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Sample records for factor crf system

  1. Stress and addiction: contribution of the corticotropin releasing factor (CRF system in neuroplasticity

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    Carolina L Haass-Koffler

    2012-09-01

    Full Text Available Corticotropin releasing factor (CRF has been shown to induce various behavioral changes related to adaptation to stress. Dysregulation of the CRF system at any point can lead to a variety of psychiatric disorders, including substance use disorders (SUDs. CRF has been associated with stress-induced drug reinforcement. Extensive literature has identified CRF to play an important role in the molecular mechanisms that lead to an increase in susceptibility that precipitates relapse to SUDs. The CRF system has a heterogeneous role in SUDs. It enhances the acute effects of drugs of abuse and is also responsible for the potentiation of drug-induced neuroplasticity evoked during the withdrawal period. We present in this review the brain regions and circuitries where CRF is expressed and may participate in stress-induced drug abuse. Finally, we attempt to evaluate the role of modulating the CRF system as a possible therapeutic strategy for treating the dysregulation of emotional behaviors that result from the acute positive reinforcement of substances of abuse as well as the negative reinforcement produced by withdrawal.

  2. Stress and addiction: contribution of the corticotropin releasing factor (CRF) system in neuroplasticity.

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    Haass-Koffler, Carolina L; Bartlett, Selena E

    2012-01-01

    Corticotropin releasing factor (CRF) has been shown to induce various behavioral changes related to adaptation to stress. Dysregulation of the CRF system at any point can lead to a variety of psychiatric disorders, including substance use disorders (SUDs). CRF has been associated with stress-induced drug reinforcement. Extensive literature has identified CRF to play an important role in the molecular mechanisms that lead to an increase in susceptibility that precipitates relapse to SUDs. The CRF system has a heterogeneous role in SUDs. It enhances the acute effects of drugs of abuse and is also responsible for the potentiation of drug-induced neuroplasticity evoked during the withdrawal period. We present in this review the brain regions and circuitries where CRF is expressed and may participate in stress-induced drug abuse. Finally, we attempt to evaluate the role of modulating the CRF system as a possible therapeutic strategy for treating the dysregulation of emotional behaviors that result from the acute positive reinforcement of substances of abuse as well as the negative reinforcement produced by withdrawal.

  3. Corticotropin releasing factor (CRF) binding protein: a novel regulator of CRF and related peptides.

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    Behan, D P; De Souza, E B; Lowry, P J; Potter, E; Sawchenko, P; Vale, W W

    1995-10-01

    A 37-kDa corticotropin releasing factor (CRF) binding protein (CRF-BP) was purified from human plasma by repeated affinity purification and subsequently sequenced and cloned. The human and rat CRF-BP cDNAs encode proteins of 322 amino acids with one putative signal sequence, one N-glycosylation site, and 10 conserved cysteines. Human CRF-BP binds human CRF with high affinity but has low affinity for the ovine peptide. In contrast, sheep CRF-BP binds human and ovine CRF with high affinity. The CRF-BP gene consists of seven exons and six introns and is located on chromosome 13 and loci 5q of the mouse and human genomes, respectively. CRF-BP inhibits the adrenocorticotrophic hormone (ACTH) releasing properties of CRF in vitro. CRF-BP dimerizes after binding CRF and clears the peptide from blood. This clearance mechanism protects the maternal pituitary gland from elevated plasma CRF levels found during the third trimester of human pregnancy. CRF-BP is expressed in the brains of all species so far tested but is uniquely expressed in human liver and placenta. In brain, CRF-BP is membrane associated and is predominantly expressed in the cerebral cortex and subcortical limbic structures. In some brain areas CRF-BP colocalizes with CRF and CRF receptors. The protein is also present in pituitary corticotropes, where it is under positive glucocorticoid control, and is likely to locally modulate CRF-induced ACTH secretion. The ligand requirements of the CRF receptor and the CRF-BP can be distinguished in that central human CRF fragments, such as CRF (6-33) and CRF (9-33), have high affinity for CRF-BP but low affinity for the CRF receptor. The binding protein's ability to inhibit CRF-induced ACTH secretion can be reversed by CRF (6-33) and CRF (9-33), suggesting that ligand inhibitors may have utility in elevating free CRF levels in disease states associated with decreased CRF. Thus, by controlling the amount of free CRF which activates CRF receptors, it is likely that the CRF

  4. [Effect of corticotropin releasing factor(CRF) on somatic pain sensitivity in conscious rats: involvement of CRF1 and CRF2 receptors].

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    Iarushkina, N I; Bagaeva, T R; Filaretova, L P

    2014-11-01

    Corticotropin-releasing factor (CRF) is involved in the regulation of pain sensitivity and can cause an analgesic effect in animals and humans. The aim of the study was to investigate the involvement of CRF1 and CRF2 receptors in CRF-induced analgesic effect (after intraperitoneal injection) on somatic pain sensitivity in conscious rats. Somatic pain sensitivity was tested by tail flick latency (tail flick test). The involvement of CRF1 and CRF2 receptors was studied by their selective antagonists NBI 27914 and astressin 2B, respectively. Systemic administration of CRF caused an increase in tail flick latency (analgesic effect). Pretreatment with NBI 27914 or astressin 2B eliminated CRF-induced analgesic effect. Besides, NBI 27914, but not astressin 2B, increased basal tail flick latency. The data obtained indicate that the analgesic effect can be mediated by both CRF1 and CRF2 receptors. CRF-1 receptor, in contrast to the CRF2 receptors, may be involved in the regulation of the basal level of pain sensitivity.

  5. CRF system recruitment mediates dark side of compulsive eating.

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    Cottone, Pietro; Sabino, Valentina; Roberto, Marisa; Bajo, Michal; Pockros, Lara; Frihauf, Jennifer B; Fekete, Eva M; Steardo, Luca; Rice, Kenner C; Grigoriadis, Dimitri E; Conti, Bruno; Koob, George F; Zorrilla, Eric P

    2009-11-24

    Dieting to control body weight involves cycles of deprivation from palatable food that can promote compulsive eating. The present study shows that rats withdrawn from intermittent access to palatable food exhibit overeating of palatable food upon renewed access and an affective withdrawal-like state characterized by corticotropin-releasing factor-1 (CRF(1)) receptor antagonist-reversible behaviors, including hypophagia, motivational deficits to obtain less palatable food, and anxiogenic-like behavior. Withdrawal was accompanied by increased CRF expression and CRF(1) electrophysiological responsiveness in the central nucleus of the amygdala. We propose that recruitment of anti-reward extrahypothalamic CRF-CRF(1) systems during withdrawal from palatable food, analogous to abstinence from abused drugs, may promote compulsive selection of palatable food, undereating of healthier alternatives, and a negative emotional state when intake of palatable food is prevented.

  6. Galanin is Co-Expressed with Substance P, Calbindin and Corticotropin-Releasing Factor (CRF) in The Enteric Nervous System of the Wild Boar (Sus scrofa) Small Intestine.

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    Czujkowska, A; Arciszewski, M B

    2016-04-01

    Galanin is a neuropeptide widely present in the enteric nervous system of numerous animal species and exhibiting neurotransmittery/neuromodulatory roles. Colocalization patterns of galanin with substance P (SP), corticotropin-releasing factor (CRF) and calbindin were studied in the small intestine of the wild boar using immunofluorescence technique. We demonstrated the presence of SP in substantial populations of galanin-immunoreactive (IR) submucous neurons. Additionally, different amounts of nerve fibres exhibiting simultaneous presence of galanin and SP were noted in the small intestinal smooth musculature, submucous ganglia, lamina muscularis mucosae and mucosa. In the wild boar duodenum, jejunum and ileum, the co-expression of galanin and calbindin was limited to minor populations of submucous neurons only. Single galanin-/CRF-IR nerve fibres were exclusively present in the duodenal and jejunal (but not ileal) mucosa. These results strongly suggest that galanin participates in neuronal control of the wild boar small intestine also by functional co-operation with other biologically active neuropeptides.

  7. Effect of central corticotropin releasing factor on hepatic circulation in rats: the role of the CRF2 receptor in the brain

    OpenAIRE

    2005-01-01

    Backgrounds: Corticotropin releasing factor (CRF) is distributed in the central nervous system and acts as a neurotransmitter to regulate gastric functions through vagal-muscarinic pathways. We have recently demonstrated that central CRF aggravates experimental acute liver injury in rats. In the present study, the central effect of CRF on hepatic circulation was investigated.

  8. Corticotropin releasing factor (CRF) modulates fear-induced alterations in sleep in mice.

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    Yang, Linghui; Tang, Xiangdong; Wellman, Laurie L; Liu, Xianling; Sanford, Larry D

    2009-06-18

    Contextual fear significantly reduces rapid eye movement sleep (REM) during post-exposure sleep in mice and rats. Corticotropin releasing factor (CRF) plays a major role in CNS responses to stressors. We examined the influence of CRF and astressin (AST), a non-specific CRF antagonist, on sleep after contextual fear in BALB/c mice. Male mice were implanted with transmitters for recording sleep via telemetry and with a guide cannula aimed into the lateral ventricle. Recordings for vehicle and handling control were obtained after ICV microinjection of saline (SAL) followed by exposure to a novel chamber. Afterwards, the mice were subjected to shock training (20 trials, 0.5 mA, 0.5 s duration) for 2 sessions. After training, separate groups of mice received ICV microinjections of SAL (0.2 microl, n=9), CRF (0.4 microg, n=8), or AST (1.0 microg, n=8) prior to exposure to the shock context alone. Sleep was then recorded for 20 h (8-hour light and 12-hour dark period). Compared to handling control, contextual fear significantly decreased REM during the 8-h light period in mice receiving SAL and in mice receiving CRF, but not in the mice receiving AST. Mice receiving CRF exhibited reductions in REM during the 12-h dark period after contextual fear, whereas mice receiving SAL or AST did not. CRF also reduced non-REM (NREM) delta (slow wave) amplitude in the EEG. Only mice receiving SAL prior to contextual fear exhibited significant reductions in NREM and total sleep. These findings demonstrate a role for the central CRF system in regulating alterations in sleep induced by contextual fear.

  9. Effects of morphine on hypothalamic corticotropin-releasing factor (CRF, norepinephrine and dopamine in non-stressed and stressed rats.

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    Suemaru,Shuso

    1985-12-01

    Full Text Available The effects of morphine on the hypothalamic corticotropin-releasing factor (CRF, norepinephrine (NE and dopamine (DA concentrations were investigated in non-stressed and stressed rats. Acutely administered morphine stimulated both the synthesis and release of CRF in the hypothalamus, thereby activating the pituitary-adrenocortical system in non-stressed rats, but inhibited the stress-induced CRF synthesis and ACTH-corticosterone secretion. Either a morphine or ether-laparotomy stress reduced NE and DA concentrations in the hypothalamus. A pretreatment with morphine inhibited the stress-induced reduction in the hypothalamic NE and DA concentrations, and induced a significant increase in the DA concentration. These observations suggest that hypothalamic NE and DA are involved in morphine-induced changes in hypothalamo-pituitary-adrenocortical (HPA activity and that endogenous opiates have a role in regulating CRF secretion by interacting with hypothalamic biogenic amines.

  10. Effects of Corticotropin Releasing Factor (CRF on Sleep and Temperature Following Predictable Controllable and Uncontrollable Stress in Mice

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    Laurie eWellman

    2015-07-01

    Full Text Available Corticotropin releasing factor (CRF is a major mediator of central nervous system responses to stressors, including alterations in wakefulness and sleep. However, its role in mediating stress-induced alterations in sleep has not been fully delineated. In this study, we assessed the role of CRF and the non-specific CRF antagonist, astressin (AST, in regulating changes in sleep produced by signaled, escapable shock (SES and signaled inescapable shock (SIS, two stressors that can increase or decrease sleep, respectively. Male BALB/cJ mice were surgically implanted with transmitters (DataSciences ETA10-F20 for recording EEG, activity and core body temperature by telemetry and a cannula for intracerebroventricular microinjections. After baseline (Base sleep recording, mice were presented tones (90 dB, 2 kHz that started 5.0 sec prior to and co-terminated with footshock (0.5 mA; 5.0 sec maximum duration. SES mice (n=9 always received shock but could terminate it by moving to the non-occupied chamber in a shuttlebox. Yoked SIS mice (n=9 were treated identically, but could not alter shock duration. Training with SES or SIS was conducted over two days to stabilize responses. Afterwards, the mice received saline, CRF (0.4 µg (0.42 mM or AST (1.0 µg (1.4 mM prior to SES or SIS. Sleep was analyzed over 20 h post-stress recordings. After administration of saline, REM was significantly greater in SES mice than in SIS mice whereas after CRF or AST, REM was similar in both groups. Total 20 h NREM did not vary across condition or group. However, after administration of saline and CRF, NREM episode duration was significantly decreased, and NREM episode number significantly increased, in SIS mice compared to SES animals. SES and SIS mice showed similar stress induced hyperthermia (SIH across all conditions. These data demonstrate that CRF can mediate stress-induced changes in sleep independently of SIH, an index of hypothalamic-pituitary-adrenal axis activation.

  11. Effect of angiotensin II, catecholamines and glucocorticoid on corticotropin releasing factor (CRF-induced ACTH release in pituitary cell cultures.

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    Murakami,Kazuharu

    1984-08-01

    Full Text Available The effects of angiotensin II, catecholamines and glucocorticoid on CRF-induced ACTH release were examined using rat anterior pituitary cells in monolayer culture. Synthetic ovine CRF induced a significant ACTH release in this system. Angiotensin II produced an additive effect on CRF-induced ACTH release. The ACTH releasing activity of CRF was potentiated by epinephrine and norepinephrine. Dopamine itself at 0.03-30 ng/ml did not show any significant effect on ACTH release, but it inhibited CRF-induced ACTH release. Corticosterone at 10(-7 and 10(-6M inhibited CRF-induced ACTH release. These results indicate that angiotensin II, catecholamines and glucocorticoid modulate ACTH release at the pituitary level.

  12. Immunolocalization of corticotropin-releasing factor (CRF) and corticotropin-releasing factor receptor 2 (CRF-R2) in the developing gut of the sea bass (Dicentrarchus labrax L.).

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    Mola, Lucrezia; Gambarelli, Andrea; Pederzoli, Aurora

    2011-05-01

    Our previous data indicated an important role for adrenocorticotropic (ACTH)-like molecules co-operating with macrophages to control the modifications in body homeostasis during the first period of the life of sea bass (up to 30 days post-hatching) before the lymphoid cells have reached complete maturation. The aim of the study was to determine the immunolocalization of corticotropin-releasing factor (CRF), which is a very important mediator of stress-related responses. Our data showed that immunostaining for CRF is localized already at 8 days after hatching in nerve fibers of the gastrointestinal tract wall from the pharynx to the anterior gut, when the larvae are still feeding on yolk. This pattern of immunolocalization appeared similar to that in 24-day-old larvae, but at this stage there were also large cells immunopositive to CRF located in the wall of the midgut and hindgut. Lipopolysaccharide (LPS) treatment, which is a known stimulator of stress hormone responses, did not modify the CRF immunostaining pattern, though it did affect the immunolocalization of the peripheral CRF receptor, i.e. CRF-R2. Immunolocalization of CRF-R2 appeared in nerve fibers of the gut wall in larvae fixed 1h after the end of lipopolysaccharide (LPS) treatment. The present results suggest that CRF plays important autocrine and/or paracrine roles in the early immune responses at the gut level in the larval stages of sea bass (Dicentrarchus labrax L.) as already proposed for ACTH. Moreover, our studies taken together with other research on fish, in comparison with mammals, suggest a phylogenetically old role of CRF in immune-endocrine interactions.

  13. CRF1 receptor-deficiency increases cocaine reward.

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    Contarino, Angelo; Kitchener, Pierre; Vallée, Monique; Papaleo, Francesco; Piazza, Pier-Vincenzo

    2017-01-27

    Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF1 receptor-deficient (CRF1-/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF1-/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF1-/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF1-/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF1-/- mice by exogenous corticosterone does not affect CRF1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF1 receptor in cocaine reward, independently of the closely related HPA axis activity.

  14. Placental urocortins and CRF in late gestation.

    NARCIS (Netherlands)

    Pepels, P.P.L.M.; Spaanderman, M.E.A.; Bulten, J.; Smits, P.; Hermus, A.R.M.M.; Lotgering, F.K.; Sweep, C.G.J.

    2009-01-01

    Placental corticotropin-releasing factor (CRF) are thought to induce labor via activation of CRF receptor type 1 (CRF-R1) leading to several feed forward mechanisms in the placental, fetal and maternal compartments. Recently, receptor type 2 (CRF-R2) selective ligands called urocortin 2 and 3 (Ucn

  15. CRF and urocortin peptides as modulators of energy balance and feeding behavior during stress

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    Andreas eStengel

    2014-03-01

    Full Text Available Early on, corticotropin-releasing factor (CRF, a hallmark brain peptide mediating many components of the stress response, was shown to affect food intake inducing a robust anorexigenic response when injected into the rodent brain. Subsequently, other members of the CRF signaling family have been identified, namely urocortin (Ucn 1, Ucn 2 and Ucn 3 which were also shown to decrease food intake upon central or peripheral injection. However, the kinetics of feeding suppression was different with an early decrease following intracerebroventricular injection of CRF and a delayed action of Ucns contrasting with the early onset after systemic injection. CRF and Ucns bind to two distinct G-protein coupled membrane receptors, the CRF1 and CRF2. New pharmacological tools such as highly selective peptide CRF1 or CRF2 agonists or antagonists along with genetic knock-in or knock-out models have allowed delineating the primary role of CRF2 involved in the anorexic response to exogenous administration of CRF and Ucns. Several stressors trigger behavioral changes including suppression of feeding behavior which are mediated by brain CRF receptor activation. The present review will highlight the state-of-knowledge on the effects and mechanisms of action of CRF/Ucns-CRF1/2 signaling under basal conditions and the role in the alterations of food intake in response to stress.

  16. Therapeutic potential of CRF receptor antagonists: a gut-brain perspective.

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    Heinrichs, S C; Taché, Y

    2001-04-01

    Activation of the corticotropin-releasing factor (CRF) family of neuropeptide receptors in the brain and periphery appears to mediate stress-related changes in a variety of physiological and functional domains. Comparative pharmacology of CRF receptor agonists suggests that CRF, urocortin, sauvagine and urotensin consistently mimic, and conversely peptide CRF receptor antagonists lessen, the functional consequences of stressor exposure. Together with the development of novel non-peptide CRF receptor antagonists, a growing number of CRF receptor selective ligands are available to elucidate the neurobiology and physiological role of CRF systems. The present review considers available preclinical evidence as well as results from one Phase II clinical trial which address the hypothesis that CRF receptor antagonists may represent a new option for pharmacotherapy of stress-related disorders.

  17. Tyrosine Pretreatment Alleviates Suppression of Schedule-Controlled Responding Produced by Corticotropin Releasing Factor (CRF) in Rats

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    1992-01-01

    specific interaction with tyrosine hydroxylase . Thus, (3,13,14). alleviation of CRF with tyrosine may result from an affect of The 200 mg/kg dose of tyrosine...G., Dana, R.; Risch, S. C.; Koob, G. F. Activating aspartame, phenylalanine , and tyrosine. Fund. Appl. Toxicol. 16: and anxiogenic effects of...Onali, P. Corticotropin-releasing factor activates ty- Pharmacol. Biochem. Behav. 32:967-970: 1989. rosine hydroxylase in rat and mouse striatal

  18. Early life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABA(A) mechanism.

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    Gondré-Lewis, Marjorie C; Warnock, Kaitlin T; Wang, Hong; June, Harry L; Bell, Kimberly A; Rabe, Holger; Tiruveedhula, Veera Venkata Naga Phani Babu; Cook, James; Lüddens, Hartmut; Aurelian, Laure; June, Harry L

    2016-01-01

    Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability are largely unknown. In this study, maternal separation (MS) stress, restricted to the pre-weaning period, was used as a model to study mechanisms of protracted effects of childhood stress/traumatic experiences on binge drinking and impulsivity. Using an operant self-administration model of binge drinking and a delay discounting assay to measure impulsive-like behavior, we report that early life stress due to MS facilitated acquisition of binge drinking and impulsivity during adulthood in rats. Previous studies have shown heightened levels of corticotropin releasing factor (CRF) after MS, and here, we add that MS increased expression levels of GABA(A) α2 subunit in central stress circuits. To investigate the precise role of these circuits in regulating impulsivity and binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A) α2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly reduced impulsivity and produced profound reductions on binge-motivated alcohol drinking, without altering responding for sucrose. Furthermore, whole-cell patch-clamp studies showed that low concentrations of 3-PBC directly reversed the effect of relatively high concentrations of ethanol on α2β3γ2 GABA(A) receptors, by a benzodiazepine site-independent mechanism. Together, our data provide strong evidence that maternal separation, i.e. early life stress, is a risk factor for binge drinking, and is linked to impulsivity, another key risk factor for excessive alcohol drinking. We further show that pharmacological manipulation of CRF and GABA receptor signaling is effective to reverse binge drinking and impulsive-like behavior in MS rats. These results provide novel insights into the role of the brain stress systems in the

  19. An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence

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    Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida

    2016-01-01

    Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides.

  20. CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress coping.

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    Ingallinesi, M; Rouibi, K; Le Moine, C; Papaleo, F; Contarino, A

    2012-12-01

    The opiate withdrawal syndrome is a severe stressor that powerfully triggers addictive drug intake. However, no treatment yet exists that effectively relieves opiate withdrawal distress and spares stress-coping abilities. The corticotropin-releasing factor (CRF) system mediates the stress response, but its role in opiate withdrawal distress and bodily strategies aimed to cope with is unknown. CRF-like signaling is transmitted by two receptor pathways, termed CRF(1) and CRF(2). Here, we report that CRF(2) receptor-deficient (CRF(2)(-/-)) mice lack the dysphoria-like and the anhedonia-like states of opiate withdrawal. Moreover, in CRF(2)(-/-) mice opiate withdrawal does not increase the activity of brain dynorphin, CRF and periaqueductal gray circuitry, which are major substrates of opiate withdrawal distress. Nevertheless, CRF(2) receptor-deficiency does not impair brain, neuroendocrine and autonomic stress-coping responses to opiate withdrawal. The present findings point to the CRF(2) receptor pathway as a unique target to relieve opiate withdrawal distress without impairing stress-coping abilities.

  1. Repeated intravenous administrations of teneurin-C terminal associated peptide (TCAP)-1 attenuates reinstatement of cocaine seeking by corticotropin-releasing factor (CRF) in rats.

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    Erb, Suzanne; McPhee, Matthew; Brown, Zenya J; Kupferschmidt, David A; Song, Lifang; Lovejoy, David A

    2014-08-01

    The teneurin c-terminal associated peptides (TCAP) have been implicated in the regulation of the stress response, possibly via a corticotropin-releasing factor (CRF)-related mechanism. We have previously shown that repeated intracerebroventricular (ICV) injections of TCAP-1 attenuate the reinstatement of cocaine seeking by CRF in rats. Here, we determined whether intravenous (IV) administrations of TCAP-1 would likewise attenuate CRF-induced reinstatement, and whether this effect would vary depending on the rat's history of cocaine self administration. Rats were trained to self-administer cocaine for 10 days, during once daily sessions that were either 3h ("short access"; ShA) or 6h ("long access"; LgA). Rats were then given five daily injections of TCAP-1 (0, 300, or 3,000 pmol, IV) in their home cage. Subsequently, they were returned to the self-administration chambers where extinction of cocaine seeking and testing for CRF-induced reinstatement of cocaine seeking was carried out. Repeated IV administrations of TCAP-1 were efficacious in attenuating CRF-induced reinstatement of cocaine seeking, but at different doses in ShA and LgA rats. Taken together, the findings extend previous work showing a consistent effect of repeated ICV TCAP-1 on CRF-induced reinstatement of cocaine seeking, and point to a potential therapeutic benefit of TCAP-1 in attenuating cocaine seeking behaviors.

  2. Central CRF neurons are not created equal: Phenotypic differences in CRF-containing neurons of the rat paraventricular hypothalamus and the bed nucleus of the stria terminalis.

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    Joanna eDabrowska

    2013-08-01

    Full Text Available Corticotrophin-releasing factor (CRF plays a key role in initiating many of the endocrine, autonomic, and behavioral responses to stress. CRF-containing neurons of the paraventricular nucleus of the hypothalamus (PVN are classically involved in regulating endocrine function through activation of the stress axis. However, CRF is also thought to play a critical role in mediating anxiety-like responses to environmental stressors, and dysfunction of the CRF system in extra-hypothalamic brain regions, like the bed nucleus of stria terminalis (BNST, has been linked to the etiology of many psychiatric disorders including anxiety and depression. Thus, although CRF neurons of the PVN and BNST share a common neuropeptide phenotype, they may represent two functionally diverse neuronal populations. Here, we employed dual-immunofluorescence, single-cell RT-PCR, and electrophysiological techniques to further examine this question and report that CRF neurons of the PVN and BNST are fundamentally different such that PVN CRF neurons are glutamatergic, whereas BNST CRF neurons are GABAergic. Moreover, these two neuronal populations can be further distinguished based on their electrophysiological properties, their co-expression of peptide neurotransmitters such as oxytocin and arginine-vasopressin, and their cognate receptors. Our results suggest that CRF neurons in the PVN and the BNST would not only differ in their response to local neurotransmitter release, but also in their action on downstream target structures.

  3. Central CRF, urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice.

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    Martínez, Vicente; Wang, Lixin; Rivier, Jean; Grigoriadis, Dimitri; Taché, Yvette

    2004-04-01

    Recently characterized selective agonists and developed antagonists for the corticotropin releasing factor (CRF) receptors are new tools to investigate stress-related functional changes. The influence of mammalian CRF and related peptides injected intracerebroventricularly (i.c.v.) on gastric and colonic motility, and the CRF receptor subtypes involved and their role in colonic response to stress were studied in conscious mice. The CRF(1)/CRF(2) agonists rat urocortin 1 (rUcn 1) and rat/human CRF (r/h CRF), the preferential CRF(1) agonist ovine CRF (oCRF), and the CRF(2) agonist mouse (m) Ucn 2, injected i.c.v. inhibited gastric emptying and stimulated distal colonic motor function (bead transit and defecation) while oCRF(9-33)OH (devoid of CRF receptor affinity) showed neither effects. mUcn 2 injected peripherally had no colonic effect. The selective CRF(2) antagonist astressin(2)-B (i.c.v.), at a 20 : 1 antagonist: agonist ratio, blocked i.c.v. r/hCRF and rUcn 1 induced inhibition of gastric transit and reduced that of mUcn 2, while the CRF(1) antagonist NBI-35965 had no effect. By contrast, the colonic motor stimulation induced by i.c.v. r/hCRF and rUcn 1 and 1h restraint stress were antagonized only by NBI-35965 while stimulation induced by mUcn 2 was equally blocked by both antagonists. None of the CRF antagonists injected i.c.v. alone influenced gut transit. These data establish in mice that brain CRF(1) receptors mediate the stimulation of colonic transit induced by central CRF, urocortins (1 and 2) and restraint stress, while CRF(2) receptors mediate the inhibitory actions of these peptides on gastric transit.

  4. Differential actions of peripheral corticotropin-releasing factor (CRF), urocortin II, and urocortin III on gastric emptying and colonic transit in mice: role of CRF receptor subtypes 1 and 2.

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    Martínez, Vicente; Wang, Lixin; Rivier, Jean E; Vale, Wylie; Taché, Yvette

    2002-05-01

    Peripheral CRF inhibits gastric emptying and stimulates colonic motor function in rats. We investigated the role of CRF(1) and CRF(2) receptors in i.p. CRF-induced alterations of gut transit in conscious mice using selective CRF(1) and CRF(2) ligands injected i.p. Gastric emptying 2 h after ingestion of a solid chow meal and colonic transit (time to expel a bead inserted into the distal colon) were determined simultaneously. Rat/human (r/h)CRF, which has CRF(1) > CRF(2) binding affinity, decreased distal colonic transit time at lower doses (6-12 microg/kg) than those inhibiting gastric emptying (20-60 microg/kg). Ovine CRF, a preferential CRF(1) receptor agonist (6-60 microg/kg), reduced significantly the colonic transit time without altering gastric emptying, whereas the selective CRF(2) receptor agonists mouse urocortin II (20-60 microg/kg) and urocortin III (120 microg/kg) inhibited significantly gastric emptying without modifying colonic transit. The CRF(1)/CRF(2) receptor antagonist, astressin (30-120 microg/kg), dose dependently prevented r/hCRF (20 microg/kg)-induced inhibition of gastric emptying and reduction of colonic transit time. The selective CRF(1) receptor antagonists, NBI-27914 (C(18)H(20)Cl(4)N(4)C(7)H(8)O(3)S) and CP-154,526 (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine) (5-30 mg/kg), dose dependently blocked r/hCRF action on the colon without influencing the gastric response, whereas the CRF(2) receptor antagonist, antisauvagine-30 (30-100 microg/kg), dose dependently abolished r/hCRF-induced delayed gastric emptying and had no effect on colonic response. These data show that i.p. r/hCRF-induced opposite actions on upper and lower gut transit in conscious mice are mediated by different CRF receptor subtypes: the activation of CRF(1) receptors stimulates colonic propulsive activity, whereas activation of CRF(2) receptors inhibits gastric emptying.

  5. Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2 receptors.

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    Eric P Zorrilla

    Full Text Available The role of brain corticotropin-releasing factor type 2 (CRF2 receptors in behavioral stress responses remains controversial. Conflicting findings suggest pro-stress, anti-stress or no effects of impeding CRF2 signaling. Previous studies have used antisauvagine-30 as a selective CRF2 antagonist. The present study tested the hypotheses that 1 potential anxiolytic-like actions of intracerebroventricular (i.c.v. administration of antisauvagine-30 also are present in mice lacking CRF2 receptors and 2 potential anxiolytic-like effects of antisauvagine-30 are not shared by the more selective CRF2 antagonist astressin2-B. Cannulated, male CRF2 receptor knockout (n = 22 and wildtype littermate mice (n = 21 backcrossed onto a C57BL/6J genetic background were tested in the marble burying, elevated plus-maze, and shock-induced freezing tests following pretreatment (i.c.v. with vehicle, antisauvagine-30 or astressin2-B. Antisauvagine-30 reduced shock-induced freezing equally in wildtype and CRF2 knockout mice. In contrast, neither astressin2-B nor CRF2 genotype influenced shock-induced freezing. Neither CRF antagonist nor CRF2 genotype influenced anxiety-like behavior in the plus-maze or marble burying tests. A literature review showed that the typical antisauvagine-30 concentration infused in previous intracranial studies (∼1 mM was 3 orders greater than its IC50 to block CRF1-mediated cAMP responses and 4 orders greater than its binding constants (Kd , Ki for CRF1 receptors. Thus, increasing, previously used doses of antisauvagine-30 also exert non-CRF2-mediated effects, perhaps via CRF1. The results do not support the hypothesis that brain CRF2 receptors tonically promote anxiogenic-like behavior. Utilization of CRF2 antagonists, such as astressin2-B, at doses that are more subtype-selective, can better clarify the significance of brain CRF2 systems in stress-related behavior.

  6. Expression of type 1 corticotropin-releasing factor receptor in the guinea pig enteric nervous system.

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    Liu, Sumei; Gao, Xiang; Gao, Na; Wang, Xiyu; Fang, Xiucai; Hu, Hong-Zhen; Wang, Guo-Du; Xia, Yun; Wood, Jackie D

    2005-01-17

    Reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiological recording, and intraneuronal injection of the neuronal tracer biocytin were integrated in a study of the functional expression of corticotropin-releasing factor (CRF) receptors in the guinea pig enteric nervous system. RT-PCR revealed expression of CRF1 receptor mRNA, but not CRF2, in both myenteric and submucosal plexuses. Immunoreactivity for the CRF1 receptor was distributed widely in the myenteric plexus of the stomach and small and large intestine and in the submucosal plexus of the small and large intestine. CRF1 receptor immunoreactivity was coexpressed with calbindin, choline acetyltransferase, and substance P in the myenteric plexus. In the submucosal plexus, CRF1 receptor immunoreactivity was found in neurons that expressed calbindin, substance P, choline acetyltransferase, or neuropeptide Y. Application of CRF evoked slowly activating depolarizing responses associated with elevated excitability in both myenteric and submucosal neurons. Histological analysis of biocytin-filled neurons revealed that both uniaxonal neurons with S-type electrophysiological behavior and neurons with AH-type electrophysiological behavior and Dogiel II morphology responded to CRF. The CRF-evoked depolarizing responses were suppressed by the CRF1/CRF2 receptor antagonist astressin and the selective CRF1 receptor antagonist NBI27914 and were unaffected by the selective CRF2 receptor antagonist antisauvagine-30. The findings support the hypothesis that the CRF1 receptor mediates the excitatory actions of CRF on neurons in the enteric nervous system. Actions on enteric neurons might underlie the neural mechanisms by which stress-related release of CRF in the periphery alters intestinal propulsive motor function, mucosal secretion, and barrier functions.

  7. Human urocortin II, a new CRF-related peptide, displays selective CRF(2)-mediated action on gastric transit in rats.

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    Million, Mulugeta; Maillot, Céline; Saunders, Paul; Rivier, Jean; Vale, Wylie; Taché, Yvette

    2002-01-01

    Human urocortin (hUcn) II is a new member of the corticotropin-releasing factor (CRF) family that selectively binds to the CRF(2) receptor. We investigated the CRF receptors involved in mediating the effects of hUcn II and human/rat CRF (h/rCRF) on gut transit. Gastric emptying, 4 h after a solid meal, and distal colonic transit (bead expulsion time) were monitored simultaneously in conscious rats. CRF antagonists were given subcutaneously 30 min before intravenous injection of peptides or partial restraint (for 90 min). hUcn II (3 or 10 microg/kg i.v.) inhibited gastric emptying (by 45% and 55%, respectively) and did not influence distal colonic transit. The CRF(2) peptide antagonist astressin(2)-B blocked hUcn II action. h/rCRF, rat Ucn, and restraint delayed gastric emptying while accelerating distal colonic transit. The gastric response to intravenous h/rCRF and restraint was blocked by the CRF(2) antagonist but not by the CRF(1) antagonist CP-154,526, whereas the colonic response was blocked only by CP-154,526. None of the CRF antagonists influenced postprandial gut transit. These data show that intravenous h/rCRF and restraint stress-induced delayed gastric emptying involve CRF(2) whereas stimulation of distal colonic transit involves CRF(1). The distinct profile of hUcn II, only on gastric transit, is linked to its CRF(2) selectivity.

  8. Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

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    Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L., E-mail: laorden@um.es

    2014-02-15

    Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.

  9. CRF-like diuretic hormone negatively affects both feeding and reproduction in the desert locust, Schistocerca gregaria.

