio; Ray-Chaudhury, Abhik; Iacono, Diego; Alho, Ana Tereza Di Lorenzo; Alho, Eduardo Joaquim Lopes; Amaro, Edson; Horovitz, Silvina G; Hallett, Mark

    2018-03-06

    The etiology of cervical dystonia is unknown. Cholinergic abnormalities have been identified in dystonia animal models and human imaging studies. Some animal models have cholinergic neuronal loss in the striatum and increased acetylcholinesterase activity in the pedunculopontine nucleus. The objective of this study was to determine the presence of cholinergic abnormalities in the putamen and pedunculopontine nucleus in cervical dystonia human brain donors. Formalin-fixed brain tissues were obtained from 8 cervical dystonia and 7 age-matched control brains (controls). Pedunculopontine nucleus was available in only 6 cervical dystonia and 5 controls. Neurodegeneration was evaluated pathologically in the putamen, pedunculopontine nucleus, and other regions. Cholinergic neurons were detected using choline acetyltransferase immunohistochemistry in the putamen and pedunculopontine nucleus. Putaminal cholinergic neurons were quantified. A total of 6 cervical dystonia patients and 6 age-matched healthy controls underwent diffusion tensor imaging to determine if there were white matter microstructural abnormalities around the pedunculopontine nucleus. Decreased or absent choline acetyltransferase staining was identified in all 6 pedunculopontine nucleus samples in cervical dystonia. In contrast, strong choline acetyltransferase staining was present in 4 of 5 pedunculopontine nucleus controls. There were no differences in pedunculopontine nucleus diffusion tensor imaging between cervical dystonia and healthy controls. There was no difference in numbers of putaminal cholinergic neurons between cervical dystonia and controls. Our findings suggest that pedunculopontine nucleus choline acetyltransferase deficiency represents a functional cholinergic deficit in cervical dystonia. Structural lesions and confounding neurodegenerative processes were excluded by absence of neuronal loss, gliosis, diffusion tensor imaging abnormalities, and beta-amyloid, tau, and alpha

  14. 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.

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

    International Nuclear Information System (INIS)

    Moehring, H.; Ranft, J.; Capella, A.; Tran Thanh Van, J.

    1993-01-01

    Λ, bar Λ, and K S 0 production is studied in a Monte Carlo dual parton model for hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions with an SU(3) symmetric sea for chain formation (chain ends) but strangeness suppression in the chain fragmentation process. Additionally, (qq)-(bar q bar q) production from the sea was introduced into the chain formation process with the same probability as for the q→qq branching within the chain decay process. With these assumptions, multiplicity ratios and Feynman-x distributions for strange particles in h-h and multiplicity ratios in heavy ion collisions are reasonably well reproduced

  16. Music and the nucleus accumbens.

    Science.gov (United States)

    Mavridis, Ioannis N

    2015-03-01

    Music is a universal feature of human societies over time, mainly because it allows expression and regulation of strong emotions, thus influencing moods and evoking pleasure. The nucleus accumbens (NA), the most important pleasure center of the human brain (dominates the reward system), is the 'king of neurosciences' and dopamine (DA) can be rightfully considered as its 'crown' due to the fundamental role that this neurotransmitter plays in the brain's reward system. Purpose of this article was to review the existing literature regarding the relation between music and the NA. Studies have shown that reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA.

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

    Science.gov (United States)

    Verbeek, Nienke E; van der Maas, Nicoline A T; Jansen, Floor E; van Kempen, Marjan J A; Lindhout, Dick; Brilstra, Eva H

    2013-01-01

    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. 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. 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. 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 and indirectly, public faith in vaccination safety.

  18. Prevalence of SCN1A-Related Dravet Syndrome among Children Reported with Seizures following Vaccination: A Population-Based Ten-Year Cohort Study

    Science.gov (United States)

    Verbeek, Nienke E.; van der Maas, Nicoline A. T.; Jansen, Floor E.; van Kempen, Marjan J. A.; Lindhout, Dick; Brilstra, Eva H.

    2013-01-01

    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 2nd or 3rd 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 and indirectly

  19. 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

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

    CERN Multimedia

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

    2007-01-01

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

  1. Nucleus accumbens surgery for addiction.

    Science.gov (United States)

    Li, Nan; Wang, Jing; Wang, Xue-lian; Chang, Chong-wang; Ge, Shun-nan; Gao, Li; Wu, He-ming; Zhao, Hai-kang; Geng, Ning; Gao, Guo-dong

    2013-01-01

    Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery because of psychological dependence. Multiple studies identify a central role of the nucleus accumbens (NAc) in addiction; several studies note decreased addictive behavior after interventions in this area. Based on animal experiments, our institute started the clinical trial for the treatment of drug addicts' psychological dependence by making lesions in the bilateral NAc with stereotactic surgery from July 2000. The short-term outcomes were encouraging and triggered rapid application of this treatment in China from 2003 to 2004. However, lack of long-term outcomes and controversy eventually led to halting the surgery for addiction by the Ministry of Health of China in November 2004 and a nationwide survey about it later. Our institute had performed this surgery in 272 patients with severe heroin addiction. The follow-up study showed that the 5-year nonrelapse rate was 58% and the quality of life was significantly improved. Patients had several kinds of side effects, but the incidence rate was relatively low. The patients gradually recovered more than 5 years after the surgery. The side effects did not severely influence an individual's life or work. Nationwide surgery showed that the nonrelapse rate was 50% in the sample of 150 cases, from 1167 patients overall who underwent stereotactic surgery in China. Although sometimes accompanied by neuropsychological adverse events, stereotactic ablation of NAc may effectively treat opiate addiction. Lesion location has a significant impact on treatment efficacy and requires further study. Because ablation is irreversible, the NAc surgery for addiction should be performed with cautiousness, and deep brain stimulation (DBS) is an ideal alternative. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. 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.

  3. Melatonin and cortisol profiles in patients with pituitary tumors.

    Science.gov (United States)

    Zielonka, Daniel; Sowiński, Jerzy; Nowak, Stanisław; Ciesielska, Anna; Moskal, Jakub; Marcinkowski, Jerzy T

    2015-01-01

    The optic tract section at the optic chiasm is expected to disturb the suprachiasmatic nucleus (SCN) rhythm, circadian rhythm and melatonin secretion rhythms in humans, although detailed studies have never been conducted. The aim of this paper was to describe melatonin and cortisol profiles in patients with a pituitary tumor exerting optic chiasm compression. Six patients with pituitary tumors of different size, four of whom had significant optic chiasm compression, were examined. In each brain, MRI, an ophthalmological examination including the vision field and laboratory tests were performed. Melatonin and cortisol concentrations were measured at 22:00 h, 02:00 h, 06:00 h, and 10:00 h in patients lying in a dark, isolated room. One of the four cases with significant optic chiasm compression presented a flattened melatonin rhythm. The melatonin rhythm was also disturbed in one patient without optic chiasm compression. Larger tumors may play a role in the destruction of neurons connecting the retina with the suprachiasmatic nucleus (SCN) and breaking of basic way for inhibiting effect to the SCN from the retina. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. Pion-nucleus cross sections approximation

    International Nuclear Information System (INIS)

    Barashenkov, V.S.; Polanski, A.; Sosnin, A.N.

    1990-01-01

    Analytical approximation of pion-nucleus elastic and inelastic interaction cross-section is suggested, with could be applied in the energy range exceeding several dozens of MeV for nuclei heavier than beryllium. 3 refs.; 4 tabs

  5. Transport of glutathione into the nucleus.

    Science.gov (United States)

    Queval, Guillaume; Foyer, Christine

    2014-10-01

    The tripeptide thiol glutathione (GSH) is present in the nucleus of plant and animal cells. However, the functions of GSH in the nucleus remain poorly characterised. GSH appears to become sequestered in the nucleus at the early stages of the cell cycle. As part of our search for proteins that may be involved in GSH transport into the nucleus, we studied the functions of the nucleoporin called Alacrima Achalasia aDrenal Insufficiency Neurologic disorder (ALADIN). ALADIN is encoded by the Achalasia-Addisonianism-Alacrimia (AAAS) gene in mammalian cells. Defects in ALADIN promote adrenal disorders and lead to the triple A syndrome in humans. The ALADIN protein localizes to the nuclear envelope in Arabidopsis thaliana and interacts with other components of the nuclear pore complex (NPC). We characterised the functions of the ALADIN protein in an Arabidopsis thaliana T-DNA insertion knockout mutant, which shows slow growth compared to the wild type. Copyright © 2014. Published by Elsevier Inc.

  6. The nucleus in Finland - The second report

    International Nuclear Information System (INIS)

    Aurela, Jorma; Korteniemi, Virpi; Halme-Tapanainen, Kristina

    1993-01-01

    The Finnish Nuclear Society (FNS) started the distribution of the Nucleus bulletin at the beginning of 1988. The volume of distribution has been extended since, including today nearly 1,000 persons. Both the English and the Finnish version of the bulletin is sent to various opinion leaders of society, i.e. the members of the parliament, ministries, the media, representatives of industry and other decision-makers of the energy field. After the five-year history of the Nucleus in Finland, it is time to look back and sum up the present status of the Nucleus. This report gives a short summary concerning the present distribution and its efficiency, the experiences gained and the influence of the bulletin in Finland. The first questionnaire was sent in November 1988, and the survey was repeated among the Finnish readers of the Nucleus in autumn 1992. The results of the latter survey are given in this report

  7. K sup + nucleus total cross sections

    Energy Technology Data Exchange (ETDEWEB)

    Sawafta, R.

    1990-01-01

    The scattering of K{sup +} mesons from nuclei has attracted considerable interest in the last few years. The K{sup +} holds a very special position as the weakest of all strongly interaction probes. The average cross section is not larger than about 10 mb at lab momenta below 800 MeV/c, corresponding to a mean free path in the nucleus larger than 5 fm. Thus the K{sup +} is capable of probing the entire volume of the nucleus. Single scattering of the K{sup +} with a nucleon in the nucleus dominates the nuclear scattering, and only small and calculable higher order corrections are needed. The nucleon is a dynamical entity and its internal structure can, in principle, be altered by its surrounding nuclear environment. This work reports an experiment in which the K{sup +} is used to compare the nucleon in the nucleus with a free nucleon.

  8. Kaon-nucleus reactions and hypernuclei

    International Nuclear Information System (INIS)

    Dover, C.B.

    1987-01-01

    Recent advances in hypernuclear physics and kaon-nucleus scattering are discussed, with emphasis on the spectroscopy of Λ single particle states in heavy systems, as revealed by the (π + ,K + ) reaction. 26 refs., 8 figs

  9. Polarization and alignment of nucleus fission fragments

    International Nuclear Information System (INIS)

    Barabanov, A.L.; Grechukhin, D.P.

    1987-01-01

    Correlation of fragment orientation with orientation axis of fissile nucleus and with n-vector f vector of fragment divergence is considered. Estimations of polarization and alignment of fission fragments of preliminarily oriented nuclei in correlation (with n-vector f recording) and integral (with n-vector f averaging) experiments were conducted. It is shown that high sensitivity of polarization and fragment alignment to the character of nucleus movement at the stage of descent from barrier to rupture point exists

  10. Advances in hard nucleus cataract surgery

    Directory of Open Access Journals (Sweden)

    Wei Cui

    2013-11-01

    Full Text Available Security and perfect vision and fewer complications are our goals in cataract surgery, and hard-nucleus cataract surgery is always a difficulty one. Many new studies indicate that micro-incision phacoemulsification in treating hard nucleus cataract is obviously effective. This article reviews the evolution process of hard nuclear cataract surgery, the new progress in the research of artificial intraocular lens for microincision, and analyse advantages and disadvantages of various surgical methods.

  11. Targeting the red nucleus for cerebellar tremor.

    Science.gov (United States)

    Lefranc, M; Manto, M; Merle, P; Tir, M; Montpellier, D; Constant, J-M; Le Gars, D; Macron, J-M; Krystkowiak, P

    2014-06-01

    Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis. We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration.

  12. Fabrication and characterization of a nanostructured TiO2/In2S3-Sb2S3/CuSCN extremely thin absorber (eta) solar cell

    Science.gov (United States)

    Huerta-Flores, Alí M.; García-Gómez, Nora A.; de la Parra-Arciniega, Salomé M.; Sánchez, Eduardo M.

    2016-08-01

    In this work we report the successful assembly and characterization of a TiO2/In2S3-Sb2S3/CuSCN extremely thin absorber solar cell. Nanostructured TiO2 deposited by screen printing on an ITO substrate was used as an n-type electrode. An ∼80 nm extremely thin layer of the system In2S3-Sb2S3 deposited by successive ionic layer adsorption and a reaction (silar) method was used as an absorber. The voids were filled with p-type CuSCN and the entire assembly was completed with a gold contact. The solar cell fabricated with this heterostructure showed an energy conversion efficiency of 4.9%, which is a promising result in the development of low cost and simple fabrication of solar cells.

  13. Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A

    DEFF Research Database (Denmark)

    Kanters, Jørgen K; Yuan, Lei; Hedley, Paula L

    2014-01-01

    BACKGROUND: Mutations in SCN5A can result in both long QT type 3 (LQT3) and Brugada syndrome (BrS), and a few mutations have been found to have an overlapping phenotype. Long QT syndrome is characterized by prolonged QT interval, and a prerequisite for a BrS diagnosis is ST elevation in the right...... precordial leads of the electrocardiogram. METHODS AND RESULTS: In a Danish family suffering from long QT syndrome, a novel missense mutation in SCN5A, changing a leucine residue into a glutamine residue at position 1786 (L1786Q), was found to be present in heterozygous form co-segregating with prolonged QT......, a negative shift in inactivation properties and a positive shift in activation properties, compatible with BrS. Furthermore, the sustained (I(Na,late)) tetrodotoxin-sensitive sodium current was found to be drastically increased, explaining the association between the mutation and LQT syndrome. CONCLUSIONS...

  14. Evidence for Weakened Intercellular Coupling in the Mammalian Circadian Clock under Long Photoperiod.

    Science.gov (United States)

    Buijink, M Renate; Almog, Assaf; Wit, Charlotte B; Roethler, Ori; Olde Engberink, Anneke H O; Meijer, Johanna H; Garlaschelli, Diego; Rohling, Jos H T; Michel, Stephan

    2016-01-01

    For animals living in temperate latitudes, seasonal changes in day length are an important cue for adaptations of their physiology and behavior to the altered environmental conditions. The suprachiasmatic nucleus (SCN) is known as the central circadian clock in mammals, but may also play an important role in adaptations to different photoperiods. The SCN receives direct light input from the retina and is able to encode day-length by approximating the waveform of the electrical activity rhythm to the duration of daylight. Changing the overall waveform requires a reorganization of the neuronal network within the SCN with a change in the degree of synchrony between the neurons; however, the underlying mechanisms are yet unknown. In the present study we used PER2::LUC bioluminescence imaging in cultured SCN slices to characterize network dynamics on the single-cell level and we aimed to provide evidence for a role of modulations in coupling strength in the photoperiodic-induced phase dispersal. Exposure to long photoperiod (LP) induced a larger distribution of peak times of the single-cell PER2::LUC rhythms in the anterior SCN, compared to short photoperiod. Interestingly, the cycle-to-cycle variability in single-cell period of PER2::LUC rhythms is also higher in the anterior SCN in LP, and is positively correlated with peak time dispersal. Applying a new, impartial community detection method on the time series data of the PER2::LUC rhythm revealed two clusters of cells with a specific spatial distribution, which we define as dorsolateral and ventromedial SCN. Post hoc analysis of rhythm characteristics of these clusters showed larger cycle-to-cycle single-cell period variability in the dorsolateral compared to the ventromedial cluster in the anterior SCN. We conclude that a change in coupling strength within the SCN network is a plausible explanation to the observed changes in single-cell period variability, which can contribute to the photoperiod-induced phase

  15. 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.

  16. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.

    Science.gov (United States)

    Blanchard, Maxime G; Willemsen, Marjolein H; Walker, Jaclyn B; Dib-Hajj, Sulayman D; Waxman, Stephen G; Jongmans, Marjolijn C J; Kleefstra, Tjitske; van de Warrenburg, Bart P; Praamstra, Peter; Nicolai, Joost; Yntema, Helger G; Bindels, René J M; Meisler, Miriam H; Kamsteeg, Erik-Jan

    2015-05-01

    Mutations of SCN8A encoding the neuronal voltage-gated sodium channel NaV1.6 are associated with early-infantile epileptic encephalopathy type 13 (EIEE13) and intellectual disability. Using clinical exome sequencing, we have detected three novel de novo SCN8A mutations in patients with intellectual disabilities, and variable clinical features including seizures in two patients. To determine the causality of these SCN8A mutations in the disease of those three patients, we aimed to study the (dys)function of the mutant sodium channels. The functional consequences of the three SCN8A mutations were assessed using electrophysiological analyses in transfected cells. Genotype-phenotype correlations of these and other cases were related to the functional analyses. The first mutant displayed a 10 mV hyperpolarising shift in voltage dependence of activation (gain of function), the second did not form functional channels (loss of function), while the third mutation was functionally indistinguishable from the wildtype channel. Comparison of the clinical features of these patients with those in the literature suggests that gain-of-function mutations are associated with severe EIEE, while heterozygous loss-of-function mutations cause intellectual disability with or without seizures. These data demonstrate that functional analysis of missense mutations detected by clinical exome sequencing, both inherited and de novo, is valuable for clinical interpretation in the age of massive parallel sequencing. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  17. 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.

  18. Turning dilemmas into opportunities: a UNU/SCN capacity development network in public nutrition in Central and Eastern Europe.

    Science.gov (United States)

    Pavlovic, Mirjana; Pepping, Fré; Demes, Michal; Biro, Lajos; Szabolcs, Peter; Dimitrovska, Zlatka; Duleva, Vesselka; Parvan, Camelia; Hadziomeragic, Aida Filipovic; Glibetic, Maria; Oshaug, Arne

    2009-08-01

    Capacity development in nutrition is a process whereby individuals, groups, institutions, organizations and societies enhance their abilities to identify and meet challenges in a sustainable manner. To address these issues, in 2001 the UN System Standing Committee on Nutrition (SCN) established a Working Group on Capacity Development under the joint coordination of the United Nations University (UNU) and the International Union of Nutritional Sciences. Several regional professional networks have developed under this working group, the latest for the Central and Eastern Europe (CEE) countries. Ten CEE countries formed a network in 2006 and identified major nutritional challenges in the region, which included: irregular meal patterns; low consumption of fruits/vegetables, milk products and fish; low intake of some micronutrients; and high intakes of fat, sugar and salt. Public policies in nutrition were either weak or absent. Some countries had recently developed nutrition plans. Higher education in nutrition was seen as very important for public nutrition work by professionals in the region, who considered it a prerequisite for reversing the negative trend of the nutrition transition. The network will continue to work on issues that are still not covered adequately. Its activities to date and prospects for the future are assessed against ten principles for good capacity development suggested by the United Nations Development Programme.

  19. The temperature dependence of the reflection intensities of the modulated composite structure Hg0.776(BEDT-TTF)SCN

    International Nuclear Information System (INIS)

    Pressprich, M.R.; Beek, C. van; Coppens, P.

    1994-01-01

    The temperature dependence between 30 and 300 K of the intensities of 24 reflections of the column-composite structure Hg 0.776 (BEDT-TTF)SCN [Wang, Beno, Carlson, Thorup, Murray, Porter, Williams, Maly, Bu, Petricek, Cisarova, Coppens, Jung, Whangbo, Shirber and Overmyer (1991). Chem. Mater. 3, 508-513; BEDT-TTF=3,4,3',4'-bis(ethylenedithio)-2,2',5,5'-tetrathiafulvalene] has been analyzed in terms of a model including phason temperature factors. The temperature dependence of the main and first-order satellite reflections is reasonably well reproduced in a refinement with 236 observations and four variables. The results are interpreted in terms of a temperature independence of the static displacement amplitudes. The room-temperature r.m.s. phason fluctuations of the mercury sublattice are 50(2) . This value implies that the mean mercury displacement amplitude will increase by ∝60% on lowering of the temperature to within the liquid-helium range. The thermal contraction on cooling is the same for the two sublattices. (orig.)

  20. 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...

  1. 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.

  2. How Anion Chaotrope Changes the Local Structure of Water. Insights from Photoelectron Spectroscopy and Theoretical Modeling of SCN- Water Clusters

    Energy Technology Data Exchange (ETDEWEB)

    Valiev, Marat [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Deng, Shihu [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wang, Xue B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-09-09

    The behavior of charged solute molecules in aqueous solutions is often classified using the concept of kosmotropes (“structure makers”) and chaotropes (“structure breakers”). There is a growing consensus that the key to kosmotropic/chaotropic behaviors lies in the local solvent region, but the exact microscopic basis for such differentiation is not well understood. This issue is examined in this work by analyzing size selective solvation of a well-known chaotrope, negatively charged SCN- molecule. Combining experimental photoelectron spectroscopy measurements with theoretical modeling we examine evolution of solvation structure up to eight waters. We observe that SCN- indeed fits the description of weakly hydrated ion and its solvation is heavily driven by stabilization of water-water interaction network. However, the impact on water structure is more subtle than that associated with “structure breaker”. In particular, we observe that the solvation structure of SCN- preserves the “packing” structure of the water network but changes local directionality of hydrogen bonds in the local solvent region. The resulting effect closer to that of “structure weakener”, where solute can be readily accommodated into the native water network, at the cost of compromising its stability due to constraints on hydrogen bonding.

  3. Quadruple or quintuple conversion of hlb, sak, sea (or sep), scn, and chp genes by bacteriophages in non-beta-hemolysin-producing bovine isolates of Staphylococcus aureus.

    Science.gov (United States)

    Kumagai, Rina; Nakatani, Kazue; Ikeya, Nanami; Kito, Yukiko; Kaidoh, Toshio; Takeuchi, Shotaro

    2007-05-16

    In 13 of 43 non-beta-hemolysin-producing bovine isolates of Staphylococcus aureus, two truncated beta-hemolysin (hlb) genes were demonstrated by PCR and sequencing, and one truncated hlb gene was located beside the integrase (int) gene of phage origin. The staphylokinase (sak) gene was detected in all 13 isolates in which the truncated hlb genes were detected by PCR. Enterotoxin A (sea) and enterotoxin P (sep) genes were also detected in 5 and 2 of the 13 isolates, respectively. Moreover, the scn and chp genes encoding staphylococcal complement inhibitor (SCIN) and chemotaxis inhibitory protein of S. aureus (CHIPS) were detected in 13 and 4 of the 13 isolates, respectively. The bacteriophage induced by mitomycin C treatment was able to lysogenize one beta-hemolysin-producing isolate of S. aureus, and the sak and scn genes were detected from the lysogenized isolate. These results suggest quadruple or quintuple conversion of hlb, sak, sea (or sep), scn, and chp genes by bacteriophages among non-beta-hemolysin-producing bovine isolates of S. aureus.

  4. LPG sensor based on complete inorganic n-Bi2S3-p-CuSCN heterojunction synthesized by a simple chemical route

    Science.gov (United States)

    Ladhe, R. D.; Baviskar, P. K.; Tan, W. W.; Zhang, J. B.; Lokhande, C. D.; Sankapal, B. R.

    2010-06-01

    An effective and versatile room temperature soft chemical route was employed to deposit n-Bi2S3 films followed by p-CuSCN films onto fluorine doped tin oxide (FTO) coated glass substrates. Well optimized preparative parameters led to the formation of a good heterojunction between the n-Bi2S3 and p-CuSCN films without any post-annealing treatment. An interconnected microflake of CuSCN on to the nanocrystalline Bi2S3 film enables a high porous structure in the top layer. The device was completed by ensuring silver as a front and FTO as a back ohmic contact, and exposed to sense the liquefied petroleum gas (LPG) at room temperature (27 °C). The upper porous structure allowed enough room for the gas species to adsorb and de-adsorb easily at the interface. The device exhibited more than 70% response at 1370 ppm of LPG, and the process suggests the possibility to develop a room temperature LPG sensing device with a low cost chemical method.

  5. The prevalence of mutations in KCNQ1, KCNH2, and SCN5A in an unselected national cohort of young sudden unexplained death cases

    DEFF Research Database (Denmark)

    Winkel, Bo Gregers; Larsen, Maiken Kudahl; Berge, Knut Erik

    2012-01-01

    on novel mutations. RESULTS: In total, 5 of 44 cases (11%) carried a mutation in 1 of the 3 genes corresponding to 11% of all investigated cases (R190W KCNQ1, F29L KCNH2 (2 cases), P297S KCNH2 and P1177L SCN5A). P1177L SCN5A has not been reported before. In vitro electrophysiological studies of P1177L SCN5......INTRODUCTION: Sudden unexplained death account for one-third of all sudden natural deaths in the young (1-35 years). Hitherto, the prevalence of genopositive cases has primarily been based on deceased persons referred for postmortem genetic testing. These deaths potentially may represent the worst...... of cases, thus possibly overestimating the prevalence of potentially disease causing mutations in the 3 major long-QT syndrome (LQTS) genes in the general population. We therefore wanted to investigate the prevalence of mutations in an unselected population of sudden unexplained deaths in a nationwide...

  6. Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx(-/-) ) and the 129sv wild type mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Rath, Martin Fredensborg; Møller, Morten

    2013-01-01

    magnocellular and parvocellular vasopressinergic systems in both genotypes. We here present a detailed mapping of all classical hypothalamo-pituitary and accessory magnocellular nuclei and neurons in the hypothalamus by use of immunohistochemistry and in situ hybridization in both genotypes. Semiquantitative...... in situ hybridization revealed a very high expression of Avp-mRNA in all the magnocellular nuclei compared to a much lower level in the parvocellular suprachiasmatic nucleus. In a series of mice killed every 4 hours, The Avp-mRNA expression in the SCN showed a significant daily rhythm with a zenith...

  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...... these observations with observations made from mice examined by wheel-running activity. The study demonstrates that VPAC2 signaling is necessary for a functional circadian clock driving locomotor activity, core body temperature, and heart rate rhythmicity, since VPAC2-deficient mice lose the rhythms in all three...

  8. 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

    Czech Academy of Sciences Publication Activity Database

    Bendová, Zdeňka; Sumová, Alena; Mikkelsen, J. D.

    2009-01-01

    Roč. 159, č. 2 (2009), s. 599-609 ISSN 0306-4522 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA309/08/0503 Grant - others:EC(XE) LSH-2004-115-4-018741 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian clock * ontogenesis * photic entrainment Subject RIV: FH - Neurology Impact factor: 3.292, year: 2009

  9. High density nuclear Mach shock waves in relativistic nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Stocker, H.; Hofmann, J.; Scheid, W.; Greiner, W.

    1976-01-01

    The occurrence of high density nuclear Mach shock waves in relativistic nucleus-nucleus collisions and related phenomena, as density isomers, highly isobaric and hot nuclear matter, pionization and granulation of dense matter, compressibility and soundwaves in nuclear matter, are discussed

  10. Study of η-nucleus interaction through the formation of η-nucleus ...

    Indian Academy of Sciences (India)

    Answer to this question will deeply enrich our understanding of -nucleus interaction which is not so well-understood. We review the experimental efforts for the search of -mesic nuclei and describe the physics motivation behind it. We present the description of an experiment for the search of -nucleus bound state using ...

  11. Cell Biology of the Caenorhabditis elegans Nucleus

    Science.gov (United States)

    Cohen-Fix, Orna; Askjaer, Peter

    2017-01-01

    Studies on the Caenorhabditis elegans nucleus have provided fascinating insight to the organization and activities of eukaryotic cells. Being the organelle that holds the genetic blueprint of the cell, the nucleus is critical for basically every aspect of cell biology. The stereotypical development of C. elegans from a one cell-stage embryo to a fertile hermaphrodite with 959 somatic nuclei has allowed the identification of mutants with specific alterations in gene expression programs, nuclear morphology, or nuclear positioning. Moreover, the early C. elegans embryo is an excellent model to dissect the mitotic processes of nuclear disassembly and reformation with high spatiotemporal resolution. We review here several features of the C. elegans nucleus, including its composition, structure, and dynamics. We also discuss the spatial organization of chromatin and regulation of gene expression and how this depends on tight control of nucleocytoplasmic transport. Finally, the extensive connections of the nucleus with the cytoskeleton and their implications during development are described. Most processes of the C. elegans nucleus are evolutionarily conserved, highlighting the relevance of this powerful and versatile model organism to human biology. PMID:28049702

  12. Structural dynamics of the cell nucleus

    Science.gov (United States)

    Wiegert, Simon; Bading, Hilmar

    2011-01-01

    Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions. In neurons, intracellular calcium levels are controlled by ion channels in the plasma membrane such as NMDA receptors (NMDARs), voltage-gated calcium channels (VGCCs) and certain α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by calcium exchange pathways between the cytosol and internal calcium stores including the endoplasmic reticulum and mitochondria. Synaptic activity and the subsequent opening of ligand and/or voltage-gated calcium channels can initiate cytosolic calcium transients which propagate towards the cell soma and enter the nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope. We recently described the discovery that in hippocampal neurons the morphology of the nucleus affects the calcium dynamics within the nucleus. Here we propose that nuclear infoldings determine whether a nucleus functions as an integrator or detector of oscillating calcium signals. We outline possible ties between nuclear mophology and transcriptional activity and discuss the importance of extending the approach to whole cell calcium signal modeling in order to understand synapse-to-nucleus communication in healthy and dysfunctional neurons. PMID:21738832

  13. Dynamics of hadron-nucleus interactions

    International Nuclear Information System (INIS)

    Wallace, S.J.

    1981-07-01

    Recent progress in diffraction theory shows that proton-nucleus scattering at nonforward angles is dominated by the interference of waves from two or more bright spots. Analytic formulas based on asymptotic theories of diffraction yield valuable new insights into the scattering and these formulas can be readily extended to illuminate the role of dynamical ingredients, i.e., the nucleon-nucleon amplitudes. The governing parameters of the diffraction and some direct connections between the observed cross sections and the input dynamics are reviewed. New information regarding the nucleon-nucleon parameters based on recent phase shift analyses show some systematic differences from the effective NN amplitudes which produce fits to proton-nucleus diffraction data. Recent progress in understanding the role of Δ-isobars in proton-nucleus dynamics is reviewed. 126 references

  14. scnRCA: a novel method to detect consistent patterns of translational selection in mutationally-biased genomes.

    Directory of Open Access Journals (Sweden)

    Patrick K O'Neill

    Full Text Available Codon usage bias (CUB results from the complex interplay between translational selection and mutational biases. Current methods for CUB analysis apply heuristics to integrate both components, limiting the depth and scope of CUB analysis as a technique to probe into the evolution and optimization of protein-coding genes. Here we introduce a self-consistent CUB index (scnRCA that incorporates implicit correction for mutational biases, facilitating exploration of the translational selection component of CUB. We validate this technique using gene expression data and we apply it to a detailed analysis of CUB in the Pseudomonadales. Our results illustrate how the selective enrichment of specific codons among highly expressed genes is preserved in the context of genome-wide shifts in codon frequencies, and how the balance between mutational and translational biases leads to varying definitions of codon optimality. We extend this analysis to other moderate and fast growing bacteria and we provide unified support for the hypothesis that C- and A-ending codons of two-box amino acids, and the U-ending codons of four-box amino acids, are systematically enriched among highly expressed genes across bacteria. The use of an unbiased estimator of CUB allows us to report for the first time that the signature of translational selection is strongly conserved in the Pseudomonadales in spite of drastic changes in genome composition, and extends well beyond the core set of highly optimized genes in each genome. We generalize these results to other moderate and fast growing bacteria, hinting at selection for a universal pattern of gene expression that is conserved and detectable in conserved patterns of codon usage bias.

  15. Decoding calcium signaling across the nucleus.

    Science.gov (United States)

    Oliveira, André G; Guimarães, Erika S; Andrade, Lídia M; Menezes, Gustavo B; Fatima Leite, M

    2014-09-01

    Calcium (Ca(2+)) is an important multifaceted second messenger that regulates a wide range of cellular events. A Ca(2+)-signaling toolkit has been shown to exist in the nucleus and to be capable of generating and modulating nucleoplasmic Ca(2+) transients. Within the nucleus, Ca(2+) controls cellular events that are different from those modulated by cytosolic Ca(2+). This review focuses on nuclear Ca(2+) signals and their role in regulating physiological and pathological processes. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.

  16. UNCOVERING THE NUCLEUS CANDIDATE FOR NGC 253

    Energy Technology Data Exchange (ETDEWEB)

    Günthardt, G. I.; Camperi, J. A. [Observatorio Astronómico, Universidad Nacional de Córdoba (Argentina); Agüero, M. P. [Observatorio Astronómico, Universidad Nacional de Córdoba, and CONICET (Argentina); Díaz, R. J.; Gomez, P. L.; Schirmer, M. [Gemini Observatory, AURA (United States); Bosch, G., E-mail: gunth@oac.uncor.edu, E-mail: camperi@oac.uncor.edu, E-mail: mpaguero@oac.uncor.edu, E-mail: rdiaz@gemini.edu, E-mail: pgomez@gemini.edu, E-mail: mschirmer@gemini.edu, E-mail: guille@fcaglp.unlp.edu.ar [Instituto de Astrofísica de La Plata (CONICET-UNLP) (Argentina)

    2015-11-15

    NGC 253 is the nearest spiral galaxy with a nuclear starburst that becomes the best candidate for studying the relationship between starburst and active galactic nucleus activity. However, this central region is veiled by large amounts of dust, and it has been so far unclear which is the true dynamical nucleus to the point that there is no strong evidence that the galaxy harbors a supermassive black hole co-evolving with the starburst as was supposed earlier. Near-infrared (NIR) spectroscopy, especially NIR emission line analysis, could be advantageous in shedding light on the true nucleus identity. Using Flamingos-2 at Gemini South we have taken deep K-band spectra along the major axis of the central structure and through the brightest infrared source. In this work, we present evidence showing that the brightest NIR and mid-infrared source in the central region, already known as radio source TH7 and so far considered just a large stellar supercluster, in fact presents various symptoms of a genuine galactic nucleus. Therefore, it should be considered a valid nucleus candidate. Mentioning some distinctive aspects, it is the most massive compact infrared object in the central region, located at 2.″0 of the symmetry center of the galactic bar, as measured in the K-band emission. Moreover, our data indicate that this object is surrounded by a large circumnuclear stellar disk and it is also located at the rotation center of the large molecular gas disk of NGC 253. Furthermore, a kinematic residual appears in the H{sub 2} rotation curve with a sinusoidal shape consistent with an outflow centered in the candidate nucleus position. The maximum outflow velocity is located about 14 pc from TH7, which is consistent with the radius of a shell detected around the nucleus candidate, observed at 18.3 μm (Qa) and 12.8 μm ([Ne ii]) with T-ReCS. Also, the Brγ emission line profile shows a pronounced blueshift and this emission line also has the highest equivalent width at this

  17. 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

  18. Consequences of hadron-nucleus multiplicity parametrization

    International Nuclear Information System (INIS)

    Singh, C.P.; Shyam, M.

    1986-01-01

    Some interesting consequences are analyzed of a new parametrization for the hadron-nucleus multiplicity distributions and they are compared with the experimental data. Further, it is illustrated how the scaling property for the average multiplicity will be modified and it is found that the experimental data support this behaviour. (orig.)

  19. The Nucleus Retroambiguus Control of Respiration

    NARCIS (Netherlands)

    Subramanian, Hari H.; Holstege, Gert

    2009-01-01

    The role of the nucleus retroambiguus (NRA) in the context of respiration control has been subject of debate for considerable time. To solve this problem, we chemically (using D, L-homocysteic acid) stimulated the NRA in unanesthetized precollicularly decerebrated cats and studied the respiratory

  20. Compound nucleus studies withy reverse kinematics

    International Nuclear Information System (INIS)

    Moretto, L.G.

    1985-06-01

    Reverse kinematics reactions are used to demonstrate the compound nucleus origin of intermediate mass particles at low energies and the extension of the same mechanism at higher energies. No evidence has appeared in our energy range for liquid-vapor equilibrium or cold fragmentation mechanisms. 11 refs., 12 figs

  1. Correlations in hadron-nucleus collisions

    International Nuclear Information System (INIS)

    Wosiek, B.

    1976-09-01

    The correlations between the particles produced in interactions of hadrons with emulsion nuclei were investigated. The data are in qualitative agreement with the models which describe the interactions with nuclei as subsequent collisions of the fast part of excited hadronic matter inside the nucleus. (author)

  2. Resonances in η-light nucleus systems

    Indian Academy of Sciences (India)

    2Departamento de Fisica, Universidad de los Andes, Bogota, Colombia. E-mail: kanchanp@magnum.barc.ernet.in. Abstract. We locate resonances in η-light nucleus elastic scattering using the time delay method. We solve few-body equations within the finite rank approximation in order to calculate the t-matrices and hence ...

  3. An organism arises from every nucleus.

    Directory of Open Access Journals (Sweden)

    Nurullah Keklikoglu

    2009-12-01

    Full Text Available The fact that, cloning using somatic cell nuclear transfer (SCNT method has been performed, opened new horizons for cloning, and changed the way of our understanding and approach to cell and nucleus. The progress in cloning technology, brought the anticipation of the ability to clone an organism from each somatic cell nucleus. Therefore, the 'Cell Theory' is about to take the additional statement as "An organism arises from every nucleus". The development of gene targeting procedures which can be applied with SCNT, showed us that it may be possible to obtain different versions of the original genetic constitution of a cell. Because of this opportunity which is provided by SCNT, in reproductive cloning, it would be possible to clone enhanced organisms which can adapt to different environmental conditions and survive. Furthermore, regaining the genetic characteristics of ancestors or reverse herediter variations would be possible. On the other hand, in therapeutic cloning, more precise and easily obtainable alternatives for cell replacement therapy could be presented. However, while producing healthier or different organisms from a nucleus, it is hard to foresee the side effects influencing natural processes in long term is rather difficult.

  4. Inside a plant nucleus: discovering the proteins

    Czech Academy of Sciences Publication Activity Database

    Petrovská, Beáta; Šebela, M.; Doležel, Jaroslav

    2015-01-01

    Roč. 66, č. 6 (2015), s. 1627-1640 ISSN 0022-0957 R&D Projects: GA ČR(CZ) GA14-28443S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Cell nucleus * chromatin * genome function Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.677, year: 2015

  5. Iliacus Abscess with Radiculopathy Mimicking Herniated Nucleus ...

    African Journals Online (AJOL)

    2016-05-02

    May 2, 2016 ... radiculopathy mimicking herniated nucleus pulposus: Aadditional diagnostic value of magnetic resonance imaging. Niger J Clin Pract. 2017;20:392-3. This is an open access article distributed under the terms of the Creative Commons. Attribution-Non Commercial-Share Alike 3.0 License, which allows ...

  6. Resonances in η-light nucleus systems

    Indian Academy of Sciences (India)

    We locate resonances in -light nucleus elastic scattering using the time delay method. We solve few-body equations within the finite rank approximation in order to calculate the -matrices and hence the time delay for the - 3He and - 4He systems. We find a resonance very close to the threshold in - 3 He elastic ...

  7. The mPer2 clock gene modulates cocaine actions in the mouse circadian system.

    Science.gov (United States)

    Brager, Allison J; Stowie, Adam C; Prosser, Rebecca A; Glass, J David

    2013-04-15

    Cocaine is a potent disruptor of photic and non-photic pathways for circadian entrainment of the master circadian clock of the suprachiasmatic nucleus (SCN). These actions of cocaine likely involve its modulation of molecular (clock gene) components for SCN clock timekeeping. At present, however, the physiological basis of such an interaction is unclear. To address this question, we compared photic and non-photic phase-resetting responses between wild-type (WT) and Per2 mutant mice expressing nonfunctional PER2 protein to systemic and intra-SCN cocaine administrations. In the systemic trials, cocaine was administered i.p. (20 mg/kg) either at midday or prior to a light pulse in the early night to assess its non-photic and photic behavioral phase-resetting actions, respectively. In the intra-SCN trial, cocaine was administered by reverse microdialysis at midday to determine if the SCN is a direct target for its non-photic phase-resetting action. Non-photic phase-advancing responses to i.p. cocaine at midday were significantly (∼3.5-fold) greater in Per2 mutants than WTs. However, the phase-advancing action of intra-SCN cocaine perfusion at midday did not differ between genotypes. In the light pulse trial, Per2 mutants exhibited larger photic phase-delays than did WTs, and the attenuating action of cocaine on this response was proportionately larger than in WTs. These data indicate that the Per2 clock gene is a potent modulator of cocaine's actions in the circadian system. With regard to non-photic phase-resetting, the SCN is confirmed as a direct target of cocaine action; however, Per2 modulation of this effect likely occurs outside of the SCN. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. An LHX1-Regulated Transcriptional Network Controls Sleep/Wake Coupling and Thermal Resistance of the Central Circadian Clockworks.

    Science.gov (United States)

    Bedont, Joseph L; LeGates, Tara A; Buhr, Ethan; Bathini, Abhijith; Ling, Jonathan P; Bell, Benjamin; Wu, Mark N; Wong, Philip C; Van Gelder, Russell N; Mongrain, Valerie; Hattar, Samer; Blackshaw, Seth

    2017-01-09

    The suprachiasmatic nucleus (SCN) is the central circadian clock in mammals. It is entrained by light but resistant to temperature shifts that entrain peripheral clocks [1-5]. The SCN expresses many functionally important neuropeptides, including vasoactive intestinal peptide (VIP), which drives light entrainment, synchrony, and amplitude of SCN cellular clocks and organizes circadian behavior [5-16]. The transcription factor LHX1 drives SCN Vip expression, and cellular desynchrony in Lhx1-deficient SCN largely results from Vip loss [17, 18]. LHX1 regulates many genes other than Vip, yet activity rhythms in Lhx1-deficient mice are similar to Vip -/- mice under light-dark cycles and only somewhat worse in constant conditions. We suspected that LHX1 targets other than Vip have circadian functions overlooked in previous studies. In this study, we compared circadian sleep and temperature rhythms of Lhx1- and Vip-deficient mice and found loss of acute light control of sleep in Lhx1 but not Vip mutants. We also found loss of circadian resistance to fever in Lhx1 but not Vip mice, which was partially recapitulated by heat application to cultured Lhx1-deficient SCN. Having identified VIP-independent functions of LHX1, we mapped the VIP-independent transcriptional network downstream of LHX1 and a largely separable VIP-dependent transcriptional network. The VIP-independent network does not affect core clock amplitude and synchrony, unlike the VIP-dependent network. These studies identify Lhx1 as the first gene required for temperature resistance of the SCN clockworks and demonstrate that acute light control of sleep is routed through the SCN and its immediate output regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Conformational behavior of CH3OC(O)SX (X = CN and SCN) pseudohalide congeners. A combined experimental and theoretical study.

    Science.gov (United States)

    Torrico-Vallejos, Sonia; Erben, Mauricio F; Ge, Mao-Fa; Willner, Helge; Della Védova, Carlos O

    2010-03-18

    Pure methoxycarbonylsulfenyl cyanide, CH(3)OC(O)SCN (I), and methoxycarbonylsulfenyl thiocyanate, CH(3)OC(O)SSCN (II), were prepared by reacting liquid CH(3)OC(O)SCl with either AgCN or AgSCN, respectively. Compounds I and II were characterized by (1)H NMR, CG-MS, and vibrational (FTIR and FT-Raman) techniques. The conformational properties have been studied by using vibrational spectroscopy [infrared (gaseous, liquid, and Ar matrix isolated), Raman (liquid) spectroscopy] together with quantum chemical calculations at the B3LYP and MP2 methods with the extended 6-311++G** and aug-cc-pVTZ basis sets. Compound I exhibits a conformational equilibrium at room temperature having the most stable form C(s) symmetry with a synperiplanar (syn) orientation of the carbonyl double bond (C=O) with respect to both the CH(3)O- and -SCN groups (syn-syn). Several bands assigned to a second conformer have been observed in the IR matrix spectra. This rotamer presents an antiperiplanar orientation of the thiocyanate group (syn-anti). Evaluating the equilibrium compositions at different temperatures by quenching the gas phase mixtures as Ar matrices allowed us to determine the conformational enthalpy difference DeltaH(0) = H(0)((syn-anti)) - H(0)((syn-syn)) = 0.80(18) kcal mol(-1). A similar conformational behavior has been determined for compound II. Thermodynamic properties were also computed at the high-level G2MP2 and G3 model chemistry methods. The importance of mesomeric (resonance) and anomeric (hyperconjugation) electronic interaction in the conformational behavior is evaluated by using the NBO approach for both species.