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    Pieter Van Wielendaele

    Full Text Available Diuretic hormones (DH related to the vertebrate Corticotropin Releasing Factor (CRF have been identified in diverse insect species. In the migratory locust, Locusta migratoria, the CRF-like DH (CRF/DH is localized in the same neurosecretory cells as the Ovary Maturating Parsin (OMP, a neurohormone that stimulates oocyte growth, vitellogenesis and hemolymph ecdysteroid levels in adult female locusts. In this study, we investigated whether CRF-like DH can influence feeding and reproduction in the desert locust, Schistocerca gregaria. We identified two highly similar S. gregaria CRF-like DH precursor cDNAs, each of which also encodes an OMP isoform. Alignment with other insect CRF-like DH precursors shows relatively high conservation of the CRF/DH sequence while the precursor region corresponding to OMP is not well conserved. Quantitative real-time RT-PCR revealed that the precursor transcripts mainly occur in the central nervous system and their highest expression level was observed in the brain. Injection of locust CRF/DH caused a significantly reduced food intake, while RNAi knockdown stimulated food intake. Therefore, our data indicate that CRF-like DH induces satiety. Furthermore, injection of CRF/DH in adult females retarded oocyte growth and caused lower ecdysteroid titers in hemolymph and ovaries, while RNAi knockdown resulted in opposite effects. The observed effects of CRF/DH may be part of a wider repertoire of neurohormonal activities, constituting an integrating control system that affects food intake and excretion, as well as anabolic processes like oocyte growth and ecdysteroidogenesis, following a meal. Our discussion about the functional relationship between CRF/DH and OMP led to the hypothesis that OMP may possibly act as a monitoring peptide that can elicit negative feedback effects.

  10. Distribution and chemical coding of corticotropin-releasing factor-immunoreactive neurons in the guinea pig enteric nervous system.

    Science.gov (United States)

    Liu, Sumei; Gao, Na; Hu, Hong-Zhen; Wang, Xiyu; Wang, Guo-Du; Fang, Xiucai; Gao, Xiang; Xia, Yun; Wood, Jackie D

    2006-01-01

    Immunofluorescence was used to study immunoreactivity (IR) for corticotropin-releasing factor (CRF) in the guinea pig enteric nervous system. CRF-IR was expressed in both the myenteric and the submucosal plexuses of all regions of the large and small intestine and the myenteric plexus of the stomach. CRF-IR nerve fibers were present in the myenteric and submucosal plexuses, in the circular muscle coat, and surrounding submucosal arterioles. Most of the CRF-IR fibers persisted in the myenteric and submucosal plexuses after 7 days in organotypic culture. CRF-IR was not coexpressed with tyrosine hydroxylase-IR or calcitonin gene-related peptide-IR fibers. The proportions of CRF-IR cell bodies in the myenteric plexus increased progressively from the stomach (0.6%) to the distal colon (2.8%). Most of the CRF-IR myenteric neurons (95%) had uniaxonal morphology; the remainder had Dogiel type II multipolar morphology. CRF-IR cell bodies in the myenteric plexus of the ileum expressed IR for choline acetyltransferase (56.9%), substance P (55.0%), and nitric oxide synthase (37.9%). CRF-IR never colocalized with IR for calbindin, calretinin, neuropeptide Y, serotonin, or somatostatin in the myenteric plexus. CRF-IR cell bodies were more abundant in the submucosal plexus (29.9-38.0%) than in the myenteric plexus. All CRF-IR neurons in submucosal ganglia expressed vasoactive intestinal peptide-IR and were likely to be secretomotor/vasodilator neurons. CRF-IR neurons did not express IR for the CRF(1) receptor. CRF(1)-IR was expressed in neuronal neighbors of those with CRF-IR. Collective evidence suggests that VIPergic secretomotor neurons might provide synaptic input to neighboring cholinergic neurons.

  11. The corticotropin-releasing factor system in inflammatory bowel disease: prospects for new therapeutic approaches.

    Science.gov (United States)

    Paschos, Konstantinos A; Kolios, George; Chatzaki, Ekaterini

    2009-07-01

    Mounting evidence suggests that stress is implicated in the development of inflammatory bowel disease (IBD), via initial nervous disturbance and subsequent immune dysfunction through brain-gut interactions. The corticotropin-releasing factor (CRF) system, being the principal neuroendocrine coordinator of stress responses, is involved in the inflammatory process within the gastrointestinal tract, via vagal and peripheral pathways, as implied by multiple reports reviewed here. Blocking of CRF receptors could theoretically exert beneficial anti-inflammatory effects in colonic tissues. The recently synthesised small-molecule CRF(1) antagonists or alternatively non-peptide CRF(2) antagonists when available, may become new reliable options in the treatment of IBD.

  12. CRF receptor antagonist astressin-B reverses and prevents alopecia in CRF over-expressing mice.

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    Lixin Wang

    Full Text Available Corticotropin-releasing factor (CRF signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 µg/mouse injected peripherally once a day for 5 days in 4-9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF₂ receptor antagonist, astressin₂-B had moderate effect on pigmentation, but not on hair re-growth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress.

  13. Role of Corticotropin-releasing Factor Signaling in Stress-related Alterations of Colonic Motility and Hyperalgesia

    Science.gov (United States)

    Taché, Yvette; Million, Mulugeta

    2015-01-01

    The corticotropin-releasing factor (CRF) signaling systems encompass CRF and the structurally related peptide urocortin (Ucn) 1, 2, and 3 along with 2 G-protein coupled receptors, CRF1 and CRF2. CRF binds with high and moderate affinity to CRF1 and CRF2 receptors, respectively while Ucn1 is a high-affinity agonist at both receptors, and Ucn2 and Ucn3 are selective CRF2 agonists. The CRF systems are expressed in both the brain and the colon at the gene and protein levels. Experimental studies established that the activation of CRF1 pathway in the brain or the colon recaptures cardinal features of diarrhea predominant irritable bowel syndrome (IBS) (stimulation of colonic motility, activation of mast cells and serotonin, defecation/watery diarrhea, and visceral hyperalgesia). Conversely, selective CRF1 antagonists or CRF1/CRF2 antagonists, abolished or reduced exogenous CRF and stress-induced stimulation of colonic motility, defecation, diarrhea and colonic mast cell activation and visceral hyperalgesia to colorectal distention. By contrast, the CRF2 signaling in the colon dampened the CRF1 mediated stimulation of colonic motor function and visceral hyperalgesia. These data provide a conceptual framework that sustained activation of the CRF1 system at central and/or peripheral sites may be one of the underlying basis of IBS-diarrhea symptoms. While targeting these mechanisms by CRF1 antagonists provided a relevant novel therapeutic venue, so far these promising preclinical data have not translated into therapeutic use of CRF1 antagonists. Whether the existing or newly developed CRF1 antagonists will progress to therapeutic benefits for stress-sensitive diseases including IBS for a subset of patients is still a work in progress. PMID:25611064

  14. CRF mediates the anxiogenic and anti-rewarding, but not the anorectic effects of PACAP.

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    Dore, Riccardo; Iemolo, Attilio; Smith, Karen L; Wang, Xiaofan; Cottone, Pietro; Sabino, Valentina

    2013-10-01

    Anxiety disorders represent the most common mental disturbances in the world, and they are characterized by an abnormal response to stress. Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor PAC1 have been proposed to have a key role in mediating the responses to stress as well as the regulation of food intake and body weight. Corticotropin-releasing factor (CRF), the major stress peptide in the brain, has been hypothesized to be involved in PACAP effects, but the reports are conflicting so far. The present study was aimed at further characterizing the behavioral effects of PACAP in rats and at determining the role of central CRF receptors. We found that intracerebroventricular PACAP treatment induced anxiety-like behavior in the elevated plus maze test and elevated intracranial self-stimulation thresholds; both of these effects were fully blocked by concurrent treatment with the CRF receptor antagonist D-Phe-CRF(12-41). Interestingly, the CRF antagonist had no effect on PACAP-induced increased plasma corticosterone, reduction of food intake, and body weight loss. Finally, we found that PACAP increased CRF levels in the paraventricular nucleus of the hypothalamus and, importantly, in the central nucleus of the amygdala, as measured by solid phase radioimmunoassay and quantitative real-time PCR. Our results strengthen the notion that PACAP is a strong mediator of the behavioral response to stress and prove for the first time that this neuropeptide has anti-rewarding (ie, pro-depressant) effects. In addition, we identified the mechanism by which PACAP exerts its anxiogenic and pro-depressant effects, via the recruitment of the central CRF system and independently from HPA axis activation.

  15. Sequences, expression patterns and regulation of the corticotropin releasing factor system in a teleost

    OpenAIRE

    Chen, Chun-Chun; Fernald, Russell D.

    2008-01-01

    Corticotropin-releasing factor (CRF) is well known for its role in regulating the stress response in vertebrate species by controlling release of glucocorticoids. CRF also influences other physiological processes via two distinct CRF receptors (CRF-Rs) and is co-regulated by a CRF binding protein (CRFBP). Although CRF was first discovered in mammals, it is important for the regulation of the stress response, motor behavior, and appetite in all vertebrates. However, it is unclear how the actio...

  16. Motor Control: CRF Regulates Coordination and Gait.

    Science.gov (United States)

    Manto, Mario

    2017-09-11

    The function of the olivo-cerebellar tract is not restricted to the supervision of plasticity in the cerebellar cortex. There is growing evidence that the climbing fibers also tune motor commands. A novel study unravels a role of corticotropin-releasing factor (CRF) in motor coordination and gait control. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Corticotropin-releasing factor (CRF) in stress and disease: A review of literature and treatment perspectives with special emphasis on psychiatric disorders

    DEFF Research Database (Denmark)

    Krohg, K.; Hageman, I.; Jorgensen, M.B.

    2008-01-01

    The CRF family of neuropeptides and receptors is involved in a variety of stress responses, in the regulation of appetite, metabolic and inflammatory processes as well as intestinal movements. From a primarily psychiatric perspective, the present paper reviews the literature on its anatomy......, physiology and its involvement in psychiatric, neurological and inflammatory diseases. Finally, recent developments in the pharmacological aspects of CRF in these diseases are reviewed Udgivelsesdato: 2008...

  18. Studies on T-cell colony formation in chronic renal failure (CRF) patients.

    Science.gov (United States)

    Wakabayashi, Y; Sugimoto, M; Ishiyama, T; Horie, S; Abe, S; Hirose, S; Okuda, T

    1989-12-01

    In order to study the possibility of abnormal differentiation and proliferation of T-cell precursors in chronic renal failure (CRF), we studied T-cell colony formation in CRF patients. The two-step monolayer method, with phytohemagglutinin-P as the inducer, was used for T-cell colony formation. In our results, colony formation was markedly reduced in CRF patients in comparison with normal controls, with about half of the former showing no colony growth. All cases showed a significant increase in colony numbers with in vitro plasmapheresis (the replacement of autologous plasma in the culture system with normal AB plasma). A significant increase in colony numbers was also seen with the addition of exogenous interleukin-2 (IL-2). The addition of IL-2 in the presence of normal plasma, in particular, induced an increase in colony numbers to near the levels in normal subjects. These results suggest that T-cell precursors exist in near normal numbers in CRF patients and that there are uremic inhibitors in the plasma. A reduced production of IL-2 is also indicated. These factors may be involved in the pathogenesis of immunodeficiency in CRF patients.

  19. Enhanced pelvic responses to stressors in female CRF-overexpressing mice.

    Science.gov (United States)

    Million, M; Wang, L; Stenzel-Poore, M P; Coste, S C; Yuan, P Q; Lamy, C; Rivier, J; Buffington, T; Taché, Y

    2007-04-01

    Acute stress affects gut functions through the activation of corticotropin-releasing factor (CRF) receptors. The impact of acute stress on pelvic viscera in the context of chronic stress is not well characterized. We investigated the colonic, urinary, and locomotor responses monitored as fecal pellet output (FPO), urine voiding, and ambulatory activity, respectively, in female and male CRF-overexpressing (CRF-OE) mice, a chronic stress model, and their wild-type littermates (WTL). Female CRF-OE mice, compared with WTL, had enhanced FPO to 2-min handling (150%) and 60-min novel environment (155%) but displayed a similar response to a 60-min partial restraint stress. Female CRF-OE mice, compared with WTL, also had a significantly increased number of urine spots (7.3 +/- 1.4 vs. 1.3 +/- 0.8 spots/h) and lower locomotor activity (246.8 +/- 47.8 vs. 388.2 +/- 31.9 entries/h) to a novel environment. Male CRF-OE mice and WTL both responded to a novel environment but failed to show differences between them in colonic and locomotor responses. Male WTL, compared with female WTL, had higher FPO (113%). In female CRF-OE mice, the CRF(1)/CRF(2) receptor antagonist astressin B and the selective CRF(2) receptor agonist mouse urocortin 2 (injected peripherally) prevented the enhanced defecation without affecting urine or locomotor responses to novel environment. RT-PCR showed that CRF(1) and CRF(2) receptors are expressed in the mouse colonic tissues. The data show that chronic stress, due to continuous central CRF overdrive, renders female CRF-OE mice to have enhanced pelvic and altered behavioral responses to superimposed mild stressors and that CRF(1)-initiated colonic response is counteracted by selective activation of CRF(2) receptor.

  20. Grin1 receptor deletion within CRF neurons enhances fear memory.

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    Georgette Gafford

    Full Text Available Corticotropin releasing factor (CRF dysregulation is implicated in mood and anxiety disorders such as posttraumatic stress disorder (PTSD. CRF is expressed in areas engaged in fear and anxiety processing including the central amygdala (CeA. Complicating our ability to study the contribution of CRF-containing neurons to fear and anxiety behavior is the wide variety of cell types in which CRF is expressed. To manipulate specific subpopulations of CRF containing neurons, our lab has developed a mouse with a Cre recombinase gene driven by a CRF promoter (CRFp3.0Cre (Martin et al., 2010. In these studies, mice that have the gene that encodes NR1 (Grin1 flanked by loxP sites (floxed were crossed with our previously developed CRFp3.0Cre mouse to selectively disrupt Grin1 within CRF containing neurons (Cre+/fGrin1+. We find that disruption of Grin1 in CRF neurons did not affect baseline levels of anxiety, locomotion, pain sensitivity or exploration of a novel object. However, baseline expression of Grin1 was decreased in Cre+/fGrin1+ mice as measured by RTPCR. Cre+/fGrin1+ mice showed enhanced auditory fear acquisition and retention without showing any significant effect on fear extinction. We measured Gria1, the gene that encodes AMPAR1 and the CREB activator Creb1 in the amygdala of Cre+/fGrin1+ mice after fear conditioning. Both Gria1 and Creb1 were enhanced in the amygdala after training. To determine if the Grin1-expressing CRF neurons within the CeA are responsible for the enhancement of fear memory in adults, we infused a lentivirus with Cre driven by a CRF promoter (LV pCRF-Cre/fGrin1+ into the CeA of floxed Grin1 mice. Cre driven deletion of Grin1 specifically within CRF expressing cells in the CeA also resulted in enhanced fear memory acquisition and retention. Altogether, these findings suggest that selective disruption of Grin1 within CeA CRF neurons strongly enhances fear memory.

  1. Swim stress differentially blocks CRF receptor mediated responses in dorsal raphe nucleus.

    Science.gov (United States)

    Lamy, Christophe M; Beck, Sheryl G

    2010-10-01

    Modulation of the serotonergic (5-HT) neurotransmitter system arising from the dorsal raphe nucleus (DR) is thought to support the behavioral effects of swim stress, i.e., immobility. In vivo pharmacological and anatomical studies suggest that corticotropin-releasing factor (CRF) and γ-aminobutyric acid (GABA) synaptic transmission closely interact to set the response of the DR to swim stress. To investigate the cellular basis of these physiological mechanisms the effects of ovine CRF (oCRF) on GABA(A)-dependent miniature inhibitory postsynaptic currents (mIPSCs) in 5-HT and non-5-HT DR neurons in acute mesencephalic slices obtained from rats either naïve or 24h after a 15 min swim stress session were tested. In this study, the effect of swim stress alone was to decrease the holding current, i.e., hyperpolarize the neuron, and to increase the amplitude and charge of mIPSCs recorded from non-5-HT neurons. Ovine CRF (10 nM) induced an increase in mIPSC frequency in 5-HT neurons recorded from naïve rats, an effect that was suppressed by swim stress. The inward current elicited by oCRF in both 5-HT and non-5-HT neurons was also blocked by swim stress. Ovine CRF increased mIPSCs amplitude and charge in both 5-HT and non-5-HT neurons, but this effect was not modified by swim stress. In concert with our previous findings that swim stress decreased input resistance, action potential threshold and action potential duration and increased glutamatergic synaptic activity the overall primary effect of swim stress is to increase the excitability of 5-HT neurons. These data provide a mechanism at the cellular level for the immobility induced by swim stress and identifies critical components of the raphe circuitry responsible for the altered output of 5-HT neurons induced by swim stress.

  2. Corticotropin-releasing factor and the brain-gut motor response to stress.

    Science.gov (United States)

    Taché, Y; Martinez, V; Million, M; Rivier, J

    1999-03-01

    The characterization of corticotropin-releasing factor (CRF) and CRF receptors, and the development of specific CRF receptor antagonists selective for the receptor subtypes have paved the way to the understanding of the biochemical coding of stress-related alterations of gut motor function. Reports have consistently established that central administration of CRF acts in the brain to inhibit gastric emptying while stimulating colonic motor function through modulation of the vagal and sacral parasympathetic outflow in rodents. Endogenous CRF in the brain plays a role in mediating various forms of stressor-induced gastric stasis, including postoperative gastric ileus, and activates colonic transit and fecal excretion elicited by psychologically aversive or fearful stimuli. It is known that brain CRF is involved in the cross-talk between the immune and gastrointestinal systems because systemic or central administration of interleukin-1-beta delays gastric emptying while stimulating colonic motor activity through activation of CRF release in the brain. The paraventricular nucleus of the hypothalamus and the dorsal vagal complex are important sites of action for CRF to inhibit gastric motor function, while the paraventricular nucleus of the hypothalamus and the locus coeruleus complex are sites of action for CRF to stimulate colonic motor function. The inhibition of gastric emptying by CRF may be mediated by the interaction with the CRF2 receptors, while the anxiogenic and colonic motor responses may involve CRF1 receptors. Hypersecretion of CRF in the brain may contribute to the pathophysiology of stress-related exacerbation of irritable bowel syndrome.

  3. Presynaptic CRF1 Receptors Mediate the Ethanol Enhancement of GABAergic Transmission in the Mouse Central Amygdala

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    Zhiguo Nie

    2009-01-01

    Full Text Available Corticotropin-releasing factor (CRF is a 41-amino-acid neuropeptide involved in stress responses initiated from several brain areas, including the amygdala formation. Research shows a strong relationship between stress, brain CRF, and excessive alcohol consumption. Behavioral studies suggest that the central amygdala (CeA is significantly involved in alcohol reward and dependence. We recently reported that the ethanol augmentation of GABAergic synaptic transmission in rat CeA involves CRF1 receptors, because both CRF and ethanol significantly enhanced the amplitude of evoked GABAergic inhibitory postsynaptic currents (IPSCs in CeA neurons from wild-type (WT and CRF2 knockout (KO mice, but not in neurons of CRF1 KO mice. The present study extends these findings using selective CRF receptor ligands, gene KO models, and miniature IPSC (mIPSC analysis to assess further a presynaptic role for the CRF receptors in mediating ethanol effects in the CeA. In whole-cell patch recordings of pharmacologically isolated GABAAergic IPSCs from slices of mouse CeA, both CRF and ethanol augmented evoked IPSCs in a concentration-dependent manner, with low EC50s. A CRF1 (but not CRF2 KO construct and the CRF1-selective nonpeptide antagonist NIH-3 (LWH-63 blocked the augmenting effect of both CRF and ethanol on evoked IPSCs. Furthermore, the new selective CRF1 agonist stressin1, but not the CRF2 agonist urocortin 3, also increased evoked IPSC amplitudes. Both CRF and ethanol decreased paired-pulse facilitation (PPF of evoked IPSCs and significantly enhanced the frequency, but not the amplitude, of spontaneous miniature GABAergic mIPSCs in CeA neurons of WT mice, suggesting a presynaptic site of action. The PPF effect of ethanol was abolished in CeA neurons of CRF1 KO mice. The CRF1 antagonist NIH-3 blocked the CRF- and ethanol-induced enhancement of mIPSC frequency in CeA neurons. These data indicate that presynaptic CRF1 receptors play a critical role in permitting

  4. The CRF family of neuropeptides and their receptors - mediators of the central stress response.

    Science.gov (United States)

    Dedic, Nina; Chen, Alon; Deussing, Jan M

    2017-03-01

    Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and consequently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2. Here we review the past and current state of the CRH/CRHR field, ranging from pharmacological studies to genetic mouse models and virus-mediated manipulations. Although it is well established that CRF/CRFR1 signaling mediates aversive responses, including anxiety and depression-like behaviors, a number of recent studies have challenged this viewpoint by revealing anxiolytic and appetitive properties of specific CRF/CRFR1 circuits. In contrast, the UCN/CRFR2 system is less well understood and may possibly also exert divergent functions on physiology and behavior depending on the brain region,underlying circuit, and/or experienced stress conditions. A plethora of available genetic tools, including conventional and conditional mouse mutants targeting CRF system components, has greatly advanced our understanding about the endogenous mechanisms underlying HPA system regulation and CRH/UCN-related neuronal circuits involved in stress-related behaviors. Yet, the deailed pathways and molecular mechanism by which the CRH/UCN-system translates negative or positive stimuli into the final, integrated biological response are not completely understood. The utilization of future complementary methodologies, such as cell-type specific Cre-driver lines, viral and optogenetic tools will help to further dissect the function of genetically defined CRH/UCN neurocircuits in the context of adaptive and maladaptive stress responses. Copyright

  5. Chronic CRF1 receptor blockade reduces heroin intake escalation and dependence-induced hyperalgesia.

    Science.gov (United States)

    Park, Paula E; Schlosburg, Joel E; Vendruscolo, Leandro F; Schulteis, Gery; Edwards, Scott; Koob, George F

    2015-03-01

    Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain-related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro-adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin-releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia-like behavior during heroin withdrawal utilizing models of both acute and chronic dependence. We found that passive or self-administered heroin produced a significant mechanical hypersensitivity. During acute opioid dependence, systemic administration of the CRF1 receptor antagonist MPZP (20 mg/kg) alleviated withdrawal-induced mechanical hypersensitivity. In contrast, several functional adrenergic system antagonists (clonidine, prazosin, propranolol) failed to alter mechanical hypersensitivity in this state. We then determined the effects of chronic MPZP or clonidine treatment on extended access heroin self-administration and found that MPZP, but not clonidine, attenuated escalation of heroin intake, whereas both drugs alleviated chronic dependence-associated hyperalgesia. These findings suggest that an early potentiation of CRF signaling occurs following opioid exposure that begins to drive both opioid-induced hyperalgesia and eventually intake escalation.

  6. Dominance of HIV-1 subtype CRF01_AE in sexually acquired cases leads to a new epidemic in Yunnan province of China.

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    Yong Zhang

    2006-11-01

    Full Text Available BACKGROUND: Dating back to the first epidemic among injection drug users in 1989, the Yunnan province has had the highest number of human immunodeficiency virus type 1 (HIV-1 infections in China. However, the molecular epidemiology of HIV-1 in Yunnan has not been fully characterized. METHODS AND FINDINGS: Using immunoassays, we identified 103,015 accumulated cases of HIV-1 infections in Yunnan between 1989 and 2004. We studied 321 patients representing Yunnan's 16 prefectures from four risk groups, 11 ethnic populations, and ten occupations. We identified three major circulating subtypes: C/CRF07_BC/CRF08_BC (53%, CRF01_AE (40.5%, and B (6.5% by analyzing the sequence of p17, which is part of the gag gene. For patients with known risk factors, 90.9% of injection drug users had C/CRF07_BC/CRF08_BC viruses, whereas 85.4% of CRF01_AE infections were acquired through sexual transmission. No distinct segregation of CRF01_AE viruses was found among the Dai ethnic group. Geographically, C/CRF07_BC/CRF08_BC was found throughout the province, while CRF01_AE was largely confined to the prefectures bordering Myanmar. Furthermore, C/CRF07_BC/CRF08_BC viruses were found to consist of a group of viruses, including C, CRF08_BC, CRF07_BC, and new BC recombinants, based on the characterization of their reverse transcriptase genes. CONCLUSIONS: This is the first report of a province-wide HIV-1 molecular epidemiological study in Yunnan. While C/CRF07_BC/CRF08_BC and CRF01_AE are codominant, the discovery of many sexually transmitted CRF01_AE cases is new and suggests that this subtype may lead to a new epidemic in the general Chinese population. We discuss implications of our results for understanding the evolution of the HIV-1 pandemic and for vaccine development.

  7. The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress

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    Stathopoulos Efstathios N

    2010-09-01

    Full Text Available Abstract Introduction Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo. Methods For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis. Results Array analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this

  8. Corticotropin-releasing factor increases GABA synaptic activity and induces inward current in 5-hydroxytryptamine dorsal raphe neurons.

    Science.gov (United States)

    Kirby, Lynn G; Freeman-Daniels, Emily; Lemos, Julia C; Nunan, John D; Lamy, Christophe; Akanwa, Adaure; Beck, Sheryl G

    2008-11-26

    Stress-related psychiatric disorders such as anxiety and depression involve dysfunction of the serotonin [5-hydroxytryptamine (5-HT)] system. Previous studies have found that the stress neurohormone corticotropin-releasing factor (CRF) inhibits 5-HT neurons in the dorsal raphe nucleus (DRN) in vivo. The goals of the present study were to characterize the CRF receptor subtypes (CRF-R1 and -R2) and cellular mechanisms underlying CRF-5-HT interactions. Visualized whole-cell patch-clamp recording techniques in brain slices were used to measure spontaneous or evoked GABA synaptic activity in DRN neurons of rats and CRF effects on these measures. CRF-R1 and -R2-selective agonists were bath applied alone or in combination with receptor-selective antagonists. CRF increased presynaptic GABA release selectively onto 5-HT neurons, an effect mediated by the CRF-R1 receptor. CRF increased postsynaptic GABA receptor sensitivity selectively in 5-HT neurons, an effect to which both receptor subtypes contributed. CRF also had direct effects on DRN neurons, eliciting an inward current in 5-HT neurons mediated by the CRF-R2 receptor and in non-5-HT neurons mediated by the CRF-R1 receptor. These results indicate that CRF has direct membrane effects on 5-HT DRN neurons as well as indirect effects on GABAergic synaptic transmission that are mediated by distinct receptor subtypes. The inhibition of 5-HT DRN neurons by CRF in vivo may therefore be primarily an indirect effect via stimulation of inhibitory GABA synaptic transmission. These results regarding the cellular mechanisms underlying the complex interaction between CRF, 5-HT, and GABA systems could contribute to the development of novel treatments for stress-related psychiatric disorders.

  9. Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala

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    Ruppert Katherine A

    2007-06-01

    Full Text Available Abstract Corticotropin-releasing factor receptor CRF1 has been implicated in the neurobiological mechanisms of anxiety and depression. The amygdala plays an important role in affective states and disorders such as anxiety and depression. The amygdala is also emerging as a neural substrate of pain affect. However, the involvement of the amygdala in the interaction of pain and anxiety remains to be determined. This study tested the hypothesis that CRF1 receptors in the amygdala are critically involved in pain-related anxiety. Anxiety-like behavior was determined in adult male rats using the elevated plus maze (EPM test. The open-arm preference (ratio of open arm entries to the total number of entries was measured. Nocifensive behavior was assessed by measuring hindlimb withdrawal thresholds for noxious mechanical stimulation of the knee. Measurements were made in normal rats and in rats with arthritis induced in one knee by intraarticular injections of kaolin/carrageenan. A selective CRF1 receptor antagonist (NBI27914 or vehicle was administered systemically (i.p. or into the central nucleus of the amygdala (CeA, by microdialysis. The arthritis group showed a decreased preference for the open arms in the EPM and decreased hindlimb withdrawal thresholds. Systemic or intraamygdalar (into the CeA administration of NBI27914, but not vehicle, inhibited anxiety-like behavior and nocifensive pain responses, nearly reversing the arthritis pain-related changes. This study shows for the first time that CRF1 receptors in the amygdala contribute critically to pain-related anxiety-like behavior and nocifensive responses in a model of arthritic pain. The results are a direct demonstration that the clinically well-documented relationship between pain and anxiety involves the amygdala.

  10. Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function.

    Science.gov (United States)

    Taché, Y; Perdue, M H

    2004-04-01

    Central corticotrophin releasing-factor (CRF) signalling pathways are involved in the endocrine, behavioural and visceral responses to stress. Recent studies indicate that peripheral CRF-related mechanisms also contribute to stress-induced changes in gut motility and intestinal mucosal function. Peripheral injection of CRF or urocortin inhibits gastric emptying and motility through interaction with CRF2 receptors and stimulates colonic transit, motility, Fos expression in myenteric neurones and defecation through activation of CRF1 receptors. With regard to intestinal epithelial cell function, intraperitoneal CRF increases ion secretion and mucosal permeability to macromolecules. The motility and mucosal changes induced by peripheral CRF mimic those induced by acute stress. In addition, CRF receptor antagonists given peripherally prevent acute restraint and water avoidance stress-induced delayed gastric emptying, stimulation of colonic motor function and mucosal permeability. Similarly, early trauma enhanced intestinal mucosal dysfunction to an acute stressor in adult rats and the response is prevented by peripheral injection of CRF antagonist. Chronic psychological stress results in reduced host defence and initiates intestinal inflammation through mast cell-dependent mechanisms. These findings provide convergent evidence that activation of peripheral CRF receptors and mast cells are important mechanisms involved in stress-related alterations of gut physiology.

  11. CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

  12. Appetite-suppressing effects and interactions of centrally administered corticotropin-releasing factor, urotensin I and serotonin in rainbow trout (Oncorhynchus mykiss

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    Van A. Ortega

    2013-10-01

    Full Text Available Corticotropin-releasing factor (CRF, urotensin I (UI and serotonin (5-HT are generally recognized as key regulators of the anorexigenic stress response in vertebrates, yet the proximal effects and potential interactions of these central messengers on food intake in salmonids are not known. Moreover, no study to date in fishes has compared the appetite-suppressing effects of CRF and UI using species-specific peptides. Therefore, the objectives of this study were to 1 assess the individual effects of synthesized rainbow trout CRF (rtCRF, rtUI as well as 5-HT on food intake in rainbow trout, and 2 determine whether the CRF and serotonergic systems interact in the regulation of food intake in this species. Intracerebroventricular (icv injections of rtCRF and rtUI both suppressed food intake in a dose-related manner but rtUI (ED50 = 17.4 ng/g body weight [BW] was significantly more potent than rtCRF (ED50 = 105.9 ng/g BW. Co-injection of either rtCRF or rtUI with the CRF receptor antagonist a-hCRF(9-41 blocked the reduction in food intake induced by CRF-related peptides. Icv injections of 5-HT also inhibited feeding in a dose-related manner (ED50 = 14.7 ng/g BW and these effects were blocked by the serotonergic receptor antagonist methysergide. While the anorexigenic effects of 5-HT were reversed by a-hCRF(9-41 co-injection, the appetite-suppressing effects of either rtCRF or rtUI were not affected by methysergide co-injection. These results identify CRF, UI and 5-HT as anorexigenic agents in rainbow trout, and suggest that 5-HT-induced anorexia may be at least partially mediated by CRF- and/or UI-secreting neurons.

  13. Urocortin 1 reduces food intake and ghrelin secretion via CRF(2) receptors.

    Science.gov (United States)

    Yakabi, Koji; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Onouchi, Tsuneko; Ochiai, Mitsuko; Takabayashi, Hidehiko; Takayama, Kiyoshige; Harada, Yumi; Sadakane, Chiharu; Hattori, Tomohisa

    2011-07-01

    Although it is known that urocortin 1 (UCN) acts on both corticotropin-releasing factor receptors (CRF(1) and CRF(2)), the mechanisms underlying UCN-induced anorexia remain unclear. In contrast, ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, stimulates food intake. In the present study, we examined the effects of CRF(1) and CRF(2) receptor antagonists (CRF(1)a and CRF(2)a) on ghrelin secretion and synthesis, c-fos mRNA expression in the caudal brain stem, and food intake following intracerebroventricular administration of UCN. Eight-week-old, male Sprague-Dawley rats were used after 24-h food deprivation. Acylated and des-acylated ghrelin levels were measured by enzyme-linked immunosorbent assay. The mRNA expressions of preproghrelin and c-fos were measured by real-time RT-PCR. The present study provided the following important insights into the mechanisms underlying the anorectic effects of UCN: 1) UCN increased acylated and des-acylated ghrelin levels in the gastric body and decreased their levels in the plasma; 2) UCN decreased preproghrelin mRNA levels in the gastric body; 3) UCN-induced reduction of plasma ghrelin and food intake were restored by CRF(2)a but not CRF(1)a; 4) UCN-induced increase of c-fos mRNA levels in the caudal brain stem containing the nucleus of the solitary tract (NTS) was inhibited by CRF(2)a; and 5) UCN-induced reduction of food intake was restored by exogenous ghrelin and rikkunshito, an endogenous ghrelin secretion regulator. Thus, UCN increases neuronal activation in the caudal brain stem containing NTS via CRF(2) receptors, which may be related to UCN-induced inhibition of both ghrelin secretion and food intake.

  14. Increased CRF signalling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal.

    Science.gov (United States)

    Zhao-Shea, Rubing; DeGroot, Steven R; Liu, Liwang; Vallaster, Markus; Pang, Xueyan; Su, Qin; Gao, Guangping; Rando, Oliver J; Martin, Gilles E; George, Olivier; Gardner, Paul D; Tapper, Andrew R

    2015-04-21

    Increased anxiety is a prominent withdrawal symptom in abstinent smokers, yet the neuroanatomical and molecular bases underlying it are unclear. Here we show that withdrawal-induced anxiety increases activity of neurons in the interpeduncular intermediate (IPI), a subregion of the interpeduncular nucleus (IPN). IPI activation during nicotine withdrawal was mediated by increased corticotropin releasing factor (CRF) receptor-1 expression and signalling, which modulated glutamatergic input from the medial habenula (MHb). Pharmacological blockade of IPN CRF1 receptors or optogenetic silencing of MHb input reduced IPI activation and alleviated withdrawal-induced anxiety; whereas IPN CRF infusion in mice increased anxiety. We identified a mesointerpeduncular circuit, consisting of ventral tegmental area (VTA) dopaminergic neurons projecting to the IPN, as a potential source of CRF. Knockdown of CRF synthesis in the VTA prevented IPI activation and anxiety during nicotine withdrawal. These data indicate that increased CRF receptor signalling within a VTA-IPN-MHb circuit triggers anxiety during nicotine withdrawal.

  15. Therapeutic Utility of Non-Peptidic CRF1 Receptor Antagonists in Anxiety, Depression, and Stress-Related Disorders: Evidence from Animal Models

    Science.gov (United States)

    Kehne, John H.; Cain, Christopher K.