  10. A novel de novo mutation of SCN8A (Nav1.6) with enhanced channel activation in a child with epileptic encephalopathy.

    Science.gov (United States)

    Estacion, Mark; O'Brien, Janelle E; Conravey, Allison; Hammer, Michael F; Waxman, Stephen G; Dib-Hajj, Sulayman D; Meisler, Miriam H

    2014-09-01

    Rare de novo mutations of sodium channels are thought to be an important cause of sporadic epilepsy. The well established role of de novo mutations of sodium channel SCN1A in Dravet Syndrome supports this view, but the etiology of many cases of epileptic encephalopathy remains unknown. We sought to identify the genetic cause in a patient with early onset epileptic encephalopathy by whole exome sequencing of genomic DNA. The heterozygous mutation c. 2003C>T in SCN8A, the gene encoding sodium channel Nav1.6, was detected in the patient but was not present in either parent. The resulting missense substitution, p.Thr767Ile, alters an evolutionarily conserved residue in the first transmembrane segment of channel domain II. The electrophysiological effects of this mutation were assessed in neuronal cells transfected with mutant or wildtype cDNA. The mutation causes enhanced channel activation, with a 10mV depolarizing shift in voltage dependence of activation as well as increased ramp current. In addition, pyramidal hippocampal neurons expressing the mutant channel exhibit increased spontaneous firing with PDS-like complexes as well as increased frequency of evoked action potentials. The identification of this new gain-of-function mutation of Nav1.6 supports the inclusion of SCN8A as a causative gene in infantile epilepsy, demonstrates a novel mechanism for hyperactivity of Nav1.6, and further expands the role of de novo mutations in severe epilepsy. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Open and closed Fermi surface contributions to the anomalous angular magnetoresistance of α-(BEDT-TTF)2RbHg(SCN)4

    International Nuclear Information System (INIS)

    Athas, G.J.; Klepper, S.J.; Brooks, J.S.; Tokumoto, M.; Kinoshita, N.; Tanaka, Y.

    1994-01-01

    Anomalous angular magnetoresistance (AMR) in the quasi-two dimensional organic conductor α-(BEDT-TTF) 2 RbHg(SCN) 4 is reported. The AMR appears as oscillations with sharp minima below the anitiferromagnetic ordering temperature. The period of these oscillations is anisotropic with respect to the plane of rotation cutting through the conducting layers. Above the ordering temperature, the nature of the AMR changes fundamentally. We propose a model for the AMR that incorporates both open and closed Fermi surfaces, and discuss how temperature and field dependent behaviors of the individual FS contribute to the conductivity. (orig.)

  12. Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A

    DEFF Research Database (Denmark)

    Kanters, Jørgen K.; Yuan, Lei; Hedley, Paula L

    2014-01-01

    precordial leads of the electrocardiogram. METHODS AND RESULTS: In a Danish family suffering from long QT syndrome, a novel missense mutation in SCN5A, changing a leucine residue into a glutamine residue at position 1786 (L1786Q), was found to be present in heterozygous form co-segregating with prolonged QT......: The L1786Q mutation is associated with a combined LQT3 and concealed BrS phenotype explained by gating characteristics of the mutated ion channel protein. Hence, sodium channel blockade should be considered in clinical evaluation of apparent LQT3 patients....

  13. Theory of and effects from elastoplasticity in nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Noerenberg, W.; Technische Hochschule Darmstadt

    1985-02-01

    Elastoplasticity of finite Fermi systems results from a coherent coupling between collective and intrinsic degrees of freedom and subsequent equilibration essentially due to two-body collisions. Within a non-markovian transport-theoretical approach referred to as dissipative diabatic dynamics (DDD), elastoplastical forms the link between giant vibrations and overdamped motion of nuclear. Obersvable effects resulting from this non-markovian behaviour in nucleus-nucleus collisions are discussed. (orig.)

  14. Study of η-nucleus interaction through the formation of η-nucleus ...

    Indian Academy of Sciences (India)

    journal of. May 2006 physics pp. 943–946. Study of η-nucleus interaction through the formation of η-nucleus bound state. V JHA1, B J ROY1, A CHATTERJEE1 and H MACHNER2 ... are being carried out or proposed in different laboratories around the world. In this work we .... be due to a virtual state near the η-threshold. 4.

  15. 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

  16. Single-Cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes and Interaction Networks Involved in the Central Circadian Clock.

    Science.gov (United States)

    Park, James; Zhu, Haisun; O'Sullivan, Sean; Ogunnaike, Babatunde A; Weaver, David R; Schwaber, James S; Vadigepalli, Rajanikanth

    2016-01-01

    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 toward understanding how a population of heterogeneous single cells organizes into cellular networks that underlie tissue-level function.

  17. 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.

  18. Why do we have a caudate nucleus?

    Science.gov (United States)

    Villablanca, Jaime R

    2010-01-01

    In order to understand the physiological role of the caudate nucleus, we combine here our laboratory data on cats with reports of patients with selective damage to this nucleus. Cats with bilateral removal of the caudate nuclei showed a stereotyped behavior consisting of persistently approaching and then following a person, another cat, or any object, and attempting to contact the target. Simultaneously, the animals exhibited a friendly disposition and persistent docility together with purring and forelimbs treading/kneading. The magnitude and duration of this behavior was proportional to the extent of the removal reaching a maximum after ablations of 65% or more of the caudate tissue. These cats were hyperactive but they had lost the feline elegance of movements. Additional features of acaudate cats were: (1) postural and accuracy deficits (plus perseveration) in paw usage tasks including bar pressing for food reward; (2) cognitive and perceptual impairments on a T-maze battery of tasks and on the bar pressing tasks; (3) blockage or blunting of the species-specific behavioral response to a single injection of morphine; Unilateral caudate nucleus removal did not produce global behavioral effects, but only deficit in the contralateral paw contact placing reaction and paw usage/bar pressing. Moreover and surprisingly, we found hypertrophy of the ipsilateral caudate nucleus following prenatal focal neocortical removal. The findings in human were also behavioral (not neurological) and also occurred with unilateral caudate damage. The main manifestations consisted of loss of drive (apathy), obsessive-compulsive behavior, cognitive deficits, stimulus-bound perseverative behavior, and hyperactivity. Based on all of the above data we propose that the specific function of the caudate nucleus is to control approach-attachment behavior, ranging from plain approach to a target, to romantic love. This putative function would account well for the caudate involvement in the

  19. The Baryon Production and Baryon Number Transfer in Hadron-Hadron, Hadron-Nucleus and Nucleus-Nucleus Collisions

    International Nuclear Information System (INIS)

    Szymanski, P.

    2006-09-01

    This work concerns soft hadronic interactions which in the Standard Model carry most of the observable cross-section but are not amenable to quantitative predictions due to the very nature of the QCD (Theory of Strong Interactions). In the low momentum transfer region the evolving coupling constant caused perturbation theory to break down. In this situation better experimental understanding of the physics phenomena is needed. One aspect of the soft hadronic interactions will be discussed in this work: transfer of the baryon number from the initial to the final state of the interaction. The past experimental knowledge on this process is presented, reasons for its unsatisfactory status are discussed and condition necessary for improvement are outlined: that is experimental apparatus with superior performance over the full range of available interactions: hadron-hadron collision, hadron-nucleus and nucleus-nucleus interactions. A consistent model-independent picture of the baryon number transfer process emerging from the data on the full range of interactions is shown. It offers serious challenge to theory to provide quantitative and detailed explanation of the measurements. (author)

  20. Thermoregulation in the cold changes depending on the time of day and feeding condition: physiological and anatomical analyses of involved circadian mechanisms.

    Science.gov (United States)

    Tokizawa, K; Uchida, Y; Nagashima, K

    2009-12-15

    The circadian rhythm of body temperature (T(b)) is a well-known phenomenon. However, it is unknown how the circadian system including the suprachiasmatic nucleus (SCN) and clock genes affects thermoregulation. Food deprivation in mice induces a greater reduction of T(b) particularly in the light phase. We examined the role of Clock, one of key clock genes and the SCN during induced hypothermia. At 20 degrees C with fasting, mice increased their metabolic heat production in the dark phase and maintained T(b), whereas in the light phase, heat production was less, resulting in hypothermia. Under these conditions, neuronal activity in the SCN, assessed by cFos expression, increased only in the light phase. However, such differences in thermoregulatory and neural responses between the phases in Clock mutant mice were less marked. The neural network between the SCN and paraventricular nucleus appeared to be important in hypothermia. These findings suggest that the circadian system per se is influenced by both the feeding condition and environmental temperature and that it modulates thermoregulation.

  1. Sex Differences in Circadian Timing Systems: Implications for Disease

    Science.gov (United States)

    Bailey, Matthew; Silver, Rae

    2014-01-01

    Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamicadrenal-pituitary (HPA) axis, and sleep-arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions. PMID:24287074

  2. Melanopsin

    DEFF Research Database (Denmark)

    Hannibal, Jens; Fahrenkrug, Jan

    2002-01-01

    The brain's biological clock located in the suprachiasmatic nucleus (SCN) generates circadian rhythms of physiology and behaviour of approximately 24 hours. The clock needs, however, like a watch that runs too fast or too slow, daily adjustment and the most important stimulus for this adjustment...... is the environmental light/dark cycle, a process know as photoentrainment. It is well established that the eye contains a separate anatomical and functional system mediating light information to the clock. Until recently, the photopigment responsible for light entrainment of the circadian system has been elusive...... but recent studies have provided evidence that melanopsin, a recently identified opsin, could be the circadian photopigment. This conclusion is based on the observation that melanopsin is expressed exclusively in retinal ganglion cells projecting to the SCN, a projection known as the retinohypothalamic tract...

  3. Diurnal rhythmicity of the canonical clock genes Per1, per2 and Bmal1 in the rat adrenal gland is unaltered after hypophysectomy

    DEFF Research Database (Denmark)

    Fahrenkrug, J.; Hannibal, J.; Georg, B.

    2008-01-01

    Circadian rhythms are generated by endogenous clocks in the central brain oscillator, the suprachiasmatic nucleus (SCN), and peripheral tissues. The molecular basis for the circadian clock consists of a number of genes and proteins that form transcriptional/translational feedback loops. Rhythmic...... expression of clock genes in the adrenal glands has previously been reported. Since the central clock in the SCN communicates with the adrenal glands via circadian release of adrenocorticotrophic hormone, we quantified the mRNAs for the canonical clock genes, Per1, Per2 and Bmal1 in the adrenal glands...... by real-time reverse transcription-polymerase chain reaction during a 24-h-cycle in normal and hypophysectomised rats. The mRNAs for all the three clock genes disclosed rhythmic oscillations with a period of 24 h and the phase did not differ between the hypophysectomised and intact rats. The expression...

  4. 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

    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...... 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...... a 24-h rhythmic expression in the adrenal of WT mice under L/D and dark conditions. During a L/D cycle, the adrenal clock gene rhythm in VPAC2-KO mice was phase-advanced by approximately 6 h compared to WT mice and became arrhythmic in constant darkness. A significant 24-h rhythmic variation...

  5. 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

    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......, recent studies have shown the presence of extrahypothalamic oscillators in other areas of the brain including the cerebellum. In the present study, the authors unravel the cerebellar molecular clock by analyzing clock gene expression in the cerebellum of the rat by use of radiochemical in situ...... hybridization and quantitative real-time polymerase chain reaction. The authors here show that all core clock genes, i.e., Per1, Per2, Per3, Cry1, Cry2, Clock, Arntl, and Nr1d1, as well as the clock-controlled gene Dbp, are expressed in the granular and Purkinje cell layers of the cerebellar cortex. Among...

  6. 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.

  7. Nucleus spectroscopy: extreme masses and deformations

    International Nuclear Information System (INIS)

    Theisen, Ch.

    2009-12-01

    The author proposes a synthesis of research activities performed since 1995 in the field of experimental nuclear physics, and more particularly in the investigation of two nucleus extreme states: deformation on the one hand, heavy and very heavy nuclei on the other hand. After a presentation of the context of investigations on deformation, rotation, and heavy nuclei, he gives an overview of developments regarding instruments (gamma spectrometers, detection of fission fragments, and detection at the focal plane of spectrometers or separators) and analysis techniques. Experiments and results are then reported and discussed, concerning super-deformed states with a high angular moment, spectroscopy of neutron-rich nuclei, very heavy nuclei close to nucleus map borders. He finally draws perspectives for middle and long term studies on the heaviest nuclei

  8. Protein quality control in the nucleus

    DEFF Research Database (Denmark)

    Nielsen, Sofie V.; Poulsen, Esben Guldahl; Rebula, Caio A.

    2014-01-01

    to be particularly active in protein quality control. Thus, specific ubiquitin-protein ligases located in the nucleus, target not only misfolded nuclear proteins, but also various misfolded cytosolic proteins which are transported to the nucleus prior to their degradation. In comparison, much less is known about......In their natural environment, cells are regularly exposed to various stress conditions that may lead to protein misfolding, but also in the absence of stress, misfolded proteins occur as the result of mutations or failures during protein synthesis. Since such partially denatured proteins are prone...... to aggregate, cells have evolved several elaborate quality control systems to deal with these potentially toxic proteins. First, various molecular chaperones will seize the misfolded protein and either attempt to refold the protein or target it for degradation via the ubiquitin-proteasome system...

  9. Development of a Mobile Ice Nucleus Counter

    Energy Technology Data Exchange (ETDEWEB)

    Kok, Gregory [Droplet Measurement Technologies, Boulder, CO (United States); Kulkarni, Gourihar [Droplet Measurement Technologies, Boulder, CO (United States)

    2014-07-10

    An ice nucleus counter has been constructed. The instrument uses built-in refrigeration systems for wall cooling. A cascade refrigeration system will allow the cold wall to operate as low as -70°C, and a single stage system can operate the warm wall at -45C. A unique optical particle counter has been constructed using polarization detection of the scattered light. This allows differentiation of the particles exiting the chamber to determine if they are ice or liquid.

  10. Resonances in η-light nucleus systems

    Indian Academy of Sciences (India)

    We locate resonances in η-light nucleus elastic scattering using the time delay method. We solve few-body ... We planned to study the resonances in η-light nuclei systems since the few-body systems can be treated .... In an eigenphase formu- lation of the S-matrix, S = ηe2iδ (with η being the inelasticity factor), one can.

  11. Parity violation in the compound nucleus

    International Nuclear Information System (INIS)

    Mitchell, G. E.; Crawford, B. E.; Grossmann, C. A.; Lowie, L. Y.; Bowman, J. D.; Knudson, J.; Penttilae, S.; Seestrom, S. J.; Smith, D. A.; Yen, Yi-Fen; Yuan, V. W.; Delheij, P. P. J.; Haseyama, T.; Masaike, A.; Matsuda, Y.; Postma, H.; Roberson, N. R.; Sharapov, E. I.; Stephenson, S. L.

    1999-01-01

    Measurements have been performed on the helicity dependence of the neutron resonance cross section for many nuclei by our TRIPLE Collaboration. A large number of parity violations are observed. Generic enhancements amplify the signal for symmetry breaking and the stochastic properties of the compound nucleus permit the strength of the symmetry-breaking interaction to be determined without knowledge of the wave functions of individual states. A total of 15 nuclei have been analyzed with this statistical approach. The results are summarized

  12. Antinucleon-nucleus elastic and inelastic scattering

    International Nuclear Information System (INIS)

    Dover, C.B.; Millener, D.J.

    1985-01-01

    A general overview of the utility of antinucleon (anti N)-nucleus inelastic scattering studies is presented, emphasizing both the sensitivity of the cross sections to various components of the N anti N transition amplitudes and the prospects for the exploration of some novel aspects of nuclear structure. We start with an examination of the relation between NN and N anti N potentials, focusing on the coherences predicted for the central, spin-orbit and tensor components, and how these may be revealed by measurements of two-body spin observables. We next discuss the role of the nucleus as a spin and isospin filter, and show how, by a judicious choice of final state quantum numbers (natural or unnatural parity states, isospin transfer ΔT = 0 or 1) and momentum transfer q, one can isolate different components of the N anti N transition amplitude. Various models for the N anti N interaction which give reasonable fits to the available two-body data are shown to lead to strikingly different predictions for certain spin-flip nuclear transitions. We suggest several possible directions for future anti N-nucleus inelastic scattering experiments, for instance the study of spin observables which would be accessible with polarized anti N beams, charge exchange reactions, and higher resolution studies of the (anti p, anti p') reaction. We compare the antinucleon and the nucleon as a probe of nuclear modes of excitation. 40 refs., 13 figs

  13. Crystal structure, EPR spectra and conductivity of the (ET)2[Hg(SCN)2I] organic conductor (ET - bis-ethylenedithiotetrathiafulvalen)

    International Nuclear Information System (INIS)

    Yudanova, E.I.; Makarova, L.N.; Konovalikhin, S.V.; D'yachenko, O.A.; Lyubovskij, R.B.; Lyubovskaya, R.N.

    1996-01-01

    A study was made on structure, conductivity and EPR spectra of a new organic conductor (ET) 2 [Hg(SCN) 2 I] (ET -bis-ethyeleneithiotetrathiafulvalen). It is shown that cation-radicals in organic layers are packed according to k-type, and anions form a polymer chain. THe existence of cation-radical layers, which differ by the number of shortened S...S-contacts and by the way of interaction with anion layer, was revealed; width of EPR line is equal to 9-11 Gs (300 K) for them. This is several times less, than widths of lines, typical for k-type salts. Existence of conducting band of small dimensions was assumed. Analysis of temperature dependences of conductivity anisotropy and EPR spectra parameters enabled to make the assumption about structural rearrangement in the region of 50 K. Correlation of structure and properties of this compound with other salts of (ET) 2 [Hg(SCN) 3-n X n ], X = Cl, Br, n = 1, 2 family was conducted. 21 refs.; 5 figs

  14. Crystal structure, NMR study, dc-conductivity and dielectric relaxation studies of a new compound [C2H10N2]Cd(SCN)2Cl2

    Science.gov (United States)

    Saidi, K.; Kamoun, S.; Ayedi, H. F.; Gargouri, M.

    2012-06-01

    The crystal structure, the solid NMR spectroscopy and the complex impedance study have been carried out on [C2H10N2]CdCl2(SCN)2. Characterization by single crystal X-ray crystallography shows that the cadmium atoms have à 2N2S2Cl hexa-coordination sphere, exhibiting pseudo-octahedral geometry. The cadmium atoms are bridged by two thiocyanate ions generating 1-D polymeric-chains. These chains are themselves interconnected by means of N-H…Cl(NCS) hydrogen bonds originating from the organic cation [(NH3)2(CH2)2]2+. 111Cd isotropic chemical shifts span a range of 268ppm. The cadmium atom exhibits multiplets that result from 111Cd-14N spin-spin coupling. Examination of 111Cd and 13C MAS line shapes shows direct measurement of the indirect spin-spin coupling constant 2J(111Cd, 14N) = 105Hz and the dipolar coupling constant of 1381Hz . Impedance spectroscopy measurements of [C2H10N2]CdCl2(SCN)2 have been studied from 209Hz to 5 MHz over the temperature range 300-370 K. The Cole-Cole (Z" versus Z') plots are fitted to two equivalent circuits models. The formalism of complex permittivity and impedance were employed to analyze the experimental data. The dc conductivity follows the Arrhenius relation with an activation energy Ea = 0.54 (3) eV.

  15. Crystal structure, NMR study, dc-conductivity and dielectric relaxation studies of a new compound [C2H10N2]Cd(SCN2Cl2

    Directory of Open Access Journals (Sweden)

    Gargouri M.

    2012-06-01

    Full Text Available The crystal structure, the solid NMR spectroscopy and the complex impedance study have been carried out on [C2H10N2]CdCl2(SCN2. Characterization by single crystal X-ray crystallography shows that the cadmium atoms have à 2N2S2Cl hexa-coordination sphere, exhibiting pseudo-octahedral geometry. The cadmium atoms are bridged by two thiocyanate ions generating 1-D polymeric-chains. These chains are themselves interconnected by means of N-H…Cl(NCS hydrogen bonds originating from the organic cation [(NH32(CH22]2+. 111Cd isotropic chemical shifts span a range of 268ppm. The cadmium atom exhibits multiplets that result from 111Cd-14N spin-spin coupling. Examination of 111Cd and 13C MAS line shapes shows direct measurement of the indirect spin-spin coupling constant 2J(111Cd, 14N = 105Hz and the dipolar coupling constant of 1381Hz . Impedance spectroscopy measurements of [C2H10N2]CdCl2(SCN2 have been studied from 209Hz to 5 MHz over the temperature range 300-370 K. The Cole-Cole (Z” versus Z’ plots are fitted to two equivalent circuits models. The formalism of complex permittivity and impedance were employed to analyze the experimental data. The dc conductivity follows the Arrhenius relation with an activation energy Ea = 0.54 (3 eV.

  16. 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.

  17. High prevalence of the SCN5A E1784K mutation in school children with long QT syndrome living on the Okinawa islands.

    Science.gov (United States)

    Takahashi, Kazuhiro; Shimizu, Wataru; Miyake, Akira; Nabeshima, Taisuke; Nakayashiro, Mami; Ganaha, Hitoshi

    2014-01-01

    Genetic testing for long QT syndrome (LQTS) is now in clinical practice. We conducted molecular genetic analyses to definitively diagnose LQTS and to determine its subtypes for gene-specific treatment. We conducted a retrospective study to determine the characteristics of schoolchildren with LQTS living on the Okinawa Islands. The study population included children identified in a school-based electrocardiographic (ECG) screening program for cardiovascular diseases who were referred to Okinawa Children's Medical Center between 2007 and 2012; 23 children met the diagnostic criteria for LQTS. Of them, 17 were genotype-positive and 14 were found to harbor theSCN5AE1784K mutation exclusively among the LQTS genotype-positive children. The children were divided into genotype-positive and -negative groups. Clinical characteristics and ECG data were analyzed and compared. The median Schwartz score was 3. The median QT interval was 521 ms. The major finding is that the prevalent subtype of LQTS in Okinawa is discordant with other cohorts living in other regions of Japan or overseas. We cannot exclude the possibility of the presence of a specific founder mutation in this geographically clustered population, particularly considering that the hospital is the only tertiary heart center for children in Okinawa. However, this uniquely high prevalence of theSCN5AE1784K mutation serves as a compelling justification to conduct a larger study.