    2012-01-01

    Adaptive responding to threatening stressors is of fundamental importance for survival. Dysfunctional hyperactivation of corticotropin releasing factor type-1 (CRF1) receptors in stress response system pathways is linked to stress-related psychopathology and CRF1 receptor antagonists (CRAs) have been proposed as novel therapeutic agents. CRA effects in diverse animal models of stress that detect anxiolytics and/or antidepressants are reviewed, with the goal of evaluating their potential therapeutic utility in depression, anxiety, and other stress-related disorders. CRAs have a distinct phenotype in animals that has similarities to, and differences from, those of classic antidepressants and anxiolytics. CRAs are generally behaviorally silent, indicating that CRF1 receptors are normally in a state of low basal activation. CRAs reduce stressor-induced HPA axis activation by blocking pituitary and possibly brain CRF1 receptors which may ameliorate chronic stress-induced pathology. In animal models sensitive to anxiolytics and/or antidepressants, CRAs are generally more active in those with high stress levels, conditions which may maximize CRF1 receptor hyperactivation. Clinically, CRAs have demonstrated good tolerability and safety, but have thus far lacked compelling efficacy in major depressive disorder, generalized anxiety disorder, or irritable bowel syndrome. CRAs may be best suited for disorders in which stressors clearly contribute to the underlying pathology (e.g. posttraumatic stress disorder, early life trauma, withdrawal/abstinence from addictive substances), though much work is needed to explore these possibilities. An evolving literature exploring the genetic, developmental and environmental factors linking CRF1 receptor dysfunction to stress-related psychopathology is discussed in the context of improving the translational value of current animal models. PMID:20826181

  16. From Hans Selye's discovery of biological stress to the identification of corticotropin-releasing factor signaling pathways: implication in stress-related functional bowel diseases.

    Science.gov (United States)

    Taché, Yvette; Brunnhuber, Stefan

    2008-12-01

    Selye pioneered the concept of biological stress in 1936, culminating in the identification of the corticotropin-releasing factor (CRF) signaling pathways by Vale's group in the last two decades. The characterization of the 41 amino-acid CRF and other peptide members of the mammalian CRF family, urocortin 1, urocortin 2, and urocortin 3, and the cloning of CRF(1) and CRF(2) receptors, which display distinct affinity for CRF ligands, combined with the development of selective CRF receptor antagonists enable us to unravel the importance of CRF(1) receptor in the stress-related endocrine (activation of pituitary-adrenal axis), behavioral (anxiety/depression, altered feeding), autonomic (activation of sympathetic nervous system), and immune responses. The activation of CRF(1) receptors is also one of the key mechanisms through which various stressors impact the gut to stimulate colonic propulsive motor function and to induce hypersensitivity to colorectal distension as shown by the efficacy of the CRF(1) receptor antagonists in blunting these stress-related components. The importance of CRF(1) signaling pathway in the visceral response to stress in experimental animals provided new therapeutic approaches for treatment of functional bowel disorder such as irritable bowel syndrome, a multifactor functional disorder characterized by altered bowel habits and visceral pain, for which stress has been implicated in the pathophysiology and is associated with anxiety-depression in a subset of patients.

  17. Conditional Random Field (CRF-Boosting: Constructing a Robust Online Hybrid Boosting Multiple Object Tracker Facilitated by CRF Learning

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    Ehwa Yang

    2017-03-01

    Full Text Available Due to the reasonably acceptable performance of state-of-the-art object detectors, tracking-by-detection is a standard strategy for visual multi-object tracking (MOT. In particular, online MOT is more demanding due to its diverse applications in time-critical situations. A main issue of realizing online MOT is how to associate noisy object detection results on a new frame with previously being tracked objects. In this work, we propose a multi-object tracker method called CRF-boosting which utilizes a hybrid data association method based on online hybrid boosting facilitated by a conditional random field (CRF for establishing online MOT. For data association, learned CRF is used to generate reliable low-level tracklets and then these are used as the input of the hybrid boosting. To do so, while existing data association methods based on boosting algorithms have the necessity of training data having ground truth information to improve robustness, CRF-boosting ensures sufficient robustness without such information due to the synergetic cascaded learning procedure. Further, a hierarchical feature association framework is adopted to further improve MOT accuracy. From experimental results on public datasets, we could conclude that the benefit of proposed hybrid approach compared to the other competitive MOT systems is noticeable.

  18. Reward devaluation and heroin escalation is associated with differential expression of CRF signaling genes.

    Science.gov (United States)

    McFalls, Ashley J; Imperio, Caesar G; Bixler, Georgina; Freeman, Willard M; Grigson, Patricia Sue; Vrana, Kent E

    2016-05-01

    One of the most damaging aspects of drug addiction is the degree to which natural rewards (family, friends, employment) are devalued in favor of seeking, obtaining and taking drugs. We have utilized an animal model of reward devaluation and heroin self-administration to explore the role of the coricotropin releasing factor (CRF) pathway. Given access to a saccharin cue followed by the opportunity to self-administer heroin, animals will parse into distinct phenotypes that suppress their saccharin intake (in favor of escalating heroin self-administration) or vice versa. We find that large saccharin suppressors (large heroin takers) demonstrate increased mRNA expression for elements of the CRF signaling pathway (CRF, CRF receptors and CRF binding protein) within the hippocampus, medial prefrontal cortex and the ventral tegmental area. Moreover, there were no gene expression changes of these components in the nucleus accumbens. Use of bisulfite conversion sequencing suggests that changes in CRF binding protein and CRF receptor gene expression may be mediated by differential promoter methylation.

  19. Study on the relationship between CRF/CRF1 receptor and SP in enteric nervous system of guinea-pig%豚鼠肠道神经系统中CRF及其受体与SP相互关系的研究

    Institute of Scientific and Technical Information of China (English)

    高翔; 胡品津; Jackie D.Wood

    2004-01-01

    目的 研究豚鼠肠道神经系统表达促皮质激素释放激素(CRF)受体CRF1的神经元与表达P物质(SP)神经元的神经解剖关系及CRF对粘膜下神经丛SP分泌的影响.方法采用免疫荧光组织化学染色及双染色研究表达CRF1受体的神经元与分泌SP神经元的神经解剖关系;通过体外神经组织培养及放射免疫分析法研究CRF对体外培养神经组织SP分泌的影响.结果豚鼠粘膜下层神经丛中所有表达SP的神经元上均有CRF1受体的表达.CRF可促进体外培养神经组织分泌SP.结论在豚鼠肠道神经系统中,CRF及其受体CRF1与表达SP神经元在神经解剖和生理功能方面均存在密切的关系,提示CRF可能通过与分泌SP神经元上的CRF1受体结合促进SP的分泌.

  20. Bidirectional LSTM-CRF Models for Sequence Tagging

    OpenAIRE

    Huang, Zhiheng; Xu, Wei; Yu, Kai

    2015-01-01

    In this paper, we propose a variety of Long Short-Term Memory (LSTM) based models for sequence tagging. These models include LSTM networks, bidirectional LSTM (BI-LSTM) networks, LSTM with a Conditional Random Field (CRF) layer (LSTM-CRF) and bidirectional LSTM with a CRF layer (BI-LSTM-CRF). Our work is the first to apply a bidirectional LSTM CRF (denoted as BI-LSTM-CRF) model to NLP benchmark sequence tagging data sets. We show that the BI-LSTM-CRF model can efficiently use both past and fu...

  1. Involvement of Nurr-1/Nur77 in corticotropin-releasing factor/urocortin1-induced tyrosinase-related protein 1 gene transcription in human melanoma HMV-II cells.

    Science.gov (United States)

    Watanuki, Yutaka; Takayasu, Shinobu; Kageyama, Kazunori; Iwasaki, Yasumasa; Sakihara, Satoru; Terui, Ken; Nigawara, Takeshi; Suda, Toshihiro

    2013-05-06

    Recent molecular and biochemical analyses have revealed the presence of corticotropin-releasing factor (CRF) and urocortin (Ucn), together with their corresponding receptors in mammalian skin. The melanosomal enzyme tyrosinase-related protein 1 (TRP1) is involved in modulation of pigment production in response to stressors. Although CRF and Ucn are thought to have potent effects on the skin system, their possible roles and regulation have yet to be fully determined. This study aimed to explore the effects of CRF and Ucn on TRP1 gene expression using human melanoma HMV-II cells. The mRNA of CRF, Ucn1, Ucn2, and CRF receptor type 1 (CRF1 receptor) was detected in HMV-II cells. CRF and Ucn1 stimulated TRP1 gene transcription via the CRF1 receptor, and increased both Nurr-1 and Nur77 mRNA expression levels. Both CRF- and Ucn1-induced Nurr-1/Nur77 acted via a NGFI-B response element on the TRP1 promoter. The combination of Nurr-1/Nur77 and microphthalmia-associated transcription factor, a melanocyte-specific transcription factor gene induced by α-melanocyte-stimulating hormone, had additive effects on activation of TRP1 gene transcription. The findings suggest that in human melanoma HMV-II cells both CRF and Ucn1 regulate TRP1 gene expression via Nurr-1/Nur77 production, independent of pro-opiomelanocortin or α-melanocyte-stimulating hormone stimulation.

  2. Stress-related modulation of inflammation in experimental models of bowel disease and post-infectious irritable bowel syndrome: role of corticotropin releasing factor receptors

    OpenAIRE

    2009-01-01

    The interaction between gut inflammatory processes and stress is gaining increasing recognition. Corticotropin releasing factor (CRF)-receptor activation in the brain is well established as a key signaling pathway initiating the various components of the stress response including in the viscera. In addition, a local CRF signaling system has been recently established in the gut. This review summarize the present knowledge on mechanisms through which both brain and gut CRF receptors modulate in...

  3. Genetic Algorithm (GA) in Feature Selection for CRF Based Manipuri Multiword Expression (MWE) Identification

    CERN Document Server

    Nongmeikapam, Kishorjit; 10.5121/ijcsit.2011.350

    2011-01-01

    This paper deals with the identification of Multiword Expressions (MWEs) in Manipuri, a highly agglutinative Indian Language. Manipuri is listed in the Eight Schedule of Indian Constitution. MWE plays an important role in the applications of Natural Language Processing(NLP) like Machine Translation, Part of Speech tagging, Information Retrieval, Question Answering etc. Feature selection is an important factor in the recognition of Manipuri MWEs using Conditional Random Field (CRF). The disadvantage of manual selection and choosing of the appropriate features for running CRF motivates us to think of Genetic Algorithm (GA). Using GA we are able to find the optimal features to run the CRF. We have tried with fifty generations in feature selection along with three fold cross validation as fitness function. This model demonstrated the Recall (R) of 64.08%, Precision (P) of 86.84% and F-measure (F) of 73.74%, showing an improvement over the CRF based Manipuri MWE identification without GA application.

  4. Constitutive Increases in Amygdalar Corticotropin-Releasing Factor and Fatty Acid Amide Hydrolase Drive an Anxious Phenotype.

    Science.gov (United States)

    Natividad, Luis A; Buczynski, Matthew W; Herman, Melissa A; Kirson, Dean; Oleata, Christopher S; Irimia, Cristina; Polis, Ilham; Ciccocioppo, Roberto; Roberto, Marisa; Parsons, Loren H

    2017-10-01

    Corticotropin-releasing factor (CRF) mediates anxiogenic responses by activating CRF type 1 (CRF1) receptors in limbic brain regions. Anxiety is further modulated by the endogenous cannabinoid (eCB) system that attenuates the synaptic effects of stress. In the amygdala, acute stress activates the enzymatic clearance of the eCB N-arachidonoylethanolamine via fatty acid amide hydrolase (FAAH), although it is unclear whether chronic dysregulation of CRF systems induces maladaptive changes in amygdalar eCB signaling. Here, we used genetically selected Marchigian Sardinian P (msP) rats carrying an innate overexpression of CRF1 receptors to study the role of constitutive upregulation in CRF systems on amygdalar eCB function and persistent anxiety-like effects. We applied behavioral, pharmacological, and biochemical methods to broadly characterize anxiety-like behaviors and amygdalar eCB clearance enzymes in msP versus nonselected Wistar rats. Subsequent studies examined the influence of dysregulated CRF and FAAH systems in altering excitatory transmission in the central amygdala (CeA). msPs display an anxious phenotype accompanied by elevations in amygdalar FAAH activity and reduced dialysate N-arachidonoylethanolamine levels in the CeA. Elevations in CRF-CRF1 signaling dysregulate FAAH activity, and this genotypic difference is normalized with pharmacological blockade of CRF1 receptors. msPs also exhibit elevated baseline glutamatergic transmission in the CeA, and dysregulated CRF-FAAH facilitates stress-induced increases in glutamatergic activity. Treatment with an FAAH inhibitor relieves sensitized glutamatergic responses in msPs and attenuates the anxiety-like phenotype. Pathological anxiety and stress hypersensitivity are driven by constitutive increases in CRF1 signaling that dysregulate N-arachidonoylethanolamine signaling mechanisms and reduce neuronal inhibitory control of CeA glutamatergic synapses. Copyright © 2017 Society of Biological Psychiatry. Published

  5. 肠道神经肽类激素促皮质激素释放激素与P物质相互关系的研究%The relationship between CRF/CRF1 receptor and SP in enteric nervous system of guinea-pig

    Institute of Scientific and Technical Information of China (English)

    高翔; 胡品津

    2005-01-01

    目的:研究肠道神经系统中神经肽类激素促皮质激素释放激素(CRF)和P物质(SP)相关神经元的神经解剖关系及CRF对黏膜下神经丛SP分泌的影响.方法:采用免疫荧光组织化学染色及双染色研究CRF神经元与SP神经元的神经解剖关系;体外肠神经组织培养及放免法研究CRF对SP分泌的影响.结果:豚鼠黏膜下层神经丛中所有表达SP的神经元上均有CRF1受体的表达.CRF可促进体外培养神经组织分泌SP.结论:在肠道神经系统CRF及其受体与SP在神经解剖和生理功能方面均存在密切的关系,CRF通过与分泌SP神经元上的CRF1受体结合促进SP的分泌.

  6. Urocortins and CRF receptor type 2 variants in the male rat colon: gene expression and regulation by endotoxin and anti-inflammatory effect.

    Science.gov (United States)

    Yuan, Pu-Qing; Wu, S Vincent; Pothoulakis, Charalabos; Taché, Yvette

    2016-03-15

    Urocortins (Ucns) 1, 2, and 3 and corticotropin-releasing factor receptor 2 (CRF2) mRNA are prominently expressed in various layers of the upper gut. We tested whether Ucns and CRF2 variants are also expressed in the different layers of the rat colon, regulated by LPS (100 μg/kg ip) and play a modulatory role in the colonic immune response to LPS. Transcripts of Ucns and CRF2b, the most common isoform in the periphery, were detected in all laser microdissected layers, including myenteric neurons. LPS increased the mRNA level of Ucn 1, Ucn 2, and Ucn 3 and decreased that of CRF2b in both the colonic mucosa and submucosa + muscle (S+M) layers at 2, 6, and 9 h after injection with a return to basal at 24 h. In addition, CRF2a, another variant more prominent in the brain, and a novel truncated splice variant CRF2a-3 mRNA were detected in all segments of the large intestine. LPS reciprocally regulated the colonic expression of these CRF2 variants by decreasing both CRF2a and CRF2b, while increasing CRF2a-3 in the mucosa and S+M. The CRF2 antagonist astressin2-B further enhanced LPS-induced increase of mRNA level of interleukin (IL)-1β, TNF-α, and inducible nitric oxide synthase in S+M layers and IL-1β in the mucosa and evoked TNF-α expression in the mucosa. These data indicate that Ucns/CRF2 variants are widely expressed in all colonic layers and reciprocally regulated by LPS. CRF2 signaling dampens the CD14/TLR4-mediated acute inflammatory response to Gram-negative bacteria in the colon.

  7. Ethanol produces corticotropin releasing factor receptor-dependent enhancement of spontaneous glutamatergic transmission in the mouse central amygdala

    Science.gov (United States)

    Silberman, Yuval; Fetterly, Tracy L.; Awad, Elias K.; Milano, Elana J.; Usdin, Ted B.; Winder, Danny G.

    2015-01-01

    Background Ethanol modulation of Central Amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin releasing factor (CRF) receptor system. Previous work has predominantly focused on ethanol/CRF interactions on the CeA GABA circuitry; however our lab recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine if ethanol modulates CeA glutamate transmission via activation of CRF signaling. Methods The effects of ethanol on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRFCeAhDTR) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post-hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRFDTA mice) ablated CRF neurons throughout the CNS, as assessed by qRT-PCR quantification of CRF mRNA. Results Acute bath application of ethanol significantly increased sEPSC frequency in a concentration dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRF receptor 1 and CRF receptor 2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, ethanol did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of ethanol to enhance CeA sEPSC frequency was not altered in CRFCeAhDTR mice despite a ~78% reduction in CeA CRF cell counts. The ability of ethanol to enhance CeA sEPSC frequency was also not altered in the CRFDTA mice despite a three-fold reduction in CRF mRNA levels. Conclusion These findings demonstrate that ethanol enhances spontaneous glutamatergic transmission in the CeA via a CRF receptor dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF

  8. Presence of CRF09_cpx and complex CRF02_AG/CRF09_cpx recombinant HIV type 1 strains in Côte d'Ivoire, West Africa.

    Science.gov (United States)

    Toni, Thomas; Adjé-Touré, Christiane; Vidal, Nicole; Minga, Albert; Huet, Charlotte; Borger, Marie-Yolande; Recordon-Pinson, Patricia; Masquelier, Bernard; Nolan, Monica; Nkengasong, John; Fleury, Hervé J; Delaporte, Eric; Peeters, Martine

    2005-07-01

    Based on partial env and pol (protease and RT) subtyping, we recently documented that the majority (>80%) of the HIV-1 strains that circulate in Côte d'Ivoire were CRF02_AG and about 11% were recombinants or could not be clearly assigned to a known subtype or CRF. In order to determine in more detail the precise structure of these viruses we sequenced the full-length genomes for six such strains. Bootscan and phylogenetic tree analysis showed that four strains were complex and unique CRF02_AG/CRF09_cpx recombinants, one was a CRF02_AG/CRF06_cpx recombinant, and one was a pure CRF09_cpx. Reanalysis of the remaining recombinants asserted the predominance of CRF09_cpx within intersubtype recombinants and circulation of CRF09_cpx in Côte d'Ivoire. More detailed analysis of the CRF09_cpx strains revealed also that part of the pol gene belonged to subtype K. This is the first time that such recombinants are described.

  9. Cell-type specific deletion of GABA(A)α1 in corticotropin-releasing factor-containing neurons enhances anxiety and disrupts fear extinction.

    Science.gov (United States)

    Gafford, Georgette M; Guo, Ji-Dong; Flandreau, Elizabeth I; Hazra, Rimi; Rainnie, Donald G; Ressler, Kerry J

    2012-10-02

    Corticotropin-releasing factor (CRF) is critical for the endocrine, autonomic, and behavioral responses to stressors, and it has been shown to modulate fear and anxiety. The CRF receptor is widely expressed across a variety of cell types, impeding progress toward understanding the contribution of specific CRF-containing neurons to fear dysregulation. We used a unique CRF-Cre driver transgenic mouse line to remove floxed GABA(A)α1 subunits specifically from CRF neurons [CRF-GABA(A)α1 KO]. This process resulted in mice with decreased GABA(A)α1 expression only in CRF neurons and increased CRF mRNA within the amygdala, bed nucleus of the stria terminalis (BNST) and paraventricular nucleus of the hypothalamus. These mice show normal locomotor and pain responses and no difference in depressive-like behavior or Pavlovian fear conditioning. However, CRF-GABA(A)α1 KO increased anxiety-like behavior and impaired extinction of conditioned fear, coincident with an increase in plasma corticosterone concentration. These behavioral impairments were rescued with systemic or BNST infusion of the CRF antagonist R121919. Infusion of Zolpidem, a GABA(A)α1-preferring benzodiazepine-site agonist, into the BNST of the CRF-GABA(A)α1 KO was ineffective at decreasing anxiety. Electrophysiological findings suggest a disruption in inhibitory current may play a role in these changes. These data indicate that disturbance of CRF containing GABA(A)α1 neurons causes increased anxiety and impaired fear extinction, both of which are symptoms diagnostic for anxiety disorders, such as posttraumatic stress disorder.

  10. Corticotropin-releasing factor enhances locomotion and medullary neuronal firing in an amphibian.

    Science.gov (United States)

    Lowry, C A; Rose, J D; Moore, F L

    1996-03-01

    Corticotropin-releasing factor (CRF) administration has been shown to act centrally to enhance locomotion in rats and amphibians. In the present study we used an amphibian, the roughskin newt (Taricha granulosa), to characterize changes in medullary neuronal activity associated with CRF-induced walking and swimming in animals chronically implanted with fine-wire microelectrodes. Neuronal activity was recorded from the raphe and adjacent reticular region of the rostral medulla. Under baseline conditions most of the recorded neurons showed low to moderate amounts of neuronal activity during periods of immobility and pronounced increases in firing that were time-locked with episodes of walking. These neurons sometimes showed further increases in discharge during swimming. Injections of CRF but not saline into the lateral ventricle produced a rapidly appearing increase in walking and pronounced changes (mostly increases) in firing rates of the medullary neurons. CRF produced diverse changes in patterns of firing in different neurons, but for these neurons as a group, the effects of CRF showed a close temporal association with the onset and expression of the peptide's effect on locomotion. In neurons that were active exclusively during movement prior to CRF treatment, the post-CRF increase in firing was evident during episodes of walking; in other neurons that also were spontaneously active during immobility prior to CRF infusion, post-CRF activity changes were evident during immobility as well as during episodes of locomotion. Thus, a principal effect of CRF was to potentiate the level of neuronal firing in a population of medullary neurons with locomotor-related properties. Due to the route of administration CRF may have acted on multiple central nervous system sites to enhance locomotion, but the results are consistent with neurophysiological effects involving medullary locomotion-regulating neurons.

  11. Delta opioid receptors colocalize with corticotropin releasing factor in hippocampal interneurons.

    Science.gov (United States)

    Williams, T J; Milner, T A

    2011-04-14

    The hippocampal formation (HF) is an important site at which stress circuits and endogenous opioid systems intersect, likely playing a critical role in the interaction between stress and drug addiction. Prior study findings suggest that the stress-related neuropeptide corticotropin releasing factor (CRF) and the delta opioid receptor (DOR) may localize to similar neuronal populations within HF lamina. Here, hippocampal sections of male and cycling female adult Sprague-Dawley rats were processed for immunolabeling using antisera directed against the DOR and CRF peptide, as well as interneuron subtype markers somatostatin or parvalbumin, and analyzed by fluorescence and electron microscopy. Both DOR- and CRF-labeling was observed in interneurons in the CA1, CA3, and dentate hilus. Males and normal cycling females displayed a similar number of CRF immunoreactive neurons co-labeled with DOR and a similar average number of CRF-labeled neurons in the dentate hilus and stratum oriens of CA1 and CA3. In addition, 70% of DOR/CRF dual-labeled neurons in the hilar region co-labeled with somatostatin, suggesting a role for these interneurons in regulating perforant path input to dentate granule cells. Ultrastructural analysis of CRF-labeled axon terminals within the hilar region revealed that proestrus females have a similar number of CRF-labeled axon terminals that contain DORs compared to males but an increased number of CRF-labeled axon terminals without DORs. Taken together, these findings suggest that while DORs are anatomically positioned to modulate CRF immunoreactive interneuron activity and CRF peptide release, their ability to exert such regulatory activity may be compromised in females when estrogen levels are high.

  12. Functional Impact of Corticotropin-Releasing Factor Exposure on Tau Phosphorylation and Axon Transport.

    Directory of Open Access Journals (Sweden)

    Michelle H Le

    Full Text Available Stress exposure or increased levels of corticotropin-releasing factor (CRF induce hippocampal tau phosphorylation (tau-P in rodent models, a process that is dependent on the type-1 CRF receptor (CRFR1. Although these preclinical studies on stress-induced tau-P provide mechanistic insight for epidemiological work that identifies stress as a risk factor for Alzheimer's disease (AD, the actual impact of stress-induced tau-P on neuronal function remains unclear. To determine the functional consequences of stress-induced tau-P, we developed a novel mouse neuronal cell culture system to explore the impact of acute (0.5hr and chronic (2hr CRF treatment on tau-P and integral cell processes such as axon transport. Consistent with in vivo reports, we found that chronic CRF treatment increased tau-P levels and caused globular accumulations of phosphorylated tau in dendritic and axonal processes. Furthermore, while both acute and chronic CRF treatment led to significant reduction in CREB activation and axon transport of brain-derived neurotrophic factor (BDNF, this was not the case with mitochondrial transport. Acute CRF treatment caused increased mitochondrial velocity and distance traveled in neurons, while chronic CRF treatment modestly decreased mitochondrial velocity and greatly increased distance traveled. These results suggest that transport of cellular energetics may take priority over growth factors during stress. Tau-P was required for these changes, as co-treatment of CRF with a GSK kinase inhibitor prevented CRF-induced tau-P and all axon transport changes. Collectively, our results provide mechanistic insight into the consequences of stress peptide-induced tau-P and provide an explanation for how chronic stress via CRF may lead to neuronal vulnerability in AD.

  13. Functional Impact of Corticotropin-Releasing Factor Exposure on Tau Phosphorylation and Axon Transport.

    Science.gov (United States)

    Le, Michelle H; Weissmiller, April M; Monte, Louise; Lin, Po Han; Hexom, Tia C; Natera, Orlangie; Wu, Chengbiao; Rissman, Robert A

    2016-01-01

    Stress exposure or increased levels of corticotropin-releasing factor (CRF) induce hippocampal tau phosphorylation (tau-P) in rodent models, a process that is dependent on the type-1 CRF receptor (CRFR1). Although these preclinical studies on stress-induced tau-P provide mechanistic insight for epidemiological work that identifies stress as a risk factor for Alzheimer's disease (AD), the actual impact of stress-induced tau-P on neuronal function remains unclear. To determine the functional consequences of stress-induced tau-P, we developed a novel mouse neuronal cell culture system to explore the impact of acute (0.5hr) and chronic (2hr) CRF treatment on tau-P and integral cell processes such as axon transport. Consistent with in vivo reports, we found that chronic CRF treatment increased tau-P levels and caused globular accumulations of phosphorylated tau in dendritic and axonal processes. Furthermore, while both acute and chronic CRF treatment led to significant reduction in CREB activation and axon transport of brain-derived neurotrophic factor (BDNF), this was not the case with mitochondrial transport. Acute CRF treatment caused increased mitochondrial velocity and distance traveled in neurons, while chronic CRF treatment modestly decreased mitochondrial velocity and greatly increased distance traveled. These results suggest that transport of cellular energetics may take priority over growth factors during stress. Tau-P was required for these changes, as co-treatment of CRF with a GSK kinase inhibitor prevented CRF-induced tau-P and all axon transport changes. Collectively, our results provide mechanistic insight into the consequences of stress peptide-induced tau-P and provide an explanation for how chronic stress via CRF may lead to neuronal vulnerability in AD.

  14. Lipopolysaccharide induces visceral hypersensitivity: role of interleukin-1, interleukin-6, and peripheral corticotropin-releasing factor in rats.

    Science.gov (United States)

    Nozu, Tsukasa; Miyagishi, Saori; Nozu, Rintaro; Takakusaki, Kaoru; Okumura, Toshikatsu

    2017-01-01

    Lipopolysaccharide (LPS) induces visceral hypersensitivity, and corticotropin-releasing factor (CRF) also modulates visceral sensation. Besides, LPS increases CRF immunoreactivity in rat colon, which raises the possibility of the existence of a link between LPS and the CRF system in modulating visceral sensation. The present study tried to clarify this possibility. Visceral sensation was assessed by abdominal muscle contractions induced by colonic balloon distention, i.e., visceromotor response, electrophysiologically in conscious rats. The threshold of visceromotor response was measured before and after administration of drugs. LPS at a dose of 1 mg/kg subcutaneously (sc) decreased the threshold at 3 h after the administration. Intraperitoneal (ip) administration of anakinra (20 mg/kg), an interleukin-1 (IL-1) receptor antagonist, or interleukin-6 (IL-6) antibody (16.6 µg/kg) blocked this effect. Additionally, IL-1β (10 µg/kg, sc) or IL-6 (10 µg/kg, sc) induced visceral allodynia. Astressin (200 µg/kg, ip), a non-selective CRF receptor antagonist, abolished the effect of LPS, but astressin2-B (200 µg/kg, ip), a CRF receptor type 2 (CRF2) antagonist, did not alter it. Peripheral CRF receptor type 1 (CRF1) stimulation by cortagine (60 µg/kg, ip) exaggerated the effect of LPS, but activation of CRF2 by urocortin 2 (60 µg/kg, ip) abolished it. LPS induced visceral allodynia possibly through stimulating IL-1 and IL-6 release. In addition, this effect was mediated through peripheral CRF signaling. Since the LPS-cytokine system is thought to contribute to altered visceral sensation in the patients with irritable bowel syndrome, these results may further suggest that CRF plays a crucial role in the pathophysiology of this disease.

  15. Intrahypothalamic neuroendocrine actions of corticotropin-releasing factor.

    Science.gov (United States)

    Almeida, O F; Hassan, A H; Holsboer, F

    1993-01-01

    Most studies of the neuroendocrine effects of corticotropin-releasing factor (CRF) have focused on its role in the regulation of the pituitary-adrenal axis; activation of this axis follows release of the peptide from CRF-containing terminals in the median eminence. However, a sizeable proportion of CRF fibres terminate within the hypothalamus itself, where synaptic contacts with other hypothalamic neuropeptidergic neurons (e.g. gonadotropin-releasing hormone-containing and opioidergic neurons) have been identified. Here, we summarize physiological and pharmacological data which provide insights into the nature and significance of these intrahypothalamic connections. It is now clear that CRF is a potent secretagogue of the three major endogenous opioid peptides (beta-endorphin, Met-enkephalin and dynorphin) and that it stimulates opioidergic neurons tonically. In the case of beta-endorphin, another hypothalamic peptide, arginine vasopressin, appears to be an essential mediator of CRF's effect, suggesting the occurrence of CRF synapses on, or in the vicinity of, vasopressin neurons; morphological support for this assumption is still wanting. Evidence for direct and indirect inhibitory effects of CRF on sexual behaviour and secretion of reproductive hormones is also presented; the indirect pathways include opioidergic neurons. An important conclusion from all these studies is that, in addition to its better known functions in producing adaptive responses during stressful situations, CRF might also contribute to the coordinated functioning of various components of the neuroendocrine system under basal conditions. Although feedback regulation of hypothalamic neuronal activity by peripheral steroids is a well-established tenet of endocrinology, data on modulation of the intrahypothalamic actions of CRF by adrenal and sex steroids are just emerging. Some of these newer findings may be useful in framing questions related to the mechanisms underlying disease states (such as

  16. HIV-1 CRF07_BC gp41重组抗原在不同体系表达效率的比较%Comparison of expression efficiency of HIV-1 CRF07_BC gp41 recombinant antigen in different expression system

    Institute of Scientific and Technical Information of China (English)

    王妮丹; 罗振武; 郝彦玲; 孙红岩; 何彦平; 邵一鸣

    2014-01-01

    目的 获得HIV-1 CRF07_BC株gp41重组抗原表达效率最佳的体系.方法 采用基因工程技术将gp41重组蛋白基因分别构建到pThioHisA,pThioHis A-1(不含标签),PBV220,PGEX-6p-1原核表达载体.转化大肠杆菌BL21和Rosetta两种宿主菌,通过IPTG诱导表达并经WB鉴定.结果 4种原核表达质粒构建完成,蛋白成功表达.PGEX-6p-1表达量明显高于pThioHis A载体;而无标签载体组中,PBV220表达量优于pThioHis A-1.BL21和Rosetta宿主菌对表达体系无影响.结论 HIV-1 CRF07_BC株gp41重组抗原在大肠杆菌中以包涵体形式存在,构建在PGEX-6p-1和PBV220载体上gp41重组蛋白表达效率较高,为gp41疫苗的研究和血清学检测提供充足的抗原.

  17. Intrahypothalamic corticotropin-releasing factor elevates gastric bicarbonate and inhibits stress ulcers in rats.

    Science.gov (United States)

    Gunion, M W; Kauffman, G L; Taché, Y

    1990-01-01

    The effects of intrahyopthalamic microinfusions of corticotropin-releasing factor (CRF) on gastric bicarbonate, acid, and pepsin content and on cold restraint-induced gastric lesion formation were tested in three experiments. Bilateral microinfusions of CRF into the hypothalamic ventromedial nucleus (0.86 nmol/rat) significantly increased both gastric bicarbonate concentration and total bicarbonate output. These effects were observed irrespective of whether rats were pretreated with the acid antisecretory drug omeprazole. In nonomeprazole-pretreated rats, CRF microinfusions also significantly reduced acid secretion and raised pH. The increase in bicarbonate content accounted for half of the observed decrease in acid output, suggesting that CRF microinfusions activated separable bicarbonate-stimulating and acid-inhibiting hypothalamic systems. In non-omeprazole-pretreated rats, CRF microinfusions significantly increased serum gastrin, whereas pepsin output was unchanged. Gastric mucosal damage produced by 4 h of cold restraint was significantly diminished by CRF microinfusion into the ventromedial hypothalamus. These data demonstrate that ventromedial hypothalamic microinfusions of CRF increase bicarbonate content, decrease gastric acid content, and confer protection against cold restraint-induced gastric mucosal damage. Hypothalamic CRF neuronal terminals and receptors may be involved in the central regulation of gastric bicarbonate secretion as well as acid secretion.

  18. Sex differences between CRF1 receptor deficient mice following naloxone-precipitated morphine withdrawal in a conditioned place aversion paradigm: implication of HPA axis.

    Directory of Open Access Journals (Sweden)

    Juan-Antonio García-Carmona

    Full Text Available Extinction period of positive affective memory of drug taking and negative affective memory of drug withdrawal, as well as the different response of men and women might be important for the clinical treatment of drug addiction. We investigate the role of corticotropin releasing factor receptor type one (CRF1R and the different response of male and female mice in the expression and extinction of the aversive memory.We used genetically engineered male and female mice lacking functional CRF1R. The animals were rendered dependent on morphine by intraperitoneally injection of increasing doses of morphine (10-60 mg/kg. Negative state associated with naloxone (1 mg/kg s.c.-precipitated morphine withdrawal was examined by using conditioned place aversion (CPA paradigm. No sex differences for CPA expression were found in wild-type (n = 29 or CRF1R knockout (KO mice (n = 29. However, CRF1R KO mice presented less aversion score than wild-type mice, suggesting that CRF1R KO mice were less responsive than wild-type to continuous associations between drug administration and environmental stimuli. In addition, CPA extinction was delayed in wild-type and CRF1R KO male mice compared with females of both genotypes. The genetic disruption of the CRF1R pathway decreased the period of extinction in males and females suggesting that CRF/CRF1R is implicated in the duration of aversive memory. Our results also showed that the increase in adrenocorticotropic hormone (ACTH levels observed in wild-type (n = 11 mice after CPA expression, were attenuated in CRF1R KO mice (n = 10. In addition, ACTH returned to the baseline levels in males and females once CPA extinction was finished.These results suggest that, at least, CPA expression is partially due to an increase in plasma ACTH levels, through activation of CRF1R, which can return when CPA extinction is finished.