  18. 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

  19. 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

  20. Jefferson Lab's Journey into the Nucleus

    International Nuclear Information System (INIS)

    Douglas Higinbotham

    2004-01-01

    The year 1969 saw the publication of the first results indicating that hard scattering centres exist deep inside protons. A collaboration between the Stanford Linear Accelerator Center (SLAC) and the Massachusetts Institute of Technology was using SLAC's new high-energy electron LINAC to pioneer a rich new field in the study of the nucleus--deep inelastic scattering. Their measurements revealed that nucleons are made up of point-like particles, which Richard Feynman dubbed ''partons''. Thirty-five years on, studies of the parton-nature of the nucleus continue, not only at the traditional high-energy centres, but also at lower-energy laboratories, and in particular at the Thomas Jefferson National Accelerator Facility (Jefferson Lab) in Virginia. Jefferson Lab is home to the Continuous Electron Beam Accelerator Facility (CEBAF). Its main mission is to explore the atomic nucleus and the fundamental building-blocks of matter. As part of this mission, researchers there study the transition from the picture of the nucleus as a bound state of neutrons and protons to its deeper structure in terms of quarks and gluons--in other words, the transition from the hadronic degrees of freedom of nuclear physics to the quark-gluon degrees of freedom of high-energy physics. In exploring this transition, a wide range of experiments has been performed, from measurements of elastic form factors at large momentum transfers to studies of deep inelastic scattering. An array of spectrometers together with electron-beam energies of up to 5.7 GeV has allowed the laboratory to make significant contributions to this field. This article describes three experiments, each aimed at improving our understanding of a different aspect of the partonic nature of matter. The first, a classic deep inelastic scattering experiment, seeks to further our understanding of the composition of nucleon spin. The second experiment studies the concept of quark-hadron duality--a link between the deep inelastic

  1. J/$\\psi$ production in proton-nucleus and nucleus-nucleus interactions at the CERN SPS

    CERN Document Server

    Abreu, M C; Alexa, C; Arnaldi, R; Ataian, M R; Baglin, C; Baldit, A; Bedjidian, Marc; Beolè, S; Boldea, V; Bordalo, P; Borges, G; Bussière, A; Capelli, L; Castanier, C; Castor, J I; Chaurand, B; Chevrot, I; Cheynis, B; Chiavassa, E; Cicalò, C; Claudino, T; Comets, M P; Constans, N; Constantinescu, S; Cortese, P; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Drapier, O; Ducroux, L; Espagnon, B; Fargeix, J; Force, P; Gallio, M; Gavrilov, Yu K; Gerschel, C; Giubellino, P; Golubeva, M B; Gonin, M; Grigorian, A A; Grossiord, J Y; Guber, F F; Guichard, A; Gulkanian, H R; Hakobyan, R S; Haroutunian, R; Idzik, M; Jouan, D; Karavitcheva, T L; Kluberg, L; Kurepin, A B; Le Bornec, Y; Lourenço, C; Macciotta, P; MacCormick, M; Marzari-Chiesa, A; Masera, M; Masoni, A; Monteno, M; Musso, A; Petiau, P; Piccotti, A; Pizzi, J R; Prado da Silva, W L; Prino, F; Puddu, G; Quintans, C; Ramello, L; Ramos, S; Rato-Mendes, P; Riccati, L; Romana, A; Santos, H; Saturnini, P; Scalas, E; Scomparin, E; Serci, S; Shahoyan, R; Sigaudo, F; Silva, S; Sitta, M; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, Ermanno; Villatte, L; Willis, N

    2002-01-01

    The NA38 and NA50 experiments at the CERN SPS have measured charmonium production in different colliding systems with the aim of observing a phase transition from ordinary hadronic matter towards a state in which quarks and gluons are deconfined (quark-gluon plasma, QGP). This experimental research is based on the prediction that the J/ psi yield should be suppressed in deconfined matter. The analysis of the data collected by the NA50 experiment with Pb-Pb collisions at 158 GeV/c per nucleon shows that the J/ psi is anomalously suppressed with respect to the pattern observed in proton-nucleus and light ion reactions. (9 refs).

  2. Limits to the formation of hot fusion nuclei in nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Peter, J.; Tamain, B.

    1987-01-01

    The maximum temperature which can be sustained by a nucleus is discussed. Methods used to measure the temperature; values measured in fusion reactors; theoretical investigations on the value of the limiting temperature; and information about dynamical limitations on excitation energy storage in nuclei are reviewed. It is concluded that thermalized fusion nuclei are formed at temperatures up to 5 MeV for heavy systems and 6 MeV for medium mass systems. Thermal energy in central nucleus-nucleus collisions might not exceed some saturation value due to two effects: a sharing of the deposited energy into compressional and thermal energies; and a dynamical competition between thermal energy deposition and fast pre-equilibrium emission

  3. High energy nucleus-nucleus collisions at CERN: Signatures, physical observables and experimental results

    International Nuclear Information System (INIS)

    Harris, J.W.

    1988-02-01

    Experimental results on high energy nucleus-nucleus collisions have become available with the recent experiments at CERN utilizing 200 GeV/n oxygen and sulfur beams. Physics motivations for these experiments are presented: a description of predicted signatures for possible formation of a quark-gluon plasma and physical observables that are expected to provide important information for understanding the dynamics of these collisions. A presentation will be made of some of the first experimental results to emerge from this new field. 28 refs., 9 figs

  4. Proton rapidity distribution in nucleus-nucleus collisions at high energy

    International Nuclear Information System (INIS)

    Liu, F.H.

    2002-01-01

    The proton rapidity distributions in nucleus-nucleus collisions at the Alternating Gradient Synchrotron (AGS) and the Super Proton Synchrotron (SPS) energies are analysed by the revised thermalized cylinder model. The calculated results are compared and found to he in agreement with the experimental data of Si-AI and Si-Pb collisions at 14.6 A GeV/c, Pb-Pb collisions at 158 A GeV/c, and S-S collisions at 200 A GeV/c. (Author)

  5. Subthreshold pion production from nucleus-nucleus collisions around 100 MeV/nucleon

    Science.gov (United States)

    Badalá, A.; Barbera, R.; Palmeri, A.; Pappalardo, G. S.; Riggi, F.; Russo, A. C.

    1993-12-01

    Several global variables were tested with the aim to determine the impact parameter in nucleus-nucleus collisions producing pions at incident energies around 100 MeV/nucleon. The experimental set-up includes the MEDEA multidetector, part of which is used as a π 0 spectrometer, and an additional hodoscope of plastic scintillators to cover very forward angles. A statistical model was used to generate both inclusive and pion-triggered events. Selection of well measured events was made through the measured total parallel momentum. Among the different global variables which were tested, the average parallel velocity was seen to give the best correlation with the impact parameter.

  6. The basic elementary particles as martensitic nucleus

    International Nuclear Information System (INIS)

    Aguinaco-Bravo, V. J.; Onoro, J.

    1999-01-01

    The martensitic transformation is a diffusional structural change that produces an important modification of the microstructure and properties of materials. In this paper we propose how the martensitic phase is nucleated from a basic elementary particle (bep). The bep is formed in several stages. Vacancies, divacancies, etc. are formed at high temperature, which collapse into prismatic dislocation loops during the cooling process. We define a bep as a dislocation loop reaching a critical radius and fulfilling certain elastic energy conditions. A martensitic nucleus is a bep that coincides crystallographically with the habit plane of the matrix. (Author) 16 refs

  7. An exceptionally bright, compact starburst nucleus

    Science.gov (United States)

    Margon, Bruce; Anderson, Scott F.; Mateo, Mario; Fich, Michel; Massey, Philip

    1988-01-01

    Observations are reported of a remarkably bright (V about 13) starburst nucleus, 0833 + 652, which has been detected at radio, infrared, optical, ultraviolet, and X-ray wavelengths. Despite an observed flux at each of these wavelengths which is comparable to that of NGC 7714, often considered the 'prototypical' example of the starburst phenomenon, 0833 + 652 appears to be a previously uncataloged object. Its ease of detectability throughout the electromagnetic spectrum should make it useful for a variety of problems in the study of compact emission-line galaxies.

  8. From the nucleus discovery to DWBA

    International Nuclear Information System (INIS)

    Fernandez, B.

    2007-01-01

    The author presents a brief review of the main events in the field of nuclear reactions that are acknowledged as milestones because of their importance due to either experimental setting or physical interpretation. It is shown that the pace of discoveries has been strongly dependent on the technical progress in detection means at the beginning of nuclear physics and now is linked to the development of simulation means. The discovery of the neutron, the development of the Geiger counter, the theory of the compound nucleus or the first direct reactions are among these milestones

  9. Lectures on the theory of the nucleus

    CERN Document Server

    Sitenko, Aleksej Grigorevich

    1975-01-01

    Provides an advanced and up-to-date account of the theory of nuclear structure and discusses in considerable detail both the superfluid and collective models of the nucleus, in addition to earlier complementary models and theories. The book also examines other important topics such as the rotational and vibrational spectra of nuclei which have not previously been treated in such depth. To summarize, it covers a large amount of theoretical ground in one volume and attempts to fill a serious gap in the literature. Many problems are included

  10. Parity violation in the compound nucleus

    International Nuclear Information System (INIS)

    Mitchell, G.E.; Crawford, B.E.; Grossmann, C.A.; Lowie, L.Y.; Bowman, J.D.; Knudson, J.; Penttilae, S.; Seestrom, S.J.; Smith, D.A.; Yen, Y.; Yuan, V.W.; Delheij, P.P.; Haseyama, T.; Masaike, A.; Matsuda, Y.; Postma, H.; Roberson, N.R.; Sharapov, E.I.; Stephenson, S.L.

    1999-01-01

    Measurements have been performed on the helicity dependence of the neutron resonance cross section for many nuclei by our TRIPLE Collaboration. A large number of parity violations are observed. Generic enhancements amplify the signal for symmetry breaking and the stochastic properties of the compound nucleus permit the strength of the symmetry-breaking interaction to be determined without knowledge of the wave functions of individual states. A total of 15 nuclei have been analyzed with this statistical approach. The results are summarized. copyright 1999 American Institute of Physics

  11. Contemporary models of the atomic nucleus

    CERN Document Server

    Nemirovskii, P E

    2013-01-01

    Contemporary Models of the Atomic Nucleus discusses nuclear structure and properties, expounding contemporary theoretical concepts of the low-energy nuclear processes underlying in nuclear models. This book focuses on subjects such as the optical nuclear model, unified or collective model, and deuteron stripping reaction. Other topics discussed include the basic nuclear properties; shell model; theoretical analysis of the shell model; and radiative transitions and alpha-decay. The deuteron theory and the liquid drop nuclear model with its application to fission theory are also mentioned, but o

  12. Role of nucleon exchange in dissipative and absorptive nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Pal, Santanu

    1988-01-01

    When a heavy nucleus impinges upon another, a number of nucleons can be exchanged between them. The number of such exchanges is a measure of the flux (a part of it) removed from the elastic channel and hence could give rise to an absorptive component in the nucleus-nucleus optical model potential. The transferred nucleons also carry certain amount of momentum which can cause an energy dissipation from the relative motion between the two nuclei. Both of these approaches have been studied in the last few years. However calculations of the flux to obtain the absorptive potential were based on nuclear models, such as fermi gas, where the tail region of the nucleus (which should be the most important region for transfer to occur) is treated inadequately. On the other hand, the proximity type of nuclear friction relies on a nucleon flux which is defined in pure classical terms. A model is presented to obtain a quantum mechanically defined particle flux. The time-dependent wave functions of single particle states in the field of two moving potential pockets are calulated. From the calculated flux, both the absorptive potential and the radial friction coefficient are obtained. The results are compared with phenomenological values for sup(16)O+sup(40)Ca and sup(40)Ca+sup(40)Ca systems. (author). 13 refs., 8 figs

  13. Experimental study of collective flow phenomena in high-energy nucleus-nucleus collisions

    CERN Document Server

    Chkhaidze, L V; Kharkhelauri, L L

    2002-01-01

    The results of the experimental study of collective flow phenomena, such as the sideward and elliptic flow of nuclear matter, discovered during the last 10-15 years in high-energy nucleus-nucleus collisions are presented in this review. Sideward (often termed directed) and elliptic flows have been observed for protons, antiprotons, light nuclei, pions, kaons, and lambdas emitted in nucleus-nucleus collisions at 0.1-1.8 GeV/nucleon of LBL Bevalac and GSI/SIS by Plastic-Ball, Streamer Chamber, EOS-NPC, FOPI, LAND, TAPS, and KAOS collaborations; at 2-4 GeV/nucleon of Dubna JINR by SKM-200-GIBS, Propane Buble Chamber, and Emulsion Chamber collaborations; at 2-14 GeV/nucleon of BNL AGS, by the E877, E895, and E917 collaborations; and at 60 and 200 GeV/nucleon of CERN SPS, by the WA98 and NA49 collaborations and more recently by the STAR at RHIC BNL. In the review, the results of the SKM-200-GIBS collaboration of JINR are presented and compared with the results of different experiments by Bevalac, GSI/SIS, BNL, and...

  14. Study of η-nucleus interaction through the formation of η-nucleus ...

    Indian Academy of Sciences (India)

    Abstract. The question of possible existence of η-mesic nuclei is quite intriguing. An- swer to this question will deeply enrich our understanding of η-nucleus interaction which is not so well-understood. We review the experimental efforts for the search of η-mesic nuclei and describe the physics motivation behind it.

  15. Thermal Bremsstrahlung probing nuclear multifragmentation in nucleus-nucleus collisions around the Fermi energy

    International Nuclear Information System (INIS)

    D'Enterria, D.G.

    2000-05-01

    The thermodynamical properties of nuclear matter at moderate temperatures and densities, in the vicinity of the predicted nuclear liquid-gas phase transition, are studied using as experimental probe the hard-photons (E γ > 30 MeV) emitted in nucleus-nucleus collisions. Photon and charged-particle production in four different heavy-ion reactions (Ar 36 + Au 197 , Ag 107 , Ni 58 , C 12 at 60 A*MeV) is measured exclusively and inclusively coupling the TAPS photon spectrometer with two charged-particle and intermediate-mass-fragment detectors covering nearly 4π. We confirm that Bremsstrahlung emission in first-chance (off-equilibrium) proton-neutron collisions (pnγ) is the dominant origin of hard photons. We also firmly establish the existence of a thermal radiation component emitted in second-chance proton-neutron collisions. This thermal Bremsstrahlung emission takes place in semi-central and central nucleus-nucleus reactions involving heavy targets. We exploit this observation i) to demonstrate that thermal equilibrium is reached during the reaction, ii) to establish a new thermometer of nuclear matter based on Bremsstrahlung photons, iii) to derive the thermodynamical properties of the excited nuclear sources and, in particular, to establish a 'caloric curve' (temperature versus excitation energy), and iv) to assess the time-scales of the nuclear break-up process. (author)

  16. Study of η-nucleus interaction through the formation of η-nucleus ...

    Indian Academy of Sciences (India)

    The question of possible existence of -mesic nuclei is quite intriguing. Answer to this question will deeply enrich our understanding of -nucleus interaction which is not so well-understood. We review the experimental efforts for the search of -mesic nuclei and describe the physics motivation behind it. We present the ...

  17. Prestress mediates force propagation into the nucleus

    International Nuclear Information System (INIS)

    Hu Shaohua; Chen Jianxin; Butler, James P.; Wang Ning

    2005-01-01

    Several reports show that the nucleus is 10 times stiffer than the cytoplasm. Hence, it is not clear if intra-nuclear structures can be directly deformed by a load of physiologic magnitudes. If a physiologic load could not directly deform intra-nuclear structures, then signaling inside the nucleus would occur only via the mechanisms of diffusion or translocation. Using a synchronous detection approach, we quantified displacements of nucleolar structures in cultured airway smooth muscle cells in response to a localized physiologic load (∼0.4 μm surface deformation) via integrin receptors. The nucleolus exhibited significant displacements. Nucleolar structures also exhibited significant deformation, with the dominant strain being the bulk strain. Increasing the pre-existing tensile stress (prestress) in the cytoskeleton significantly increased the stress propagation efficiency to the nucleolus (defined as nucleolus displacement per surface deformation) whereas decreasing the prestress significantly lowered the stress propagation efficiency to the nucleolus. Abolishing the stress fibers/actin bundles by plating the cells on poly-L-lysine-coated dishes dramatically inhibited stress propagation to the nucleolus. These results demonstrate that the prestress in the cytoskeleton is crucial in mediating stress propagation to the nucleolus, with implications for direct mechanical regulation of nuclear activities and functions

  18. Investigation on the structure of thiocyanatoruthenate (3) complex by isotopic exchange method in the system [Ru(SCN)6]-3-S14CN-

    International Nuclear Information System (INIS)

    Wajda, S.; Rachlewicz, K.

    1973-01-01

    Because of the discrepancy in the literature data and the difficulties in the synthesis of Ru(3) thiocyanate complexes, an attempt was made to obtain them under different conditions than usual. Our attempts turned out to be successful. This allowed to examine the radioisotopic exchange in the system [Ru(SCN) 6 ] -3 -S 14 CN - . The experimental data indicated that the thiocyanate groups in the complex are nonequivalent and exchange with various rate. The two groups in the axial plane exchange with a rate by two orders higher than the remaining four groups in the equatorial plane. On this ground the electronic structure of the examined complex was discussed and its symmetry was determined. (author)

  19. 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

  20. Measurements of activity coefficients at infinite dilution of aromatic and aliphatic hydrocarbons, alcohols, and water in the new ionic liquid [EMIM][SCN] using GLC

    International Nuclear Information System (INIS)

    Domanska, Urszula; Marciniak, Andrzej

    2008-01-01

    A new ionic liquid was chosen for the separation of aromatic hydrocarbons from aliphatic hydrocarbons. The activity coefficients at infinite dilution, γ 13 ∞ for 29 solutes: alkanes, alkenes, alkynes, cycloalkanes, aromatic hydrocarbons, alcohols, and water in the ionic liquid 1-ethyl-3-methyl-imidazolium thiocyanate [EMIM][SCN] were determined by gas-liquid chromatography at the temperatures from 298.15 K to 368.15 K. The values of the partial molar excess enthalpies at infinite dilution ΔH 1 E,∞ were calculated from the experimental γ 13 ∞ values obtained over the temperature range. The selectivities for the hexane/benzene and cyclohexane/benzene separation problems were calculated from the γ 13 ∞ and compared to the other ionic liquids, NMP and sulfolane, taken from the recent literature. This work demonstrates that with chosen ionic liquid it is possible to separate different organic compounds with the highest selectivity ever published

  1. Measurements of activity coefficients at infinite dilution of aliphatic and aromatic hydrocarbons, alcohols, thiophene, tetrahydrofuran, MTBE, and water in ionic liquid [BMIM][SCN] using GLC

    International Nuclear Information System (INIS)

    Domanska, Urszula; Laskowska, Marta

    2009-01-01

    The activity coefficients at infinite dilution, γ 13 ∞ for 32 solutes: alkanes, alken-1-es, alkyn-1-es, cycloalkanes, aromatic hydrocarbons, alcohols, thiophene, tetrahydrofuran, tert-butyl methyl ether, and water in the ionic liquid 1-butyl-3-methylimidazolium thiocyanate [BMIM][SCN] were determined by gas-liquid chromatography at the temperatures from 298.15 K to 368.15 K. The values of the partial molar excess enthalpies at infinite dilution ΔH 1 E,∞ were calculated from the experimental γ 13 ∞ values obtained over the temperature range. The selectivities for the hexane/benzene, cyclohexane/benzene, hexane/thiophene, and other separation problems were calculated from the γ 13 ∞ and compared to the other ionic liquids, N-methyl-2-pyrrolidinone, and sulfolane, taken from the recent literature. This work demonstrates that with chosen ionic liquid it is possible to separate different organic compounds with the highest selectivity, ever published

  2. Effects of an epilepsy-causing mutation in the SCN1A sodium channel gene on cocaine-induced seizure susceptibility in mice.

    Science.gov (United States)

    Purcell, Ryan H; Papale, Ligia A; Makinson, Christopher D; Sawyer, Nikki T; Schroeder, Jason P; Escayg, Andrew; Weinshenker, David

    2013-07-01

    High doses of cocaine can elicit seizures in humans and in laboratory animals. Several mechanisms have been proposed for the induction of seizures by cocaine, including enhanced monoaminergic signaling, blockade of ion channels, and alterations in GABA and glutamate transmission. Mutations in the SCN1A gene, which encodes the central nervous system (CNS) voltage-gated sodium channel (VGSC) Nav1.1, are responsible for several human epilepsy disorders including Dravet syndrome and genetic (generalized) epilepsy with febrile seizures plus (GEFS+). Mice heterozygous for the R1648H GEFS+ mutation (RH mice) exhibit reduced interneuron excitability, spontaneous seizures, and lower thresholds to flurothyl- and hyperthermia-induced seizures. However, it is unknown whether impaired CNS VGSC function or a genetic predisposition to epilepsy increases susceptibility to cocaine-induced seizures. Our primary goal was to determine whether Scn1a dysfunction caused by the RH mutation alters sensitivity to cocaine-induced behavioral and electrographic (EEG) seizures. We also tested novelty- and cocaine-induced locomotor activity and assessed the expression of Nav1.1 in midbrain dopaminergic neurons. We found that RH mice had a profound increase in cocaine-induced behavioral seizure susceptibility compared to wild-type (WT) controls, which was confirmed with cortical EEG recordings. By contrast, although the RH mice were hyperactive in novel environments, cocaine-induced locomotor activity was comparable between the mutants and WT littermates. Finally, immunofluorescence experiments revealed a lack of Nav1.1 immunoreactivity in dopaminergic neurons. These data indicate that a disease-causing CNS VGSC mutation confers susceptibility to the proconvulsant, but not motoric, effects of cocaine.

  3. Nucleus and nucleus-cytoskeleton connections in 3D cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lingling, E-mail: liulingling2012@163.com; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Sun, Jinghui, E-mail: sunjhemail@163.com; Song, Guanbin, E-mail: song@cqu.edu.cn

    2016-10-15

    Cell migration plays an important role in many physiological and pathological settings, ranging from embryonic development to cancer metastasis. Currently, accumulating data suggest that cells migrating in three-dimensional (3D) environments show well-defined differences compared to their well-established two-dimensional (2D) counterparts. During 3D migration, the cell body and nucleus must deform to allow cellular passage through the available spaces, and the deformability of the relatively rigid nucleus may constitute a limiting step. Here, we highlight the key evidence regarding the role of the nuclear mechanics in 3D migration, including the molecular components that govern the stiffness of the nucleus and review how the nuclear dynamics are connected to and controlled by cytoskeleton-based migration machinery. Intriguingly, nuclear movement must be coordinated with the cytoskeletal dynamics at the leading and trailing edges, which in turn impact the cytoplasmic dynamics that affect the migration efficiency. Thus, we suggest that alterations in the nuclear structure may facilitate cellular reorganizations that are necessary for efficient migration. - Graphical abstract: Schematic representations of a cell migrating on a 2D substrate and a cell migrating in a 3D extracellular matrix environment. (A) Nucleus-cytoskeleton connections are essential to 3D migration. Mechanical signals are transduced by integrins at the cell surface and channeled to cytoskeletal proteins, which generates prestress. The nucleus-cytoskeleton connections can either act as a stable skeleton to anchor the nuclei or provide active force to move the nuclei. The LINC complex is responsible for the nucleo-cytoskeletal coupling. Nesprins connect the cytoskeletal proteins to the inner nuclear membrane proteins SUN1 and SUN2. The SUN proteins connect to the lamins that form the lamina, which attaches to the chromatin. This physical connectivity transmits the mechanical signals from receptors at

  4. Nucleus and nucleus-cytoskeleton connections in 3D cell migration

    International Nuclear Information System (INIS)

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Song, Guanbin

    2016-01-01

    Cell migration plays an important role in many physiological and pathological settings, ranging from embryonic development to cancer metastasis. Currently, accumulating data suggest that cells migrating in three-dimensional (3D) environments show well-defined differences compared to their well-established two-dimensional (2D) counterparts. During 3D migration, the cell body and nucleus must deform to allow cellular passage through the available spaces, and the deformability of the relatively rigid nucleus may constitute a limiting step. Here, we highlight the key evidence regarding the role of the nuclear mechanics in 3D migration, including the molecular components that govern the stiffness of the nucleus and review how the nuclear dynamics are connected to and controlled by cytoskeleton-based migration machinery. Intriguingly, nuclear movement must be coordinated with the cytoskeletal dynamics at the leading and trailing edges, which in turn impact the cytoplasmic dynamics that affect the migration efficiency. Thus, we suggest that alterations in the nuclear structure may facilitate cellular reorganizations that are necessary for efficient migration. - Graphical abstract: Schematic representations of a cell migrating on a 2D substrate and a cell migrating in a 3D extracellular matrix environment. (A) Nucleus-cytoskeleton connections are essential to 3D migration. Mechanical signals are transduced by integrins at the cell surface and channeled to cytoskeletal proteins, which generates prestress. The nucleus-cytoskeleton connections can either act as a stable skeleton to anchor the nuclei or provide active force to move the nuclei. The LINC complex is responsible for the nucleo-cytoskeletal coupling. Nesprins connect the cytoskeletal proteins to the inner nuclear membrane proteins SUN1 and SUN2. The SUN proteins connect to the lamins that form the lamina, which attaches to the chromatin. This physical connectivity transmits the mechanical signals from receptors at

  5. Spectroscopic Studies of the Nucleus GOLD-195

    Science.gov (United States)

    Fischer, Susan Marie

    The nucleus ^{195}Au has been studied via in-beam gamma -ray and electron spectroscopy with the reactions ^{196}Pt(p,2n)^ {195}Au at beam energies of 12 and 16 MeV, and the reaction ^{rm nat }Ir(alpha,2n) ^{195}Au at a beam energy of 26 MeV. All experiments were performed at the University of Notre Dame tandem accelerator facility and utilized elements of the University of Pittsburgh multi-detector gamma-array and ICEBall mini-orange electron spectrometer. Fifty-five new transitions and thirty-six new energy levels have been observed. The U(6/4) supersymmetric algebra has been proposed to provide a simultaneous description for the positive parity states of the pair of nuclei ^{194 }Pt and ^{195}Au. The observed energy spectra for these nuclei show satisfactory agreement with the U(6/4) predicted spectra. The collective properties including relative B(E2) values for the Pt and Au nuclei in this mass region are also consistent with theoretical predictions. However, the measured E2/M1 mixing ratios for transitions in ^{195} Au indicate that the single particle description for the odd-A nucleus is incomplete. The new data for ^{195}Au is further combined with the existing data for ^{194} Pt and ^{195}Pt within the context of the larger U_{ nu}(6/12) otimes U_{pi}(6/4) supersymmetry. A consistent fit to the energy eigenvalue equation is obtained and a modified prediction for the negative parity states in the odd-odd nucleus ^{196} Au is made. Thus, the proposal of an underlying supersymmetry for the quartet of nuclei ^ {194}Pt-^{195} Pt-^{195}Au- ^{196}Au also appears valid. New transitions and levels involved in the negative parity h_{11/2} decoupled band in ^{195}Au have also been observed. The band appears to be much more fragmented at high spins than the analogous structures in the lighter odd-A Au nuclei, but it is unclear what the source of this difference is. It is, however, proposed that a consistent description for both the positive and negative parity

  6. Delta-nucleus dynamics: proceedings of symposium

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T.S.H.; Geesaman, D.F.; Schiffer, J.P. (eds.)

    1983-10-01

    The appreciation of the role in nuclear physics of the first excited state of the nucleon, the delta ..delta..(1232), has grown rapidly in the past decade. The delta resonance dominates nuclear reactions induced by intermediate energy pions, nucleons, and electromagnetic probes. It is also the most important non-nucleonic degree of freedom needed to resolve many fundamental problems encountered in the study of low-energy nuclear phenomena. Clearly, a new phase of nuclear physics has emerged and conventional thinking must be extended to account for this new dimension of nuclear dynamics. The most challenging problem we are facing is how a unified theory can be developed to describe ..delta..-nucleus dynamics at all energies. In exploring this new direction, it is important to have direct discussions among researchers with different viewpoints. Separate entries were prepared for the 49 papers presented. (WHK)

  7. High energy hadron-nucleus collision

    International Nuclear Information System (INIS)

    Takagi, Fujio

    1983-02-01

    This is a lecture note concerning high energy hadron-nucleus collision. The lecture gives the inelastic total cross section and the Glanber approximate multiple scattering formula at first. The mechanism of nuclear spallation is described in a cylindrical image. The multiplicity, the one particle distribution and the time-space structure of particle production are discussed. Various models are presented. The attenuation of forward particles and the structure of hadrons are discussed for each model. The atomic number (A) dependence of the production of large transverse momentum particles and jet, and the A dependence of charged multiplicity are presented. The backward production of particles and many body correlation are discussed. Lepton pair production and the initial interaction of constituents, collective interaction, multi quark state and phase transition are described. (Kato, T.)

  8. Electronic equipment for atomic nucleus structure studying

    International Nuclear Information System (INIS)

    Brudanin, V.B.; Vasilev, D.; Vylov, Ts.; Zhuravlev, N.I.; Salamatin, A.V.; Sidorov, V.T.; Sinaev, A.N.; Churin, I.N.

    1985-01-01

    The CAMAC electronic equipment used in data acquisition systems for spectrometers intended for investigation of the structure of an atomic nucleus is considered. Specific features of electronic units forming a part of spectrometers for determination of neutrino helicity and three-dimensional amplitude-time measurements as well as electrostatic beta-spectrometer are discussed. Parameters of the MAK-1, the MAK-2 and the MAK-3 multichannel amplitude analyzers developed specially for these spectrometers are given. Accumulation of data coming from analog-to-digital converters and output of recorded spectra on the screens of displays is realized without use of the crate dataway that permits to avoid time losses and to place several analyzers in a crate. Observation of spectra is realized simultaneously with their registration

  9. Parity violation in the compound nucleus

    International Nuclear Information System (INIS)

    Bowman, J.D.; Frankle, C.M.; Green, A.A.; Knudson, J.N.; Penttilae, S.I.; Seestrom, S.J.; Yen, Y.; Yuan, V.W.; Crawford, B.E.; Roberson, N.R.; Gould, C.R.; Haase, D.G.; Lowie, L.Y.; Mitchell, G.E.; Stevenson, S.I.; Delheij, P.P.J.; Sharapov, E.I.; Postma, H.; Masuda, Y.; Shimizu, H.M.; Iinuma, M.; Masaike, A.; Matsuda, Y.; Fukuda, K.

    1995-01-01

    The status of parity violation in the compound nucleus is reviewed. The results of previous experimental results obtained by scattering polarized epithermal neutrons from heavy nuclei in the 3-p and 4-p p-wave strength function peaks are presented. Experimental techniques are presented. The extraction of the mean squared matrix element of the parity-violating interaction, M 2 , between compound-nuclear levels and the relationship of M 2 to the coupling strengths in the meson exchange weak nucleon-nucleon potential are discussed. The tendency of measured asymmetries to have a common sign and theoretical implications are discussed. New experimental results are presented that show that the common sign phenomenon is not universal, as theoretical models developed up to now would predict. copyright 1995 American Institute of Physics

  10. Observation of the antimatter helium-4 nucleus.

    Science.gov (United States)

    2011-05-19

    High-energy nuclear collisions create an energy density similar to that of the Universe microseconds after the Big Bang; in both cases, matter and antimatter are formed with comparable abundance. However, the relatively short-lived expansion in nuclear collisions allows antimatter to decouple quickly from matter, and avoid annihilation. Thus, a high-energy accelerator of heavy nuclei provides an efficient means of producing and studying antimatter. The antimatter helium-4 nucleus (4He), also known as the anti-α (α), consists of two antiprotons and two antineutrons (baryon number B = -4). It has not been observed previously, although the α-particle was identified a century ago by Rutherford and is present in cosmic radiation at the ten per cent level. Antimatter nuclei with B antimatter nuclei and a benchmark for possible future observations of 4He in cosmic radiation.

  11. Delta-nucleus dynamics: proceedings of symposium

    International Nuclear Information System (INIS)

    Lee, T.S.H.; Geesaman, D.F.; Schiffer, J.P.

    1983-10-01

    The appreciation of the role in nuclear physics of the first excited state of the nucleon, the delta Δ(1232), has grown rapidly in the past decade. The delta resonance dominates nuclear reactions induced by intermediate energy pions, nucleons, and electromagnetic probes. It is also the most important non-nucleonic degree of freedom needed to resolve many fundamental problems encountered in the study of low-energy nuclear phenomena. Clearly, a new phase of nuclear physics has emerged and conventional thinking must be extended to account for this new dimension of nuclear dynamics. The most challenging problem we are facing is how a unified theory can be developed to describe Δ-nucleus dynamics at all energies. In exploring this new direction, it is important to have direct discussions among researchers with different viewpoints. Separate entries were prepared for the 49 papers presented

  12. Calcium microdomains in mitochondria and nucleus.

    Science.gov (United States)

    Alonso, María Teresa; Villalobos, Carlos; Chamero, Pablo; Alvarez, Javier; García-Sancho, Javier

    2006-01-01

    Endomembranes modify the progression of the cytosolic Ca(2+) wave and contribute to generate Ca(2+) microdomains, both in the cytosol and inside the own organella. The concentration of Ca(2+) in the cytosol ([Ca(2+)](C)), the mitochondria ([Ca(2+)](M)) and the nucleus ([Ca(2+)](N)) are similar at rest, but may become very different during cell activation. Mitochondria avidly take up Ca(2+) from the high [Ca(2+)](C) microdomains generated during cell activation near Ca(2+) channels of the plasma membrane and/or the endomembranes and prevent propagation of the high Ca(2+) signal to the bulk cytosol. This shaping of [Ca(2+)](C) signaling is essential for independent regulation of compartmentalized cell functions. On the other hand, a high [Ca(2+)](M) signal is generated selectively in the mitochondria close to the active areas, which tunes up respiration to the increased local needs. The progression of the [Ca(2+)](C) signal to the nucleus may be dampened by mitochondria, the nuclear envelope or higher buffering power inside the nucleoplasm. On the other hand, selective [Ca(2+)](N) signals could be generated by direct release of stored Ca(2+) into the nucleoplasm. Ca(2+) release could even be restricted to subnuclear domains. Putative Ca(2+) stores include the nuclear envelope, their invaginations inside the nucleoplasm (nucleoplasmic reticulum) and nuclear microvesicles. Inositol trisphosphate, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate have all been reported to produce release of Ca(2+) into the nucleoplasm, but contribution of these mechanisms under physiological conditions is still uncertain.

  13. Transverse and radial flow in intermediate energy nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Vestfall, D. Gary

    1997-01-01

    We have studied transverse and radial flow in nucleus-nucleus collisions ranging in energy from 15 to 155 MeV/nucleon. We have measured the impact parameter dependence of the balance energy for Ar + Sc and compared the results with Quantum Molecular Dynamics calculations with and without momentum dependence. We have shown that transverse flow and the balance energy dependence on the isospin of the system using the systems 58 Fe + 58 Fe, 58 Ni + 58 Ni, and 58 Mn + 58 Fe. These results are compared with Boltzmann-Uehling-Uehlenbeck calculations incorporating isospin-dependence. We have measured radial flow for Ar + Sc and find that about 50% of the observed energy is related to radial flow. (author)

  14. Study of Strange and Multistrange Particles in Ultrarelativistic Nucleus-Nucleus Collisions

    CERN Multimedia

    Vande vyvre, P; Feofilov, G; Snoeys, W; Hetland, K F; Campbell, M; Klempt, W

    2002-01-01

    % NA57\\\\ \\\\ The goal of the experiment is to study the production of strange and multi-strange particles in nucleus-nucleus collisions. This study was initiated at the OMEGA spectrometer, where three ion experiments have been performed: WA85 (S-W and p-W collisions at 200 A GeV/c), WA94 (S-S and p-S collisions at 200 A GeV/c) and WA97 (Pb-Pb, p-Pb and p-Be collisions at 160 A GeV/c).\\\\ \\\\ The experiment aims at extending the scope of WA97 by:\\\\ \\\\ - investigating the beam energy dependence of the enhancements of multi-strange particle production reported by the previous experiments, and by\\\\ \\\\\\\\ \\\\- measuring the yields of strange and multi-strange particles over an extended centrality range compared with the previous experiments.\\\\ \\\\ The apparatus consists mainly of silicon pixel detector planes.

  15. Linear extrapolation of ultrarelativistic nucleon-nucleon scattering to nucleus-nucleus collisions

    Science.gov (United States)

    Jeon, Sangyong; Kapusta, Joseph

    1997-07-01

    We use a Glauber-like approach to describe very energetic nucleus-nucleus collisions as a sequence of binary nucleon-nucleon collisions. No free parameters are needed: All the information comes from simple parametrizations of nucleon-nucleon collision data. Produced mesons are assumed not to interact with each other or with the original baryons. Comparisons are made to published experimental measurements of baryon rapidity and transverse momentum distributions, negative hadron rapidity and transverse momentum distributions, average multiplicities of pions, kaons, hyperons, and antihyperons, and zero degree energy distributions for sulfur-sulfur collisions at 200 GeV/c per nucleon and for lead-lead collisions at 158 GeV/c per nucleon. Good agreement is found except that the number of strange particles produced, especially antihyperons, is too small compared with experiment. We call this model LEXUS: It is a base-line linear extrapolation of ultrarelativistic nucleon-nucleon scattering to heavy ion collisions.

  16. Peculiarities of Λ hyperon and π meson production in nucleus-nucleus collisions at high energies

    International Nuclear Information System (INIS)

    Gazdzicki, M.; Skrzypscak, E.; Iovchev, K.; Kladnitskaya, E.; Okonov, E.

    1985-01-01

    The analysis of experimental data on the production of lambda hyperons and anti π mesons in He-Li, C-C, C-Ne and O-Ne collisions at 4.5 Gev/c per nucleon and C-C collisions at 4.2 Gev/c per nucleon is presented. Kinematical features of lambda are shown to depend on the collision centrality in contrast to the stable behaviour of the pion characteristics. The correlation between the characteristics of lambda and accompanying pions is observed. The effects seem to be incompatible with the intranuclear cascade approach. The data suggest the formation of a fully stopped and themalized hot source in central nucleus-nucleus collisions in which lambda hyperons are produced

  17. Experimental and phenomenological investigations of QCD matter in high-energy nucleus-nucleus collisions

    Energy Technology Data Exchange (ETDEWEB)

    Andronic, Anton

    2014-07-15

    This thesis is heterogeneous, comprising experimental papers at low energies (SIS-18 at GSI) and at the LHC, papers on phenomenology of high-energy nucleus-nucleus collisions, and papers on detectors. The overview covers the experimental papers and those on phenomenology. I have chosen to write it in a general manner, intended to be accessible to non-experts. It emphasizes recent measurements and their understanding at the LHC. The detector papers, which address many principle aspects of gaseous detectors, are summarized and placed in context in the review I co-wrote and which closes the stack. The detector papers included here are the outcome of an R and D program for the Transition Radiation Detector of ALICE.

  18. Experimental and phenomenological investigations of QCD matter in high-energy nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Andronic, Anton

    2014-07-01

    This thesis is heterogeneous, comprising experimental papers at low energies (SIS-18 at GSI) and at the LHC, papers on phenomenology of high-energy nucleus-nucleus collisions, and papers on detectors. The overview covers the experimental papers and those on phenomenology. I have chosen to write it in a general manner, intended to be accessible to non-experts. It emphasizes recent measurements and their understanding at the LHC. The detector papers, which address many principle aspects of gaseous detectors, are summarized and placed in context in the review I co-wrote and which closes the stack. The detector papers included here are the outcome of an R and D program for the Transition Radiation Detector of ALICE.

  19. Method of a fast selection of inelastic nucleus-nucleus collisions for the CMS experiment

    International Nuclear Information System (INIS)

    Krasnov, V.A.; Malakhov, A.I.; Savina, M.V.; Shmatov, S.V.; Zarubin, P.I.

    1998-01-01

    On the basis of the HIJING generator simulation of heavy ion collisions at ultrarelativistic energy scale, a method of a fast selection of inelastic nucleus-nucleus interactions is proposed for the CMS experiment at LHC. The basic idea is to use the time coincidence of signals with resolution better than 1 ns from the two very forward calorimeter arms covering the acceptance 3<|η|<5. The method efficiency is investigated by variation of energy thresholds in the calorimeters for different colliding ion species, namely, PbPb, NbNb, CaCa, OO, pPb, pCa, pp. It is shown that a stable efficiency of event selection (∼98%) is provided in an energy threshold range up to 100 GeV for nuclear collisions at 5 TeV/nucleon in the centre of mass system. In the pp collision case the relevant efficiency drops from 93% down to 80%

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

    Science.gov (United States)

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

    2016-05-01

    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 set by our biological clock, such as shift work, jet lag, sleep deprivation, or simply eating at the wrong time of the day, may have deleterious effects on health. This infringement, also known as circadian desynchronization, is associated with chronic diseases like diabetes, hypertension, cancer, and psychiatric disorders. In this review, we will evaluate evidence that these diseases stem from the need of the SCN for peripheral feedback to fine-tune its output and adjust physiological processes to the requirements of the moment. This feedback can vary from neuronal or hormonal signals from the liver to changes in blood pressure. Desynchronization renders the circadian network dysfunctional, resulting in a breakdown of many functions driven by the SCN, disrupting core clock rhythms in the periphery and disorganizing cellular processes that are normally driven by the synchrony between behavior and peripheral signals with neuronal and humoral output of the hypothalamus. Consequently, we propose that the loss of synchrony between the different elements of this circadian network as may occur during shiftwork and jet lag is the reason for the occurrence of health problems. ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

  1. 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.

  2. Lack of food anticipation in Per2 mutant mice.

    Science.gov (United States)

    Feillet, Céline A; Ripperger, Jürgen A; Magnone, Maria Chiara; Dulloo, Abdul; Albrecht, Urs; Challet, Etienne

    2006-10-24

    Predicting time of food availability is key for survival in most animals. Under restricted feeding conditions, this prediction is manifested in anticipatory bouts of locomotor activity and body temperature. This process seems to be driven by a food-entrainable oscillator independent of the main, light-entrainable clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus . Although the SCN clockwork involves self-sustaining transcriptional and translational feedback loops based on rhythmic expression of mRNA and proteins of clock genes , the molecular mechanisms responsible for food anticipation are not well understood. Period genes Per1 and Per2 are crucial for the SCN's resetting to light . Here, we investigated the role of these genes in circadian anticipatory behavior by studying rest-activity and body-temperature rhythms of Per1 and Per2 mutant mice under restricted feeding conditions. We also monitored expression of clock genes in the SCN and peripheral tissues. Whereas wild-type and Per1 mutant mice expressed regular food-anticipatory activity, Per2 mutant mice did not show food anticipation. In peripheral tissues, however, phase shifts of clock-gene expression in response to timed food restriction were comparable in all genotypes. In conclusion, a mutation in Per2 abolishes anticipation of mealtime, without interfering with peripheral synchronization by feeding cycles.

  3. Synchronization of biological clock neurons by light and peripheral feedback systems promotes circadian rhythms and health

    Directory of Open Access Journals (Sweden)

    Ashna eRamkisoensing

    2015-06-01

    Full Text Available In mammals, the suprachiasmatic nucleus (SCN functions as a circadian clock that drives 24-hour rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase synchronization between individual cells have consequences on the amplitude of the SCN’s electrical activity rhythm, and these changes play a major role in the ability to adapt to seasonal changes. Both aging and sleep deprivation negatively affect the circadian amplitude of the SCN, whereas behavioral activity (i.e., exercise has a positive effect on amplitude. Given that the amplitude of the SCN’s electrical activity rhythm is essential for achieving robust rhythmicity in physiology and behavior, the mechanisms that underlie neuronal synchronization warrant further study. A growing body of evidence suggests that the functional integrity of the SCN contributes to health, well-being, cognitive performance, and alertness; in contrast, deterioration of the 24-hour rhythm is a risk factor for neurodegenerative disease, cancer, depression, and sleep disorders.

  4. HIJET: a Monte Carlo event generator for P-nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Ludlam, T.; Pfoh, A.; Shor, A.