  19. Bullet Environmental Measurement OS for a Tiny CRF-STACK Used in Wireless Network

    Directory of Open Access Journals (Sweden)

    Vasanth Iyer

    2008-04-01

    Full Text Available To respond to the new development needs of sensor networks and their unique deployment, there are many available processors and varying target footprints for deploying sensor networks. The most common needs are supporting many different types of wireless radios and an environmental measuring operating system which allows interfacing to 8, 16 bit target microcontrollers. The constraints of the sensor nodes (that form the network however, are that they have limited processing power, limited wireless range, limited memory, low data transmission rates and low cost packaging. The design of the software stack being proposed in this paper is based on the previous work by the authors who focused on implementation of Control Radio Flooding (CRF protocol to self organizing sensor networks. The proposed stack, which is fully power-aware, is referred to as CRF-STACK. It integrates the hierarchical space partitioning tree with a data transaction model that allows seamless exchanges between data collecting sensors and its parent nodes in the hierarchy and could be compatible with emerging IEEE standards. This heart of model is a scalable real-time OS which allows a programming interface to develop sensor application and underlying radio communication. Through routing simulations we demonstrate that the energy-aware reusability of resources in sensor networks has a QUOTE O(logN complexity where N is the total number of nodes. In sensor network the processing power for a given operation is typically measured as a collaborative processing of a group of nodes which is always higher than the individual sensors capabilities, the residual energy remaining of the sensor network at the end of the simulation is a good measure of the collaborative factor (lesser the residual value the better the collaborative factor. We show by simulation the optimal values for reusability to attain max lifetime converges without sensor faults for N <= 20% for CRF and LEACH-E. Even

  20. Corticotropin-releasing factor receptor type 1 and type 2 interaction in irritable bowel syndrome.

    Science.gov (United States)

    Nozu, Tsukasa; Okumura, Toshikatsu

    2015-08-01

    Irritable bowel syndrome (IBS) displays chronic abdominal pain or discomfort with altered defecation, and stress-induced altered gut motility and visceral sensation play an important role in the pathophysiology. Corticotropin-releasing factor (CRF) is a main mediator of stress responses and mediates these gastrointestinal functional changes. CRF in brain and periphery acts through two subtype receptors such as CRF receptor type 1 (CRF1) and type 2 (CRF2), and activating CRF1 exclusively stimulates colonic motor function and induces visceral hypersensitivity. Meanwhile, several recent studies have demonstrated that CRF2 has a counter regulatory action against CRF1, which may imply that CRF2 inhibits stress response induced by CRF1 in order to prevent it from going into an overdrive state. Colonic contractility and sensation may be explained by the state of the intensity of CRF1 signaling. CRF2 signaling may play a role in CRF1-triggered enhanced colonic functions through modulation of CRF1 activity. Blocking CRF2 further enhances CRF-induced stimulation of colonic contractility and activating CRF2 inhibits stress-induced visceral sensitization. Therefore, we proposed the hypothesis, i.e., balance theory of CRF1 and CRF2 signaling as follows. Both CRF receptors may be activated simultaneously and the signaling balance of CRF1 and CRF2 may determine the functional changes of gastrointestinal tract induced by stress. CRF signaling balance might be abnormally shifted toward CRF1, leading to enhanced colonic motility and visceral sensitization in IBS. This theory may lead to understanding the pathophysiology and provide the novel therapeutic options targeting altered signaling balance of CRF1 and CRF2 in IBS.

  1. Increased CRF signaling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal

    Science.gov (United States)

    Zhao-Shea, Rubing; DeGroot, Steven R.; Liu, Liwang; Vallaster, Markus; Pang, Xueyan; Su, Qin; Gao, Guangping; Rando, Oliver J.; Martin, Gilles E.; George, Olivier; Gardner, Paul D.; Tapper, Andrew R.

    2015-01-01

    Increased anxiety is a predominant withdrawal symptom in abstinent smokers, yet the neuroanatomical and molecular bases underlying it are unclear. Here, we show that withdrawal-induced anxiety increases activity of neurons in the interpeduncular intermediate (IPI), a subregion of the interpeduncular nucleus (IPN). IPI activation during nicotine withdrawal was mediated by increased corticotropin releasing factor (CRF) receptor-1 expression and signaling, which modulated glutamatergic input from the medial habenula (MHb). Pharmacological blockade of IPN CRF1 receptors or optogenetic silencing of MHb input reduced IPI activation and alleviated withdrawal-induced anxiety; whereas IPN CRF infusion in mice increased anxiety. We identified a meso-interpeduncular circuit, consisting of ventral tegmental area (VTA) dopaminergic neurons projecting to the IPN, as a potential source of CRF. Knock-down of CRF synthesis in the VTA prevented IPI activation and anxiety during nicotine withdrawal. These data indicate that increased CRF receptor signaling within a VTA-IPN-MHb circuit triggers anxiety during nicotine withdrawal. PMID:25898242

  2. Stress and central Urocortin increase anxiety-like behavior in the social interaction test via the CRF1 receptor.

    Science.gov (United States)

    Gehlert, Donald R; Shekhar, Anantha; Morin, S Michelle; Hipskind, Phillip A; Zink, Charity; Gackenheimer, Susan L; Shaw, Janice; Fitz, Stephanie D; Sajdyk, Tammy J

    2005-02-21

    Corticotropin releasing factor (CRF) and Urocortin are important neurotransmitters in the regulation of physiological and behavioral responses to stress. Centrally administered CRF or Urocortin produces anxiety-like responses in numerous animal models of anxiety disorders. Previous studies in our lab have shown that Urocortin infused into the basolateral nucleus of the amygdala produces anxiety-like responses in the social interaction test. Subsequently, in the current study we prepared a specific CRF1 receptor antagonist (N-Cyclopropylmethyl-2,5-dimethyl-N-propyl-N'-(2,4,6-trichloro-phenyl)-pyrimidine-4,6-diamine, NBI3b1996) to examine in this paradigm. This CRF1 receptor antagonist inhibited the ex vivo binding of 125I-sauvagine to rat cerebellum with an ED50 of 6 mg/kg, i.p. NBI3b1996 produced a dose-dependent antagonism of Urocortin-induced anxiety-like behavior in Social Interaction test with an ED50 of 6 mg/kg, i.p. The compound had no effect on baseline social interaction. In addition, the CRF1 receptor antagonist prevented the stress-induced decrease in social interaction. These results provide further support for the CRF1 receptor in anxiety-like behavior and suggest this pathway is quiescent in unstressed animals.

  3. The role of non-CRF inhibition in contour detection

    NARCIS (Netherlands)

    Grigorescu, Cosmin; Petkov, Nicolai; Westenberg, Michel A.; Skala,

    2003-01-01

    We propose a biologically motivated computational step, called non-classical receptive field (non-CRF) inhibition, to improve the performance of contour detectors. Non-CRF inhibition is exhibited by 80% of the orientation selective neurons in the primary visual cortex of macaque monkeys and has been

  4. Corticotropin-releasing factor receptors and stress-related alterations of gut motor function.

    Science.gov (United States)

    Taché, Yvette; Bonaz, Bruno

    2007-01-01

    Over the past few decades, corticotropin-releasing factor (CRF) signaling pathways have been shown to be the main coordinators of the endocrine, behavioral, and immune responses to stress. Emerging evidence also links the activation of CRF receptors type 1 and type 2 with stress-related alterations of gut motor function. Here, we review the role of CRF receptors in both the brain and the gut as part of key mechanisms through which various stressors impact propulsive activity of the gastrointestinal system. We also examine how these mechanisms translate into the development of new approaches for irritable bowel syndrome, a multifactorial disorder for which stress has been implicated in the pathophysiology.

  5. Neuroendocrine control of the gut during stress: corticotropin-releasing factor signaling pathways in the spotlight.

    Science.gov (United States)

    Stengel, Andreas; Taché, Yvette

    2009-01-01

    Stress affects the gastrointestinal tract as part of the visceral response. Various stressors induce similar profiles of gut motor function alterations, including inhibition of gastric emptying, stimulation of colonic propulsive motility, and hypersensitivity to colorectal distension. In recent years, substantial progress has been made in our understanding of the underlying mechanisms of stress's impact on gut function. Activation of corticotropin-releasing factor (CRF) signaling pathways mediates both the inhibition of upper gastrointestinal (GI) and the stimulation of lower GI motor function through interaction with different CRF receptor subtypes. Here, we review how various stressors affect the gut, with special emphasis on the central and peripheral CRF signaling systems.

  6. Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway.

    Science.gov (United States)

    Walsh, Jessica J; Friedman, Allyson K; Sun, Haosheng; Heller, Elizabeth A; Ku, Stacy M; Juarez, Barbara; Burnham, Veronica L; Mazei-Robison, Michelle S; Ferguson, Deveroux; Golden, Sam A; Koo, Ja Wook; Chaudhury, Dipesh; Christoffel, Daniel J; Pomeranz, Lisa; Friedman, Jeffrey M; Russo, Scott J; Nestler, Eric J; Han, Ming-Hu

    2014-01-01

    Mechanisms controlling release of brain-derived neurotrophic factor (BDNF) in the mesolimbic dopamine reward pathway remain unknown. We report that phasic optogenetic activation of this pathway increases BDNF amounts in the nucleus accumbens (NAc) of socially stressed mice but not of stress-naive mice. This stress gating of BDNF signaling is mediated by corticotrophin-releasing factor (CRF) acting in the NAc. These results unravel a stress context-detecting function of the brain's mesolimbic circuit.

  7. Corticotropin releasing factor impairs sustained attention in male and female rats.

    Science.gov (United States)

    Cole, Robert D; Kawasumi, Yushi; Parikh, Vinay; Bangasser, Debra A

    2016-01-01

    Stressful life events and stress-related psychiatric disorders impair sustained attention, the ability to monitor rare and unpredictable stimulus events over prolonged periods of time. Despite the link between stress and attentional disruptions, the neurobiological basis for stress regulation of attention systems remains underexplored. Here we examined whether corticotropin releasing factor (CRF), which orchestrates stress responses and is hypersecreted in patients with stress-related psychiatric disorders, impairs sustained attention. To this end, male and female rats received central infusions of CRF prior to testing on an operant sustained attention task (SAT), where rats were trained to discriminate signaled from non-signaled events. CRF caused a dose-dependent decrease in SAT performance in both male and female rats. Females were more impaired than males following a moderate dose of CRF, particularly during the middle part of the session. This sex difference was moderated by ovarian hormones. Females in the estrous cycle stage characterized by lower ovarian hormones had a greater CRF-induced attentional impairment than males and females in other cycle stages. Collectively, these studies highlight CRF as a critical stress-related factor that can regulate attentional performance. As sustained attention subserves other cognitive processes, these studies suggest that mitigating high levels of CRF in patients with stress-related psychiatric disorders may ameliorate their cognitive deficits.

  8. Regulation of duodenal bicarbonate secretion during stress by corticotropin-releasing factor and beta-endorphin.

    Science.gov (United States)

    Lenz, H J

    1989-02-01

    Proximal duodenal mucosal bicarbonate secretion is an important factor in the pathogenesis of duodenal ulcer disease. To examine the central nervous system regulation of duodenal bicarbonate secretion, an animal model was developed that allowed cerebroventricular and intravenous injections as well as collection of duodenal perfusates in awake, freely moving rats. The hypothalamic peptide corticotropin-releasing factor (CRF) and stress (physical restraint) significantly stimulated duodenal bicarbonate secretion. These responses were abolished by pretreatment of the animals with the CRF receptor antagonist alpha-helical CRF-(9-41), hypophysectomy, and naloxone. In contrast, blockade of autonomic efferents by surgical and pharmacological means did not prevent the stimulatory effects of stress and CRF. Intravenous, but not cerebroventricular, administration of beta-endorphin that produced plasma concentrations of beta-endorphin that were similar to those produced by exogenous CRF and stress significantly stimulated duodenal bicarbonate secretion. These results indicate that endogenous CRF released during stress and exogenously administered CRF stimulate duodenal bicarbonate secretion by release of beta-endorphin from the pituitary, thus, demonstrating a functional hypothalamus-pituitary-gut axis.

  9. Urocortins and CRF receptor type 2 variants in the male rat colon: gene expression and regulation by endotoxin and anti-inflammatory effect

    OpenAIRE

    2016-01-01

    Urocortin 1, 2 and 3 (Ucns) and corticotropin releasing factor receptor 2 (CRF2) are prominently expressed in various layers of the upper gut while current knowledge of their expression and regulation in the colonic layers are limited. We investigated Ucns and CRF2 isoforms expression by RT-PCR in the proximal colon separated into mucosa and submucosa plus muscle (S+M), or in laser captured layers, their regulations by lipopolysaccharide (LPS, 100 μg/kg ip) and the effects of the CRF2 antagon...

  10. The newly developed CRF1-receptor antagonists, NGD 98-2 and NGD 9002, suppress acute stress-induced stimulation of colonic motor function and visceral hypersensitivity in rats.

    Directory of Open Access Journals (Sweden)

    Mulugeta Million

    Full Text Available Corticotropin releasing factor receptor 1 (CRF1 is the key receptor that mediates stress-related body responses. However to date there are no CRF1 antagonists that have shown clinical efficacy in stress-related diseases. We investigated the inhibitory effects of a new generation, topology 2 selective CRF1 antagonists, NGD 98-2 and NGD 9002 on exogenous and endogenous CRF-induced stimulation of colonic function and visceral hypersensitivity to colorectal distension (CRD in conscious rats. CRF1 antagonists or vehicle were administered orogastrically (og or subcutaneously (sc before either intracerebroventricular (icv or intraperitoneal (ip injection of CRF (10 µg/kg, exposure to water avoidance stress (WAS, 60 min or repeated CRD (60 mmHg twice, 10 min on/off at a 30 min interval. Fecal pellet output (FPO, diarrhea and visceromotor responses were monitored. In vehicle (og-pretreated rats, icv CRF stimulated FPO and induced diarrhea in >50% of rats. NGD 98-2 or NGD 9002 (3, 10 and 30 mg/kg, og reduced the CRF-induced FPO response with an inhibitory IC50 of 15.7 and 4.3 mg/kg respectively. At the highest dose, og NGD 98-2 or NGD 9002 blocked icv CRF-induced FPO by 67-87% and decreased WAS-induced-FPO by 23-53%. When administered sc, NGD 98-2 or NGD 9002 (30 mg/kg inhibited icv and ip CRF-induced-FPO. The antagonists also prevented the development of nociceptive hyper-responsivity to repeated CRD. These data demonstrate that topology 2 CRF1 antagonists, NGD 98-2 and NGD 9002, administered orally, prevented icv CRF-induced colonic secretomotor stimulation, reduced acute WAS-induced defecation and blocked the induction of visceral sensitization to repeated CRD.

  11. Glutamatergic transmission in the central nucleus of the amygdala is selectively altered in Marchigian Sardinian alcohol-preferring rats: Alcohol and CRF effects.

    Science.gov (United States)

    Herman, Melissa A; Varodayan, Florence P; Oleata, Christopher S; Luu, George; Kirson, Dean; Heilig, Markus; Ciccocioppo, Roberto; Roberto, Marisa

    2016-03-01

    The CRF system of the central nucleus of the amygdala (CeA) is important for the processing of anxiety, stress, and effects of acute and chronic ethanol. We previously reported that ethanol decreases evoked glutamate transmission in the CeA of Sprague Dawley rats and that ethanol dependence alters glutamate release in the CeA. Here, we examined the effects of ethanol, CRF and a CRF1 receptor antagonist on spontaneous and evoked glutamatergic transmission in CeA neurons from Wistar and Marchigian Sardinian Preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and characterized by heightened activity of the CRF1 system. Basal spontaneous and evoked glutamate transmission in CeA neurons from msP rats was increased compared to Wistar rats. Ethanol had divergent effects, either increasing or decreasing spontaneous glutamate release in the CeA of Wistar rats. This bidirectional effect was retained in msP rats, but the magnitude of the ethanol-induced increase in glutamate release was significantly smaller. The inhibitory effect of ethanol on evoked glutamatergic transmission was similar in both strains. CRF also either increased or decreased spontaneous glutamate release in CeA neurons of Wistar rats, however, in msP rats CRF only increased glutamate release. The inhibitory effect of CRF on evoked glutamatergic transmission was also lost in neurons from msP rats. A CRF1 antagonist produced only minor effects on spontaneous glutamate transmission, which were consistent across strains, and no effects on evoked glutamate transmission. These results demonstrate that the genetically altered CRF system of msP rats results in alterations in spontaneous and stimulated glutamate signaling in the CeA that may contribute to both the anxiety and drinking behavioral phenotypes.

  12. Chronic renal failure (CRF in children in Jugoslavia

    Directory of Open Access Journals (Sweden)

    Peco-Antić Amira

    2003-01-01

    Full Text Available The aim of this study was to analyse the demographic variables of chronic non-terminal (CRF and terminal (TRF renal failure patients (pts younger than 19 years treated in Serbia in June 2001. The prevalence of CRF pts was registered as 4,7 per million total population (pmtp or 14,1 per million child population (pmcp while corresponding values for TRF pts were 4,5 pmtp or 13,5 pmcp. The incidence of TRF pts during the period Jan.2000-Jan.2002 was 4,35 pmcp. Boys dominated only among CRF pts (34:14; 60,4% beeing between the ages of 6 and 19 yrs while at the time of diagnosis of HBI, 33,3 % of boys were yanger than 2 yrs.The causes of CRF were: reflux nephropathy 58,3%, congenital kidney disease 16,7%, familial/hereditary 14,6% glomerulonephritis 6,2% and Willms tu 4,1%. Reflux nephropathy was also the most common underlying disease of TRF accounted for 36,9% of total cases while glomerulonephritis was responsible for 23,9 %. Reflux nephropathy was associated with neural tube defect in 53,3% and with congenital lower urinary tract obstruction in 66,7%. The most of CRF (81,25% and TRF pts (95,6% were from Serbia, the others were from Monte Negro and Republic Srpska. The most of CRF (65% and TRF (80% pts were treated in University Children’s Hospital in Belgrade. Of CRF pts 46% had serum sreatinine 100-200 μmol/l, in 11% of pts it was 400-600 μmol/l and 2% of pts were in pre-terminal CRF. One third of CRF pts had proteinuria 150-500 mg/l, and second third had proteinuria greater of 1000 mg/l. Anemia was present in 54% of CRf pts, and arterial hypertension in 56%. Hemodialysis was dominant treatment modality for TRF pts and only 23,9% had functioning transplant. Conclusion: This is the first national study of demographic characteristics of pediatric CRF in Serbia. Since its prevalence is considerably lower than that in Western and North European countries the true prevalence is some what higher. The increasing incidence of pediatric TRF from 2

  13. A corticotropin releasing factor pathway for ethanol regulation of the ventral tegmental area in the bed nucleus of the stria terminalis.

    Science.gov (United States)

    Silberman, Yuval; Matthews, Robert T; Winder, Danny G

    2013-01-16

    A growing literature suggests that catecholamines and corticotropin-releasing factor (CRF) interact in a serial manner to activate the bed nucleus of the stria terminalis (BNST) to drive stress- or cue-induced drug- and alcohol-seeking behaviors. Data suggest that these behaviors are driven in part by BNST projections to the ventral tegmental area (VTA). Together, these findings suggest the existence of a CRF-signaling pathway within the BNST that is engaged by catecholamines and regulates the activity of BNST neurons projecting to the VTA. Here we test three aspects of this model to determine: (1) whether catecholamines modify CRF neuron activity in the BNST; (2) whether CRF regulates excitatory drive onto VTA-projecting BNST neurons; and (3) whether this system is altered by ethanol exposure and withdrawal. A CRF neuron fluorescent reporter strategy was used to identify BNST CRF neurons for whole-cell patch-clamp analysis in acutely prepared slices. Using this approach, we found that both dopamine and isoproterenol significantly depolarized BNST CRF neurons. Furthermore, using a fluorescent microsphere-based identification strategy we found that CRF enhances the frequency of spontaneous EPSCs onto VTA-projecting BNST neurons in naive mice. This action of CRF was occluded during acute withdrawal from chronic intermittent ethanol exposure. These findings suggest that dopamine and isoproterenol may enhance CRF release from local BNST sources, leading to enhancement of excitatory neurotransmission on VTA-projecting neurons, and that this pathway is engaged by patterns of alcohol exposure and withdrawal known to drive excessive alcohol intake.

  14. CRF: detection of CRISPR arrays using random forest

    Directory of Open Access Journals (Sweden)

    Kai Wang

    2017-04-01

    Full Text Available CRISPRs (clustered regularly interspaced short palindromic repeats are particular repeat sequences found in wide range of bacteria and archaea genomes. Several tools are available for detecting CRISPR arrays in the genomes of both domains. Here we developed a new web-based CRISPR detection tool named CRF (CRISPR Finder by Random Forest. Different from other CRISPR detection tools, a random forest classifier was used in CRF to filter out invalid CRISPR arrays from all putative candidates and accordingly enhanced detection accuracy. In CRF, particularly, triplet elements that combine both sequence content and structure information were extracted from CRISPR repeats for classifier training. The classifier achieved high accuracy and sensitivity. Moreover, CRF offers a highly interactive web interface for robust data visualization that is not available among other CRISPR detection tools. After detection, the query sequence, CRISPR array architecture, and the sequences and secondary structures of CRISPR repeats and spacers can be visualized for visual examination and validation. CRF is freely available at http://bioinfolab.miamioh.edu/crf/home.php.

  15. Localization and functional roles of corticotropin-releasing factor receptor type 2 in the cerebellum

    NARCIS (Netherlands)

    Gounko, Natalia V.; Gramsbergen, Albert; van der Want, Johannes J. L.

    2008-01-01

    The corticotropin-releasing factor (CRF) type 2 receptor has three splice variants alpha, beta, and gamma. In the rodent brain only CRF-R2 alpha is present. In the cerebellum, CRF-R2 alpha has two different isoforms: a full-length form (fl) and truncated (tr). Both forms CRF-R2 have a unique cellula

  16. Stress-related modulation of inflammation in experimental models of bowel disease and post-infectious irritable bowel syndrome: role of corticotropin-releasing factor receptors.

    Science.gov (United States)

    Kiank, Cornelia; Taché, Yvette; Larauche, Muriel

    2010-01-01

    The interaction between gut inflammatory processes and stress is gaining increasing recognition. Corticotropin-releasing factor (CRF)-receptor activation in the brain is well established as a key signaling pathway initiating the various components of the stress response including in the viscera. In addition, a local CRF signaling system has been recently established in the gut. This review summarize the present knowledge on mechanisms through which both brain and gut CRF receptors modulate intestinal inflammatory processes and its relevance towards increased inflammatory bowel disease (IBD) activity and post-infectious irritable bowel syndrome (IBS) susceptibility induced by stress.

  17. Molecular evolution of HIV-1 CRF01_AE Env in Thai patients.

    Directory of Open Access Journals (Sweden)

    Samatchaya Boonchawalit

    Full Text Available BACKGROUND: The envelope glycoproteins (Env, gp120 and gp41, are the most variable proteins of human immunodeficiency virus type 1 (HIV-1, and are the major targets of humoral immune responses against HIV-1. A circulating recombinant form of HIV-1, CRF01_AE, is prevalent throughout Southeast Asia; however, only limited information regarding the immunological characteristics of CRF01_AE Env is currently available. In this study, we attempted to examine the evolutionary pattern of CRF01_AE Env under the selection pressure of host immune responses. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood samples were collected periodically over 3 years from 15 HIV-1-infected individuals residing in northern Thailand, and amplified env genes from the samples were subjected to computational analysis. The V5 region of gp120 showed highest variability in several samples over 3 years, whereas the V1/V2 and/or V4 regions of gp120 also showed high variability in many samples. In addition, the N-terminal part of the C3 region of gp120 showed highest amino acid diversity among the conserved regions of gp120. Chronological changes in the numbers of amino acid residues in gp120 variable regions and potential N-linked glycosylation (PNLG sites are involved in increasing the variability of Env gp120. Furthermore, the C3 region contained several amino acid residues potentially under positive selection, and APOBEC3 family protein-mediated G to A mutations were frequently detected in such residues. CONCLUSIONS/SIGNIFICANCE: Several factors, including amino acid substitutions particularly in gp120 C3 and V5 regions as well as changes in the number of PNLG sites and in the length of gp120 variable regions, were revealed to be involved in the molecular evolution of CRF01_AE Env. In addition, a similar tendency was observed between CRF01_AE and subtype C Env with regard to the amino acid variation of gp120 V3 and C3 regions. These results may provide important information for

  18. Internalization of the human CRF receptor 1 is independent of classical phosphorylation sites and of beta-arrestin 1 recruitment

    DEFF Research Database (Denmark)

    Rasmussen, Trine N; Novak, Ivana; Nielsen, Søren M

    2004-01-01

    The corticotropin releasing factor receptor 1 (CRFR1) belongs to the superfamily of G-protein coupled receptors. Though CRF is involved in the aetiology of several stress-related disorders, including depression and anxiety, details of CRFR1 regulation such as internalization remain uncharacterize...

  19. Effects of corticotropin releasing factor on spontaneous burst activity in the piriform-amygdala complex of in vitro brain preparations from newborn rats.

    Science.gov (United States)

    Fujii, Tomoko; Onimaru, Hiroshi; Homma, Ikuo

    2011-10-01

    The amygdala is an important higher regulatory center of the autonomic nervous system, involved in respiratory and cardiovascular control, and it also plays a role in the formation of emotions. Corticotropin-releasing factor (CRF) is a neuropeptide involved in stress responses. We have examined the effects of CRF on the spontaneous burst activity in the piriform-amygdala complex of rat brain preparations in vitro. Limbic-brainstem-spinal cord preparations of 0- to 1-day-old Wistar rats were isolated under deep ether anesthesia, and were superperfused in a modified Krebs solution. Bath application of 50nM CRF substantially increased the frequency of burst activity in the piriform-amygdala complex, whereas this polypeptide exerted only minor effects on C4 inspiratory activity. The excitatory effect of CRF on the amygdala burst was effectively blocked by the CRF1 antagonist, antalarmin, but not the CRF2 antagonist, astressin-2B, suggesting that CRF1 mediated the excitatory effect. The spatio-temporal pattern of the burst activity according to optical recordings was basically identical to the controls; the burst activity initially appeared in the piriform cortex and then propagated to the amygdala. The present experimental model could be useful for the study of role of the limbic system, including the amygdala, in stress responses.

  20. GABA and NMDA receptors in CRF neurons have opposing effects in fear acquisition and anxiety in central amygdala vs. bed nucleus of the stria terminalis.

    Science.gov (United States)

    Gafford, Georgette M; Ressler, Kerry J

    2015-11-01

    This article is part of a Special Issue "SBN 2014". Beginning with Vale and Colleagues in 1981, corticotropin releasing factor (CRF) also called corticotropin releasing hormone (CRH) has repeatedly been identified as an important contributor to fear and anxiety behavior. These findings have proven useful to further our understanding of disorders that have significant fear-dysregulation, such as post-traumatic stress, as well as other stress- and anxiety-related disorders. Unfortunately, the data are not all in agreement. In particular the role of CRF in fear learning is controversial, with studies pointing to contradictory effects from CRF manipulation even within the same brain structure. Further, very few studies address the potentially promising role of CRF manipulation in fear extinction behavior. Here, we briefly review the role of CRF in anxiety, fear learning and extinction, focusing on recent cell-type and neurotransmitter-specific studies in the amygdala and bed nucleus of the stria terminalis (BNST) that may help to synthesize the available data on the role of CRF in fear and anxiety-related behaviors.

  1. Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

    Science.gov (United States)

    Burke, Andrew R.; Miczek, Klaus A.

    2014-01-01

    Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

  2. Corticotropin-releasing factor administration elicits a stress-like activation of cerebral catecholaminergic systems.

    Science.gov (United States)

    Dunn, A J; Berridge, C W

    1987-08-01

    The cerebral content of the biogenic amines, dopamine (DA), norepinephrine (NE), and serotonin (5-HT) and their catabolites 30 min after CRF or saline injections was determined using HPLC with electrochemical detection. Injection of CRF (1.0 micrograms) into the lateral ventricles (ICV) of mice produced a behavioral activation in which their motor movements appeared as bursts of activity followed by periods of immobility. CRF administration (ICV or SC) did not alter the concentrations of DA, NE, tryptophan, 5-HT, or 5-hydroxyindoleacetic acid (5-HIAA) in any brain region measured. ICV CRF increased the concentrations of dihydroxyphenylacetic acid (DOPAC), the major catabolite of DA, and of 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG), the major catabolite of NE, in several brain regions. DOPAC:DA ratios were consistently increased in prefrontal cortex, septum, hypothalamus, and brain stem relative to animals injected with saline. MHPG:NE ratios were also increased in the prefrontal cortex and hypothalamus, with a marginal effect (p = 0.06) in brain stem. SC CRF significantly increased DOPAC:DA in prefrontal cortex, and MHPG:NE in prefrontal cortex, hypothalamus and brain stem. Pretreatment with naloxone did not prevent any of the neurochemical responses to ICV CRF, but naloxone alone increased DOPAC:DA in medial profrontal cortex, and decreased MHPG:NE in nucleus accumbens in CRF-injected mice. These results suggest that administration of CRF either centrally or peripherally induces an activation of both dopaminergic and noradrenergic systems in several regions of mouse brain.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Pavlovian conditioning of corticotropin-releasing factor-induced increase of blood pressure and corticosterone secretion in the rat.

    Science.gov (United States)

    Kreutz, M; Hellhammer, D; Murison, R; Vetter, H; Krause, U; Lehnert, H

    1992-05-01

    Corticotropin-releasing factor (CRF) is clearly involved in the central regulation of the pituitary-adrenal axis and, moreover, of autonomic nervous system functions. Enhanced sympathetic activity with subsequent increases in blood pressure and heart rate and attenuation of the baroreceptor reflex results from the intracerebroventricular (i.c.v.) administration of CRF. Additionally, the peptide has a variety of potent effects on behavioural responses in animals similar to those observed after an experimentally evoked stress. It was therefore of obvious interest to examine whether CRF is a possible mediator of the learning processes associated with physiological stress reaction patterns. This report clearly demonstrates a classical conditioning of the endocrine (i.e. corticosterone secretion) and haemodynamic (i.e. blood pressure) sequelae following central CRF application and thus indicates that this mechanism is of physiological significance for learned stress responses.

  4. Opposing roles of corticotropin-releasing factor and neuropeptide Y within the dorsolateral bed nucleus of the stria terminalis in the negative affective component of pain in rats.

    Science.gov (United States)

    Ide, Soichiro; Hara, Taiki; Ohno, Atsushi; Tamano, Ryuta; Koseki, Kana; Naka, Tomonori; Maruyama, Chikashi; Kaneda, Katsuyuki; Yoshioka, Mitsuhiro; Minami, Masabumi

    2013-04-01

    Pain is a complex experience composed of sensory and affective components. Although the neural systems of the sensory component of pain have been studied extensively, those of its affective component remain to be determined. In the present study, we examined the effects of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) injected into the dorsolateral bed nucleus of the stria terminalis (dlBNST) on pain-induced aversion and nociceptive behaviors in rats to examine the roles of these peptides in affective and sensory components of pain, respectively. In vivo microdialysis showed that formalin-evoked pain enhanced the release of CRF in this brain region. Using a conditioned place aversion (CPA) test, we found that intra-dlBNST injection of a CRF1 or CRF2 receptor antagonist suppressed pain-induced aversion. Intra-dlBNST CRF injection induced CPA even in the absence of pain stimulation. On the other hand, intra-dlBNST NPY injection suppressed pain-induced aversion. Coadministration of NPY inhibited CRF-induced CPA. This inhibitory effect of NPY was blocked by coadministration of a Y1 or Y5 receptor antagonist. Furthermore, whole-cell patch-clamp electrophysiology in dlBNST slices revealed that CRF increased neuronal excitability specifically in type II dlBNST neurons, whereas NPY decreased it in these neurons. Excitatory effects of CRF on type II dlBNST neurons were suppressed by NPY. These results have uncovered some of the neuronal mechanisms underlying the affective component of pain by showing opposing roles of intra-dlBNST CRF and NPY in pain-induced aversion and opposing actions of these peptides on neuronal excitability converging on the same target, type II neurons, within the dlBNST.

  5. Seasonal changes in CRF-I and urotensin I transcript levels in masu salmon: correlation with cortisol secretion during spawning.

    Science.gov (United States)

    Westring, Christian G; Ando, Hironori; Kitahashi, Takashi; Bhandari, Ramji Kumar; Ueda, Hiroshi; Urano, Akihisa; Dores, Robert M; Sher, Anna A; Danielson, Phillip B

    2008-01-01

    Pacific salmon employ a semelparous reproductive strategy where sexual maturation is followed by rapid senescence and death. Cortisol overproduction has been implicated as the central physiologic event responsible for the post-spawning demise of these fish. Cortisol homeostasis is regulated through the action of hormones of the hypothalamus-pituitary-interrenal (HPI) axis. These include corticotropin-releasing factor (CRF) and urotensin-I (UI). In the present study, masu salmon (Oncorhynchus masou) were assayed for changes in the levels CRF-I and UI mRNA transcripts by quantitative real-time PCR (qRT-PCR). These results were compared to plasma cortisol levels in juvenile, adult, and spawning masu salmon to identify specific regulatory factors that appear to be functionally associated with changes in cortisol levels. Intramuscular implantation of GnRH analog (GnRHa) capsules was also used to determine whether GnRH influences stress hormone levels. In both male and female masu salmon, spawning fish experienced a 5- to 7-fold increase in plasma cortisol levels relative to juvenile non-spawning salmon. Changes in CRF-I mRNA levels were characterized by 1-2 distinctive short-term surges in adult masu salmon. Conversely, seasonal changes in UI mRNA levels displayed broad and sustained increases during the pre-spawning and spawning periods. The increases in UI mRNA levels were positively correlated (R(2)=0.21 male and 0.26 female, pcortisol in the pre-spawning and spawning periods. Despite the importance of GnRH in sexual maturation and reproduction, the administration of GnRHa to test animals failed to produce broad changes in CRF-I, UI or plasma cortisol levels. These findings suggest a more direct role for UI than for CRF-I in the regulation of cortisol levels in spawning Pacific salmon.

  6. Phylogeographic Analyses Reveal a Crucial Role of Xinjiang in HIV-1 CRF07_BC and HCV 3a Transmissions in Asia

    Science.gov (United States)

    Liu, Jun; Zhang, Chiyu

    2011-01-01

    Background China faces an increasing prevalence of two HIV-1 circulating recombinant forms (CRFs) 07_BC and 08_BC. Both CRFs_BC were previously demonstrated to originate in Yunnan and spread to Liaoning from Yunnan via injection drug use (IDU) in China. Supposing it is true, we are unable to answer why only CRF07_BC, rather than both CRFs_BC together, was transmitted to Xinjiang. Methodology/Principal Findings We investigated the phylogeography of CRF07_BC and CRF08_BC using multiple HIV-1 genomic regions with Bayesian phylogeography method. Phylogenetic reconstructions showed that all CRF07_BC sequences were divided into two clades, Yunnan and Xinjiang, and all strains from other regions of mainland China clustered within the Xinjiang clade. Significant geographic diffusion links of Xinjiang with other regions (including Liaoning, Beijing, Jiangsu and Guangdong) were supported by Bayes factor tests. The temporal dynamics analyses showed that CRF07_BC spread from Xinjiang to Liaoning in 1996.10, and to Jiangsu in 2000.9. The analyses of CRF08_BC not only confirmed the previous conclusion on temporal and spatial dynamics of CRF08_BC, but also indicated that the CRF08_BC strains from Guangdong and Shanghai originated from Yunnan. The analyses of HCV 3a showed that it was introduced into Xinjiang in the early 1980s, and spread from Xinjiang to Yunnan in 1990.10 and to Jiangsu in 1999.2, and further from Yunnan to Guangxi in 1995.3. The temporal and spatial dynamics of HCV 3a were similar to some extent to that of HIV-1 CRF07_BC and/or CRF08_BC, suggesting a possible association in migration patterns between HCV and HIV-1 through IDU. In addition, HCV 3a spread from Xinjiang to Pakistan, implying a drug trafficking route linking them. Conclusions/Significance Xinjiang, as the most important transfer station for drug trafficking from Golden Crescent to other regions of China, plays a very crucial role in the transmission of viruses (e.g., HIV-1 and HCV) through IDU in

  7. Predator stress engages corticotropin-releasing factor and opioid systems to alter the operating mode of locus coeruleus norepinephrine neurons.

    Science.gov (United States)

    Curtis, Andre L; Leiser, Steven C; Snyder, Kevin; Valentino, Rita J

    2012-03-01

    The norepinephrine nucleus, locus coeruleus (LC), has been implicated in cognitive aspects of the stress response, in part through its regulation by the stress-related neuropeptide, corticotropin-releasing factor (CRF). LC neurons discharge in tonic and phasic modes that differentially modulate attention and behavior. Here, the effects of exposure to an ethologically relevant stressor, predator odor, on spontaneous (tonic) and auditory-evoked (phasic) LC discharge were characterized in unanesthetized rats. Similar to the effects of CRF, stressor presentation increased tonic LC discharge and decreased phasic auditory-evoked discharge, thereby decreasing the signal-to-noise ratio of the sensory response. This stress-induced shift in LC discharge toward a high tonic mode was prevented by a CRF antagonist. Moreover, CRF antagonism during stress unmasked a large decrease in tonic discharge rate that was opioid mediated because it was prevented by pretreatment with the opiate antagonist, naloxone. Elimination of both CRF and opioid influences with an antagonist combination rendered LC activity unaffected by the stressor. These results demonstrate that both CRF and opioid afferents are engaged during stress to fine-tune LC activity. The predominant CRF influence shifts the operational mode of LC activity toward a high tonic state that is thought to facilitate behavioral flexibility and may be adaptive in coping with the stressor. Simultaneously, stress engages an opposing opioid influence that restrains the CRF influence and may facilitate recovery toward pre-stress levels of activity. Changes in the balance of CRF:opioid regulation of the LC could have consequences for stress vulnerability.

  8. [Role of the Periaqueductal Gray Matter of the Midbrain in Regulation of Somatic Pain Sensitivity During Stress: Participation of Corticotropin-Releasing Factor and Glucocorticoid Hormones].

    Science.gov (United States)

    Yarushkina, N I; Filaretova, L P

    2015-01-01

    Periaqueductal gray matter of the midbrain (PAGM) plays a crucial role in the regulation of pain sensitivity under stress, involving in the stress-induced analgesia. A key hormonal system of adaptation under stress is the hypothalamic-pituitary-adrenocortical (HPA) axis. HPA axis's hormones, corticotropin-releasing factor (CRF) and glucocorticoids, are involved in stress-induced analgesia. Exogenous hormones of the HPA axis, similarly to the hormones produced under stress, may cause an analgesic effect. CRF-induced analgesia may be provided by glucocorticoid hormones. CRF and glucocorticoids-induced effects on somatic pain sensitivity may be mediated by PAGM. The aim of the review was to analyze the data of literature on the role of PAGM in the regulation of somatic pain sensitivity under stress and in providing of CRF and glucocorticoid-induced analgesia.

  9. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

    Directory of Open Access Journals (Sweden)

    Andreas Stengel

    2017-04-01

    Full Text Available Corticotropin-releasing factor (CRF is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  10. The blockage of ventromedial hypothalamus CRF type 2 receptors impairs escape responses in the elevated T-maze.

    Science.gov (United States)

    Silva, Mariana S C F; Souza, Thaissa M O; Pereira, Bruno A; Ribeiro, Daniel A; Céspedes, Isabel C; Bittencourt, Jackson C; Viana, Milena B

    2017-06-30

    In a previous study, the administration of corticotrophin-releasing factor (CRF) into the dorsomedial hypothalamus (DMH), a region that modulates defensive reactions, was shown to facilitate elevated T-maze (ETM) avoidance responses, an anxiogenic-like effect. Intra-DMH administration of the CRF type 1 receptor (CRFR1) antagonist antalarmin induced anxiolytic-like effects and counteracted the anxiogenic effects of CRF. The present study further investigates the role played by CRF receptors of the medial hypothalamus in anxiety. For that, male wistar rats were treated with CRFR1 and CRFR2-modulating drugs in the DMH or VMH, another hypothalamic nucleus implicated with defensive and emotional behavior, and tested in the ETM for inhibitory avoidance and escape measurements. In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. The results showed that intra-VMH CRF or antalarmin did not alter ETM avoidance or escape performance. Intra-VMH injection of the CRFR2 preferential antagonist antisauvagine-30 or of the selective CRFR2 antagonist astressin 2-B inhibited escape performance, a panicolytic-like effect, without altering avoidance reactions. The CRFR2 agonist urocortin-2 intra-VMH was by itself without effect but blocked the effects of astressin 2-B. None of the drugs administered into the DMH altered ETM measurements. Additionally, none of the compounds altered locomotor activity measurements. These results suggest that VMH CRFR2 modulate a defensive response associated with panic disorder and are of relevance to the better understanding of the neural mechanisms underlying this pathological condition. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Molecular detection of HIV-1 subtype B, CRF01_AE, CRF33_01B, and newly emerging recombinant lineages in Malaysia.

    Science.gov (United States)

    Chook, Jack Bee; Ong, Lai Yee; Takebe, Yutaka; Chan, Kok Gan; Choo, Martin; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-03-01

    A molecular genotyping assay for human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia is difficult to design because of the high level of genetic diversity. We developed a multiplex real-time polymerase chain reaction (PCR) assay to detect subtype B, CRF01_AE, CRF33_01B, and three newly described circulating recombinant forms, (CRFs) (CRF53_01B, CRF54_01B, and CRF58_01B). A total of 785 reference genomes were used for subtype-specific primers and TaqMan probes design targeting the gag, pol, and env genes. The performance of this assay was compared and evaluated with direct sequencing and phylogenetic analysis. A total of 180 HIV-infected subjects from Kuala Lumpur, Malaysia were screened and 171 samples were successfully genotyped, in agreement with the phylogenetic data. The HIV-1 genotype distribution was as follows: subtype B (16.7%); CRF01_AE (52.8%); CRF33_01B (24.4%); CRF53_01B (1.1%); CRF54_01B (0.6%); and CRF01_AE/B unique recombinant forms (4.4%). The overall accuracy of the genotyping assay was over 95.0%, in which the sensitivities for subtype B, CRF01_AE, and CRF33_01B detection were 100%, 100%, and 97.7%, respectively. The specificity of genotyping was 100%, inter-subtype specificities were > 95% and the limit of detection of 10(3) copies/mL for plasma. The newly developed real-time PCR assay offers a rapid and cost-effective alternative for large-scale molecular epidemiological surveillance for HIV-1. © The American Society of Tropical Medicine and Hygiene.

  12. From Hans Selye’s Discovery of Biological Stress to the Identification of Corticotropin Releasing Factor signaling pathways: Implication in Stress-Related Functional Bowel Diseases

    OpenAIRE

    2008-01-01

    Selye’s pioneer the concept of biological stress in 1936 culminating to the identification of the corticotropin releasing factor (CRF) signaling pathways by Vale’s group in the last two decades. The characterization of the 41 amino-acid CRF and other peptide members of the mammalian CRF family, urocortin 1, urocortin 2 and urocortin 3, the cloning of CRF1 and CRF2 receptors, which display distinct affinity for CRF ligands, combined with the development of selective CRF receptor antagonists en...

  13. Enduring Effects Of Traumatic Stress On Brain Neuropeptide Y (NPY) and Corticotropin-Releasing Factor (CRF) Systems: Molecular and Neuropharmacologic Studies

    Science.gov (United States)

    2009-12-01

    nucleus of the hypothalamus, and medial amygdala post-defeat. AcN Control Defeated 0 10 20 30 40 50 60 70 80 # Treatment VMH Control Defeated 0 10 20...ains to be determined. Defeat also increased the number of Fos-positive cells n the VMH, another androgen receptor–expressing nu- leus that is larger...Finally, the androgen - ependent sexual dimorphism of VMH volume is seen electively in the ventrolateral, but not dorsomedial, sub- ivision (Dugger et al

  14. Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats

    Directory of Open Access Journals (Sweden)

    Yeh C

    2016-10-01

    Full Text Available Chun Yeh,1 Ching-Heng Ting,2 Ming-Luen Doong,3 Chin-Wen Chi,4,5 Shou-Dong Lee,1 Chih-Yen Chen6–8 1Division of Gastroenterology, Department of Internal Medicine, Cheng-Hsin General Hospital, 2Department of Pathology, Mackay Memorial Hospital, 3Institute of Physiology, 4Institute of Pharmacology, National Yang-Ming University School of Medicine, 5Department of Medical Research, Taipei Veterans General Hospital, 6Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 7Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, 8Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan Purpose: Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin on food intake and gastric emptying remain uninvestigated.Methods: We examined the differential effects of central O-n-octanoylated ghrelin, des-Gln14-ghrelin, and urocortin 3 on food intake, as well as on charcoal nonnutrient semiliquid gastric emptying in conscious rats that were chronically implanted with intracerebroventricular (ICV catheters. The functional importance of corticotropin-releasing factor (CRF receptor 2 in urocortin 3-induced responses was examined by ICV injection of the selective CRF receptor 2 antagonist, astressin2-B.Results: ICV infusion of urocortin 3 opposed central acyl ghrelin-elicited hyperphagia via CRF receptor 2 in satiated rats. ICV injection of O-n-octanoylated ghrelin and des-Gln14-ghrelin were equally potent in accelerating gastric emptying in fasted rats, whereas ICV administration of urocortin 3 delayed gastric emptying. In addition, ICV infusion of urocortin 3 counteracted central acyl ghrelin-induced gastroprokinetic effects via CRF receptor 2

  15. Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin-releasing factor and nerve growth factor interplay.

    Science.gov (United States)

    Barreau, Frederick; Cartier, Christel; Leveque, Mathilde; Ferrier, Laurent; Moriez, Raphael; Laroute, Valerie; Rosztoczy, Andras; Fioramonti, Jean; Bueno, Lionel

    2007-04-01

    Neonatal maternal deprivation (NMD) increases gut paracellular permeability (GPP) through mast cells and nerve growth factor (NGF), and modifies corticotrophin-releasing factor (CRF) and corticosterone levels. CRF, corticosterone and mast cells are involved in stress-induced mucosal barrier impairment. Consequently, this study aimed to specify whether corticosteronaemia and colonic expression of both preproCRF and CRF are modified by NMD, and to determine if altered expression may participate in the elevated GPP in connection with NGF and mast cells. Male Wistar rat pups were either separated from postnatal days 2-14, or left undisturbed with their dam. At 12 weeks of age, adult rats were treated with mifepristone (an antagonist of corticoid receptors), alpha-helical CRF((9-41)) (a non-specific CRF receptor antagonist), or SSR-125543 (CRF-R(1) receptor antagonist). We also determined corticosteronaemia and both colonic preproCRF and CRF expression. Then, control rats were treated by CRF, doxantrazole (mast cell stabilizer), BRX-537A (a mast cell activator) and anti-NGF antibody. NMD did not modify colonic CRF level but increased colonic preproCRF expression and corticosteronaemia. Peripheral CRF, via CRF-R(1) receptor, but not corticosterone, was involved in the elevated GPP observed in these rats, through a mast-cell-mediated mechanism, since the increase of GPP induced by exogenous CRF was abolished by doxantrazole. Anti-NGF antibody treatment also reduced the elevated GPP induced by CRF or BRX-537A. CRF acts through CRF-R(1) receptors to stimulate NGF release from mast cells, which participates in the elevated GPP observed in NMD adult rats. This suggests that early traumatic experience induced neuro-endocrine dysfunction, involved in alterations of gut mucosal barrier.

  16. Corticotropin-releasing factor has an anxiogenic action in the social interaction test.

    Science.gov (United States)

    Dunn, A J; File, S E

    1987-06-01

    The effects of intracerebroventricular (icv) injections of corticotropin-releasing factor (CRF, 100 and 300 ng) were investigated in the social interaction test of anxiety in rats. Both doses of CRF significantly decreased active social interaction without a concomitant decrease in locomotor activity. CRF also significantly increased self-grooming, an effect that was independent of the decrease in social interaction. These results indicate an anxiogenic action for CRF. Chlordiazepoxide (CDP, 5 mg/kg ip) pretreatment reversed the anxiogenic effects of icv CRF (100 ng), but CRF did not prevent the sedative effects of CDP. There were no statistically significant changes due to CRF in locomotor activity or rears or head dipping in the holeboard test. Both doses of CRF significantly increased plasma concentrations of corticosterone. The possible mechanisms of the behavioral effects of CRF are discussed.

  17. Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

    Science.gov (United States)

    Peciña, Susana; Schulkin, Jay; Berridge, Kent C

    2006-01-01

    Background Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 μl) or amphetamine (20 μg/0.2 μl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 μg) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent

  18. Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

    Directory of Open Access Journals (Sweden)

    Schulkin Jay

    2006-04-01

    Full Text Available Abstract Background Corticotropin-releasing factor (CRF is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior. Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 μl or amphetamine (20 μg/0.2 μl. Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results Microinjections of the highest dose of CRF (500 ng or amphetamine (20 μg selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress

  19. Regulation of gonadotropins by corticotropin-releasing factor and urocortin

    Directory of Open Access Journals (Sweden)

    Kazunori eKageyama

    2013-02-01

    Full Text Available While stress activates the hypothalamic-pituitary-adrenal (HPA axis, it suppresses the hypothalamic-pituitary-gonadal (HPG axis. Corticotropin-releasing factor (CRF is a major regulatory peptide in the HPA axis during stress. Urocortin1 (Ucn1, a member of the CRF family of peptides, has a variety of physiological functions and both CRF and Ucn1 contribute to the stress response via G protein-coupled seven transmembrane receptors. Ucn2 and Ucn3, which belong to a separate paralogous lineage from CRF, are highly selective for the CRF type 2 receptor (CRF2 receptor. The HPA and HPG axes interact with each other, and gonadal function and reproduction are suppressed in response to various stressors. In this review, we focus on the regulation of gonadotropins by CRF and Ucn2 in pituitary gonadotrophs and of gonadotropin-releasing hormone (GnRH via CRF receptors in the hypothalamus. In corticotrophs, stress-induced increases in CRF stimulate Ucn2 production, which leads to the inhibition of gonadotropin secretion via the CRF2 receptor in the pituitary. GnRH in the hypothalamus is regulated by a variety of stress conditions. CRF is also involved in the suppression of the HPG axis, especially the GnRH pulse generator, via CRF receptors in the hypothalamus. Thus, complicated regulation of GnRH in the hypothalamus and gonadotropins in the pituitary via CRF receptors contributes to stress responses and adaptation of gonadal functions.

  20. Phylodynamic analysis reveals CRF01_AE dissemination between Japan and neighboring Asian countries and the role of intravenous drug use in transmission.

    Directory of Open Access Journals (Sweden)

    Teiichiro Shiino

    Full Text Available BACKGROUND: One major circulating HIV-1 subtype in Southeast Asian countries is CRF01_AE, but little is known about its epidemiology in Japan. We conducted a molecular phylodynamic study of patients newly diagnosed with CRF01_AE from 2003 to 2010. METHODS: Plasma samples from patients registered in Japanese Drug Resistance HIV-1 Surveillance Network were analyzed for protease-reverse transcriptase sequences; all sequences undergo subtyping and phylogenetic analysis using distance-matrix-based, maximum likelihood and Bayesian coalescent Markov Chain Monte Carlo (MCMC phylogenetic inferences. Transmission clusters were identified using interior branch test and depth-first searches for sub-tree partitions. Times of most recent common ancestor (tMRCAs of significant clusters were estimated using Bayesian MCMC analysis. RESULTS: Among 3618 patient registered in our network, 243 were infected with CRF01_AE. The majority of individuals with CRF01_AE were Japanese, predominantly male, and reported heterosexual contact as their risk factor. We found 5 large clusters with ≥5 members and 25 small clusters consisting of pairs of individuals with highly related CRF01_AE strains. The earliest cluster showed a tMRCA of 1996, and consisted of individuals with their known risk as heterosexual contacts. The other four large clusters showed later tMRCAs between 2000 and 2002 with members including intravenous drug users (IVDU and non-Japanese, but not men who have sex with men (MSM. In contrast, small clusters included a high frequency of individuals reporting MSM risk factors. Phylogenetic analysis also showed that some individuals infected with HIV strains spread in East and South-eastern Asian countries. CONCLUSIONS: Introduction of CRF01_AE viruses into Japan is estimated to have occurred in the 1990s. CFR01_AE spread via heterosexual behavior, then among persons connected with non-Japanese, IVDU, and MSM. Phylogenetic analysis demonstrated that some viral

  1. Effects of antalarmin, a CRF receptor 1 antagonist, on fright reaction and endocrine stress response in crucian carp (Carassius carassius)

    DEFF Research Database (Denmark)

    Lastein, Stine; Höglund, Erik; Overli, Oyvind

    2008-01-01

    and stress reactions in non-mammalian vertebrates are largely unknown. Crucian carp displays the olfactory-mediated fright reaction, a stereotypic behavioral response to waterborne cues from damaged skin of conspecifics. This reaction shows several similarities to basic components of avoidance behavior......The corticotrophin-releasing factor (CRF) receptors show striking homogeneity throughout the vertebrate subphylum. In mammals, the CRF1 receptor (CRFR1) plays an important role in mediating behavioral and endocrine responses to fear and stress. The specific roles of this receptor subtype in fear...... in mammals. In the present study, we applied the non-peptide CRFR1 antagonist, antalarmin, to crucian carp 1 h before exposure to conspecific skin extract. This treatment resulted in a suppression of the fright reaction. After skin extract exposure, antalarmin treatment also lead to lower plasma cortisol...

  2. Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin-releasing factor and nerve growth factor interplay

    OpenAIRE

    2007-01-01

    Neonatal maternal deprivation (NMD) increases gut paracellular permeability (GPP) through mast cells and nerve growth factor (NGF), and modifies corticotrophin-releasing factor (CRF) and corticosterone levels. CRF, corticosterone and mast cells are involved in stress-induced mucosal barrier impairment. Consequently, this study aimed to specify whether corticosteronaemia and colonic expression of both preproCRF and CRF are modified by NMD, and to determine if altered expression may participate...

  3. Deletion of Corticotropin-releasing Factor Binding Protein Selectively Impairs Maternal, but not Intermale Aggression

    OpenAIRE

    Gammie, Stephen C.; Seasholtz, Audrey F.; Stevenson, Sharon A.

    2008-01-01

    Corticotropin-releasing factor (CRF) binding protein (CRF-BP) is a secreted protein that acts to bind and limit the activity of the neuropeptides, CRF and urocortin (Ucn) 1. We previously selected for high maternal defense (protection of offspring) in mice and found CRF-BP to be elevated in the CNS of selected mice. We also previously determined that both CRF and Ucn 1 are potent inhibitors of offspring protection when administered centrally. Thus, elevated CRF-BP could promote defense by lim...

  4. Risk factors for osteoporosis and fragility fractures in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Carli, L; Tani, C; Spera, V; Vagelli, R; Vagnani, S; Mazzantini, M; Di Munno, O; Mosca, M

    2016-01-01

    Osteoporosis (OP) and fragility fractures (FFx) are a known comorbidity in patients with systemic lupus erythematosus (SLE). This work aimed at evaluating (1) the prevalence of OP and FFx in a cohort of SLE and (2) the risk factors associated with both OP and FFx. The following data were collected from clinical charts: age, sex, menopausal status (MP), body mass index, smoking habits, disease duration, daily dose and cumulative glucocorticoids (GCs), type of organ involvement, comorbidities and medications. Data on bone metabolism, calcium and vitamin D supplementation and treatment with bisphosphonates, teriparatide or denosumab were collected, together with bone mineral density (BMD) values (measured by dual-energy X-ray absorptiometry (DXA)) and history of FFx (occurred after the onset of SLE and unrelated to trauma). OP and reduced BMD were defined according to the WHO. 186 patients were included (women 175, men 11; mean age 46.4±13 years, mean disease duration 14.9±9 years). At their last visit, 97 patients (52.2%) had a reduced BMD and 52 (27.9%) had OP. 22 patients (11.8%), all women, had at least one FFx; six patients (27.3%) were pre-menopausal. On univariate analysis, age, cumulative dose of GC, MP, therapy with antiepileptics and chronic renal failure (CRF) were correlated with OP (p<0.03); age, total amount of GC, MP, CRF, anticoagulants (AC) and antiepileptic therapy were correlated with FFx (p<0.05). The multivariate logistic model confirmed a direct association of OP and age, MP and antiepileptic therapy (p≤0.01) and of FFx and age, chronic therapy with AC and antiepileptics (p<0.03). In conclusion, low BMD is frequently observed in SLE, and FFx are observed also in premenopausal patients. Together with traditional risk factors (age, MP and GC), CRF and chronic treatments with AC or antiepileptics seem to be associated with a higher risk profile for OP and FFx occurrence.

  5. Erp Systems Critical Success Factors

    Directory of Open Access Journals (Sweden)

    Islam K. Sowan

    2015-06-01

    Full Text Available The Enterprise Resources Planning (ERP systems are one of the highly complex systems in the information systems field; the implementations of this type of systems need a long time, high cost, and a lot of resources. Many factors affect the successful implementation of ERP system. The critical success factors (CSFs can be categorized as general, ICT related and software engineering or system life cycle (SLC related. This paper is a survey paper that identifies ERP systems CSFs in general and software engineering CSFs in specific. Also an agile methodology for ERP systems' implementations will be presented. Many existing ERP systems were surveyed and presented from ICT / software engineering point of view.

  6. Influence of bombesin, CCK, secretin and CRF on corticosterone concentration in the rat.

    Science.gov (United States)

    Sander, L D; Porter, J R

    1988-01-01

    The ingestion of food increases adrenoglucocorticoid secretion in humans and rats and influences the circadian periodicity of ACTH and corticosterone in rats fed on restricted schedules. The purpose of this study was to determine the influence of the brain-gut polypeptides CCK33 (10 U/kg), bombesin (10 micrograms/kg) and secretin (10 U/kg) on corticosterone concentrations in fed rats. The responses were compared to that of CRF (1 micrograms/kg). All experiments were begun at 10 a.m., 3 hours after the lights came on. The rats were given single, IP injections of peptide or vehicle (1 ml/kg) then sacrificed 0, 5, 10, 15, 30 or 60 minutes later. Corticosterone was measured fluorometrically. The control injection (vehicle) alone caused a mild stress response with corticosterone levels peaking between 10 and 15 minutes after the injection then returning to baseline. Both CCK33 and bombesin significantly increased corticosterone to approximately 2.5-fold above the control level in a fashion similar to that of CRF. In all three instances corticosterone levels peaked at 30 minutes post-injection. Secretin had no effect on corticosterone secretion. None of the peptides tested stimulated in vitro corticosterone output from isolated adrenal cells. These findings indicate that both CCK and bombesin cause pituitary-adrenal activation which may be related to the response of this system to food ingestion.

  7. Lifelong disturbance of serotonin transporter functioning results in fear learning deficits: Reversal by blockade of CRF1 receptors.

    Science.gov (United States)

    Bijlsma, Elisabeth Y; Hendriksen, Hendrikus; Baas, Johanna M P; Millan, Mark J; Groenink, Lucianne

    2015-10-01

    The inability to associate aversive events with relevant cues (i.e. fear learning) may lead to maladaptive anxiety. To further study the role of the serotonin transporter (SERT) in fear learning, classical fear conditioning was studied in SERT knockout rats (SERT(-/-)) using fear potentiation of the startle reflex. Next, fear acquisition and concomitant development of contextual conditioned fear were monitored during training. To differentiate between developmental and direct effects of reduced SERT functioning, effects of acute and chronic SSRI treatment were studied in adult rats. Considering the known interactions between serotonin and corticotropin-releasing factor (CRF), we studied the effect of the CRFR1 antagonist CP154,526 on behavioral changes observed and determined CRF1 receptor levels in SERT(-/-) rats. SERT(-/-) showed blunted fear potentiation and enhanced contextual fear, which resulted from a deficit in fear acquisition. Paroxetine treatment did not affect acquisition or expression of fear-potentiated startle, suggesting that disturbed fear learning in SERT(-/-) results from developmental changes and not from reduced SERT functioning. Although CRF1 receptor levels did not differ significantly between genotypes, CP154,526 treatment normalized both cue- and contextual fear in SERT(-/-) during acquisition, but not expression of fear-potentiated startle. The disrupted fear acquisition and concomitant increase in contextual conditioned fear-potentiated startle fear in SERT(-/-) resembles the associative learning deficit seen in patients with panic disorder and suggests that normal SERT functioning is crucial for the development of an adequate fear neuro-circuitry. Moreover, the normalization of fear acquisition by CP154,526 suggests a role for central CRF signaling in the generalization of fear.

  8. Regulation and Roles of Urocortins in the Vascular System

    Directory of Open Access Journals (Sweden)

    Kazunori Kageyama

    2012-01-01

    Full Text Available Urocortins (Ucns are members of the corticotropin-releasing factor (CRF family of peptides. Ucns would have potent effects on the cardiovascular system via the CRF receptor type 2 (CRF2 receptor. Regulation and roles of each Ucn have been determined in the vascular system. Ucns have more potent vasodilatory effects than CRF. Human umbilical vein endothelial cells (HUVECs express Ucns1-3 mRNAs, and the receptor, CRF2a receptor mRNA. Ucns1-3 mRNA levels are differentially regulated in HUVECs. Differential regulation of Ucns may suggest differential roles of those in HUVECs. Ucn1 and Ucn2 have strong effects on interleukin (IL-6 gene expression and secretion in rat aortic smooth muscle A7r5 cells. The increase that we observed in IL-6 levels following Ucn treatment of A7r5 cells suggests that smooth muscle cells may be a source of IL-6 secretion under physiological stress conditions. Ucns are important and unique modulators of vascular smooth muscle cells and act directly or indirectly as autocrine and paracrine factors in the vascular system.

  9. Associations of cardiorespiratory fitness with cardiovascular disease risk factors in middle-aged Chinese women: a cross-sectional study

    OpenAIRE

    Zhu, Wenfei; Hooker, Steven P; Sun, Yuliang; Xie, Minhao; Su, Hao; Cao, Jianmin

    2014-01-01

    Background High levels of physical activity (PA) and cardiorespiratory fitness (CRF) are each associated with a favorable cardiovascular disease (CVD) risk profile. However, the relationship between CRF and obesity is still inconsistent across studies, and there has been no thorough exploration of the independent contribution of CRF to different CVD risk factors in Chinese women. This study investigated the relationship between CRF and CVD risk factors in 40–49 year old women in Beijing. Meth...

  10. Corticotropin-Releasing Factor and the Brain-Gut Motor Response to Stress

    OpenAIRE

    1999-01-01

    The characterization of corticotropin-releasing factor (CRF) and CRF receptors, and the development of specific CRF receptor antagonists selective for the receptor subtypes have paved the way to the understanding of the biochemical coding of stress-related alterations of gut motor function. Reports have consistently established that central administration of CRF acts in the brain to inhibit gastric emptying while stimulating colonic motor function through modulation of the vagal and sacral pa...

  11. Psychological stress impairs hepatic blood flow via central CRF receptors in mice.

    Science.gov (United States)

    Chida, Yoichi; Sudo, Nobuyuki; Kubo, Chiharu

    2005-02-25

    Some previous works have further expanded the 'Brain-Gut axis', that is a bi-directional interaction between the gut and brain function, into a relationship of the brain with the liver. However, all the details of such brain-liver relationship were not fully understood because appropriate animal models had not been established yet. Here we developed a novel animal model, in which hepatic blood flow of conscious mice could be measured in real-time. In addition, using this model, we also demonstrated that exposure to psychological stress considerably reduced hepatic blood flow via central CRF receptors. Thus, this new model is considered to be a useful and promising tool for elucidating the precise effects of emotional factors on liver function.

  12. Identification of an HIV-1 BG Intersubtype Recombinant Form (CRF73_BG), Partially Related to CRF14_BG, Which Is Circulating in Portugal and Spain.

    Science.gov (United States)

    Fernández-García, Aurora; Delgado, Elena; Cuevas, María Teresa; Vega, Yolanda; Montero, Vanessa; Sánchez, Mónica; Carrera, Cristina; López-Álvarez, María José; Miralles, Celia; Pérez-Castro, Sonia; Cilla, Gustavo; Hinojosa, Carmen; Pérez-Álvarez, Lucía; Thomson, Michael M

    2016-01-01

    HIV-1 exhibits a characteristically high genetic diversity, with the M group, responsible for the pandemic, being classified into nine subtypes, 72 circulating recombinant forms (CRFs) and numerous unique recombinant forms (URFs). Here we characterize the near full-length genome sequence of an HIV-1 BG intersubtype recombinant virus (X3208) collected in Galicia (Northwest Spain) which exhibits a mosaic structure coincident with that of a previously characterized BG recombinant virus (9601_01), collected in Germany and epidemiologically linked to Portugal, and different from currently defined CRFs. Similar recombination patterns were found in partial genome sequences from three other BG recombinant viruses, one newly derived, from a virus collected in Spain, and two retrieved from databases, collected in France and Portugal, respectively. Breakpoint coincidence and clustering in phylogenetic trees of these epidemiologically-unlinked viruses allow to define a new HIV-1 CRF (CRF73_BG). CRF73_BG shares one breakpoint in the envelope with CRF14_BG, which circulates in Portugal and Spain, and groups with it in a subtype B envelope fragment, but the greatest part of its genome does not appear to derive from CRF14_BG, although both CRFs share as parental strain the subtype G variant circulating in the Iberian Peninsula. Phylogenetic clustering of partial pol and env segments from viruses collected in Portugal and Spain with X3208 and 9691_01 indicates that CRF73_BG is circulating in both countries, with proportions of around 2-3% Portuguese database HIV-1 isolates clustering with CRF73_BG. The fact that an HIV-1 recombinant virus characterized ten years ago as a URF has been shown to represent a CRF suggests that the number of HIV-1 CRFs may be much greater than currently known.

  13. Identification of an HIV-1 BG Intersubtype Recombinant Form (CRF73_BG, Partially Related to CRF14_BG, Which Is Circulating in Portugal and Spain.

    Directory of Open Access Journals (Sweden)

    Aurora Fernández-García

    Full Text Available HIV-1 exhibits a characteristically high genetic diversity, with the M group, responsible for the pandemic, being classified into nine subtypes, 72 circulating recombinant forms (CRFs and numerous unique recombinant forms (URFs. Here we characterize the near full-length genome sequence of an HIV-1 BG intersubtype recombinant virus (X3208 collected in Galicia (Northwest Spain which exhibits a mosaic structure coincident with that of a previously characterized BG recombinant virus (9601_01, collected in Germany and epidemiologically linked to Portugal, and different from currently defined CRFs. Similar recombination patterns were found in partial genome sequences from three other BG recombinant viruses, one newly derived, from a virus collected in Spain, and two retrieved from databases, collected in France and Portugal, respectively. Breakpoint coincidence and clustering in phylogenetic trees of these epidemiologically-unlinked viruses allow to define a new HIV-1 CRF (CRF73_BG. CRF73_BG shares one breakpoint in the envelope with CRF14_BG, which circulates in Portugal and Spain, and groups with it in a subtype B envelope fragment, but the greatest part of its genome does not appear to derive from CRF14_BG, although both CRFs share as parental strain the subtype G variant circulating in the Iberian Peninsula. Phylogenetic clustering of partial pol and env segments from viruses collected in Portugal and Spain with X3208 and 9691_01 indicates that CRF73_BG is circulating in both countries, with proportions of around 2-3% Portuguese database HIV-1 isolates clustering with CRF73_BG. The fact that an HIV-1 recombinant virus characterized ten years ago as a URF has been shown to represent a CRF suggests that the number of HIV-1 CRFs may be much greater than currently known.

  14. Phylogenetic and temporal dynamics of human immunodeficiency virus type 1 CRF01_AE in China.

    Directory of Open Access Journals (Sweden)

    Jingrong Ye

    Full Text Available To explore the epidemic history of HIV-1 CRF01_AE in China, 408 fragments of gag gene sequences of CRF01_AE sampled in 2002-2010 were determined from different geographical regions and risk populations in China. Phylogenetic analysis indicates that the CRF01_AE sequences can be grouped into four clusters, suggesting that at least four genetically independent CRF01_AE descendants are circulating in China, of which two were closely related to the isolates from Thailand and Vietnam. Cluster 1 has the most extensive distribution in China. In North China, cluster 1 and cluster 4 were mainly transmitted through homosexuality.The real substance of the recent HIV-1 epidemic in men who have sex with men(MSM of North China is a rapid spread of CRF01_AE, or rather two distinctive natives CRF01_AE.The time of the most recent common ancestor (tMRCA of four CRF01_AE clusters ranged from the years 1990.9 to 2003.8 in different regions of China. This is the first phylogenetic and temporal dynamics study of HIV-1 CRF01_AE in China.

  15. Identification of Two New HIV-1 Circulating Recombinant Forms (CRF87_cpx and CRF88_BC) from Reported Unique Recombinant Forms in Asia.