    1985-01-01

    Comparisons are shown for the HIJET generated data and measured data for average multiplicities, rapidity distributions, and leading proton spectra in proton-nucleus and heavy ion reactions. The algorithm for the generator is one of an incident particle on a target of uniformly distributed nucleons. The dynamics of the interaction limit secondary interactions in that only the leading baryon may re-interact with the nuclear volume. Energy and four momentum are globally conserved in each event. 6 refs., 6 figs

  5. New quasibound states of the compound nucleus in α -particle capture by the nucleus

    Science.gov (United States)

    Maydanyuk, Sergei P.; Zhang, Peng-Ming; Zou, Li-Ping

    2017-07-01

    We generalize the theory of nuclear decay and capture of Gamow that is based on tunneling through the barrier and internal oscillations inside the nucleus. In our formalism an additional factor is obtained, which describes distribution of the wave function of the the α particle inside the nuclear region. We discover new most stable states (called quasibound states) of the compound nucleus (CN) formed during the capture of α particle by the nucleus. With a simple example, we explain why these states cannot appear in traditional calculations of the α capture cross sections based on monotonic penetrabilities of a barrier, but they appear in a complete description of the evolution of the CN. Our result is obtained by a complete description of the CN evolution, which has the advantages of (1) a clear picture of the formation of the CN and its disintegration, (2) a detailed quantum description of the CN, (3) tests of the calculated amplitudes based on quantum mechanics (not realized in other approaches), and (4) high accuracy of calculations (not achieved in other approaches). These peculiarities are shown with the capture reaction of α +44Ca . We predict quasibound energy levels and determine fusion probabilities for this reaction. The difference between our approach and theory of quasistationary states with complex energies applied for the α capture is also discussed. We show (1) that theory does not provide calculations for the cross section of α capture (according to modern models of the α capture), in contrast with our formalism, and (2) these two approaches describe different states of the α capture (for the same α -nucleus potential).

  6. Impact parameter measurements in nucleus-nucleus collisions at the ISR

    International Nuclear Information System (INIS)

    Frankel, S.

    1981-01-01

    There are two complementary ways to measure impact parameters in nucleus-nucleus collisions. A collision between two nuclei with atomic number A is illustrated, the overlap of N nucleons in each nucleus determined by the geometric impact parameter. The non-interacting A-N nucleons, the spectators, are roughly confined to an inner cone surrounding the incident projectile direction. They consist of fragments from A-N to 1. The transverse momentum distributions has been measured at energies of 1 to 2 GeV/nucleon and recently at the ISR (by group 418) at 500GeV/nucleon. The distribution at both energies fall exponentially with the square of the transverse momentum. The falloff is twice as slow at 1000 as compared with 2 GeV/c. This is the result of the very large multiplicity at ISR energies, the pions blowing out the fragments. The important feature to understand is that these fragments are essentially independent of the mechanisms that take place in the interaction between the 2N interacting nucleons. Therefore the detection of the number of nucleons in this region is a mechanism independent way to measure the impact parameter

  7. Transverse-momentum distribution of produced particles in ultrarelativistic nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Ban-Hao, S.; Wong, C.

    1985-01-01

    In order to discern coherent or collective processes from incoherent processes in nucleus-nucleus reactions at high energies, we study the transverse-momentum distribution of the produced particles with an incoherent-multiple-collision model. In this model, the projectile nucleon makes successive inelastic collisions with nucleons in the target nucleus, the probability of such collisions being given by the thickness function and the nucleon-nucleon inelastic cross section. It is assumed that each baryon-baryon collision produces particles and degrades momenta just as a baryon-baryon collision in free space, and that there are no secondary collisions between the produced particles and the nucleons. We found that the average transverse momentum and the charged-multiplicity data at Fermilab and CERN ISR energies can be well explained by such a model. However, the average transverse momentum for some events observed by the Japanese-American cooperative emulsion experiment (JACEE) associated with large energy density in the central rapidity region differ markedly from the model results. Such a deviation indicates the presence of coherent or collective effects for these collisions and may indicate the possibility of a formation of quark-gluon plasma

  8. The Confined Hydrogen Atom with a Moving Nucleus

    Science.gov (United States)

    Fernandez, Francisco M.

    2010-01-01

    We study the hydrogen atom confined to a spherical box with impenetrable walls but, unlike earlier pedagogical articles on the subject, we assume that the nucleus also moves. We obtain the ground-state energy approximately by means of first-order perturbation theory and show that it is greater than that for the case in which the nucleus is clamped…

  9. Nucleon emission via electromagnetic excitation in relativistic nucleus-nucleus collisions: Reanalysis of the Weizsaecker-Williams method

    International Nuclear Information System (INIS)

    Norbury, J.W.

    1989-01-01

    Previous analyses of the comparison of Weizsaecker-Williams theory to experiment for nucleon emission via electromagnetic excitations in nucleus-nucleus collisions have not been definitive because of different assumptions concerning the value of the minimum impact parameter. This situation is corrected by providing criteria that allow one to make definitive statements concerning agreement or disagreement between Weizsaescker-Williams theory and experiment

  10. Inside a plant nucleus: discovering the proteins.

    Science.gov (United States)

    Petrovská, Beáta; Šebela, Marek; Doležel, Jaroslav

    2015-03-01

    Nuclear proteins are a vital component of eukaryotic cell nuclei and have a profound effect on the way in which genetic information is stored, expressed, replicated, repaired, and transmitted to daughter cells and progeny. Because of the plethora of functions, nuclear proteins represent the most abundant components of cell nuclei in all eukaryotes. However, while the plant genome is well understood at the DNA level, information on plant nuclear proteins remains scarce, perhaps with the exception of histones and a few other proteins. This lack of knowledge hampers efforts to understand how the plant genome is organized in the nucleus and how it functions. This review focuses on the current state of the art of the analysis of the plant nuclear proteome. Previous proteome studies have generally been designed to search for proteins involved in plant response to various forms of stress or to identify rather a modest number of proteins. Thus, there is a need for more comprehensive and systematic studies of proteins in the nuclei obtained at individual phases of the cell cycle, or isolated from various tissue types and stages of cell and tissue differentiation. All this in combination with protein structure, predicted function, and physical localization in 3D nuclear space could provide much needed progress in our understanding of the plant nuclear proteome and its role in plant genome organization and function. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. Subthalamic nucleus detects unnatural android movement.

    Science.gov (United States)

    Ikeda, Takashi; Hirata, Masayuki; Kasaki, Masashi; Alimardani, Maryam; Matsushita, Kojiro; Yamamoto, Tomoyuki; Nishio, Shuichi; Ishiguro, Hiroshi

    2017-12-19

    An android, i.e., a realistic humanoid robot with human-like capabilities, may induce an uncanny feeling in human observers. The uncanny feeling about an android has two main causes: its appearance and movement. The uncanny feeling about an android increases when its appearance is almost human-like but its movement is not fully natural or comparable to human movement. Even if an android has human-like flexible joints, its slightly jerky movements cause a human observer to detect subtle unnaturalness in them. However, the neural mechanism underlying the detection of unnatural movements remains unclear. We conducted an fMRI experiment to compare the observation of an android and the observation of a human on which the android is modelled, and we found differences in the activation pattern of the brain regions that are responsible for the production of smooth and natural movement. More specifically, we found that the visual observation of the android, compared with that of the human model, caused greater activation in the subthalamic nucleus (STN). When the android's slightly jerky movements are visually observed, the STN detects their subtle unnaturalness. This finding suggests that the detection of unnatural movements is attributed to an error signal resulting from a mismatch between a visual input and an internal model for smooth movement.

  12. Control of nucleus accumbens activity with neurofeedback.

    Science.gov (United States)

    Greer, Stephanie M; Trujillo, Andrew J; Glover, Gary H; Knutson, Brian

    2014-08-01

    The nucleus accumbens (NAcc) plays critical roles in healthy motivation and learning, as well as in psychiatric disorders (including schizophrenia and attention deficit hyperactivity disorder). Thus, techniques that confer control of NAcc activity might inspire new therapeutic interventions. By providing second-to-second temporal resolution of activity in small subcortical regions, functional magnetic resonance imaging (fMRI) can resolve online changes in NAcc activity, which can then be presented as "neurofeedback." In an fMRI-based neurofeedback experiment designed to elicit NAcc activity, we found that subjects could increase their own NAcc activity, and that display of neurofeedback significantly enhanced their ability to do so. Subjects were not as capable of decreasing their NAcc activity, however, and enhanced control did not persist after subsequent removal of neurofeedback. Further analyses suggested that individuals who recruited positive aroused affect were better able to increase NAcc activity in response to neurofeedback, and that NAcc neurofeedback also elicited functionally correlated activity in the medial prefrontal cortex. Together, these findings suggest that humans can modulate their own NAcc activity and that fMRI-based neurofeedback may augment their efforts. The observed association between positive arousal and effective NAcc control further supports an anticipatory affect account of NAcc function. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Parity Measurements in the 70Ga Nucleus

    Science.gov (United States)

    Venegas Vargas, D. C.; Haring-Kaye, R. A.; Jones, K. D.; Le, K. Q.; Harbin, B. L.; Döring, J.; Abromeit, B.; Dungan, R.; Lubna, R.; Tabor, S. L.; Tai, P.-L.; Tripati, Vandana; Vonmoss, J. M.; Morrow, S. I.

    2017-09-01

    The odd-odd 70Ga nucleus was studied at high spin after being produced at Florida State University using the 62Ni(14C,αpn) fusion-evaporation reaction at a beam energy of 50 MeV. The resulting γ rays were detected in coincidence using an array of Compton-suppressed Ge detectors consisting of three Clover detectors and seven single-crystal detectors. The linear polarizations of eight γ-ray transitions in 70Ga were measured by comparing their scattering yields within a Clover detector in the parallel and perpendicular directions relative to the beam axis, under the requirement that at least one other γ ray in 70Ga was recorded by a single-crystal detector in the array. As a result of these measurements, the parities of six states were confirmed and those of two other states were established for the first time based on a comparison of the experimental polarizations with the predicted ones determined from known spin assignments. The resulting level spectrum of 70Ga shows both similarities and differences with the predictions of previous shell-model calculations. This work was supported by the U.S. National Science Foundation and the Ohio Wesleyan University Summer Science Research Program.

  14. Comprehensive mapping of regional expression of the clock protein PERIOD2 in rat forebrain across the 24-h day.

    Directory of Open Access Journals (Sweden)

    Valerie L Harbour

    Full Text Available In mammals, a light-entrainable clock located in the suprachiasmatic nucleus (SCN regulates circadian rhythms by synchronizing oscillators throughout the brain and body. Notably, the nature of the relation between the SCN clock and subordinate oscillators in the rest of the brain is not well defined. We performed a high temporal resolution analysis of the expression of the circadian clock protein PERIOD2 (PER2 in the rat forebrain to characterize the distribution, amplitude and phase of PER2 rhythms across different regions. Eighty-four LEW/Crl male rats were entrained to a 12-h: 12-h light/dark cycle, and subsequently perfused every 30 min across the 24-h day for a total of 48 time-points. PER2 expression was assessed with immunohistochemistry and analyzed using automated cell counts. We report the presence of PER2 expression in 20 forebrain areas important for a wide range of motivated and appetitive behaviors including the SCN, bed nucleus, and several regions of the amygdala, hippocampus, striatum, and cortex. Eighteen areas displayed significant PER2 rhythms, which peaked at different times of day. Our data demonstrate a previously uncharacterized regional distribution of rhythms of a clock protein expression in the brain that provides a sound basis for future studies of circadian clock function in animal models of disease.

  15. 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.

  16. 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.

  17. From Di-Nucleus to Mono-Nucleus - Neck Evolution in Fusion of Massive Systems -

    OpenAIRE

    Abe, Y.; Shen, Caiwan; Boilley, D.; Giraud, B.G.

    2009-01-01

    6 pages, 3 figures, Proceedings of the Japanese French Symposium - New paradigms in Nuclear Physics, Paris, 29th September - 2nd October, to be published in Int. J. of Modern Physics E; International audience; Dynamics of the neck degree of freedom during fusioning process between heavy ions is studied. Time scales of the three degrees of freedom (the relative distance, the neck and the mass-asymmetry) are studied, showing an early equilibration of the neck. This means that a di-nucleus forme...

  18. On angular distribution of nucleus fission fragments by fast neutrons

    International Nuclear Information System (INIS)

    Barabanov, A.L.; Grechukhin, D.P.

    1987-01-01

    Evaluation of amplitudes of quadrupole and hexadecapole components of angular distribution of nucleus fission fragments by neutrons with the energies E n < or approx. 6 MeV is conducted. Stability of this amplitude to permeability optical coefficient variations for neutrons is revealed. It is shown, that the ratio of these amplitudes as well as the character of their dependence on the target nucleus orientation degree are sensitive to the type of fission probability distribution along K projection if fissile nucleus J spin to the fragment scattering axis. This sensitivity may be used for fragment angular distribution anisotropy formation statistical model verification

  19. Theoretical interpretation of medium energy nucleon nucleus inelastic scattering

    International Nuclear Information System (INIS)

    Lagrange, Christian

    1970-06-01

    A theoretical study is made of the medium energy nucleon-nucleus inelastic scattering (direct interaction), by applying the distorted wave Born approximation such as can be deduced from the paired equation method. It is applied to the interpretation of the inelastic scattering of 12 MeV protons by 63 Cu; this leads us to make use of different sets of wave functions to describe the various states of the target nucleus. We analyze the nature of these states and the shape of the nucleon-nucleus interaction potential, and we compare the results with those obtained from other theoretical and experimental work. (author) [fr

  20. Quarkonium-nucleus bound states from lattice QCD

    Energy Technology Data Exchange (ETDEWEB)

    Beane, S.  R. [Univ. of Washington, Seattle, WA (United States); Chang, E. [Univ. of Washington, Seattle, WA (United States); Cohen, S.  D. [Univ. of Washington, Seattle, WA (United States); Detmold, W. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Lin, H. -W. [Univ. of Washington, Seattle, WA (United States); Orginos, K. [College of William and Mary, Williamsburg, VA (United States); Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Parreño, A. [Univ., de Barcelona, Marti Franques (Spain); Savage, M.  J. [Univ. of Washington, Seattle, WA (United States)

    2015-06-11

    Quarkonium-nucleus systems are composed of two interacting hadronic states without common valence quarks, which interact primarily through multi-gluon exchanges, realizing a color van der Waals force. We present lattice QCD calculations of the interactions of strange and charm quarkonia with light nuclei. Both the strangeonium-nucleus and charmonium-nucleus systems are found to be relatively deeply bound when the masses of the three light quarks are set equal to that of the physical strange quark. Extrapolation of these results to the physical light-quark masses suggests that the binding energy of charmonium to nuclear matter is B < 40 MeV.

  1. 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.

  2. {Ba[Au(SCN2]2}n: a three-dimensional net comprised of monomeric and trimeric gold(I units

    Directory of Open Access Journals (Sweden)

    A. Darren Back

    2010-07-01

    Full Text Available The noteworthy structural feature of the title complex, poly[acetonitriletetra-μ2-thiocyanato-barium(IIdigold(I], {[Au2Ba(SCN4(CH3CN]}n, is that the bis(thiocyanatoaurate(I anion adopts both monomeric and trimeric motifs. The trimer unit has an Au...Au distance of 3.1687 (3 Å. In both the monomeric and trimeric units, the AuI atoms are also bonded to two S atoms. Within the trimeric unit, the AuI atoms exist in differing environments; one Au atom has a T-shaped three-coordinate geometry while the other has a square-planar four-coordinate geometry. The AuI atom of the monomer adopts a linear two-coordinate geometry. The extended structure can be described as a three-dimensional coordination polymer consisting of chains of Ba atoms bridged by thiocyanate N atoms. These chains are cross-linked via the gold monomeric and trimeric units.

  3. The role of known variants of KCNQ1, KCNH2, KCNE1, SCN5A, and NOS1AP in water-related deaths.

    Science.gov (United States)

    Tzimas, Iliana; Zingraf, Jana-Christin; Bajanowski, Thomas; Poetsch, Micaela

    2016-11-01

    Drowning is one of the most frequent causes of accidental deaths worldwide, and still it remains a diagnosis of exclusion. Moreover, sudden cardiac deaths (SCD) or, if no actual cardiac alterations can be found, sudden unexplained deaths (SUD) represent a major group within mortality statistics as well. This leads to the assumption that there might be a general underlying cause for at least some cases of drowning, SCD, or SUD, for example, genetic aberrations in arrhythmia-associated genes. In the present study, blood samples of 171 corpses found in water (drowning, death after almost drowning, and unclear deaths) were analyzed in 19 known variants of the genes KCNQ1, KCNH2, KCNE1, SCN5A, and NOS1AP by minisequencing. In three variants of NOS1AP, significant differences of allele and/or genotype frequencies could be demonstrated between victims of drowning and published controls as well as own controls. Moreover, similar differences were found comparing unexplained deaths in water and controls. Regarding the other genes, especially one single nucleotide polymorphism (SNP) of KCNQ1 could be associated with drowning. These results propose that performing a molecular autopsy analyzing known variants of arrhythmia-associated genes, in particular NOS1AP, may assist in establishing a cause of death for bodies found in water without clear drowning signs.

  4. Angle-dependent magnetoresistance oscillations and Fermi surface reordering at high magnetic fields in {alpha}-(ET){sub 2}KHg(SCN){sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Caulfield, J. [Clarendon Lab. (United Kingdom); Blundell, S.J. [Clarendon Lab. (United Kingdom); Singleton, J. [Clarendon Lab. (United Kingdom); House, A. [Clarendon Lab. (United Kingdom); Du Croo de Jongh, M.S.L. [Clarendon Lab. (United Kingdom); Hendriks, P.T.J. [High Field Magnet Lab. and Research Inst. for Materials, Univ. of Nijmegen (Netherlands); Perenboom, J.A.A.J. [High Field Magnet Lab. and Research Inst. for Materials, Univ. of Nijmegen (Netherlands); Hayes, W. [Clarendon Lab. (United Kingdom); Kurmoo, M. [Clarendon Lab. (United Kingdom)]|[Royal Institution, London (United Kingdom); Day, P. [Royal Institution, London (United Kingdom)

    1995-03-15

    Angle dependent magnetoresistance oscillations (AMRO) have been studied in the charge transfer salt {alpha}-(ET){sub 2}KHg(SCN){sub 4} for magnetic fields in the range 0 - 30 T. This salt exhibits the onset of antiferromagnetic order at temperatures T{sub N} {approx}8-10 K and the presence below this temperature of a region of sharp negative magnetoresistance at a field around 22 T known as the ``kink``. AMRO have been measured in this salt for a wide range of applied fields since the period, amplitude, and nature of the oscillations can be used to directly infer the character of the Fermi surface (FS) as a function of field. The data indicate that a profound change in the band structure occurs at this kink transition; the high field phase is characterised by quasi-2D oscillations from a closed cylindrical FS which is elongated in the c direction; the low field phase appears to be a spin density wave groundstate, with a FS consisting of a sheet (which is quasi-1D in character and tilted at an angle of {approx}21 to the b{sup *}c plane) and small closed 2D pockets. It is suggested that the breakdown orbits between the pockets and the 1D sheets are able to account for the various Shubnikov-de Haas frequencies observed below the kink. (orig.)

  5. Formation and identification of Centauro and Strangelets in nucleus- nucleus collisions at the LHC

    CERN Document Server

    Angelis, Aris L S; Bogolyubsky, M Yu; Filippov, S N; Gladysz-Dziadus, E; Kharlov, Yu V; Kurepin, A B; Maevskaya, A I; Mavromanolakis, G; Panagiotou, A D; Sadovsky, S A; Stefanski, P; Wlodarczyk, Z

    1999-01-01

    We present a phenomenological model for the formation and decay of a cosmic ray Centauro fireball in the baryon-rich projectile fragmentation rapidity region in nucleus-nucleus interactions. Our model naturally incorporates the $9 possibility of strangelet formation, Strangelets being conjectured to be the "strongly penetrating component" observed in hadron-rich cosmic ray events. Based on this model we have performed Monte-Carlo simulations to study the $9 Centauro and strangelet dynamic and kinematic characteristics in central Pb+Pb collisions at LHC energies, as well as their identification by the detector system CASTOR. CASTOR is being developed for the ALICE heavy ion experiment at $9 the LHC and will probe the very forward pseudorapidity region 5.6

  6. Experiment NA 38: a study of high energy nucleus-nucleus interactions. Progress report

    International Nuclear Information System (INIS)

    1986-01-01

    The research being reported consists of a study of high energy nucleus-nucleus interactions using the enlarged Dimuon Spectrometer. The main goal of the experiment is to search for evidence of a quark-gluon plasma by studying correlations in the distributions of mass, transverse momentum, transverse energy and rapidity on an event by event basis, and comparing these distributions to those at similar energies where the incident particle is a proton rather than an ion. The experiment uses a multimuons spectrometer supplemented with a new detectors in the target region. New equipment in the target region is required to measure the transverse electromagnetic energy as a function of rapidity (electromagnetic calorimeter), detect reinteractions in the target and identify the vertex of the interaction (active target), identify incident ions and possible outgoing fragments, center beam on targets, and fight against pile-up in the detector (Cherenkov quartz counters and beam hodoscope). Design, testing, and calibration of this new equipment and associated electronics and software is discussed. 1 ref

  7. Study of chemical equilibrium in nucleus-nucleus collisions at AGS and SPS energies

    CERN Document Server

    Becattini, F; Keränen, A; Manninen, J; Stock, Reinhard

    2003-01-01

    We present a detailed study of chemical freeze-out in nucleus-nucleus collisions at beam energies of 11.6, 30, 40, 80 and 158A GeV. By analyzing hadronic multiplicities within the statistical hadronization approach, we have studied the strangeness production as a function of centre of mass energy and of the parameters of the source. We have tested and compared different versions of the statistical model, with special emphasis on possible explanations of the observed strangeness hadronic phase space under-saturation. We show that, in this energy range, the use of hadron yields at midrapidity instead of in full phase space artificially enhances strangeness production and could lead to incorrect conclusions as far as the occurrence of full chemical equilibrium is concerned. In addition to the basic model with an extra strange quark non-equilibrium parameter, we have tested three more schemes: a two-component model superimposing hadrons coming out of single nucleon-nucleon interactions to those emerging from larg...

  8. Statistical analysis of secondary particle distributions in relativistic nucleus-nucleus collisions

    Science.gov (United States)

    Mcguire, Stephen C.