    Science.gov (United States)

    Hu, Yihong; Wan, Zhenzhou; Zhou, Yan-Heng; Smith, Davey; Zheng, Yong-Tang; Zhang, Chiyu

    2017-04-01

    The on-going generation of HIV-1 intersubtype recombination has led to new circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in Asia. In this study, we evaluated whether previously reported URFs were actually CRFs. All available complete or near full-length HIV-1 URF sequences from Asia were retrieved from the HIV Los Alamos National Laboratory Sequence database, and phylogenetic, transmission cluster, and bootscan analyses were performed using MEGA 6.0, Cluster Picker 1.2.1, and SimPlot3.5.1. According to the criterion of new CRFs, two new HIV-1 CRFs (CRF87_cpx and CRF88_BC) were identified from these available URFs. CRF87_cpx comprised HIV-1 subtypes B, C, and CRF01_AE, and CRF88_BC comprised subtypes B and C. HIV Blast and bootscan analysis revealed that besides the three representative strains, there were two additional CRF87_cpx strains. Furthermore, we defined seven dominant URFs (dURF01-dURF07), each of which contained two strains sharing same recombination map and can be used as sequence references to facilitate the finding of new potential CRFs in future. These results will benefit the molecular epidemiological investigation of HIV-1 in Asia.

  16. Cell-type specific deletion of GABA(A)α1 in corticotropin-releasing factor-containing neurons enhances anxiety and disrupts fear extinction

    OpenAIRE

    Gafford, Georgette M.; Guo, Ji-Dong; Flandreau, Elizabeth I.; Hazra, Rimi; Rainnie, Donald G.; Ressler, Kerry J.

    2012-01-01

    Corticotropin-releasing factor (CRF) is critical for the endocrine, autonomic, and behavioral responses to stressors, and it has been shown to modulate fear and anxiety. The CRF receptor is widely expressed across a variety of cell types, impeding progress toward understanding the contribution of specific CRF-containing neurons to fear dysregulation. We used a unique CRF-Cre driver transgenic mouse line to remove floxed GABA(A)α1 subunits specifically from CRF neurons [CRF-GABA(A)α1 KO]. This...

  17. Spatiotemporal dynamics of the HIV-1 CRF06_cpx epidemic in Western Africa.

    Science.gov (United States)

    Delatorre, Edson; Bello, Gonzalo

    2013-05-15

    To investigate the origin and spatiotemporal dynamics of dissemination of the HIV-1 CRF06_cpx clade in western Africa. A total of 180 HIV-1 CRF06_cpx-like pol sequences isolated from 12 different countries from west and west-central Africa over a period of 16 years (1995-2010) were analyzed. Evolutionary, phylogeographic and demographic parameters were jointly estimated from sequence data using a Bayesian coalescent-based method and combined with molecular epidemiology and spatial accessibility data. The CRF06_cpx most probably emerged in Burkina Faso in 1979 (1970-1985). From Burkina Faso, the virus was first disseminated to Mali and Nigeria during the 1980s and later to other countries from west and west-central Africa. Demographic reconstruction indicates that the CRF06_cpx epidemic grew exponentially during the 1980s, with a median growth rate of 0.82 year (0.60-1.09 year), and after stabilize. We found a negative correlation between CRF06_cpx prevalence and the geographical distance to Burkina Faso's capital. Regional accessibility information agrees with the overall geographical range of the CRF06_cpx, but not fully explains the highly heterogeneous distribution pattern of this CRF at regional level. The CRF06_cpx epidemic in western Africa probably emerged at the late 1970s and grew during the 1980s at a rate comparable to the HIV-1 epidemics in the United States and Europe. Burkina Faso seems to be the most important epicenter of dissemination of the HIV-1 CRF06_cpx strain at regional level. The explanation for the current geographical distribution of CRF06_cpx is probably multifactorial.

  18. 小麦TaCRF2基因的克隆及其在烟草中的初步功能验证%TaCRF2 Gene Isolation from Triticum aestivum and Primary Function Validation in Tobacco (Nicotiana tabacum L.)

    Institute of Scientific and Technical Information of China (English)

    郭丽香; 高世庆; 唐益苗; 王永波; 刘美英; 张朝; 徐蓓; 赵昌平

    2011-01-01

    通过RT-PCR方法从小麦cDNA中扩增获得1个锌指蛋白基因TaCRF2,该基因的cDNA长度为843 bp,序列分析表明它编码1个含有280个氨基酸的蛋白质.在线软件预测该蛋白质的相对分子质量为30.97 kD,等电点为7.03,且在C-末端含有1个典型的RING-H2型锌指蛋白结构域,在N-末端含有2个跨膜结构域.氨基酸序列比对发现,TaCRF2与水稻中1个RING型锌指蛋白(ABF95226)的相似度为82%.亚细胞定位分析显示,该蛋白分布在细胞核和细胞膜上.real-time RT-PCR表达特性分析显示,TaCRF2基因的表达受干旱、高盐和外源ABA的强烈诱导,低温对该基因的表达量影响不明显.初步功能验证发现过表达TaCRF2基因增强了转基因烟草对干旱和高盐胁迫的耐性.%Wheat, like other crops, suffers from drought, salt, low-temperature and other abiotic stresses, seriously resulting in yield decline. It is an effective way for crop breeding to improve resistance via molecular biology techniques. Zinc finger protein, an important transcription factor commonly found in plant, can regulate the expression of multiple stress-inducible genes and enhance comprehensive resistances effectively. In this study, a RING-H2 zinc finger protein gene, designated as TaCRF2, was isolated from Triticum aestivum by RT-PCR. Its cDN A was 843 bp and encoded a putative protein of 280 amino acids with a predicted molecular mass of 30.97 kD and an isoelectric point (PI) of 7.03. A typical RING-H2 finger domain was found at the C-terminal region of TaCRF2 protein, and two transmembrane domains were found at the N-terminal region. Alignment of amino acid sequence showed that TaCRF2 was 82% identical to Oryza saliva putative RING zinc finger protein ABF95226. Subcellular localization analysis showed that the TaCRF2 was expressed in both nuclear and cytoplasm membrane, real-time PCR showed that the transcript of TaCRF2 was strongly induced by drought, salinity and cold to some extent. The TaCRF

  19. High prevalence of CXCR4 usage among treatment-naive CRF01_AE and CRF51_01B-infected HIV-1 subjects in Singapore

    Directory of Open Access Journals (Sweden)

    Ng Kah Ying

    2013-02-01

    Full Text Available Abstract Background Recent studies suggest HIV-1 inter-subtype differences in co-receptor usage. We examined the correlation between HIV-1 subtype and co-receptor usage among treatment-naïve HIV-1 subjects in Singapore. Additionally, we investigated whether the subtype co-receptor association was influenced by stage of infection. Methods V3 sequences of HIV-1 envelope protein gp120 were obtained from 110 HIV treatment-naïve patients and genotypic co-receptor tropism determination was performed using Geno2pheno. Two false-positive rate (FPR cut-offs, 10% and 5.75% were selected for tropism testing. Results Subtype assignment of viral strains from 110 HIV-infected individuals based on partial sequencing of HIV-1 pol, gp120 and gp41 were as follows: 27 subtype B, 64 CRF01_AE, 10 CRF51_01B, and 9 other subtypes. At FPR=10%, 10 (100% CRF51_01B-infected subjects and 26 (40.6% CRF01_AE-infected subjects had CXCR4-using virus, compared to 7 (25.9% subtype B subjects and 1 (11.1% CRF33_01B-infected subject (P P Conclusion CRF51_01B and CRF01_AE-infected individuals have higher prevalence of CXCR4-usage compared to subtype B infected individuals. Further studies examining these differences could help optimise the use of CCR5-antagonist in populations with these subtypes, and increase our understanding of HIV-1 biology.

  20. Blockade of CRF1 receptors in the central nucleus of the amygdala attenuates the dysphoria associated with nicotine withdrawal in rats.

    Science.gov (United States)

    Bruijnzeel, Adrie W; Ford, Jenna; Rogers, Jessica A; Scheick, Stacey; Ji, Yue; Bishnoi, Mahendra; Alexander, Jon C

    2012-03-01

    The majority of smokers relapse during the acute withdrawal phase when withdrawal symptoms are most severe. The goal of the present studies was to investigate the role of corticotropin-releasing factor (CRF) and noradrenergic transmission in the central nucleus of the amygdala (CeA) in the dysphoria associated with smoking cessation. It was investigated if blockade of CRF1 receptors, blockade of α1-adrenergic receptors, or stimulation of α2-adrenergic receptors in the CeA diminishes the deficit in brain reward function associated with nicotine withdrawal in rats. Nicotine dependence was induced by implanting minipumps that delivered a nicotine solution. Withdrawal was precipitated with the nicotinic acetylcholine receptor antagonist mecamylamine. A discrete-trial intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. In all the experiments, mecamylamine elevated the brain reward thresholds of the rats chronically treated with nicotine and did not affect the brain reward thresholds of the saline-treated control rats. Intra-CeA administration of the CRF1 receptor antagonist R278995/CRA0450 completely prevented the mecamylamine-induced elevations in brain reward thresholds in the nicotine-treated rats and did not affect the brain reward thresholds of the saline-treated control rats. R278995/CRA0450 has also been shown to block sigma-1 receptors but there is no evidence that this could affect negative mood states. Intra-CeA administration of the α1-adrenergic receptor antagonist prazosin or the α2-adrenergic receptor agonist clonidine did not affect the brain reward thresholds of the nicotine or saline-treated rats. These studies suggest that CRF1 receptor antagonists may diminish the dysphoria associated with smoking cessation by blocking CRF1 receptors in the CeA.

  1. 豚鼠结肠肌间神经丛促皮质激素释放激素神经元的表达及其生理特性%The expression and physiological function of CRF neuron in the myenteric plexus of enteric nervous system of guinea pig

    Institute of Scientific and Technical Information of China (English)

    高翔; 胡品津

    2004-01-01

    目的:研究促皮质激素释放激素(ccrticotrophin releasing hormone,CRF)在豚鼠结肠肌间神经丛的表达和生理功能.方法:RT-PCR、免疫荧光组织化学染色检测CRF在结肠肠肌层神经丛的表达;细胞内电生理记录结合生物素示踪法研究CRF在肠道的生理功能.结果:豚鼠的肠肌间神经丛有CRF mRNA的表达;豚鼠结肠肠肌间神经丛中有表达CRF的神经元,其形态均为Dogiel Ⅰ型神经元.CRF对豚鼠结肠肌间神经丛有很强的兴奋作用,可诱发慢的兴奋性去极化反应,而且CRF所兴奋的神经元均为表达CRF1受体的神经元.结论:CRF是肠道神经系统的兴奋性神经递质.

  2. Stimulation of rat B-lymphocyte proliferation by corticotropin-releasing factor.

    Science.gov (United States)

    McGillis, J P; Park, A; Rubin-Fletter, P; Turck, C; Dallman, M F; Payan, D G

    1989-07-01

    The mitogenic effect of corticotropin-releasing factor (CRF) on rat lymphocytes was investigated. When rat splenocytes were cultured for 48 hr with CFR, a dose-dependent increase in incorporation of 3H-thymidine (3H-Tdr) was observed, with a maximal response at 10 nM CRF. Comparison of the proliferative effect of CRF on enriched populations of B lymphocytes, T lymphocytes, or macrophages revealed that only B lymphocytes responded following treatment with CRF. When lymphocytes derived from different lymphoid tissues were compared, CRF had a greater proliferative effect on lymphocytes derived from gut-associated lymphoid tissue (mesenteric lymph nodes and Peyer's patches) than on lymphocytes from spleen or inguinal lymph nodes; CRF had no effect on thymocytes. Synthetic fragments of CRF were used to determine which portions of the peptide are recognized by lymphocytes. The C-terminal fragments alpha-helical CRF9-41 and CRF21-41 were as potent as native CRF in stimulating B-lymphocyte proliferation, whereas CRF1-20 did not stimulate proliferation. The activity of these peptides suggests that CRF stimulates lymphocyte proliferation by cellular recognition of structural determinants in the C-terminal one-half of the peptide.

  3. The effect of the leptin and its receptor expression in CRF rat by the Reinforcing Kidney and Exhausting Toxin Mixture

    Institute of Scientific and Technical Information of China (English)

    Yu Junsheng; Zhuang Wen Qing; Du Ya jing; Luo Bing

    2004-01-01

    Objective :To investigate the adjusting malnutrition mechanism by the Reinforcing Kidney and Exhausting Toxic Mixture(REM) on the chronic renal failure (CRF) rat. Methods :60 wistar rats weved ivided into 3 groups randomly :the normal controc group(group Ⅰ ), CRF group(group Ⅱ ), and CRF rat perfusing with REM group(group Ⅲ ). Taking their fat, kidney tissue for detecting the protein expression of the leptin, leptin receptor (Ob- R) by the means of immunohistochemistry. Result :Comparing with control group, the leptin protein express intensely in CRF rat; In kidney tissue, the ob -R express weakly. After perfusing the REM, comparing with CRF group the renal ob - R express strongly than CRF group. Conclusion: Maybe the REM could do a little better with the malnutrition of CRF rats by adjustting the activity of ob - R in kidney.

  4. Laos Organization Name Using Cascaded Model Based on SVM and CRF

    Directory of Open Access Journals (Sweden)

    Duan Shaopeng

    2017-01-01

    Full Text Available According to the characteristics of Laos organization name, this paper proposes a two layer model based on conditional random field (CRF and support vector machine (SVM for Laos organization name recognition. A layer of model uses CRF to recognition simple organization name, and the result is used to support the decision of the second level. Based on the driving method, the second layer uses SVM and CRF to recognition the complicated organization name. Finally, the results of the two levels are combined, And by a subsequent treatment to correct results of low confidence recognition. The results show that this approach based on SVM and CRF is efficient in recognizing organization name through open test for real linguistics, and the recalling rate achieve 80. 83%and the precision rate achieves 82. 75%.

  5. A balance theory of peripheral corticotropin-releasing factor receptor type 1 and type 2 signaling to induce colonic contractions and visceral hyperalgesia in rats.

    Science.gov (United States)

    Nozu, Tsukasa; Takakusaki, Kaoru; Okumura, Toshikatsu

    2014-12-01

    Several recent studies suggest that peripheral corticotropin-releasing factor (CRF) receptor type 1 (CRF1) and CRF2 have a counter regulatory action on gastrointestinal functions. We hypothesized that the activity balance of each CRF subtype signaling may determine the changes in colonic motility and visceral sensation. Colonic contractions were assessed by the perfused manometry, and contractions of colonic muscle strips were measured in vitro in rats. Visceromotor response was determined by measuring contractions of abdominal muscle in response to colorectal distensions (CRDs) (60 mm Hg for 10 min twice with a 30-min rest). All drugs were administered through ip route in in vivo studies. CRF increased colonic contractions. Pretreatment with astressin, a nonselective CRF antagonist, blocked the CRF-induced response, but astressin2-B, a selective CRF2 antagonist, enhanced the response by CRF. Cortagine, a selective CRF1 agonist, increased colonic contractions. In in vitro study, CRF increased contractions of muscle strips. Urocortin 2, a selective CRF2 agonist, itself did not alter the contractions but blocked this increased response by CRF. Visceromotor response to the second CRD was significantly higher than that of the first. Astressin blocked this CRD-induced sensitization, but astressin2-B or CRF did not affect it. Meanwhile, astressin2-B together with CRF significantly enhanced the sensitization. Urocortin 2 blocked, but cortagine significantly enhanced, the sensitization. These results indicated that peripheral CRF1 signaling enhanced colonic contractility and induced visceral sensitization, and these responses were modulated by peripheral CRF2 signaling. The activity balance of each subtype signaling may determine the colonic functions in response to stress.

  6. Tracing the origin of a singular HIV-1 CRF45_cpx clade identified in Brazil.

    Science.gov (United States)

    Delatorre, Edson; de Azevedo, Suwellen S D; Rodrigues-Pedro, Adriana; Velasco-de-Castro, Carlos Augusto; Couto-Fernandez, José Carlos; Pilotto, Jose H; Morgado, Mariza G

    2016-12-01

    The HIV-1 epidemiology has changed over the past decade toward a marked increase in the circulation of strains previously restricted to local epidemics. Recent molecular epidemiological surveys identified some HIV-1 strains of probable African origin circulating in Brazil, including the Circulating Recombinant Form (CRF) 45_cpx, a complex A1/K/U recombinant that circulates in Central Africa. Here, we characterize partial genomic sequences and reconstruct the evolutionary history of HIV-1 CRF45_cpx-related recombinant samples identified in independent studies carried out with HIV+ individuals in Brazil. The sequences were obtained by overlapping PCR amplifications followed by direct sequencing. Recombination profiles were determined by phylogenetic and bootscaning analyses. The evolutionary history was estimated by a Bayesian coalescent-based method using datasets representing the gag, pol and env gene fragments. Six of the 10 samples isolated in Rio de Janeiro showed a CRF45_cpx-like pattern throughout the sequenced genome. The remaining were classified as second-generation recombinants, showing the mosaic patterns: CRF45_cpx/B/D/F1/U, CRF45_cpx/B/F1/U, CRF45_cpx/B/U and CRF45_cpx/F1. All Brazilian CRF45_cpx sequences, except one, formed a monophyletic clade (CRF45-BR), which seems to be the result of a single introduction event that has spread to the Rio de Janeiro, São Paulo and Minas Gerais states and is related to sequences from Argentina, Italy and Belgium. The Bayesian analyses pointed out quite consistent onset dates for CRF45-BR clade (~1984: 1976-1996) in the three gene datasets. These results indicate that the CRF45-BR clade has been circulating in the Southeastern Brazilian region for about 30years, although its presence was not detected until recently due to its very low prevalence. This reinforces the relevance of large-scale molecular surveillance data to identify the emergence of new HIV variants and their impact on local epidemics. Copyright

  7. Effects of corticoliberin fragment CRF(4-6) on sexual behavior in male rats [corrected].

    Science.gov (United States)

    Andreev-Andrievskii, A A; Tsvirkun, D V; Makarenko, E Yu; Andreeva, L A; Mart'yanov, A A

    2006-09-01

    Centrally administered doses of the tripeptide corticoliberin fragment CRF(4-6) (Pro-Pro-Ile) suppressed mating behavior in male rats. Doses of 1 and 2 microg of the tripeptide produced dose-dependent increases in the latent periods of mounting, intromission, and ejaculation. Changes in measures of sexual behavior demonstrated that the corticoliberin fragment CRF(4-6) suppressed both sexual motivation and sexual performance.

  8. The CRF-method for semiconductors' intravalley collision kernels: II – The 3D case

    Directory of Open Access Journals (Sweden)

    Claudio Barone

    1993-05-01

    Full Text Available If the collisions are redefined as a flux a kinetic conservation law can be written in divergence form. This can be handled numerically, in the framework of Finite Particle Approximation, using the CRF-method. In this paper we use the CRF-method for semiconductors' intravalley collision kernels. We extend the results obtained in a previous paper to the case of a 3D momentum space.

  9. The CRF-method for semiconductors' intravalley collision kernels: I – the 2D case

    Directory of Open Access Journals (Sweden)

    Claudio Barone

    1992-05-01

    Full Text Available If the collisions are redefined as a flux a kinetic conservation law can be written in divergence form. This can be handled numerically, in the framework of Finite Particle Approximation, using the CRF-method. In the present paper the relevant quantities needed for computer implementation of the CRF-method are derived in the case of a 2D momentum space for the semiconductors' intravalley collision kernels.

  10. Distribution of corticotropin-releasing factor neurons in the mouse brain: a study using corticotropin-releasing factor-modified yellow fluorescent protein knock-in mouse.

    Science.gov (United States)

    Kono, Junko; Konno, Kohtarou; Talukder, Ashraf Hossain; Fuse, Toshimitsu; Abe, Manabu; Uchida, Katsuya; Horio, Shuhei; Sakimura, Kenji; Watanabe, Masahiko; Itoi, Keiichi

    2017-05-01

    We examined the morphological features of corticotropin-releasing factor (CRF) neurons in a mouse line in which modified yellow fluorescent protein (Venus) was expressed under the CRF promoter. We previously generated the CRF-Venus knock-in mouse, in which Venus is inserted into the CRF gene locus by homologous recombination. In the present study, the neomycin phosphotransferase gene (Neo), driven by the pgk-1 promoter, was deleted from the CRF-Venus mouse genome, and a CRF-Venus∆Neo mouse was generated. Venus expression is much more prominent in the CRF-Venus∆Neo mouse when compared to the CRF-Venus mouse. In addition, most Venus-expressing neurons co-express CRF mRNA. Venus-expressing neurons constitute a discrete population of neuroendocrine neurons in the paraventricular nucleus of the hypothalamus (PVH) that project to the median eminence. Venus-expressing neurons were also found in brain regions outside the neuroendocrine PVH, including the olfactory bulb, the piriform cortex (Pir), the extended amygdala, the hippocampus, the neocortices, Barrington's nucleus, the midbrain/pontine dorsal tegmentum, the periaqueductal gray, and the inferior olivary nucleus (IO). Venus-expressing perikarya co-expressing CRF mRNA could be observed clearly even in regions where CRF-immunoreactive perikarya could hardly be identified. We demonstrated that the CRF neurons contain glutamate in the Pir and IO, while they contain gamma-aminobutyric acid in the neocortex, the bed nucleus of the stria terminalis, the hippocampus, and the amygdala. A population of CRF neurons was demonstrated to be cholinergic in the midbrain tegmentum. The CRF-Venus∆Neo mouse may be useful for studying the structural and functional properties of CRF neurons in the mouse brain.

  11. Short Communication: Reassessing the Origin of the HIV-1 CRF02_AG Lineages Circulating in Brazil.

    Science.gov (United States)

    Delatorre, Edson; Velasco-De-Castro, Carlos A; Pilotto, José H; Couto-Fernandez, José Carlos; Bello, Gonzalo; Morgado, Mariza G

    2015-12-01

    HIV-1 CRF02_AG is responsible for at least 8% of the HIV-1 infections worldwide and is distributed mainly in West Africa. CRF02_AG has recently been reported in countries where it is not native, including Brazil. In a previous study including 10 CRF02_AG Brazilian samples, we found at least four independent introductions and two autochthonous transmission networks of this clade in Brazil. As more CRF02_AG samples have been identified in Brazil, we performed a new phylogeographic analysis using a larger dataset than before. A total of 20 Brazilian (18 from Rio de Janeiro and two from São Paulo) and 1,485 African HIV-1 CRF02_AG pol sequences were analyzed using maximum likelihood (ML). The ML tree showed that the Brazilian sequences were distributed in five different lineages. The Bayesian phylogeographic analysis of the Brazilian and their most closely related African sequences (n = 212) placed the origin of all Brazilian lineages in West Africa, probably Ghana, Senegal, and Nigeria. Two monophyletic clades were identified, comprising only sequences from Rio de Janeiro, and their date of origin was estimated at around 1985 (95% highest posterior density: 1979-1992). These results support the existence of at least five independent introductions of the CRF02_AG lineage from West Africa into Brazil and further indicate that at least two of these lineages have been locally disseminated in the Rio de Janeiro state over the past 30 years.

  12. Role of CRF in stress-related alterations of gastric and colonic motor function.

    Science.gov (United States)

    Taché, Y; Mönnikes, H; Bonaz, B; Rivier, J

    1993-10-29

    Major advances have been made in the understanding of the pathophysiology of stress-related alteration of gut function. A wealth of information indicates that CRF is involved in the central mechanisms by which stress inhibits gastric emptying while stimulating colonic motor function. CRF acts in the PVN to trigger both the inhibition of gastric emptying and the stimulation of colonic motor function in response to stress, in addition to previously established endocrine and behavioral responses. Preliminary evidence exists that CRF acts in the locus coeruleus to induce a selective stimulation of colonic transit without influencing gastric emptying. The central actions of CRF to alter gastric and colonic motor function are conveyed by autonomic pathways and are unrelated to the associated stimulation of pituitary hormone secretion. The demonstration that central CRF plays a role in mediating gastric stasis resulting from surgery, peritonitis or high levels of central interleukin-1 provides new insight into the mechanisms involved in gastric ileus induced postoperatively or by infectious disease. Likewise, the demonstration that CRF in the PVN and locus coeruleus induce the anxiogenic and colonic motor responses to stress and that colonic distention activates neurons in the locus coeruleus opens new avenues for the understanding of the pathogenesis of a subset of IBS patients with colonic hypersensitivity associated with psychopathological disturbance and diarrhea-predominant symptoms.

  13. Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala.

    Science.gov (United States)

    Itoga, Christy A; Roltsch Hellard, Emily A; Whitaker, Annie M; Lu, Yi-Ling; Schreiber, Allyson L; Baynes, Brittni B; Baiamonte, Brandon A; Richardson, Heather N; Gilpin, Nicholas W

    2016-09-01

    Hyperalgesia is an exaggerated response to noxious stimuli produced by peripheral or central plasticity. Stress modifies nociception, and humans with post-traumatic stress disorder (PTSD) exhibit co-morbid chronic pain and amygdala dysregulation. Predator odor stress produces hyperalgesia in rodents. Systemic blockade of corticotropin-releasing factor (CRF) type 1 receptors (CRFR1s) reduces stress-induced thermal hyperalgesia. We hypothesized that CRF-CRFR1 signaling in central amygdala (CeA) mediates stress-induced hyperalgesia in rats with high stress reactivity. Adult male Wistar rats were exposed to predator odor stress in a conditioned place avoidance paradigm and indexed for high (Avoiders) and low (Non-Avoiders) avoidance of predator odor-paired context, or were unstressed Controls. Rats were tested for the latency to withdraw hindpaws from thermal stimuli (Hargreaves test). We used pharmacological, molecular, and immunohistochemical techniques to assess the role of CRF-CRFR1 signaling in CeA in stress-induced hyperalgesia. Avoiders exhibited higher CRF peptide levels in CeA that did not appear to be locally synthesized. Intra-CeA CRF infusion mimicked stress-induced hyperalgesia. Avoiders exhibited thermal hyperalgesia that was reversed by systemic or intra-CeA injection of a CRFR1 antagonist. Finally, intra-CeA infusion of tetrodotoxin produced thermal hyperalgesia in unstressed rats and blocked the anti-hyperalgesic effect of systemic CRFR1 antagonist in stressed rats. These data suggest that rats with high stress reactivity exhibit hyperalgesia that is mediated by CRF-CRFR1 signaling in CeA.

  14. Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction.

    Science.gov (United States)

    Micioni Di Bonaventura, Maria Vittoria; Ciccocioppo, Roberto; Romano, Adele; Bossert, Jennifer M; Rice, Kenner C; Ubaldi, Massimo; St Laurent, Robyn; Gaetani, Silvana; Massi, Maurizio; Shaham, Yavin; Cifani, Carlo

    2014-08-20

    We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This "frustration stress" manipulation also activates the hypothalamic-pituitary-adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10-20 mg/kg) and BNST (25-50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist D-Phe-CRF(12-41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders.

  15. Associations between proteinuria, systemic hypertension and glomerular filtration rate in dogs with renal and non-renal diseases.

    Science.gov (United States)

    Wehner, A; Hartmann, K; Hirschberger, J

    2008-02-02

    Proteinuria and systemic hypertension are well recognised risk factors in chronic renal failure (CRF). They are consequences of renal disease but also lead to a further loss of functional kidney tissue. The objectives of this study were to investigate the associations between proteinuria, systemic hypertension and glomerular filtration rate (GFR) in dogs with naturally occurring renal and non-renal diseases, and to determine whether proteinuria and hypertension were associated with shorter survival times in dogs with CRF. Measurements of exogenous creatinine plasma clearance (ECPC), urine protein:creatinine ratio (UPC), and Doppler sonographic measurements of systolic blood pressure (SBP) were made in 60 dogs with various diseases. There was a weak but significant inverse correlation between UPC and ECPC, a significant inverse correlation between SBP and ECPC and a weak but significant positive correlation between UPC and SBP. Some of the dogs with CRF were proteinuric and almost all were hypertensive. Neoplasia was commonly associated with proteinuria in the dogs with a normal ECPC. CRF was the most common cause leading to hypertension. In the dogs with CRF, hypertension and marked proteinuria were associated with significantly shorter survival times.

  16. Isolation and characterization of a replication-competent molecular clone of an HIV-1 circulating recombinant form (CRF33_01B.

    Directory of Open Access Journals (Sweden)

    Kok Keng Tee

    Full Text Available A growing number of emerging HIV-1 recombinants classified as circulating recombinant forms (CRFs have been identified in Southeast Asia in recent years, establishing a molecular diversity of increasing complexity in the region. Here, we constructed a replication-competent HIV-1 clone for CRF33_01B (designated p05MYKL045.1, a newly identified recombinant comprised of CRF01_AE and subtype B. p05MYKL045.1 was reconstituted by cloning of the near full-length HIV-1 sequence from a newly-diagnosed individual presumably infected heterosexually in Kuala Lumpur, Malaysia. The chimeric clone, which contains the 5' LTR (long terminal repeat region of p93JP-NH1 (a previously isolated CRF01_AE infectious clone, showed robust viral replication in the human peripheral blood mononuclear cells. This clone demonstrated robust viral propagation and profound syncytium formation in CD4+, CXCR4-expressing human glioma NP-2 cells, indicating that p05MYKL045.1 is a CXCR4-using virus. Viral propagation, however, was not detected in various human T cell lines including MT-2, M8166, Sup-T1, H9, Jurkat, Molt-4 and PM1. p05MYKL045.1 appears to proliferate only in restricted host range, suggesting that unknown viral and/or cellular host factors may play a role in viral infectivity and replication in human T cell lines. Availability of a CRF33_01B molecular clone will be useful in facilitating the development of vaccine candidates that match the HIV-1 strains circulating in Southeast Asia.

  17. CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia.

    Science.gov (United States)

    Mogami, Sachiko; Sadakane, Chiharu; Nahata, Miwa; Mizuhara, Yasuharu; Yamada, Chihiro; Hattori, Tomohisa; Takeda, Hiroshi

    2016-06-08

    Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities.

  18. Five new CRF07_BC near full-length sequences isolated from Sichuan, China.

    Science.gov (United States)

    Meng, Zhefeng; Xin, Ruolei; Abubakar, Yassir F; Sun, Jun; Wu, Huanmei; Lu, Jianxin; Ni, Ya; Zhang, Xiaoyan; Xu, Jianqing

    2013-01-01

    The main heroine traffic from Yunnan province to the Xinjiang Autonomous Region is believed to initiate the transmission of CRF07_BC which is the predominant strain in intravenous drug users (IDUs) in China. However, the great distances between Yunnan and Xinjiang lead to an unclear and elusive diffusion process of CRF07_BC due to the absence of an important middle site such as Sichuan province. Moreover, in recent years the rapidly increasing infection rate among IDUs in the Liangshan region of Sichuan made it necessary to characterize the genetic character of the circulating strain of Sichuan IDUs. In this study, we characterized the genetic character of seven newly isolated CRF07_BC genomes (five from Sichuan and two from Xinjiang) and analyzed the transmission linkage among strains from IDUs in different regions. By conducting Markov chain Monte Carlo (MCMC) analysis and reconstruction of neighbor-joining trees and maximum-likelihood trees, our results revealed the genetic variation and important role of Sichuan-derived CRF07_BC strains during the transmission of CRF07_BC.

  19. Human Factors Considerations in System Design

    Science.gov (United States)

    Mitchell, C. M. (Editor); Vanbalen, P. M. (Editor); Moe, K. L. (Editor)

    1983-01-01

    Human factors considerations in systems design was examined. Human factors in automated command and control, in the efficiency of the human computer interface and system effectiveness are outlined. The following topics are discussed: human factors aspects of control room design; design of interactive systems; human computer dialogue, interaction tasks and techniques; guidelines on ergonomic aspects of control rooms and highly automated environments; system engineering for control by humans; conceptual models of information processing; information display and interaction in real time environments.

  20. Fundamentals of systems ergonomics/human factors.

    Science.gov (United States)

    Wilson, John R

    2014-01-01

    Ergonomics/human factors is, above anything else, a systems discipline and profession, applying a systems philosophy and systems approaches. Many things are labelled as system in today's world, and this paper specifies just what attributes and notions define ergonomics/human factors in systems terms. These are obviously a systems focus, but also concern for context, acknowledgement of interactions and complexity, a holistic approach, recognition of emergence and embedding of the professional effort involved within organization system. These six notions are illustrated with examples from a large body of work on rail human factors.

  1. Robust rooftop extraction from visible band images using higher order CRF

    KAUST Repository

    Li, Er

    2015-08-01

    In this paper, we propose a robust framework for building extraction in visible band images. We first get an initial classification of the pixels based on an unsupervised presegmentation. Then, we develop a novel conditional random field (CRF) formulation to achieve accurate rooftops extraction, which incorporates pixel-level information and segment-level information for the identification of rooftops. Comparing with the commonly used CRF model, a higher order potential defined on segment is added in our model, by exploiting region consistency and shape feature at segment level. Our experiments show that the proposed higher order CRF model outperforms the state-of-the-art methods both at pixel and object levels on rooftops with complex structures and sizes in challenging environments. © 1980-2012 IEEE.

  2. Reconstituting the epidemic history of mono lineage of HIV-1 CRF01_AE in Guizhou province, Southern China.

    Science.gov (United States)

    Zeng, Haiyan; Sun, Binlian; Li, Lingnuo; Li, Yanpeng; Liu, Yong; Xiao, Yao; Jiang, Yan; Yang, Rongge

    2014-08-01

    Guizhou province, located between border provinces and Central province of China, plays a crucial role in the transmission of HIV-1, implying it is important to monitor the epidemic of HIV-1 in this region. Available HIV-1 infected patients' plasma (n=78) were collected from Tongren city, Eastern Guizhou. Full-length gag, partial pol and env gene sequences were amplified and analyzed using phylogenetic, recombinant and Bayesian molecular clock approaches. Phylogenetic and recombinant analyses showed that CRF01_AE predominated among injecting drug users and heterosexuals in Tongren city with 85.9% proportion, it was followed by B' (5.1%), CRF07_BC (3.8%), CRF08_BC (3.8%), and B (1.3%). Moreover, 98.5% of CRF01_AE strains belonged to the distinct lineage CRF01_AE-v previously found in Guangxi province. To infer the most probable origin of CRF01_AE-v in Guizhou province, we download all available full length of CRF01_AE gag, pol and env gene region sequences from China in Los Alamos HIV sequence database. Phylodynamic and phylogeographic analyses revealed that the expanding CRF01_AE-v epidemic in Guizhou province was the result of local epidemic driven by multiple independent introductions of CRF01_AE-v strains from Guangxi province in early 2000s. High prevalence of CRF01_AE in Guizhou province may bridge the epidemic to Central China. It provides a new insight for the understanding of HIV-1 epidemic in Guizhou province and makes the evolutionary history of CRF01_AE in China more intact. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Local Optogenetic Induction of Fast (20-40 Hz) Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity.