    1987-01-01

    The use is described of several statistical techniques to characterize structure in the angular distributions of secondary particles from nucleus-nucleus collisions in the energy range 24 to 61 GeV/nucleon. The objective of this work was to determine whether there are correlations between emitted particle intensity and angle that may be used to support the existence of the quark gluon plasma. The techniques include chi-square null hypothesis tests, the method of discrete Fourier transform analysis, and fluctuation analysis. We have also used the method of composite unit vectors to test for azimuthal asymmetry in a data set of 63 JACEE-3 events. Each method is presented in a manner that provides the reader with some practical detail regarding its application. Of those events with relatively high statistics, Fe approaches 0 at 55 GeV/nucleon was found to possess an azimuthal distribution with a highly non-random structure. No evidence of non-statistical fluctuations was found in the pseudo-rapidity distributions of the events studied. It is seen that the most effective application of these methods relies upon the availability of many events or single events that possess very high multiplicities.

  9. Experimental problems of search for quark-gluon plasma in nucleus-nucleus interactions

    International Nuclear Information System (INIS)

    Okonov, Eh.O.

    1987-01-01

    Experimental problems for searching for quark-gluon (quagma) plasma in nucleus-nucleus interactions (NbNb,CaCa, ArPb, CnE, ONe) in the energy range E=0.4-1 GeV/A and 3.67 GeV/A and 200 GeV/A energies are discussed. Peculiarities of performing experiments on Dubna synchrophasotron and SPS Bevalac are discussed. The first results prove hadron matter thermalization sufficient for quagma manifestation. It is found that such characteristics of studied interactions as relative λ-hyperon yield, spectral (temperature) characteristics of λ k -hyperons (with higher values of transferred transverse momenta) and associatively produced peons are of greatest interest. The necessity of precise establishment of λ-hyperon group as excessive and differing in its origin from the other particles of the hadron phase is noted. It is shown that experimental approach used in Dubna research proved efficient and requires further development. It includes : selection of rare events (fluctuations) in central interactions of nuclei with high local excitation; search and research of peculiarities in the production of strange particles and in associative pion production; use of streamer spectrometer with a trigger system of rigid selection of central interactions

  10. Pathological gambling after bilateral subthalamic nucleus stimulation in Parkinson disease

    NARCIS (Netherlands)

    Smeding, H. M. M.; Goudriaan, A. E.; Foncke, E. M. J.; Schuurman, P. R.; Speelman, J. D.; Schmand, B.

    2007-01-01

    We describe a patient with advanced Parkinson's disease who developed pathological gambling within a month after successful bilateral subthalamic nucleus (STN) stimulation. There was no history of gambling. On neuropsychological testing, slight cognitive decline was evident 1 year after surgery.

  11. Excited states in the neutron-rich nucleus F-25

    Czech Academy of Sciences Publication Activity Database

    Vajta, Zs.; Stanoiu, M.; Sohler, D.; Jansen, G. R.; Azaiez, F.; Dombrádi, Zs.; Sorlin, O.; Brown, B. A.; Belleguic, M.; Borcea, C.; Bourgeois, C.; Dlouhý, Zdeněk; Elekes, Z.; Fülöp, Zs.; Grévy, S.; Guillemaud-Mueller, D.; Hagen, G.; Hjorth-Jensen, M.; Ibrahim, F.; Kerek, A.; Krasznahorkay, A.; Lewitowicz, M.; Lukyanov, S.; Mandal, S.; Mayet, P.; Mrázek, Jaromír; Negoita, F.; Penionzhkevich, Y. E.; Podolyák, Zs.; Roussel-Chomaz, P.; Saint-Laurent, M. G.; Savajols, H.; Sletten, G.; Timár, J.; Timis, C.; Yamamoto, A.

    2014-01-01

    Roč. 89, č. 5 (2014), 054323 ISSN 0556-2813 Institutional support: RVO:61389005 Keywords : nucleus F-25 * gamma-ray spectroscopy Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 3.733, year: 2014

  12. Radiological study of the calcanean ossification secondary nucleus development

    International Nuclear Information System (INIS)

    Carvalho Filho, Guaracy.

    1994-01-01

    This work describes the normal aspects of the calcanean ossification secondary nucleus radiological development, the appearing time, his form, localization, fragmentation and evolution of area, from a sample of normal individuals. (author). 14 refs., 16 figs., 8 tabs

  13. Strangeness production in proton–proton and proton–nucleus ...

    Indian Academy of Sciences (India)

    ) and proton–nucleus () reactions within an effective Lagrangian model. The kaon production proceeds mainly via excitations of * (1650), * (1710), and * (1720) resonant intermediate nucleonic states, in the collision of two initial state ...

  14. The picture of the nuclei disintegration mechanism - from hadron-nucleus and nucleus-nucleus collisions experimental investigations at high energies

    International Nuclear Information System (INIS)

    Strugalska-Gola, E.; Strugalski, Z.; Chmielowski, W.

    1997-01-01

    The mechanism of the nuclei disintegration process in collisions of high-energy hadrons with nuclei is revealed experimentally. The disintegration appears as a complicated nuclear process developing in time and space in intranuclear matter, consisting at least of three stages which last together about 10 -24 - 10 -17 s after the impact. At the first stage, which lasts about 10 -24 - 10 -22 s, fast nucleons are densely emitted and the target-nucleus is locally damaged. At the second stage, lasting about 10 -22 - 10 -1 7 s, the damaged and unstable residual target nucleus uses to evaporate light fragments - mainly nucleons, deuterons, tritons, α-particles. At the final stage, the residual target-nucleus uses to split sometimes into two or more nuclear fragments

  15. Di-nucleus dynamics towards fusion of heavy nuclei

    OpenAIRE

    Abe, Y.; Shen, Caiwan; Kosenko, G.; Boilley, D.; Giraud, B.G.

    2008-01-01

    International audience; The Two-Step Model for fusion of massive systems is briefly recapitulated, which clar- ifies the mechanism of so-called fusion hindrance. Since the neck changes the potential landscape, especially the height of the conditional saddle point, time evolution of the neck degree of freedom plays a crucial role in fusion. We analytically solve time-evolution of nuclear shape of the composite system from di-nucleus to mono-nucleus. The time- dependent distribution function of...

  16. Ion-beam spectroscopic studies of the 69As nucleus

    International Nuclear Information System (INIS)

    Badica, T.; Cojocaru, V.; Olariu, A.; Petre, M.; Popescu, I. V.; Gheboianu, A.

    2009-01-01

    Excited state of the neutron deficient 69 As nucleus were investigated in the 58 Ni( 14 N,2pn) reaction by ion-beam γ spectroscopic methods (excitation functions, γγ-coincidences, angular distributions and linear polarization gated with neutrons). A new more complete level scheme of 69 As has been proposed with spin-parity values. The structure of the nucleus is discussed in the framework of the interaction boson-fermion model (IBFM). (authors)

  17. Colour, albedo and nucleus size of Halley's comet

    Science.gov (United States)

    Cruikshank, D. P.; Tholen, D. J.; Hartmann, W. K.

    1985-01-01

    Photometry of Halley's comet in the B, J, V, and K broadband filters during a time when the coma was very weak and presumed to contribute negligibly to the broadband photometry is reported. The V-J and J-K colors suggest that the color of the nucleus of Halley's comet is similar to that of the D-type asteroids, which in turn suggests that the surface of the nucleus has an albedo less than 0.1.

  18. New computational methods for determining antikaon-nucleus bound states

    International Nuclear Information System (INIS)

    Fink, P.J. Jr.

    1989-01-01

    Optical potential for antikaon-nucleus strong interactions are constructed using elementary antikaon-nucleus potentials determined previously. The optical potentials are used to determine the existence of a kaon hypernucleus. Modern three dimensional visualization techniques are used to study model dependences, new methods for speeding the calculation of the optical potential are developed, and previous approximation to avoid full Fermi averaging are eliminated. 19 refs., 21 figs., 3 tabs

  19. Violation of time reversal symmetry in compound nucleus reactions

    International Nuclear Information System (INIS)

    Lanza, E.G.

    1989-01-01

    In this thesis the author presents a general formulation for the description of time-reversal violation in compound-nucleus reactions on the base of the S matrix and calculates an expression describing this violation by means of the statistical model of Bose, Harney, and Weidenmueller (1986). The result is applied to the compound-nucleus 28 Si for which a time-reversal parameter has been explicitely calculated. (HSI)

  20. Finding of increased caudate nucleus in patients with Alzheimer's disease.

    Science.gov (United States)

    Persson, K; Bohbot, V D; Bogdanovic, N; Selbaek, G; Braekhus, A; Engedal, K

    2018-02-01

    A recently published study using an automated MRI volumetry method (NeuroQuant®) unexpectedly demonstrated larger caudate nucleus volume in patients with Alzheimer's disease dementia (AD) compared to patients with subjective and mild cognitive impairment (SCI and MCI). The aim of this study was to explore this finding. The caudate nucleus and the hippocampus volumes were measured (both expressed as ratios of intracranial volume) in a total of 257 patients with SCI and MCI according to the Winblad criteria and AD according to ICD-10 criteria. Demographic data, cognitive measures, and APOE-ɛ4 status were collected. Compared with non-dementia patients (SCI and MCI), AD patients were older, more of them were female, and they had a larger caudate nucleus volume and smaller hippocampus volume (P<.001). In multiple linear regression analysis, age and female sex were associated with larger caudate nucleus volume, but neither diagnosis nor memory function was. Age, gender, and memory function were associated with hippocampus volume, and age and memory function were associated with caudate nucleus/hippocampus ratio. A larger caudate nucleus volume in AD patients was partly explained by older age and being female. These results are further discussed in the context of (1) the caudate nucleus possibly serving as a mechanism for temporary compensation; (2) methodological properties of automated volumetry of this brain region; and (3) neuropathological alterations. Further studies are needed to fully understand the role of the caudate nucleus in AD. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. International Halley Watch: Discipline specialists for near-nucleus studies

    Science.gov (United States)

    Larson, S.; Sekanina, Z.; Rahe, J.

    1986-01-01

    The purpose of the Near-Nucleus Studies Net is to study the processes taking place in the near-nucleus environment as they relate to the nature of nucleus. This is accomplisghed by measuring the spatial and temporal distribution of dust, gases and ions in the coma on high resolution images taken from many observatories around the world. By modeling the motions of discrete dust features in Comet Halley, it is often possible to determine the locations of the emission sources on the surface and learn about the nucleus structure. In addition to the general goals shared by all IHW nets, the scientific goals of the net has been to determine (1)the gross surface structure of the nucleus, (2)the nucleus spin vector, (3)the distribution and evolution of jet sources and (4)the interrelationships between the gas, dust and ion components of the coma. An additional Comet Giacobini-Zinner watch was carried out by the NNSN in support of the NASA International Cometary Explorer flyby.

  2. Study of high energy densities over extended nuclear volumes via nucleus-nucleus collisions at the SPS

    CERN Multimedia

    2002-01-01

    This experiment examines in detail the characteristics of ultra-relativistic nucleus-nucleus interactions using $^{16}$O beams of 200 GeV/A from the SPS. The experiment combines 4$\\pi$ calorimeter coverage with measurements of inclusive particle spectra, two-particle correlations, low and high-mass lepton pairs and photons. A multiwire active target allows maximum interaction rates with a minimum of secondary interactions. Additional data are taken with an emulsion target.

  3. Fluctuations and correlations in nucleus-nucleus collisions within transport approaches

    International Nuclear Information System (INIS)

    Konchakovski, Volodymyr P.

    2009-01-01

    The current thesis is devoted to a systematic study of fluctuations and correlations in heavy-ion collisions, which might be considered as probes for the phase transition and the critical point in the phase diagram, within the Hadron-String- Dynamics (HSD) microscopic transport approach. This is a powerful tool to study nucleus-nucleus collisions and allows to completely simulate experimental collisions on an event-by-event basis. Thus, the transport model has been used to study fluctuations and correlations including the influence of experimental acceptance as well as centrality, system size and collision energy. The comparison to experimental data can separate the effects induced by a phase transition since there is no phase transition in the HSD version used here. Firstly the centrality dependence of multiplicity fluctuations has been studied. Different centrality selections have been performed in the analysis in correspondence to the experimental situation. For the fixed target experiment NA49 events with fixed numbers of the projectile participants have been studied while in the collider experiment PHENIX centrality classes of events have been defined by the multiplicity in certain phase space region. A decrease of participant number fluctuations (and thus volume fluctuations) in more central collisions for both experiments has been obtained. Another area of this work addresses to transport model calculations of multiplicity fluctuations in nucleus-nucleus collisions as a function of colliding energy and system size. This study is in full correspondence to the experimental program of the NA61 Collaboration at the SPS. Central C+C, S+S, In+In, and Pb+Pb nuclear collisions at Elab = 10, 20, 30, 40, 80, 158 AGeV have been investigated. The expected enhanced fluctuations - attributed to the critical point and phase transition - can be observed experimentally on top of a monotonic and smooth 'hadronic background'. These findings should be helpful for the optimal

  4. Fluctuations and correlations in nucleus-nucleus collisions within transport approaches

    Energy Technology Data Exchange (ETDEWEB)

    Konchakovski, Volodymyr P.

    2009-10-01

    The current thesis is devoted to a systematic study of fluctuations and correlations in heavy-ion collisions, which might be considered as probes for the phase transition and the critical point in the phase diagram, within the Hadron-String- Dynamics (HSD) microscopic transport approach. This is a powerful tool to study nucleus-nucleus collisions and allows to completely simulate experimental collisions on an event-by-event basis. Thus, the transport model has been used to study fluctuations and correlations including the influence of experimental acceptance as well as centrality, system size and collision energy. The comparison to experimental data can separate the effects induced by a phase transition since there is no phase transition in the HSD version used here. Firstly the centrality dependence of multiplicity fluctuations has been studied. Different centrality selections have been performed in the analysis in correspondence to the experimental situation. For the fixed target experiment NA49 events with fixed numbers of the projectile participants have been studied while in the collider experiment PHENIX centrality classes of events have been defined by the multiplicity in certain phase space region. A decrease of participant number fluctuations (and thus volume fluctuations) in more central collisions for both experiments has been obtained. Another area of this work addresses to transport model calculations of multiplicity fluctuations in nucleus-nucleus collisions as a function of colliding energy and system size. This study is in full correspondence to the experimental program of the NA61 Collaboration at the SPS. Central C+C, S+S, In+In, and Pb+Pb nuclear collisions at Elab = 10, 20, 30, 40, 80, 158 AGeV have been investigated. The expected enhanced fluctuations - attributed to the critical point and phase transition - can be observed experimentally on top of a monotonic and smooth 'hadronic background'. These findings should be helpful for the

  5. Influence of recipient cytoplasm cell stage on transcription in bovine nucleus transfer embryos

    DEFF Research Database (Denmark)

    Smith, S. D.; Soloy, E.; Kanka, J.

    1996-01-01

    Nucleus transfer for the production of multiple embryos derived from a donor embryo relies upon the reprogramming of the donor nucleus so that it behaves similar to a zygotic nucleus. One indication of nucleus reprogramming is the RNA synthetic activity. In normal bovine embryogenesis, the embryo...

  6. PREFACE: 11th International Conference on Nucleus-Nucleus Collisions (NN2012)

    Science.gov (United States)

    Li, Bao-An; Natowitz, Joseph B.

    2013-03-01

    The 11th International Conference on Nucleus-Nucleus Collisions (NN2012) was held from 27 May to 1 June 2012, in San Antonio, Texas, USA. It was jointly organized and hosted by The Cyclotron Institute at Texas A&M University, College Station and The Department of Physics and Astronomy at Texas A&M University-Commerce. Among the approximately 300 participants were a large number of graduate students and post-doctoral fellows. The Keynote Talk of the conference, 'The State of Affairs of Present and Future Nucleus-Nucleus Collision Science', was given by Dr Robert Tribble, University Distinguished Professor and Director of the TAMU Cyclotron Institute. During the conference a very well-received public lecture on neutrino astronomy, 'The ICEcube project', was given by Dr Francis Halzen, Hilldale and Gregory Breit Distinguished Professor at the University of Wisconsin, Madison. The Scientific program continued in the general spirit and intention of this conference series. As is typical of this conference a broad range of topics including fundamental areas of nuclear dynamics, structure, and applications were addressed in 42 plenary session talks, 150 parallel session talks, and 21 posters. The high quality of the work presented emphasized the vitality and relevance of the subject matter of this conference. Following the tradition, the NN2012 International Advisory Committee selected the host and site of the next conference in this series. The 12th International Conference on Nucleus-Nucleus Collisions (NN2015) will be held 21-26 June 2015 in Catania, Italy. It will be hosted by The INFN, Laboratori Nazionali del Sud, INFN, Catania and the Dipartimento di Fisica e Astronomia of the University of Catania. The NN2012 Proceedings contains the conference program and 165 articles organized into the following 10 sections 1. Heavy and Superheavy Elements 2. QCD and Hadron Physics 3. Relativistic Heavy-Ion Collisions 4. Nuclear Structure 5. Nuclear Energy and Applications of

  7. Heterogeneous calretinin expression in the avian cochlear nucleus angularis.

    Science.gov (United States)

    Bloom, S; Williams, A; MacLeod, K M

    2014-08-01

    Multiple calcium-binding proteins (CaBPs) are expressed at high levels and in complementary patterns in the auditory pathways of birds, mammals, and other vertebrates, but whether specific members of the CaBP family can be used to identify neuronal subpopulations is unclear. We used double immunofluorescence labeling of calretinin (CR) in combination with neuronal markers to investigate the distribution of CR-expressing neurons in brainstem sections of the cochlear nucleus in the chicken (Gallus gallus domesticus). While CR was homogeneously expressed in cochlear nucleus magnocellularis, CR expression was highly heterogeneous in cochlear nucleus angularis (NA), a nucleus with diverse cell types analogous in function to neurons in the mammalian ventral cochlear nucleus. To quantify the distribution of CR in the total NA cell population, we used antibodies against neuronal nuclear protein (NeuN), a postmitotic neuron-specific nuclear marker. In NA neurons, NeuN label was variably localized to the cell nucleus and the cytoplasm, and the intensity of NeuN immunoreactivity was inversely correlated with the intensity of CR immunoreactivity. The percentage of CR + neurons in NA increased from 31 % in embryonic (E)17/18 chicks, to 44 % around hatching (E21), to 51 % in postnatal day (P) 8 chicks. By P8, the distribution of CR + neurons was uniform, both rostrocaudal and in the tonotopic (dorsoventral) axis. Immunoreactivity for the voltage-gated potassium ion channel Kv1.1, used as a marker for physiological type, showed broad and heterogeneous postsynaptic expression in NA, but did not correlate with CR expression. These results suggest that CR may define a subpopulation of neurons within nucleus angularis.

  8. Classical cadherins control nucleus and centrosome position and cell polarity.

    Science.gov (United States)

    Dupin, Isabelle; Camand, Emeline; Etienne-Manneville, Sandrine

    2009-06-01

    Control of cell polarity is crucial during tissue morphogenesis and renewal, and depends on spatial cues provided by the extracellular environment. Using micropatterned substrates to impose reproducible cell-cell interactions, we show that in the absence of other polarizing cues, cell-cell contacts are the main regulator of nucleus and centrosome positioning, and intracellular polarized organization. In a variety of cell types, including astrocytes, epithelial cells, and endothelial cells, calcium-dependent cadherin-mediated cell-cell interactions induce nucleus and centrosome off-centering toward cell-cell contacts, and promote orientation of the nucleus-centrosome axis toward free cell edges. Nucleus and centrosome off-centering is controlled by N-cadherin through the regulation of cell interactions with the extracellular matrix, whereas the orientation of the nucleus-centrosome axis is determined by the geometry of N-cadherin-mediated contacts. Our results demonstrate that in addition to the specific function of E-cadherin in regulating baso-apical epithelial polarity, classical cadherins control cell polarization in otherwise nonpolarized cells.

  9. Qualitative analysis neurons in the adult human dentate nucleus

    Directory of Open Access Journals (Sweden)

    Marić Dušica

    2012-01-01

    Full Text Available Although many relevant findings regarding to the morphology and cytoarchitectural development of the dentate nucleus have been presented so far, very little qualitative information has been collected on neuronal morphology in the adult human dentate nucleus. The neurons were labelled by Golgi staining from thirty human cerebella, obtained from medico-legal forensic autopsies of adult human bodies and free of significant brain pathology. The human dentate neurons were qualitatively analyzed and these cells were classified into two main classes: the small and the large multipolar neurons. Considering the shape of the cell body, number of the primary dendrites, shape of the dendritic tree and their position within the dentate nucleus, three subclasses of the large multipolar neurons have been recognized. The classification of neurons from the human dentate nucleus has been qualitatively confirmed in fetuses and premature infants. This study represents the first qualitative analysis and classification of the large multipolar neurons in the dentate nucleus of the adult human.

  10. Alteration of Paramecium candatum germinal nucleus morphology after UV irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Fokin, S.I. (Leningradskij Gosudarstvennyj Univ. (USSR). Biologicheskij Nauchno-Issledovatel' skij Inst.)

    1982-09-01

    A study was made on morphologic changes of micronucleus (Mi) after whole-body ultraviolet (UV) irradiation of paramecia as well as after local irradiation of this nucleus or the area of macronucleus (Ma). The whole-body irradiation of its Ma part leads to generative nucleus growth in sizes and chromatin structure change, which is expressed in occurence of large chromatin bodies. Aftereffects of local action on Mi for viable descendants are expressed in nucleus size transformation (usually in reduction), gaining ''comet-shaped'' form and probably in reduction of dna amount. Irradiation of Ma and total effect on cell cause Mi changes of reversible character. All morphologic changes of Mi after local ultraviolet irradiation are conserved in descendants and are not photoreactivated. Possible reasons for this phenomenon are discussed. The results obtained make it possible to speak about different mechanisms of action on Mi in the case of local and whole-body UV irradiation of cell. The effect of irradiated Ma on generative nucleus, but not direct damage of this nucleus is the reason for Mi morphologic reconstruction after whole-body action on paramecium.

  11. Circadian and pharmacological regulation of casein kinase I in the ...

    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 ...

  12. 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 ...

  13. Statistical emission of complex fragments from highly excited compound nucleus

    International Nuclear Information System (INIS)

    Matsuse, T.

    1991-01-01

    A full statistical analysis has been given in terms of the Extended Hauser-Feshbach method. The charge and kinetic energy distributions of 35 Cl+ 12 C reaction at E lab = 180, 200 MeV and 23 Na+ 24 Mg reaction at E lab = 89 MeV which form the 47 V compound nucleus are investigated as a prototype of the light mass system. The measured kinetic energy distributions of the complex fragments are shown to be well reproduced by the Extended Hauser-Feshbach method, so the observed complex fragment production is understood as the statistical binary decay from the compound nucleus induced by heavy-ion reaction. Next, this method is applied to the study of the complex production from the 111 In compound nucleus which is formed by the 84 Kr+ 27 Al reaction at E lab = 890 MeV. (K.A.) 18 refs., 10 figs

  14. Proton decay in a nucleus: Nonrelativistic treatment of nuclear effects

    International Nuclear Information System (INIS)

    Fernandez, L.A.; Alvarez-Estrada, R.F.; Sanchez-Gomez, J.L.

    1983-01-01

    In this paper, proton decay in a large nucleus is studied in the framework of SU(5) grand unification theory (GUT). By using a method based upon the Green's-function technique of many-body physics, nuclear effects on spectator and pole terms are computed. The decay width in the nucleus is found to be practically the same as in free space. However, nuclear effects are of considerable importance concerning the positron spectrum. A density-correlation expansion is introduced which is useful for carrying out a systematic study of nuclear effects in proton decay in a large nucleus. The method presented here can be easily extended to other GUT's or supersymmetric GUT's

  15. Analysis of a deep nucleus of Tehuantepec Gulf

    International Nuclear Information System (INIS)

    Ordonez R, E.; Lopez M, J.; Ramirez T, J. J.; Machain C, M. L.

    2009-10-01

    A nucleus of sediments obtained in the deep of Tehuantepec Gulf is analyzed; this nucleus has the particularity of to be a sampling of longitude of 18.3 m that include the total of last period glacial, few times obtained in our country. The physical chemistry composition of 10 selected fractions are analyzed with the purpose of to understand the formation processes of deep ocean along the period of 120 000 years, that includes the extracted fraction. Crystallography analysis, morphology, physical chemistry characterization and activity gamma were made. Finding that the content of organic matter falls as the superficial area increases, also was found the presence of natural uranium in similar concentration and balance with its radiogenic descendants along the nucleus profile what suggests the uranium migration to interior of mineral grains. (Author)

  16. Insulin induces calcium signals in the nucleus of rat hepatocytes.

    Science.gov (United States)

    Rodrigues, Michele A; Gomes, Dawidson A; Andrade, Viviane A; Leite, M Fatima; Nathanson, Michael H

    2008-11-01

    Insulin is an hepatic mitogen that promotes liver regeneration. Actions of insulin are mediated by the insulin receptor, which is a receptor tyrosine kinase. It is currently thought that signaling via the insulin receptor occurs at the plasma membrane, where it binds to insulin. Here we report that insulin induces calcium oscillations in isolated rat hepatocytes, and that these calcium signals depend upon activation of phospholipase C and the inositol 1,4,5-trisphosphate receptor, but not upon extracellular calcium. Furthermore, insulin-induced calcium signals occur in the nucleus, and are temporally associated with selective depletion of nuclear phosphatidylinositol bisphosphate and translocation of the insulin receptor to the nucleus. These findings suggest that the insulin receptor translocates to the nucleus to initiate nuclear, inositol 1,4,5-trisphosphate-mediated calcium signals in rat hepatocytes. This novel signaling mechanism may be responsible for insulin's effects on liver growth and regeneration.

  17. Models of the atomic nucleus. With interactive software

    International Nuclear Information System (INIS)

    Cook, N.D.

    2006-01-01

    This book-and-CD-software package supplies users with an interactive experience for nuclear visualization via a computer-graphical interface, similar in principle to the molecular visualizations already available in chemistry. Models of the Atomic Nucleus, a largely non-technical introduction to nuclear theory, explains the nucleus in a way that makes nuclear physics as comprehensible as chemistry or cell biology. The book/software supplements virtually any of the current textbooks in nuclear physics by providing a means for 3D visual display of the diverse models of nuclear structure. For the first time, an easy-to-master software for scientific visualization of the nucleus makes this notoriously ''non-visual'' field become immediately 'visible.' After a review of the basics, the book explores and compares the competing models, and addresses how the lattice model best resolves remaining controversies. The appendix explains how to obtain the most from the software provided on the accompanying CD. (orig.)

  18. Nuclear radius deduced from proton diffraction by a black nucleus

    Science.gov (United States)

    Kohama, Akihisa; Iida, Kei; Oyamatsu, Kazuhiro

    2004-06-01

    We find a new method to deduce nuclear radii from proton-nucleus elastic scattering data. In this method, a nucleus is viewed as a “black” sphere. A diffraction pattern of protons by this sphere is equivalent to that of the Fraunhofer diffraction by a circular hole of the same radius embedded in a screen. We determine the black sphere radius in such a way as to reproduce the empirical value of the angle of the observed first diffraction peak. It is useful to identify this radius multiplied by √(3/5 ) with the root-mean-square matter radius of the target nucleus. For most stable isotopes of masses heavier than 50, it agrees, within the error bars, with the values that were deduced in previous elaborate analyses from the data obtained at proton incident energies higher than ˜800 MeV .

  19. Silk fibroin porous scaffolds for nucleus pulposus tissue engineering

    International Nuclear Information System (INIS)

    Zeng, Chao; Yang, Qiang; Zhu, Meifeng; Du, Lilong; Zhang, Jiamin; Ma, Xinlong; Xu, Baoshan; Wang, Lianyong

    2014-01-01

    Intervertebral discs (IVDs) are structurally complex tissue that hold the vertebrae together and provide mobility to spine. The nucleus pulposus (NP) degeneration often results in degenerative IVD disease that is one of the most common causes of back and neck pain. Tissue engineered nucleus pulposus offers an alternative approach to regain the function of the degenerative IVD. The aim of this study is to determine the feasibility of porous silk fibroin (SF) scaffolds fabricated by paraffin-sphere-leaching methods with freeze-drying in the application of nucleus pulposus regeneration. The prepared scaffold possessed high porosity of 92.38 ± 5.12% and pore size of 165.00 ± 8.25 μm as well as high pore interconnectivity and appropriate mechanical properties. Rabbit NP cells were seeded and cultured on the SF scaffolds. Scanning electron microscopy, histology, biochemical assays and mechanical tests revealed that the porous scaffolds could provide an appropriate microstructure and environment to support adhesion, proliferation and infiltration of NP cells in vitro as well as the generation of extracellular matrix. The NP cell–scaffold construction could be preliminarily formed after subcutaneously implanted in a nude mice model. In conclusion, The SF porous scaffold offers a potential candidate for tissue engineered NP tissue. - Highlights: • Paraffin microsphere-leaching method is used to fabricate silk fibroin scaffold. • The scaffold has appropriate mechanical property, porosity and pore size • The scaffold supports growth and infiltration of nucleus pulposus cells. • Nucleus pulposus cells can secrete extracellular matrix in the scaffolds. • The scaffold is a potential candidate for tissue engineered nucleus pulposus

  20. Brain networks modulated by subthalamic nucleus deep brain stimulation.

    Science.gov (United States)

    Accolla, Ettore A; Herrojo Ruiz, Maria; Horn, Andreas; Schneider, Gerd-Helge; Schmitz-Hübsch, Tanja; Draganski, Bogdan; Kühn, Andrea A

    2016-09-01

    Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. © The

  1. Silk fibroin porous scaffolds for nucleus pulposus tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Chao; Yang, Qiang [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhu, Meifeng [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Du, Lilong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhang, Jiamin [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ma, Xinlong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Xu, Baoshan, E-mail: xubaoshan99@126.com [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Wang, Lianyong, E-mail: wly@nankai.edu.cn [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2014-04-01

    Intervertebral discs (IVDs) are structurally complex tissue that hold the vertebrae together and provide mobility to spine. The nucleus pulposus (NP) degeneration often results in degenerative IVD disease that is one of the most common causes of back and neck pain. Tissue engineered nucleus pulposus offers an alternative approach to regain the function of the degenerative IVD. The aim of this study is to determine the feasibility of porous silk fibroin (SF) scaffolds fabricated by paraffin-sphere-leaching methods with freeze-drying in the application of nucleus pulposus regeneration. The prepared scaffold possessed high porosity of 92.38 ± 5.12% and pore size of 165.00 ± 8.25 μm as well as high pore interconnectivity and appropriate mechanical properties. Rabbit NP cells were seeded and cultured on the SF scaffolds. Scanning electron microscopy, histology, biochemical assays and mechanical tests revealed that the porous scaffolds could provide an appropriate microstructure and environment to support adhesion, proliferation and infiltration of NP cells in vitro as well as the generation of extracellular matrix. The NP cell–scaffold construction could be preliminarily formed after subcutaneously implanted in a nude mice model. In conclusion, The SF porous scaffold offers a potential candidate for tissue engineered NP tissue. - Highlights: • Paraffin microsphere-leaching method is used to fabricate silk fibroin scaffold. • The scaffold has appropriate mechanical property, porosity and pore size • The scaffold supports growth and infiltration of nucleus pulposus cells. • Nucleus pulposus cells can secrete extracellular matrix in the scaffolds. • The scaffold is a potential candidate for tissue engineered nucleus pulposus.

  2. Final State Interactions Effects in Neutrino-Nucleus Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Golan, Tomasz [Univ. of Wroctaw (Poland); Juszczak, Cezary [Univ. of Wroctaw (Poland); Sobczyk, Jan T. [Fermi National Accelerator Laboratory (FNAL), Batavia, IL (United States)

    2012-07-01

    Final State Interactions effects are discussed in the context of Monte Carlo simulations of neutrino-nucleus interactions. A role of Formation Time is explained and several models describing this effect are compared. Various observables which are sensitive to FSI effects are reviewed including pion-nucleus interaction and hadron yields in backward hemisphere. NuWro Monte Carlo neutrino event generator is described and its ability to understand neutral current $\\pi^0$ production data in $\\sim 1$ GeV neutrino flux experiments is demonstrated.

  3. Recent Developments in Neutrino/Antineutrino-Nucleus Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Morfín, Jorge G.; Nieves, Juan; Sobczyk, Jan T.

    2012-01-01

    Recent experimental results and developments in the theoretical treatment of neutrino-nucleus interactions in the energy range of 1–10 GeV are discussed. Difficulties in extracting neutrino-nucleon cross sections from neutrino-nucleus scattering data are explained and significance of understanding nuclear effects for neutrino oscillation experiments is stressed. Detailed discussions of the status of two-body current contribution in the kinematic region dominated by quasielastic scattering and specific features of partonic nuclear effects in weak DIS scattering are presented.

  4. Hypertrophy of the inferior olivary nucleus impacts perception of gravity.

    Science.gov (United States)

    Tarnutzer, Alexander A; Palla, Antonella; Marti, Sarah; Schuknecht, Bernhard; Straumann, Dominik

    2012-01-01

    Interruption of the dentato-olivary projections, interconnecting the dentate nucleus (DN) and the contralateral inferior olivary nucleus (ION), is predicted to interfere with the DN' role in estimating direction of gravity. In a patient with pendular nystagmus due to hypertrophy of the ION secondary to predominantly right-sided ponto-mesencephalic hemorrhage, perceived vertical shifted from clockwise to counter-clockwise deviations within 4 months. We hypothesize that synchronized oscillations of ION neurons induce a loss of inhibitory control, leading to hyperactivity of the contralateral DN and, as a result, to perceived vertical roll-tilt to the side of the over-active DN.

  5. On the hadron formation time in pion-nucleus interaction

    International Nuclear Information System (INIS)

    Bravina, L.V.; Korotkikh, V.L.; Sarycheva, L.I.; Sivoklokov, S.Yu.

    1992-01-01

    Differences in the observable characteristics of pion-nucleus interactions at high energy are investigated for two definitions of the hadron formation time. The Monte Carlo simulation of hadron-nucleus interactions and quark-gluon string model for hadron-hadron collisions are used. It is shown that the momentum spectrum of the protons in the target fragmentation region is most sensitive to the definition of the formation time. The inclusive meson and meson resonance spectra are similar in the both versions. 20 refs.; 4 figs.; 1 tab

  6. Progressive activation of paratrigeminal nucleus during entrance to hibernation

    International Nuclear Information System (INIS)

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

    1988-01-01

    The paratrigeminal nucleus (Pa5) undergoes a progressive increase in its uptake of 2-[ 14 C]deoxyglucose (2DG) relative to other brain structures during entrance to hibernation in the ground squirrel. This highly significant increase results in the Pa5 becoming the most highly labeled brain region during hibernation, even though it exhibits one of the lowest levels of 2DG uptake in the brain during the nonhibernating state. The progressive activation of the Pa5 observed during entrance is reversed during arousal from hibernation. These observations and the neuroanatomical projections of the Pa5 implicate this nucleus as playing a role in the entrance and maintenance of the hibernating state

  7. 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.

  8. Circadian rhythms of hedonic drinking behavior in mice.

    Science.gov (United States)

    Bainier, Claire; Mateo, Maria; Felder-Schmittbuhl, Marie-Paule; Mendoza, Jorge

    2017-05-04

    In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is the site of the main circadian clock, synchronized by the light-dark cycle, which generates behavioral rhythms like feeding, drinking and activity. Notwithstanding, the main role of the SCN clock on the control of all circadian rhythms has been questioned due to the presence of clock activity in many brain areas, including those implicated in the regulation of feeding and reward. Moreover, whether circadian rhythms of particular motivated behaviors exist is unknown. Here, we evaluated the spontaneous daily and circadian behavior of consumption of a sweet caloric solution (5-10% sucrose), and the effects of sucrose intake on the expression of clock genes in the mouse brain. Mice showed a daily (in a light-dark cycle) and a circadian (in constant darkness conditions) rhythm in the intake and sucrose preference with a rise for both parameters at night (or subjective night). In addition, we observed changes in the circadian day-night expression of the clock gene Per2 in the SCN, cortex and striatum of animals ingesting sucrose compared to control mice on pure water. Finally, daily rhythms of sucrose intake and preference were abolished in Per2 Brdm1 - and double Per1 -/- Per2 Brdm1 -mutant animals. These data indicate that the expression of circadian rhythms of hedonic feeding behaviors may be controlled by brain circadian clocks and Per gene expression. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. 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.

  10. Early doors (Edo) mutant mouse reveals the importance of period 2 (PER2) PAS domain structure for circadian pacemaking.

    Science.gov (United States)

    Militi, Stefania; Maywood, Elizabeth S; Sandate, Colby R; Chesham, Johanna E; Barnard, Alun R; Parsons, Michael J; Vibert, Jennifer L; Joynson, Greg M; Partch, Carrie L; Hastings, Michael H; Nolan, Patrick M

    2016-03-08

    The suprachiasmatic nucleus (SCN) defines 24 h of time via a transcriptional/posttranslational feedback loop in which transactivation of Per (period) and Cry (cryptochrome) genes by BMAL1-CLOCK complexes is suppressed by PER-CRY complexes. The molecular/structural basis of how circadian protein complexes function is poorly understood. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced mutation, early doors (Edo), in the PER-ARNT-SIM (PAS) domain dimerization region of period 2 (PER2) (I324N) that accelerates the circadian clock of Per2(Edo/Edo) mice by 1.5 h. Structural and biophysical analyses revealed that Edo alters the packing of the highly conserved interdomain linker of the PER2 PAS core such that, although PER2(Edo) complexes with clock proteins, its vulnerability to degradation mediated by casein kinase 1ε (CSNK1E) is increased. The functional relevance of this mutation is revealed by the ultrashort (Edo/Edo); Csnk1e(Tau/Tau) mice and the SCN. These periods are unprecedented in mice. Thus, Per2(Edo) reveals a direct causal link between the molecular structure of the PER2 PAS core and the pace of SCN circadian timekeeping.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington’s Disease

    Science.gov (United States)

    Kuljis, Dika A.; Gad, Laura; Loh, Dawn H.; MacDowell Kaswan, Zoë; Hitchcock, Olivia N.; Ghiani, Cristina A.; Colwell, Christopher S.

    2016-01-01

    Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies indicate there may be sex differences in disease progression. One of the early symptoms of HD is disruptions in the circadian timing system, but it is currently unknown whether sex is a factor in these alterations. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s) and designing early intervention strategies, we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in circadian behavioral rhythms are detectable in an animal model of the disease. Similar to BACHD males, BACHD females display circadian disruptions at both 3 and 6 months of age; however, deficits to BACHD female mouse activity levels, rhythm precision, and behavioral fragmentation are either delayed or less severe relative to males. These sex differences are associated with a smaller suprachiasmatic nucleus (SCN) in BACHD male mice at age of symptom onset (3 months), but are not associated with sex-specific differences in SCN daytime electrical activity deficits, or peptide expression (arginine vasopressin, vasoactive intestinal peptide) within the SCN. Notably, BACHD females exhibited delayed motor coordination deficits, as measured using rotarod and challenge beam. These findings suggest a sex specific factor plays a role both in non-motor and motor symptom progression for the BACHD mouse. PMID:26871695

  16. A comparative analysis of mechanisms of fast light particles production in nucleus-nucleus collisions at low and intermediate energies

    CERN Document Server

    Denikin, A S

    2002-01-01

    The dynamics and the mechanisms of formation of pre-equilibrium light particles in nucleus-nucleus collisions at low and intermediate energies are discussed in terms of a classical four-body model. The energy and angular distributions of light particles have been calculated. It has been found that at energies lower than 50A MeV the formation of the most high-energy part of the nuclear spectrum occurs at the expense of the acceleration of light target particles with the mean field of the projectile. The obtained data are in good agreement with available experimental data

  17. Photon and neutral pion distributions in 60 and 200 A.GeV 16O + nucleus and proton + nucleus reactions

    International Nuclear Information System (INIS)

    Albrecht, R.; Bock, R.; Claesson, G.; Gutbrod, H.H.; Kolb, B.W.; Lund, I.; Schmidt, H.R.; Siemiarczuk, T.; Awes, T.C.; Baktash, C.; Ferguson, R.L.; Lee, I.Y.; Plasil, F.; Young, G.R.; Beckmann, P.; Berger, F.; Dragon, L.; Glasow, R.; Kampert, K.H.; Loehner, H.; Peitzmann, T.; Purschke, M.; Santo, R.; Franz, A.; Kristiansson, P.; Poskanzer, A.M.; Ritter, H.G.; Garpman, S.; Gustafsson, H.A.; Oskarsson, A.; Otterlund, I.; Persson, S.; Stenlund, E.; Obenshain, F.E.; Sorensen, S.P.

    1987-12-01

    Transverse momentum (p T ) distributions of inclusive photons and neutral pions at midrapidity are measured with a lead glass calorimeter in 60 and 200 A.GeV 16 O + nucleus and proton + nucleus reactions. The variation of the average transverse momentum is investigated as function of centrality, determined by measurements of the remaining energy of the projectile and the charged particle multiplicity. For small values of the entropy, deduced from the multiplicity density, an increase in average p T is observed levelling off for larger values of entropy. The target-mass and energy dependence of π 0 p T distributions are presented. (orig.)

  18. Photon and neutral pion distributions in 60 and 200 A GeV 16O + nucleus and proton + nucleus reactions

    International Nuclear Information System (INIS)

    Albrecht, R.; Bock, R.; Claesson, G.; Gutbrod, H.H.; Kolb, B.W.; Lund, I.; Schmidt, H.R.; Siemiarczuk, T.; Awes, T.C.; Baktash, C.; Ferguson, R.L.; Lee, I.Y.; Plasil, F.; Young, G.R.; Beckmann, P.; Berger, F.; Dragon, L.; Glasow, R.; Kampert, K.H.; Loehner, H.; Peitzmann, T.; Purschke, M.; Santo, R.; Franz, A.; Kristiansson, P.; Poskanzer, A.M.; Ritter, H.G.; Garpman, S.; Gustafsson, H.A.; Oskarsson, A.; Otterlund, I.; Persson, S.; Stenlund, E.; Obenshain, F.E.; Sorensen, S.P.

    1988-01-01

    Transverse momentum (p T ) distributions of inclusive photons and neutral pions at midrapidity are measured with a lead glass calorimeter in 60 and 200 A GeV 16 O+ nucleus and proton + nucleus reactions. The variation of the average transverse momentum is investigated as function of centrality, determined by measurements of the remaining energy of the projectile and the charged particle multiplicity. For small values of the entropy, deduced from the multiplicity density, and increase in average p T is observed levelling off for larger values of entropy. The target-mass and energy dependence of π 0 p T distributions are presented. (orig.)

  19. Experimental limits on the production of fractionally charged particles in proton-nucleus and neutrino-nucleus collisions

    International Nuclear Information System (INIS)

    Bergsma, F.; Dorenbosch, J.; Jonker, M.; Nieuwenhuis, C.; Allaby, J.V.; Amaldi, U.; Barbielli, G.; Barone, L.; Capone, A.; Flegel, W.; Lanceri, L.; Metcalf, M.; Panman, J.; Plunkett, R.; Santoni, C.; Winter, K.; Abt, I.; Aspiazu, J.; Buesser, F.W.; Daumann, H.; Gall, P.D.; Hebbeker, T.; Niebergall, F.; Schuett, P.; Staehelin, P.

    1984-01-01

    A search for fractionally charged Q=1/3 (2/3) particles of different properties of interaction produced in (anti)neutrino-nucleus and in proton-nucleus collisions was performed using the scintillator system of the CHARM neutrino detector at the CERN SPS. No events of the cases considered were found. In (anti)neutrino beams production was found to be less than a few times 10 -5 per interaction of a beam particle. In a proton beam an upper limit on the production cross section of proportional10 -40 cm 2 was obtained. (orig.)

  20. On the Measurement of D-meson Yield in Nucleus-Nucleus Collisions at the CERN SPS

    CERN Document Server

    Gazdzicki, M; Gazdzicki, Marek; Markert, Christina

    2000-01-01

    We argue that the measurement of open charm gives a unique opportunity to test the validity of pQCD-based and statistical models of nucleus-nucleus collisions at high energies. We show that various approaches used to estimate D-meson multiplicity in central Pb+Pb collisions at 158 A GeV give predictions which differ by more than a factor of 100. Finally we demonstrate that decisive experimental results concerning the open charm yield in A+A collisions can be obtained using data of the NA49 experiment at the CERN SPS.