    Science.gov (United States)

    Dine, Julien; Genewsky, Andreas; Hladky, Florian; Wotjak, Carsten T; Deussing, Jan M; Zieglgänsberger, Walter; Chen, Alon; Eder, Matthias

    2016-01-01

    The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz) network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2) expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz) field potential oscillations in hippocampal area CA1 in vitro (at 25°C) and in vivo (i.e., slightly anesthetized NEX-Cre-ChR2 mice). As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer) and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I) oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells) and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM) in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC) in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1→PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive) P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

  4. Local Optogenetic Induction of Fast (20-40 Hz Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity

    Directory of Open Access Journals (Sweden)

    Julien eDine

    2016-04-01

    Full Text Available The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2 expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz field potential oscillations in hippocampal area CA1 in vitro (at 25°C and in vivo (i.e., slightly anaesthetized NEX-Cre-ChR2 mice. As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

  5. Multiple independent introductions of HIV-1 CRF01_AE identified in China: what are the implications for prevention?

    Directory of Open Access Journals (Sweden)

    Yassir F Abubakar

    Full Text Available BACKGROUND: HIV-1 CRF01_AE accounts for an important fraction of HIV infections in Asia including China, but little is known about the phylogenetic and evolutionary history of this CRF (circulating recombinant form. In the current study, we collected a large number of 1,957 CRF01_AE gag p17 sequences with known sampling year (1990-2010 from 5 global regions representing 15 countries to better understand the phylogenetic relationships and epidemic history of CRF01_AE strains in China. METHODOLOGY/PRINCIPAL FINDINGS: CRF01_AE gag p17 sequences were retrieved from public databases to explore phylogenetic relationships and phylogeographic dynamics of CRF01_AE in Asia by using maximum-likelihood phylogenetics and Bayesian coalescent-based analyses. We found close phylogenetic relationships between sequences from Thailand, Vietnam and China. Moreover, at least 5 independent introductions and 5 independent autochthonous clades of CRF01_AE, which descended from Thailand or Vietnam were identified in China from 1991 through 2003. CONCLUSION/SIGNIFICANCE: The current study not only defines the migration of CRF01_AE clades to/in Asia, but also demonstrates the criticalness of identifying the circulating strains in the population for the development of vaccine and microbicides.

  6. CDC Behavioral Risk Factor Surveillance System (BRFSS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Behavioral Risk Factor Surveillance System (BRFSS) is a state-based system of health surveys that collects information on health risk behaviors, preventive...

  7. SEMANTIC LABELLING OF ULTRA DENSE MLS POINT CLOUDS IN URBAN ROAD CORRIDORS BASED ON FUSING CRF WITH SHAPE PRIORS

    Directory of Open Access Journals (Sweden)

    W. Yao

    2017-09-01

    Full Text Available In this paper, a labelling method for the semantic analysis of ultra-high point density MLS data (up to 4000 points/m2 in urban road corridors is developed based on combining a conditional random field (CRF for the context-based classification of 3D point clouds with shape priors. The CRF uses a Random Forest (RF for generating the unary potentials of nodes and a variant of the contrastsensitive Potts model for the pair-wise potentials of node edges. The foundations of the classification are various geometric features derived by means of co-variance matrices and local accumulation map of spatial coordinates based on local neighbourhoods. Meanwhile, in order to cope with the ultra-high point density, a plane-based region growing method combined with a rule-based classifier is applied to first fix semantic labels for man-made objects. Once such kind of points that usually account for majority of entire data amount are pre-labeled; the CRF classifier can be solved by optimizing the discriminative probability for nodes within a subgraph structure excluded from pre-labeled nodes. The process can be viewed as an evidence fusion step inferring a degree of belief for point labelling from different sources. The MLS data used for this study were acquired by vehicle-borne Z+F phase-based laser scanner measurement, which permits the generation of a point cloud with an ultra-high sampling rate and accuracy. The test sites are parts of Munich City which is assumed to consist of seven object classes including impervious surfaces, tree, building roof/facade, low vegetation, vehicle and pole. The competitive classification performance can be explained by the diverse factors: e.g. the above ground height highlights the vertical dimension of houses, trees even cars, but also attributed to decision-level fusion of graph-based contextual classification approach with shape priors. The use of context-based classification methods mainly contributed to smoothing of

  8. Semantic Labelling of Ultra Dense Mls Point Clouds in Urban Road Corridors Based on Fusing Crf with Shape Priors

    Science.gov (United States)

    Yao, W.; Polewski, P.; Krzystek, P.

    2017-09-01

    In this paper, a labelling method for the semantic analysis of ultra-high point density MLS data (up to 4000 points/m2) in urban road corridors is developed based on combining a conditional random field (CRF) for the context-based classification of 3D point clouds with shape priors. The CRF uses a Random Forest (RF) for generating the unary potentials of nodes and a variant of the contrastsensitive Potts model for the pair-wise potentials of node edges. The foundations of the classification are various geometric features derived by means of co-variance matrices and local accumulation map of spatial coordinates based on local neighbourhoods. Meanwhile, in order to cope with the ultra-high point density, a plane-based region growing method combined with a rule-based classifier is applied to first fix semantic labels for man-made objects. Once such kind of points that usually account for majority of entire data amount are pre-labeled; the CRF classifier can be solved by optimizing the discriminative probability for nodes within a subgraph structure excluded from pre-labeled nodes. The process can be viewed as an evidence fusion step inferring a degree of belief for point labelling from different sources. The MLS data used for this study were acquired by vehicle-borne Z+F phase-based laser scanner measurement, which permits the generation of a point cloud with an ultra-high sampling rate and accuracy. The test sites are parts of Munich City which is assumed to consist of seven object classes including impervious surfaces, tree, building roof/facade, low vegetation, vehicle and pole. The competitive classification performance can be explained by the diverse factors: e.g. the above ground height highlights the vertical dimension of houses, trees even cars, but also attributed to decision-level fusion of graph-based contextual classification approach with shape priors. The use of context-based classification methods mainly contributed to smoothing of labelling by removing

  9. Sprint interval training (SIT) is an effective method to maintain cardiorespiratory fitness (CRF) and glucose homeostasis in Scottish adolescents.

    Science.gov (United States)

    Martin, R; Buchan, D S; Baker, J S; Young, J; Sculthorpe, N; Grace, F M

    2015-11-01

    The present study examined the physiological impact of a school based sprint interval training (SIT) intervention in replacement of standard physical education (SPE) class on cardio-respiratory fitness (CRF) and glucose homeostasis during the semester following summer vacation. Participants (n=49) were randomly allocated to either intervention (SIT; n=26, aged 16.9 ± 0.3 yrs) or control group who underwent standard physical education (SPE; n=23, aged 16.8 ± 0.6 yrs). CRF (VO2max) and glucose homeostasis were obtained prior-to and following 7 weeks of SIT exercise. Significant group x time interaction was observed for CRF (P SIT exercise is an effective method of maintaining (but not improving) CRF and fasting insulin homeostasis amongst school-going adolescents. SIT exercise demonstrates potential as a time efficient physiological adjunct to standard PE class in order to maintain CRF during the school term.

  10. Coprime factorization for regular linear systems

    NARCIS (Netherlands)

    Curtain, R; Weiss, G; Weiss, M

    1996-01-01

    Mild sufficient conditions are given for the existence of a doubly coprime factorization of the transfer function of a regular linear system, as well as formulae for such a factorization. The results are illustrated by two examples of delay systems, one of which has infinitely many unstable poles. C

  11. Corticotropin-releasing factor overexpression gives rise to sex differences in Alzheimer's disease-related signaling.

    Science.gov (United States)

    Bangasser, D A; Dong, H; Carroll, J; Plona, Z; Ding, H; Rodriguez, L; McKennan, C; Csernansky, J G; Seeholzer, S H; Valentino, R J

    2016-10-18

    Several neuropsychiatric and neurodegenerative disorders share stress as a risk factor and are more prevalent in women than in men. Corticotropin-releasing factor (CRF) orchestrates the stress response, and excessive CRF is thought to contribute to the pathophysiology of these diseases. We previously found that the CRF1 receptor (CRF1) is sex biased whereby coupling to its GTP-binding protein, Gs, is greater in females, whereas β-arrestin-2 coupling is greater in males. This study used a phosphoproteomic approach in CRF-overexpressing (CRF-OE) mice to test the proof of principle that when CRF is in excess, sex-biased CRF1 coupling translates into divergent cell signaling that is expressed as different brain phosphoprotein profiles. Cortical phosphopeptides that distinguished female and male CRF-OE mice were overrepresented in unique pathways that were consistent with Gs-dependent signaling in females and β-arrestin-2 signaling in males. Notably, phosphopeptides that were more abundant in female CRF-OE mice were overrepresented in an Alzheimer's disease (AD) pathway. Phosphoproteomic results were validated by demonstrating that CRF overexpression in females was associated with increased tau phosphorylation and, in a mouse model of AD pathology, phosphorylation of β-secretase, the enzyme involved in the formation of amyloid β. These females exhibited increased formation of amyloid β plaques and cognitive impairments relative to males. Collectively, the findings are consistent with a mechanism whereby the excess CRF that characterizes stress-related diseases initiates distinct cellular processes in male and female brains, as a result of sex-biased CRF1 signaling. Promotion of AD-related signaling pathways through this mechanism may contribute to female vulnerability to AD.Molecular Psychiatry advance online publication, 18 October 2016; doi:10.1038/mp.2016.185.

  12. Contextual Classification of Point Clouds Using a Two-Stage Crf

    Science.gov (United States)

    Niemeyer, J.; Rottensteiner, F.; Soergel, U.; Heipke, C.

    2015-03-01

    In this investigation, we address the task of airborne LiDAR point cloud labelling for urban areas by presenting a contextual classification methodology based on a Conditional Random Field (CRF). A two-stage CRF is set up: in a first step, a point-based CRF is applied. The resulting labellings are then used to generate a segmentation of the classified points using a Conditional Euclidean Clustering algorithm. This algorithm combines neighbouring points with the same object label into one segment. The second step comprises the classification of these segments, again with a CRF. As the number of the segments is much smaller than the number of points, it is computationally feasible to integrate long range interactions into this framework. Additionally, two different types of interactions are introduced: one for the local neighbourhood and another one operating on a coarser scale. This paper presents the entire processing chain. We show preliminary results achieved using the Vaihingen LiDAR dataset from the ISPRS Benchmark on Urban Classification and 3D Reconstruction, which consists of three test areas characterised by different and challenging conditions. The utilised classification features are described, and the advantages and remaining problems of our approach are discussed. We also compare our results to those generated by a point-based classification and show that a slight improvement is obtained with this first implementation.

  13. CONTEXT MODELS FOR CRF-BASED CLASSIFICATION OF MULTITEMPORAL REMOTE SENSING DATA

    Directory of Open Access Journals (Sweden)

    T. Hoberg

    2012-07-01

    Full Text Available The increasing availability of multitemporal satellite remote sensing data offers new potential for land cover analysis. By combining data acquired at different epochs it is possible both to improve the classification accuracy and to analyse land cover changes at a high frequency. A simultaneous classification of images from different epochs that is also capable of detecting changes is achieved by a new classification technique based on Conditional Random Fields (CRF. CRF provide a probabilistic classification framework including local spatial and temporal context. Although context is known to improve image analysis results, so far only little research was carried out on how to model it. Taking into account context is the main benefit of CRF in comparison to many other classification methods. Context can be already considered by the choice of features and in the design of the interaction potentials that model the dependencies of interacting sites in the CRF. In this paper, these aspects are more thoroughly investigated. The impact of the applied features on the classification result as well as different models for the spatial interaction potentials are evaluated and compared to the purely label-based Markov Random Field model.

  14. Transmission of new CRF07_BC Strains with 7 amino acid deletion in Gag p6

    Directory of Open Access Journals (Sweden)

    Jianxin Lu

    2011-02-01

    Full Text Available Abstract A 7 amino acid deletion in Gag p6 (P6delta7 emerged in Chinese prevalent HIV-1 strain CRF07_BC from different epidemic regions. It is important to determine whether this mutation could be transmitted and spread. In this study, HIV-1 Gag sequences from 5 different epidemic regions in China were collected to trace the transmission linkage and to analyze genetic evolution of P6delta7 strains. The sequence analysis demonstrated that P6delta7 is a CRF07_BC specific deletion, different P6delta7 strains could be originated from different parental CRF07_BC recombinants in different epidemic regions, and the transmission of P6delta7 strain has occurred in IDU populations. This is for the first time to identify the transmission linkage for P6delta7 strains and serves as a wake-up call for further monitoring in the future; In addition, P6delta7 deletion may represent an evolutionary feature which might exert influence on the fitness of CRF07_BC strain.

  15. [Genetic characteristics of viral quasispecies of HIV-1 CRF07_BC among intravenous drug users].

    Science.gov (United States)

    Xin, Ruo-Lei; Ma, Ze-Qin; Cheng, Chun-Lin; Xing, Hui; Hong, Kun-Xue; Ruan, Yu-Hua; Li, Jia; Lu, Hong-Yan; Shao, Yi-Ming; He, Xiang

    2013-05-01

    To explore the genetic characteristics of viral quasispecies in HIV-1 CRF07_BC infections among intravenous drug users (IDU), the gp120 fragments of HIV-1 env gene were amplified from plasma samples collected from 6 CRF07_BC infected persons using single genome amplification and sequencing (SGA/ SGS) method, and 11 to 28 sequences were obtained from these samples, respectively, A neighbor-joining phylogenetic tree was reconstructed to describe the genetic characteristics of viral quasispecies. The Simplot, segments' phylogenetic trees and diversity plots based on average pairwise distance (APD) were used to identify the recombination events between quasispecies. The SGA sequences derived from single specimen formed a large monophyletic cluster in the neighbor-joining phylogenetic tree and showed the complex topologic structures of viral quasispecies. Of the 6 CRF07_BC infected patients, only one possessed the high genetic homogeneity, whereas the other five individuals showed high heterogeneity, with two to four subclusters inside the monophyletic cluster for each specimen. In addition, the recombinant events were identified among viral quasispecies from 3 cases. The results show SGA technique and phylogenetic analyses are useful tool to investigate the intrahost CRF07_BC gp120 complex quasispecies variation and high genetic diversity.

  16. Urocortin 1, urocortin 3/stresscopin, and corticotropin-releasing factor receptors in human adrenal and its disorders.

    Science.gov (United States)

    Fukuda, Tsuyoshi; Takahashi, Kazuhiro; Suzuki, Takashi; Saruta, Masayuki; Watanabe, Mika; Nakata, Taisuke; Sasano, Hironobu

    2005-08-01

    Urocortin 1 (Ucn1) and urocortin 3 (Ucn3)/stresscopin are new members of the corticotropin-releasing factor (CRF) neuropeptide family. Ucn1 binds to both CRF type 1 (CRF1) and type 2 receptors (CRF2), whereas Ucn3 is a specific agonist for CRF2. Recently, direct involvement of the locally synthesized CRF family in adrenocortical function has been proposed. We examined in situ expression of Ucn and CRF receptors in nonpathological human adrenal gland and its disorders using immunohistochemistry and mRNA in situ hybridization. Ucn immunoreactivity was localized in the cortex and medulla of nonpathological adrenal glands. Ucn1 immunoreactivity was marked in the medulla, whereas Ucn3 was immunostained mostly in the cortex. Both CRF type 1 and CRF2 were expressed in the cortex, particularly in the zonae fasciculata and reticularis but very weakly or undetectably in the medulla. Immunohistochemistry in serial tissue sections with mirror images revealed that both Ucn3 and CRF2 were colocalized in more than 85% of the adrenocortical cells. mRNA in situ hybridization confirmed these findings above. In fetal adrenals, Ucn and CRF receptors were expressed in both fetal and definitive zones of the cortex. Ucn and CRF receptors were all expressed in the tumor cells of pheochromocytomas, adrenocortical adenomas, and carcinomas, but its positivity was less than that in nonpathological adrenal glands, suggesting that Ucn1, Ucn3, and CRF receptors were down-regulated in these adrenal neoplasms. Ucn1, Ucn3, and CRF receptors are all expressed in human adrenal cortex and medulla and may play important roles in physiological adrenal functions.

  17. Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine.

    Science.gov (United States)

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I; Ferré, Sergi; McCormick, Peter J

    2015-04-29

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the σ1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking.

  18. A newly emerging HIV-1 recombinant lineage (CRF58_01B) disseminating among people who inject drugs in Malaysia.

    Science.gov (United States)

    Chow, Wei Zhen; Takebe, Yutaka; Syafina, Nur Ezreen; Prakasa, Malarvelli Soorya; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2014-01-01

    The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B), CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.

  19. A newly emerging HIV-1 recombinant lineage (CRF58_01B disseminating among people who inject drugs in Malaysia.

    Directory of Open Access Journals (Sweden)

    Wei Zhen Chow

    Full Text Available The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K and to date 55 circulating recombinant forms (CRFs. In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B, CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%, CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258. Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.

  20. Emerging role for corticotropin releasing factor signaling in the bed nucleus of the stria terminalis at the intersection of stress and reward.

    Science.gov (United States)

    Silberman, Yuval; Winder, Danny G

    2013-01-01

    Stress and anxiety play an important role in the development and maintenance of drug and alcohol addiction. The bed nucleus of the stria terminalis (BNST), a brain region involved in the production of long-term stress-related behaviors, plays an important role in animal models of relapse, such as reinstatement to previously extinguished drug-seeking behaviors. While a number of neurotransmitter systems have been suggested to play a role in these behaviors, recent evidence points to the neuropeptide corticotropin releasing factor (CRF) as being critically important in BNST-mediated reinstatement behaviors. Although numerous studies indicate that the BNST is a complex brain region with multiple afferent and efferent systems and a variety of cell types, there has only been limited work to determine how CRF modulates this complex neuronal system at the circuit level. Recent work from our lab and others have begun to unravel these BNST neurocircuits and explore their roles in CRF-related reinstatement behaviors. This review will examine the role of CRF signaling in drug addiction and reinstatement with an emphasis on critical neurocircuitry within the BNST that may offer new insights into treatments for addiction.

  1. Corticotropin-releasing factor receptors and stress-related alterations of gut motor function.

    OpenAIRE

    2007-01-01

    International audience; Over the past few decades, corticotropin-releasing factor (CRF) signaling pathways have been shown to be the main coordinators of the endocrine, behavioral, and immune responses to stress. Emerging evidence also links the activation of CRF receptors type 1 and type 2 with stress-related alterations of gut motor function. Here, we review the role of CRF receptors in both the brain and the gut as part of key mechanisms through which various stressors impact propulsive ac...

  2. Virulence Factors IN Fungi OF Systemic Mycoses

    Directory of Open Access Journals (Sweden)

    KUROKAWA Cilmery Suemi

    1998-01-01

    Full Text Available Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.

  3. Solving the factorization problem with P systems

    Institute of Scientific and Technical Information of China (English)

    Alberto Leporati; Claudio Zandron; Giancarlo Mauri

    2007-01-01

    P systems have been used many times to face with computationally difficult problems, such as NP-complete decision problems and NP-hard optimization problems. In this paper we focus our attention on another computationally intractable problem: factorization. In particular, we first propose a simple method to encode binary numbers using multisets. Then, we describe three families of P systems: the first two allow to add and to multiply two binary encoded numbers, respectively, and the third solves the factorization problem.

  4. Interconnection of electronic medical record with clinical data management system by CDISC ODM.

    Science.gov (United States)

    Matsumura, Yasushi; Hattori, Atsushi; Manabe, Shiro; Takeda, Toshihiro; Takahashi, Daiyo; Yamamoto, Yuichiro; Murata, Taizo; Mihara, Naoki

    2014-01-01

    EDC system has been used in the field of clinical research. The current EDC system does not connect with electronic medical record system (EMR), thus a medical staff has to transcribe the data in EMR to EDC system manually. This redundant process causes not only inefficiency but also human error. We developed an EDC system cooperating with EMR, in which the data required for a clinical research form (CRF) is transcribed automatically from EMR to electronic CRF (eCRF) and is sent via network. We call this system as "eCRF reporter". The interface module of eCRF reporter can retrieves the data in EMR database including patient biography data, laboratory test data, prescription data and data entered by template in progress notes. The eCRF reporter also enables users to enter data directly to eCRF. The eCRF reporter generates CDISC ODM file and PDF which is a translated form of Clinical data in ODM. After storing eCRF in EMR, it is transferred via VPN to a clinical data management system (CDMS) which can receive the eCRF files and parse ODM. We started some clinical research by using this system. This system is expected to promote clinical research efficiency and strictness.

  5. Ontogeny of corticotropin-releasing factor effects on locomotion and foraging in the Western spadefoot toad (Spea hammondii).

    Science.gov (United States)

    Crespi, Erica J; Denver, Robert J

    2004-11-01

    We investigated the effects of corticotropin-releasing factor (CRF) and corticosterone (CORT) on foraging and locomotion in Western spadefoot toad (Spea hammondii) tadpoles and juveniles to assess the behavioral functions of these hormones throughout development. We administered intracerebroventricular injections of ovine CRF or CRF receptor antagonist alphahelical CRF((9-41)) to tadpoles and juveniles, and observed behavior within 1.5 h after injection. In both premetamorphic (Gosner stage 33) and prometamorphic (Gosner stages 35-37) tadpoles, CRF injections increased locomotion and decreased foraging. Injections of alphahelical CRF((9-41)) reduced locomotion but did not affect foraging in premetamorphic tadpoles, but dramatically increased foraging in prometamorphic tadpoles compared to both placebo and uninjected controls. Similarly, alphahelical CRF((9-41)) injections stimulated food intake and prey-catching behavior in juveniles. These results suggest that in later-staged amphibians, endogenous CRF secretion modulates feeding by exerting a suppressive effect on appetite. By contrast to the inhibitory effect of CRF, 3-h exposure to CORT (500 nM added to the aquarium water) stimulated foraging in prometamorphic tadpoles. These tadpoles also exhibited a CORT-mediated increase in foraging 6 h after CRF injection, which was associated with elevated whole-body CORT content and blocked by glucocorticoid receptor (GR) antagonist (RU486) injections. Thus, exogenous CRF influences locomotion and foraging in both pre- and prometamorphic tadpoles, but endogenous CRF secretion in relatively unstressed animals does not affect foraging until prometamorphic stages. Furthermore, the opposing actions of CRF and CORT on foraging suggest that they are important regulators of energy balance and food intake in amphibians throughout development.

  6. Predominance of CRF06_cpx and Transmitted HIV Resistance in Algeria: Update 2013-2014.

    Science.gov (United States)

    Abdellaziz, Akila; Papuchon, Jennifer; Khaled, Safia; Ouerdane, Dalila; Fleury, Hervé; Recordon-Pinson, Patricia

    2016-04-01

    Since 2008, no data on HIV diversity or the transmission rate of HIV resistance mutations in naive patients have been presented for Algeria, a country of MENA region. Between 2013 and 2014, we studied 152 samples including 89 naive patients. The current study describes the change in HIV diversity in Algeria with the predominance of CRF06_cpx and the huge increase of transmitted HIV resistance, which now reaches 15%.

  7. High-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of corticotropin-releasing factor and its type-1 receptors

    Institute of Scientific and Technical Information of China (English)

    Xue-qun CHEN; Fan-ping KONG; Yang ZHAO; Ji-zeng DU

    2012-01-01

    High-altitude hypoxia can induce physiological dysfunction and mountain sickness,but the underlying mechanism is not fully understood.Corticotrophin-releasing factor (CRF) and CRF type-1 receptors (CRFR1) are members of the CRF family and the essential controllers of the physiological activity of the hypothalamo-pituitary-adrenal (HPA) axis and modulators of endocrine and behavioral activity in response to various stressors.We have previously found that high-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of CRF and CRFR1 in the brain and periphery that include activation of the HPA axis in a time-and dose-dependent manner,impaired or improved learning and memory,and anxiety-like behavioral change.Meanwhile,hypoxia induces dysfunctions of the hypothalamo-pituitary-endocrine and immune systems,including suppression of growth and development,as well as inhibition of reproductive,metabolic and immune functions.In contrast,the small mammals that live on the Qinghai-Tibet Plateau alpine meadow display low responsiveness to extreme high-altitudehypoxia challenge,suggesting well-acclimatized genes and a physiological strategy that developed during evolution through interact-ions between the genes and environment.All the findings provide evidence for understanding the neuroendocrine mechanisms of hypoxia-induced physiological dysfunction.This review extends these findings.

  8. Innovation factors in Belgrade University library system

    Directory of Open Access Journals (Sweden)

    Biljana Stosic

    2011-11-01

    Full Text Available The aim of this paper is to present research shedding some light on innovation factors identification and measurement in the University of Belgrade’s library system by means of innovation questionnaire, since one of the main innovation management elements is to recognize and measure innovation factors of influence. In that sense, the key innovation factors important for this domain have been identified, based on selected research in the broader area of innovation management. Survey results give one of the rare insights in innovativeness level and characteristics in this important part of the nonprofit sector of a transition economy. In this specific case, that should be the prior investigation with the intention of helping managers to improve organization propensity to innovate and to define/reexamine innovation strategy. Research findings revealed that innovation factors measurement should be considered very important for ICT innovation management in the library system, and that further research would be necessary.

  9. The Epidemic Dynamics of Four Major Lineages of HIV-1 CRF01_AE Strains After Their Introduction into China.

    Science.gov (United States)

    Zeng, Haiyan; Li, Tingting; Wang, Yan; Sun, Binlian; Yang, Rongge

    2016-05-01

    The epidemic of HIV-1 CRF01_AE in China was driven by multiple lineages of HIV-1 viruses introduced in the 1990s and increasing; it is important to investigate their epidemic status in China. In this study, we download all available CRF01_AE sequences (n = 2,931) from China and their associated epidemiological information in the Los Alamos HIV database for our analysis to explore their epidemic status in China. The results showed there were 11 distinct clusters of CRF01_AE strains in China, and 4 major clusters that accounted for 80.0% (1,793/2,241) of Chinese CRF01_AE strains in total had led a real epidemic. Clusters 1 and 2 were epidemic among heterosexuals and injecting drug users in southern and southwestern China, while Clusters 3 and 4 were predominant among homosexuals in eastern and central China and northeastern China, respectively. HIV-1 CRF01_AE strains detected in heterosexuals had the most complex characteristic, underscoring its important role in the occurrence of multiple CRF01_AE lineages. Furthermore, epidemic history reconstruction analysis using the birth-death susceptible-infected-removed package revealed that the four clusters had gone through varying epidemic stages. Clusters 2 and 3 were near the peak of the local epidemic, while Clusters 1 and 4 were just in the very early stage of their epidemic. The epidemic status of CRF01_AE clusters in the future is mainly determined by the effect of prevention and control. Our study provides new insights into the understanding of the epidemic dynamics of CRF01_AE in China.

  10. Critical Success Factors for Risk Management Systems

    OpenAIRE

    Yaraghi, Niam

    2009-01-01

    Despite the existence of extensive literature regarding risk management, there still seems to be lack of knowledge in identification of Critical Success Factors (CSFs) in this area. In this research Grounded Theory is implemented to identify CSFs in Risk Management Systems (RMS). Factor analysis and one-sample t-test are then used to refine and rank the CSFs based on the results of a survey which has been performed among Risk Management practitioners in various types of Swedish corporations. ...

  11. Evaluating Human Factors in Augmented Reality Systems

    Science.gov (United States)

    2005-12-01

    user’s location and then per- forming the (cognitive) task of Mark A. Livingston Naval Research Laboratory Evaluating Human Factors in Augmented Reality ...00-00-2005 4. TITLE AND SUBTITLE Evaluating Human Factors in Augmented Reality Systems 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...the basis for situation awareness or—in combina- tion with visual cues—a navigation task. Tactile tasks. Via haptic devices, we can apply vir- tual

  12. Molecular Epidemiology of HIV Type 1 CRF02_AG in Cameroon and African Patients Living in Italy

    Science.gov (United States)

    Véras, Nazle Mendonca Collaço; Santoro, Maria Mercedes; Gray, Rebecca R.; Tatem, Andrew J.; Presti, Alessandra Lo; Olearo, Flaminia; Cappelli, Giulia; Colizzi, Vittorio; Takou, Desiré; Torimiro, Judith; Russo, Gianluca; Callegaro, Annapaola; Salpini, Romina; D'Arrigo, Roberta; Perno, Carlo-Federico; Goodenow, Maureen M.; Ciccozzi, Massimo

    2011-01-01

    Abstract HIV-1 CRF02_AG accounts for >50% of infected individuals in Cameroon. CRF02_AG prevalence has been increasing both in Africa and Europe, particularly in Italy because of migrations from the sub-Saharan region. This study investigated the molecular epidemiology of CRF02_AG in Cameroon by employing Bayesian phylodynamics and analyzed the relationship between HIV-1 CRF02_AG isolates circulating in Italy and those prevalent in Africa to understand the link between the two epidemics. Among 291 Cameroonian reverse transcriptase sequences analyzed, about 70% clustered within three distinct clades, two of which shared a most recent common ancestor, all related to sequences from Western Africa. The major Cameroonian clades emerged during the mid-1970s and slowly spread during the next 30 years. Little or no geographic structure was detected within these clades. One of the major driving forces of the epidemic was likely the high accessibility between locations in Southern Cameroon contributing to the mobility of the population. The remaining Cameroonian sequences and the new strains isolated from Italian patients were interspersed mainly within West and Central African sequences in the tree, indicating a continuous exchange of CRF02_AG viral strains between Cameroon and other African countries, as well as multiple independent introductions in the Italian population. The evaluation of the spread of CRF02_AG may provide significant insight about the future dynamics of the Italian and European epidemic. PMID:21453131

  13. Corticotropin-Releasing Factor-Overexpressing Mice Exhibit Reduced Neuronal Activation in the Arcuate Nucleus and Food Intake in Response to Fasting

    OpenAIRE

    2008-01-01

    Corticotropin-releasing factor (CRF) overexpressing (OE) mice are a genetic model that exhibits features of chronic stress. We investigated whether the adaptive feeding response to a hypocaloric challenge induced by food deprivation is impaired under conditions of chronic CRF overproduction. Food intake response to a 16-h overnight fast and ip injection of gut hormones regulating food intake were compared in CRF-OE and wild type (WT) littermate mice along with brain Fos expression, circulatin...

  14. Physiological and behavioral effects of chronic intracerebroventricular infusion of corticotropin-releasing factor in the rat

    NARCIS (Netherlands)

    Buwalda, B; deBoer, SF; VanKalkeren, AA; Koolhaas, JM; Kalkeren, A.A. van

    1997-01-01

    The present study was conducted to investigate the Long-term effects of chronic elevation of centrally circulating levels of corticotropin-releasing factor (CRF) on behavior and physiology. For this purpose ovine CRF was infused continuously far a period of 10 days into the lateral ventricle of rats

  15. Physiological and behavioral effects of chronic intracerebroventricular infusion of corticotropin-releasing factor in the rat

    NARCIS (Netherlands)

    Buwalda, B; deBoer, SF; VanKalkeren, AA; Koolhaas, JM; Kalkeren, A.A. van

    1997-01-01

    The present study was conducted to investigate the Long-term effects of chronic elevation of centrally circulating levels of corticotropin-releasing factor (CRF) on behavior and physiology. For this purpose ovine CRF was infused continuously far a period of 10 days into the lateral ventricle of rats

  16. CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba.

    Science.gov (United States)

    Kouri, Vivian; Khouri, Ricardo; Alemán, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

    2015-03-01

    Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.

  17. In vitro analysis of the susceptibility of HIV-1 subtype A and CRF01_AE integrases to raltegravir.

    Science.gov (United States)

    Bellecave, Pantxika; Malato, Laurent; Calmels, Christina; Reigadas, Sandrine; Parissi, Vincent; Andreola, Marie-Line; Fleury, Hervé

    2014-08-01

    The antiviral efficacy of raltegravir (RAL) has been proven against human immunodeficiency virus type 1 (HIV-1) subtypes B and C but remained to be determined against other subtypes. Therefore, the enzymatic activities as well as RAL resistance of HIV-1 subtype A and CRF01_AE integrases (INs) were investigated. Previously published subtype A and CRF01_AE IN sequences from RAL-naïve patients were aligned to generate consensus sequences for both IN subtypes. Subtype A and CRF01_AE INs encoded by these consensus sequences as well as the corresponding enzymes harbouring the N155H resistance mutation were expressed and purified. Enzymatic activities of subtype A and CRF01_AE INs were analysed with regard to typical 3'-end processing (3'-P) and strand transfer (ST) activities both in the presence and absence of RAL and were compared with subtype B IN as well as with the corresponding INs harbouring the N155H resistance mutation. Subtypes B, A and CRF01_AE INs showed similar 3'-P and ST activities. In the presence of RAL, the three wild-type INs exhibited ST activity IC50 values (50% inhibitory concentrations) of 86.3 ± 32.5, 158.3 ± 99.0 and 100.0 ± 65.7 nM, respectively. Analysis of 3'-P activity in the presence of RAL revealed IC(50) > 10 μM for all three enzymes. The three INs harbouring the N155H mutation presented in vitro low but similar resistance levels to RAL. In conclusion, INs from HIV-1 subtypes B, A and CRF01_AE showed similar responses to RAL in vitro, suggesting the potency of this antiretroviral drug to treat HIV-1 subtype A- and CRF01_AE-infected patients.

  18. CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba

    Science.gov (United States)

    Kouri, Vivian; Khouri, Ricardo; Alemán‬, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B.; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

    2015-01-01

    Background Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Methods Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Findings Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. Interpretation CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba. PMID:26137563

  19. Decoding the Role of Water Dynamics in Ligand-Protein Unbinding: CRF1R as a Test Case.

    Science.gov (United States)

    Bortolato, Andrea; Deflorian, Francesca; Weiss, Dahlia R; Mason, Jonathan S

    2015-09-28

    The residence time of a ligand-protein complex is a crucial aspect in determining biological effect in vivo. Despite its importance, the prediction of ligand koff still remains challenging for modern computational chemistry. We have developed aMetaD, a fast and generally applicable computational protocol to predict ligand-protein unbinding events using a molecular dynamics (MD) method based on adiabatic-bias MD and metadynamics. This physics-based, fully flexible, and pose-dependent ligand scoring function evaluates the maximum energy (RTscore) required to move the ligand from the bound-state energy basin to the next. Unbinding trajectories are automatically analyzed and translated into atomic solvation factor (SF) values representing the water dynamics during the unbinding event. This novel computational protocol was initially tested on two M3 muscarinic receptor and two adenosine A2A receptor antagonists and then evaluated on a test set of 12 CRF1R ligands. The resulting RTscores were used successfully to classify ligands with different residence times. Additionally, the SF analysis was used to detect key differences in the degree of accessibility to water molecules during the predicted ligand unbinding events. The protocol provides actionable working hypotheses that are applicable in a drug discovery program for the rational optimization of ligand binding kinetics.

  20. Comparison of fitness of HIV-1 CRF01-AE, CRFO7/08-BC and B' subtype strains using chimeric provirus in vitro%HIV-1 CRF01-AE、CRF07/08-BC和B'构造病毒株体外适应性比较

    Institute of Scientific and Technical Information of China (English)

    张麒; 蒋岩

    2010-01-01

    目的 构建NIA-3 env-EGFP/DsRed2前病毒,观察中国主要流行的HIV-1 CRF01-AE、CRF07/08-BC和B'亚型构造病毒株体外适应性.方法 5份HIV-1B',CRF07/08-BC,CRF01-AE亚型感染的干血斑样本和1份Zambia C亚型PBMC DNA样本,经单基因组扩增技术获得env全长基因,克隆、亚克隆、转染等步骤构建14个NL4-3 env-EGFP/DsRed2前病毒,按顺序进行配对竞争实验,流式细胞仪定量检测被感染细胞的数量.结果 CRF01-AE亚型前病毒适应性最强,适应性值W>1,其次为B',Zambia C,CRF07-BC/CRF08-BC,P<0.05.结论 可利用NL4-3 env7-EGFP/DsRed2构造前病毒,通过竞争实验比较流行病毒株的体外适应性,推测env聊基因对适应性的影响.

  1. Cross-border sexual transmission of the newly emerging HIV-1 clade CRF51_01B.

    Directory of Open Access Journals (Sweden)

    Hui Ting Cheong

    Full Text Available A novel HIV-1 recombinant clade (CRF51_01B was recently identified among men who have sex with men (MSM in Singapore. As cases of sexually transmitted HIV-1 infection increase concurrently in two socioeconomically intimate countries such as Malaysia and Singapore, cross transmission of HIV-1 between said countries is highly probable. In order to investigate the timeline for the emergence of HIV-1 CRF51_01B in Singapore and its possible introduction into Malaysia, 595 HIV-positive subjects recruited in Kuala Lumpur from 2008 to 2012 were screened. Phylogenetic relationship of 485 amplified polymerase gene sequences was determined through neighbour-joining method. Next, near-full length sequences were amplified for genomic sequences inferred to be CRF51_01B and subjected to further analysis implemented through Bayesian Markov chain Monte Carlo (MCMC sampling and maximum likelihood methods. Based on the near full length genomes, two isolates formed a phylogenetic cluster with CRF51_01B sequences of Singapore origin, sharing identical recombination structure. Spatial and temporal information from Bayesian MCMC coalescent and maximum likelihood analysis of the protease, gp120 and gp41 genes suggest that Singapore is probably the country of origin of CRF51_01B (as early as in the mid-1990s and featured a Malaysian who acquired the infection through heterosexual contact as host for its ancestral lineages. CRF51_01B then spread rapidly among the MSM in Singapore and Malaysia. Although the importation of CRF51_01B from Singapore to Malaysia is supported by coalescence analysis, the narrow timeframe of the transmission event indicates a closely linked epidemic. Discrepancies in the estimated divergence times suggest that CRF51_01B may have arisen through multiple recombination events from more than one parental lineage. We report the cross transmission of a novel CRF51_01B lineage between countries that involved different sexual risk groups. Understanding

  2. Cross-border sexual transmission of the newly emerging HIV-1 clade CRF51_01B.

    Science.gov (United States)

    Cheong, Hui Ting; Ng, Kim Tien; Ong, Lai Yee; Chook, Jack Bee; Chan, Kok Gan; Takebe, Yutaka; Kamarulzaman, Adeeba; Tee, Kok Keng

    2014-01-01

    A novel HIV-1 recombinant clade (CRF51_01B) was recently identified among men who have sex with men (MSM) in Singapore. As cases of sexually transmitted HIV-1 infection increase concurrently in two socioeconomically intimate countries such as Malaysia and Singapore, cross transmission of HIV-1 between said countries is highly probable. In order to investigate the timeline for the emergence of HIV-1 CRF51_01B in Singapore and its possible introduction into Malaysia, 595 HIV-positive subjects recruited in Kuala Lumpur from 2008 to 2012 were screened. Phylogenetic relationship of 485 amplified polymerase gene sequences was determined through neighbour-joining method. Next, near-full length sequences were amplified for genomic sequences inferred to be CRF51_01B and subjected to further analysis implemented through Bayesian Markov chain Monte Carlo (MCMC) sampling and maximum likelihood methods. Based on the near full length genomes, two isolates formed a phylogenetic cluster with CRF51_01B sequences of Singapore origin, sharing identical recombination structure. Spatial and temporal information from Bayesian MCMC coalescent and maximum likelihood analysis of the protease, gp120 and gp41 genes suggest that Singapore is probably the country of origin of CRF51_01B (as early as in the mid-1990s) and featured a Malaysian who acquired the infection through heterosexual contact as host for its ancestral lineages. CRF51_01B then spread rapidly among the MSM in Singapore and Malaysia. Although the importation of CRF51_01B from Singapore to Malaysia is supported by coalescence analysis, the narrow timeframe of the transmission event indicates a closely linked epidemic. Discrepancies in the estimated divergence times suggest that CRF51_01B may have arisen through multiple recombination events from more than one parental lineage. We report the cross transmission of a novel CRF51_01B lineage between countries that involved different sexual risk groups. Understanding the cross

  3. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-02-15

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

  4. A Class of Effective of Decarboxylative Perfluoroalkylating Reagents: [(phen)2Cu](O2CRF)

    KAUST Repository

    Huang, Yangjie

    2016-04-13

    This article describes the invention of a class of effective reagents [(phen)2Cu](O2CRF) (1) for the decarboxylative perfluoroalkylation of aryl and heteroaryl halides. Treatment of the copper tert-butyloxide with phenanthroline ligands, with subsequent addition of perfluorocarboxylic acids afforded the air-stable copper(I) perfluorocarboxylato complexes 1. These complexes reacted with a variety of aryl and heteroaryl halides to form perfluoroalkyl(hetero)arenes in moderate to high yields. Computational studies suggested that the coordination of the second phen ligand may reduce the energy barrier for the decarboxylation of perfluorocarboxylate to facilitate the perfluoroalkylation.

  5. Circulation of HIV-1 CRF02_AG among MSM Population in Central Italy: A Molecular Epidemiology-Based Study

    Directory of Open Access Journals (Sweden)

    Massimo Giuliani

    2013-01-01

    Full Text Available Introduction. The evolutionary and demographic history of the circular recombinant form CRF02_AG in a selected retrospective group of HIV-1 infected men who have sex with men (MSM resident in Central Italy was investigated. Methods. A total of 55 HIV-1 subtype CRF02_AG pol sequences were analyzed using Bayesian methods and a relaxed molecular clock to reconstruct their dated phylogeny and estimate population dynamics. Results. Dated phylogeny indicated that the HIV-1 CRF02_AG strains currently circulating in Central Italy originated in the early 90's. Bayesian phylogenetic analysis revealed the existence of a main HIV-1 CRF02_AG clade, introduced in the area of Rome before 2000 and subsequently differentiated in two different subclades with a different date of introduction (2000 versus 2005. All the sequences within clusters were interspersed, indicating that the MSM analyzed form a close and restricted network where the individuals, also moving within different clinical centers, attend the same places to meet and exchange sex. Conclusions. It was suggested that the HIV-1 CRF02_AG epidemic entered central Italy in the early 1990s, with a similar trend observed in western Europe.

  6. A simian-human immunodeficiency virus carrying the rt gene from Chinese CRF01_AE strain of HIV is sensitive to nucleoside reverse transcriptase inhibitors and has a highly genetic stability in vivo.

    Science.gov (United States)

    Wang, Wei; Yao, Nan; Ju, Bin; Dong, Zhihui; Cong, Zhe; Jiang, Hong; Qin, Chuan; Wei, Qiang

    2014-06-01

    Human immunodeficiency virus (HIV)-1 subtype CRF01_AE is one of the major HIV-1 subtypes that dominate the global epidemic. However, its drug resistance, associated mutations, and viral fitness have not been systemically studied, because available chimeric simian-HIVs (SHIVs) usually express the HIV-1 reverse transcriptase (rt) gene of subtype B HIV-1, which is different from subtype CRF01_AE HIV-1. In this study, a recombinant plasmid, pRT-SHIV/AE, was constructed to generate a chimeric RT-SHIV/AE by replacing the rt gene of simian immunodeficiency virus (SIVmac239) with the counterpart of Chinese HIV-1 subtype CRF01_AE. The infectivity, replication capacity, co-receptor tropism, drug sensitivity, and genetic stability of RT-SHIV/AE were characterized. The new chimeric RT-SHIV/AE effectively infected and replicated in human T cell line and rhesus peripheral blood mononuclear cells (rhPBMC). The rt gene of RT-SHIV/AE lacked the common mutation (T215I) associated with drug resistance. RT-SHIV-AE retained infectivity and immunogenicity, similar to that of its counterpart RT-SHIV/TC virus following intravenous inoculation in Chinese rhesus macaque. RT-SHIV-AE was more sensitive to nucleoside reverse transcriptase inhibitors (NRTIs) than the RT-SHIV/TC. RT-SHIV/AE was genetically stable in Chinese rhesus macaque. The new chimeric RT-SHIV/AE may be a valuable tool for evaluating the efficacy of the rt-based antiviral drugs against the subtype CRF01_AE HIV-1.

  7. NERP-CRF: uma ferramenta para o reconhecimento de entidades nomeadas por meio de Conditional Random Fields

    Directory of Open Access Journals (Sweden)

    Daniela Oliveira F. do Amaral

    2014-07-01

    Full Text Available Conditional Random Fields (CRF é um método probabilístico de predição estruturada que tem sido amplamente aplicado em diversas áreas, tais como a de Processamento da Linguagem Natural (PLN, incluindo o Reconhecimento de Entidades Nomeadas (REN, visão computacional e bioinformática. Nesse sentido, propõe-se a realização da tarefa de REN aplicando o método CRF e, sequencialmente, é feita uma avaliação do seu desempenho com base no corpus do HAREM. Conclui-se que, nos testes realizados, o sistema NERP-CRF obteve os melhores resultados de Precisão quando comparado com os sistemas avaliados no mesmo corpus, com plenas condições de ser um sistema competitivo e eficaz.

  8. Corticotropin releasing factor dose-dependently modulates excitatory synaptic transmission in the noradrenergic nucleus locus coeruleus.

    Science.gov (United States)

    Prouty, Eric W; Waterhouse, Barry D; Chandler, Daniel J

    2017-03-01

    The noradrenergic nucleus locus coeruleus (LC) is critically involved in the stress response and receives afferent input from a number of corticotropin releasing factor (CRF) containing structures. Several in vivo and in vitro studies in rat have shown that CRF robustly increases the firing rate of LC neurons in a dose-dependent manner. While it is known that these increases are dependent on CRF receptor subtype 1 and mediated by effects of cAMP intracellular signaling cascades on potassium conductance, the impact of CRF on synaptic transmission within LC has not been clarified. In the present study, we used whole-cell patch clamp electrophysiology to assess how varying concentrations of bath-applied CRF affect AMPA-receptor dependent spontaneous excitatory post-synaptic currents (sEPSCs). Compared to vehicle, 10, 25, and 100 nm CRF had no significant effects on any sEPSC parameters. Fifty nanomolar CRF, however, significantly increased sEPSC amplitude, half-width, and charge transfer, while these measures were significantly decreased by 200 nm CRF. These observations suggest that stress may differentially affect ongoing excitatory synaptic transmission in LC depending on how much CRF is released from presynaptic terminals. Combined with the well-documented effects of CRF on membrane properties and spontaneous LC discharge, these observations may help explain how stress and CRF release are able to modulate the signal to noise ratio of LC neurons. These findings have implications for how stress affects the fidelity of signal transmission and information flow through LC and how it might impact norepinephrine release in the CNS.

  9. LU factorization for accelerator-based systems

    KAUST Repository

    Agullo, Emmanuel

    2011-12-01

    Multicore architectures enhanced with multiple GPUs are likely to become mainstream High Performance Computing (HPC) platforms in a near future. In this paper, we present the design and implementation of an LU factorization using tile algorithm that can fully exploit the potential of such platforms in spite of their complexity. We use a methodology derived from previous work on Cholesky and QR factorizations. Our contributions essentially consist of providing new CPU/GPU hybrid LU kernels, studying the impact on performance of the looking variants as well as the storage layout in presence of pivoting, tuning the kernels for two different machines composed of multiple recent NVIDIA Tesla S1070 (four GPUs total) and Fermi-based S2050 GPUs (three GPUs total), respectively. The hybrid tile LU asymptotically achieves 1 Tflop/s in single precision on both hardwares. The performance in double precision arithmetic reaches 500 Gflop/s on the Fermi-based system, twice faster than the old GPU generation of Tesla S1070. We also discuss the impact of the number of tiles on the numerical stability. We show that the numerical results of the tile LU factorization will be accurate enough for most applications as long as the computations are performed in double precision arithmetic. © 2011 IEEE.

  10. Systemic factors dominate mammal protein evolution.

    Science.gov (United States)

    Vinogradov, Alexander E

    2010-05-07

    Proteins encoded by highly expressed genes evolve more slowly. This correlation is thought to arise owing to purifying selection against toxicity of misfolded proteins (that should be more crucial for highly expressed genes). It is now widely accepted that this individual (by-gene) effect is a dominant cause in protein evolution. Here, I show that in mammals, the evolutionary rate of a protein is much more strongly related to the evolutionary rate of coexpressed proteins (and proteins of the same biological pathway) than to the expression level of its encoding gene. The complexity of gene regulation (estimated by the numbers of transcription factor targets and regulatory microRNA targets in the encoding gene) is another important cause, which is much stronger than gene expression level. Proteins encoded by complexly regulated genes evolve more slowly. The intronic length and the ratio of intronic to coding sequence lengths also correlate negatively with protein evolutionary rate (which contradicts the expectation from the negative link between expression level and evolutionary rate). One more important factor, which is much stronger than gene expression level, is evolutionary age. More recent proteins evolve faster, and expression level of an encoding gene becomes quite a minor cause in the evolution of mammal proteins of metazoan origin. These data suggest that, in contrast to a widespread opinion, systemic factors dominate mammal protein evolution.

  11. Role of CRF on 5-HT Signaling Pathway and Visceral Hypersensitivity in Rats%CRF在大鼠5-HT信号通路和内脏高敏感中的作用

    Institute of Scientific and Technical Information of China (English)

    张璐; 周鸿; 吕宾; 鉏莉; 李蒙

    2011-01-01

    肠易激综合征(IBS)是一种常见的胃肠功能紊乱性疾病,内脏高敏感为其重要生物学指标.5-羟色胺(5-HT)信号通路在介导外周和中枢内脏感觉的传递中发挥重要作用,且与促肾上腺皮质激素释放因子(CRF)关系密切.目的:研究CRF及其不同受体亚型对内脏高敏感大鼠5-HT信号通路的调控作用,探讨IBS内脏高敏感的可能机制.方法:60只Sprague-Dawley大鼠随机分为空白对照组、内脏高敏感模型组、干预对照组、干预一组和干预二组,每组12只.三组干预组大鼠分别于造模前1d侧脑室注射0.9% NaCl溶液、CRF-R1拮抗剂和CRF-R2激动剂.腹部收缩反射(AWR)试验评估大鼠内脏敏感性,免疫组化法检测大鼠脑、脊髓、结肠组织5-HT表达.结果:模型组和干预对照组内脏敏感性显著高于空白对照组,干预一组和干预二组显著低于干预对照组(P<0.05).模型组和干预对照组脑组织5-HT表达显著低于空白对照组,脊髓后角和结肠组织5-HT表达显著高于空白对照组(P<0.05);干预一组和干预二组脑组织5-HT表达较干预对照组显著上调,脊髓后角和结肠组织5-HT表达较干预对照组显著下调(P<0.05).结论:中枢CRF-RI抑制或CRF-R2激活可改变内脏高敏感大鼠脑-肠轴不同部位的5-HT表达,证实CRF对5-HT信号通路具有调控作用,可能是引起IBS内脏高敏感的机制之一.%Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, and visceral hypersensitivity is the key biological parameter of IBS. 5-Hydroxytryptamine (5-HT) signaling pathway plays an important role in mediating both the peripheral and central visceral sensory transmission and has a close relationship with corticotropin-releasing factor (CRF). Aims: To study the regulatory role of CRF and its receptors on 5-HT signaling pathway in visceral hypersensitivity rats, so as to explore the possible mechanism of visceral hypersensitivity in IBS. Methods

  12. Genetic variation in the corticotrophin-releasing factor receptors: identification of single-nucleotide polymorphisms and association studies with obesity in UK Caucasians.

    Science.gov (United States)

    Challis, B G; Luan, J; Keogh, J; Wareham, N J; Farooqi, I S; O'Rahilly, S

    2004-03-01

    To investigate whether genetic variation at the loci encoding the corticotropin-releasing factor receptors-1 and -2 (CRF-R1 and CRF-R2) contributes to human obesity. The coding region of the CRF-R1 and CRF-R2 genes was screened in 51 severely obese children (body mass index (BMI)>4 kg/m(2) standard deviations above the age-related mean) using denaturing high-performance liquid chromatography and direct nucleotide sequencing. Common polymorphisms that were identified were typed from a UK Caucasian population-based cohort by a PCR-based forced restriction digestion. A repeated measures analysis was used to determine associations between the C861T and G1047A genotypes and anthropometric and biochemical indices relevant to obesity. In subjects with extreme early-onset obesity, four missense mutations were found, each in a single individual: CRF-R1 (Val161Met) and CRF-R2 (Glu220Asp, Val240Ile and Val411Met). However, none of these missense mutations clearly cosegregated with obesity in family studies. Two common single-nucleotide polymorphisms, C861T (Cys287Cys) in CRF-R1 and G1047A (Ser349Ser) in CRF-R2, were also detected. G1047A did not associate with any obesity-related phenotype. In contrast, carriers of the CRF-R1 polymorphism, C861T, had a significantly higher body mass index (BMI). Mutations in the coding sequence of the CRF-R1 and CRF-R2 genes are unlikely to be a common monogenic cause of early-onset obesity. In an adult UK Caucasian population, the CRF-R1 C861T polymorphism is associated with increased BMI.

  13. Global dispersal pattern of HIV type 1 subtype CRF01-AE : A genetic trace of human mobility related to heterosexual sexual activities centralized in southeast Asia

    NARCIS (Netherlands)

    Angelis, Konstantinos; Albert, Jan; Mamais, Ioannis; Magiorkinis, Gkikas; Hatzakis, Angelos; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie M J; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Camacho, Ricardo J.; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Andrzej; Kostrikis, Leondios G.; Lepej, Snjezana; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Schmit, Jean Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Boucher, Charles A B; Kaplan, Lauren; Vandamme, Anne Mieke; Paraskevis, Dimitrios

    2015-01-01

    Background. Human immunodeficiency virus type 1 (HIV-1) subtype CRF01-AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01-AE, little is known about its subsequent dispersal pattern. Methods. We assembled a global data set

  14. Molecular characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and impact of T-cell epitope mutations on HLA recognition (ANRS 12159.

    Directory of Open Access Journals (Sweden)

    Estibaliz Lazaro

    Full Text Available BACKGROUND: To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding. METHODS: We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores and HLA binding (MHC score. RESULTS: All sequences clustered with CRF01_AE. HLA class I genotyping showed the predominance of Asian alleles as A*11:01 and B*46:01 with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (±0.9 versus 2 (±0.7 in non-divergent ones (p<0.0001. CONCLUSIONS: Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area.

  15. Regulation of gonadotropins by corticotropin-releasing factor and urocortin

    OpenAIRE

    Kageyama, Kazunori

    2013-01-01

    While stress activates the hypothalamic–pituitary–adrenal (HPA) axis, it suppresses the hypothalamic–pituitary–gonadal (HPG) axis. Corticotropin-releasing factor (CRF) is a major regulatory peptide in the HPA axis during stress. Urocortin 1 (Ucn1), a member of the CRF family of peptides, has a variety of physiological functions and both CRF and Ucn1 contribute to the stress response via G protein-coupled seven transmembrane receptors. Ucn2 and Ucn3, which belong to a separate paralogous linea...

  16. Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala.

    Science.gov (United States)

    Silberman, Yuval; Winder, Danny G

    2013-07-01

    Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses. While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism(s) by which these signals modify CeA glutamatergic neurotransmission remains unclear. Utilizing whole-cell patch-clamp electrophysiology recordings from neurons in the lateral subdivision of the CeA (CeAL), we show that CRF, dopamine (DA) and the β-adrenergic receptor agonist isoproterenol (ISO) all enhance the frequency of spontaneous excitatory postsynaptic currents (sEPSC) without altering sEPSC kinetics, suggesting they increase presynaptic glutamate release. The effect of CRF on sEPSCs was mediated by a combination of CRFR1 and CRFR2 receptors. While previous work from our lab suggests that CRFRs mediate the effect of catecholamines on excitatory transmission in other subregions of the extended amygdala, blockade of CRFRs in the CeAL failed to significantly alter effects of DA and ISO on glutamatergic transmission. These findings suggest that catecholamine and CRF enhancement of glutamatergic transmission onto CeAL neurons occurs via distinct mechanisms. While CRF increased spontaneous glutamate release in the CeAL, CRF caused no significant changes to optogenetically evoked glutamate release in this region. The dissociable effects of CRF on different types of glutamatergic neurotransmission suggest that CRF may specifically regulate spontaneous excitatory transmission. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Structural evolution of urotensin-I: reflections of life before corticotropin releasing factor.

    Science.gov (United States)

    Lovejoy, David A

    2009-10-01

    Peptides have a long evolutionary history that predates the appearance of metazoans. The corticotropin releasing factor (CRF) family of peptides is among the most ancient peptide lineages. The identification and characterization of urotensin-I and related orthologues led the way for the elucidation of the entire CRF peptide family. A comparative analysis of the CRF paralogue sequences suggest that CRF is the most derived of these peptides and has lost many of its ancestral characteristics after it became associated with the hypothalamic-pituitary-adrenal/interrenal (HPA/I axis). In vertebrates, the urotensin-I group of orthologues, which includes sauvagine and urocortin, possess a number of shared characteristics that may be indicative of the ancestral peptide. Given the early origin of the CRF family peptides, it is likely that other peptide lineages are distantly related to the CRF family. In silico or cDNA library screening using probes based on urotensin-I/urocortin characteristics have been used to identify novel CRF family and related sequences that provide clues the evolutionary origin of the CRF family.

  18. Economic Factors Affecting Diversified Farming Systems

    Directory of Open Access Journals (Sweden)

    Maria S. Bowman

    2013-03-01

    Full Text Available In response to a shift toward specialization and mechanization during the 20th century, there has been momentum on the part of a vocal contingent of consumers, producers, researchers, and policy makers who call for a transition toward a new model of agriculture. This model employs fewer synthetic inputs, incorporates practices which enhance biodiversity and environmental services at local, regional, and global scales, and takes into account the social implications of production practices, market dynamics, and product mixes. Within this vision, diversified farming systems (DFS have emerged as a model that incorporates functional biodiversity at multiple temporal and spatial scales to maintain ecosystem services critical to agricultural production. Our aim is to provide an economists' perspective on the factors which make diversified farming systems (DFS economically attractive, or not-so-attractive, to farmers, and to discuss the potential for and roadblocks to widespread adoption. We focus on how a range of existing and emerging factors drive profitability and adoption of DFS. We believe that, in order for DFS to thrive, a number of structural changes are needed. These include: 1 public and private investment in the development of low-cost, practical technologies that reduce the costs of production in DFS, 2 support for and coordination of evolving markets for ecosystem services and products from DFS and 3 the elimination of subsidies and crop insurance programs that perpetuate the unsustainable production of staple crops. We suggest that subsidies and funding be directed, instead, toward points 1 and 2, as well as toward incentives for consumption of nutritious food.

  19. Sympathetic nervous system and chronic renal failure.

    Science.gov (United States)

    Boero, R; Pignataro, A; Ferro, M; Quarello, F

    2001-01-01

    The aim of this work was to review evidence on the role of the sympathetic nervous system (SNS) in chronic renal failure (CRF). Three main points are discussed: 1) SNS and pathogenesis of arterial hypertension; 2) SNS and cardiovascular risk; 3) implication of SNS in arterial hypotension during hemodialysis. Several lines of evidence indicate the presence of a sympathetic hyperactivity in CRF, and its relationship with arterial hypertension. It is suggested that diseased kidneys send afferent nervous signals to central integrative sympathetic nuclei, thus contributing to the development and maintenance of arterial hypertension. The elimination of these impulses with nephrectomy could explain the concomitant reduction of blood pressure. Several experiments confirmed this hypothesis. Regarding SNS and cardiovascular risk, some data suggest that reduced heart rate variability identifies an increased risk for both all causes and sudden death, independently from other recognized risk factors. Symptomatic hypotension is a common problem during hemodialysis treatment, occurring in approximately 20-30% of all hemodialysis sessions and is accompanied by acute withdrawal of sympathetic activity, vasodilation and relative bradicardia. This reflex is thought to be evoked by vigorous contraction of a progressively empty left ventricle, activating cardiac mechanoceptors. This inhibits cardiovascular centers through vagal afferents, and overrides the stimulation by baroreceptor deactivation. Alternative explanations include cerebral ischemia and increased production of nitric oxide, which inhibit central sympathetic activity. It is hoped that therapies aimed at modulating sympathetic nerve activity in patients with CRF will ameliorate their prognosis and quality of life.

  20. PET Imaging of CRF1 with [{sup 11}C]R121920 and [{sup 11}C]DMP696: is the target of sufficient density?

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, Gregory M. [Division of Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032 (United States)]. E-mail: gms11@columbia.edu; Parsey, Ramin V. [Division of Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032 (United States); Kumar, J.S. Dileep [Division of Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032 (United States); Arango, Victoria [Division of Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032 (United States); Kassir, Suham A. [Division of Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032 (United States); Huang, Yung-yu [Division of Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032 (United States); Simpson, Norman R. [Division of Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032 (United States); Van Heertum, Ronald L. [Department of Radiology, Columbia University, New York, NY 10032 (United States); Mann, J. John [Division of Neuroscience, Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032 (United States); Department of Radiology, Columbia University, New York, NY 10032 (United States)

    2007-05-15

    Aim: Overstimulation of the CRF type 1 receptor (CRF1) is implicated in anxiety and depressive disorders. The aim of this study was to investigate the in vivo binding characteristics of [{sup 11}C]R121920 and [{sup 11}C]DMP696 in the nonhuman primate for application in positron emission tomography (PET) studies of CRF1. Methods: PET imaging with the two novel CRF1 radioligands was performed in baboon. In vitro binding studies for CRF1 were performed in postmortem brain tissue of baboon and human to assess sufficiency of receptor density for PET. Results: Both [{sup 11}C]R121920 and [{sup 11}C]DMP696 distributed rapidly and uniformly throughout the brain. Washout was comparable across brain regions, without differences in volume of distribution between regions reported to have high and low in vitro CRF1 binding. Membrane-enriched tissue homogenate assay using [{sup 125}I]Tyr{sup 0}-sauvagine and specific CRF1 antagonists CP154,526 and SN003 in human occipital cortex yielded maximal binding (B {sub max}) of 63.3 and 147.3 fmol/mg protein, respectively, and in human cerebellar cortex yielded B {sub max} of 103.6 and 64.6 fmol/mg protein, respectively. Dissociation constants (K {sub D}) were subnanomolar. In baboon, specific binding was not detectable in the same regions; therefore, B {sub max} and K {sub D} were not measurable. Autoradiographic results were consistent except there was also detectable CRF1-specific binding in baboon cerebellum. Conclusion: Neither [{sup 11}C]R121920 nor [{sup 11}C]DMP696 demonstrated quantifiable regional binding in vivo in baboon. In vitro results suggest CRF1 density in baboon may be insufficient for PET. Studies in man may generate more promising results due to the higher CRF1 density compared with baboon in cerebral cortex and cerebellum.

  1. The parametrization of radio source coordinates in VLBI and its impact on the CRF

    Science.gov (United States)

    Karbon, Maria; Heinkelmann, Robert; Mora-Diaz, Julian; Xu, Minghui; Nilsson, Tobias; Schuh, Harald

    2016-04-01

    Usually celestial radio sources in the celestial reference frame (CRF) catalog are divided in three categories: defining, special handling, and others. The defining sources are those used for the datum realization of the celestial reference frame, i.e. they are included in the No-Net-Rotation (NNR) constraints to maintain the axis orientation of the CRF, and are modeled with one set of totally constant coordinates. At the current level of precision, the choice of the defining sources has a significant effect on the coordinates. For the ICRF2 295 sources were chosen as defining sources, based on their geometrical distribution, statistical properties, and stability. The number of defining sources is a compromise between the reliability of the datum, which increases with the number of sources, and the noise which is introduced by each source. Thus, the optimal number of defining sources is a trade-off between reliability, geometry, and precision. In the ICRF2 only 39 of sources were sorted into the special handling group as they show large fluctuations in their position, therefore they are excluded from the NNR conditions and their positions are normally estimated for each VLBI session instead of as global parameters. All the remaining sources are classified as others. However, a large fraction of these unstable sources show other favorable characteristics, e.g. large flux density (brightness) and a long history of observations. Thus, it would prove advantageous including these sources into the NNR condition. However, the instability of these objects inhibit this. If the coordinate model of these sources would be extended, it would be possible to use these sources for the NNR condition as well. All other sources are placed in the "others" group. This is the largest group of sources, containing those which have not shown any very problematic behavior, but still do not fulfill the requirements for defining sources. Studies show that the behavior of each source can vary

  2. Multi-Hypothesis CRF-Segmentation of Neural Tissue in Anisotropic EM Volumes

    CERN Document Server

    Funke, Jan; Hamprecht, Fred; Cardona, Albert; Cook, Matthew

    2011-01-01

    We present an approach for the joint segmentation and grouping of similar components in anisotropic 3D image data and use it to segment neural tissue in serial sections electron microscopy (EM) images. We first construct a nested set of neuron segmentation hypotheses for each slice. A conditional random field (CRF) then allows us to evaluate both the compatibility of a specific segmentation and a specific inter-slice assignment of neuron candidates with the underlying observations. The model is solved optimally for an entire image stack simultaneously using integer linear programming (ILP), which yields the maximum a posteriori solution in amortized linear time in the number of slices. We evaluate the performance of our approach on an annotated sample of the Drosophila larva neuropil and show that the consideration of different segmentation hypotheses in each slice leads to a significant improvement in the segmentation and assignment accuracy.

  3. 75 FR 35096 - Federal Employees' Retirement System; Present Value Factors

    Science.gov (United States)

    2010-06-21

    ... MANAGEMENT Federal Employees' Retirement System; Present Value Factors AGENCY: Office of Personnel Management... conform the present value factors to changes in demographic factors adopted by the Board of Actuaries of the Civil Service Retirement System. DATES: The revised present value factors apply to...

  4. Effects of Xiaoyaosan on Stress-Induced Anxiety-Like Behavior in Rats: Involvement of CRF1 Receptor

    Directory of Open Access Journals (Sweden)

    You-Ming Jiang

    2016-01-01

    Full Text Available Background. Compared with antidepressant activity of Xiaoyaosan, the role of Xiaoyaosan in anxiety has been poorly studied. Objective. To observe the effects of Xiaoyaosan on anxiety-like behavior induced by chronic immobilization stress (CIS and further explore whether these effects were related to CRF1R signaling. Methods. Adult male SD rats were randomly assigned to five groups (n=12: the nonstressed control group, vehicle-treated (saline, p.o. group, Xiaoyaosan-treated (3.854 g/kg, p.o. group, vehicle-treated (surgery group, and antalarmin-treated (surgery group. Artificial cerebrospinal fluid (0.5 μL/side or CRF1R antagonist antalarmin (125 ng/0.5 μL, 0.5 μL/side was bilaterally administered into the basolateral amygdala in the surgery groups. Except for the nonstressed control group, the other four groups were exposed to CIS (14 days, 3 h/day 30 minutes after treatment. On days 15 and 16, all animals were subjected to the elevated plus-maze (EPM and novelty suppressed feeding (NSF test. We then examined the expression of CRF1R, pCREB, and BDNF in the amygdala. Results. Chronic pretreatment with Xiaoyaosan or antalarmin significantly reversed elevated anxiety-like behavior and the upregulated level of CRF1R and BDNF in the amygdala of stressed rats. pCREB did not differ significantly among the groups. Conclusions. These results suggest that Xiaoyaosan exerts anxiolytic-like effects in behavioral tests and the effects may be related to CRF1R signaling in the amygdala.

  5. Healthcare system factors and colorectal cancer screening.

    Science.gov (United States)

    Zapka, Jane G; Puleo, Elaine; Vickers-Lahti, Maureen; Luckmann, Roger

    2002-07-01

    Developing effective programs to promote colorectal cancer (CRC) screening requires understanding of the effect of healthcare system factors on access to screening and adherence to guidelines. This study assessed the role of insurance status, type of plan, the frequency of preventive health visits, and provider recommendation on utilization of CRC screening tests using a cross-sectional, random-digit-dial survey of 1002 Massachusetts residents aged > or =50. A broad definition of CRC screening status included colonoscopy or barium enema (screening or diagnostic) within 10 years, flexible sigmoidoscopy (FSIG) within 5 years, and fecal occult blood testing (FOBT) in the past year as options; 51.7% of subjects aged 50 to 64 and 61.5% of older subjects were current. The uninsured had the lowest current testing rate. Among insured participants, type of insurance had little impact on CRC testing; older subjects enrolled in HMOs had marginally higher rates, although not statistically significant. Increased frequency of preventive health visits and ever receiving a physician's recommendation for FSIG or ever receiving FOBT cards were associated with higher rates of CRC screening among both age groups. Even when broad criteria are used to define current CRC screening status, a substantial proportion of the age-eligible population remains underscreened. Obtaining regular preventive care and receiving a physician's recommendation for screening appear to be potent facilitators of screening that should be considered in designing promotional efforts.

  6. Hypothalamic corticotropin-releasing factor immunoreactivity is reduced during induction of pituitary tumors by chronic estrogen treatment

    Energy Technology Data Exchange (ETDEWEB)

    Haas, D.A.; Borgundvaag, B.; Sturtridge, W.C.; George, S.R.

    1987-11-02

    The role that estrogen plays in the regulation of corticotropin-releasing factor (CRF) is not known. A radioimmunoassay specific for rat CRF was utilized to measure the CRF-like immunoreactivity (CRF-ir) in the hypothalamus of ovariectomized rats treated with estradiol for periods up to 12 weeks. Compared to ovariectomized controls, estradiol treatment resulted in significantly reduced CRF-ir after 3 and 12 weeks, although no significant change was seen after 8 weeks. Anterior pituitary (AP) weight was greatly increased by estradiol treatment at all time points studied. Bromocriptine treatment for the last 3 weeks of the 12-week period, or removal of estradiol for 3 weeks after 9 weeks of treatment did not reverse the changes in CRF-ir even though significant regressions of tumor size was achieved. There was no correlation between AP weight and CRF-ir in individual animals. These data show that chronic treatment with estrogen reduced hypothalamic CRF-ir content. Neither a direct estrogenic effect or an indirect effect mediated through alterations in the adenohypophysis could be ruled out. 21 references, 3 figures.

  7. A Review of Cardiorespiratory Fitness in Adolescent and Young Adult Survivors of Childhood Cancer: Factors that Affect its Decline and Opportunities for Intervention.

    Science.gov (United States)

    Berkman, Amy M; Lakoski, Susan G

    2016-03-01

    Childhood cancer incidence and survivorship rates are increasing, leading to a growing population of survivors that are at risk for competing causes of death, most notably cardiovascular disease (CVD). Cardiorespiratory fitness (CRF), a key modifiable CVD risk factor, is lower than expected among childhood survivors 5-20 years post-diagnosis. This review discusses the studies that demonstrate lower CRF in survivors of childhood cancer and the potential mechanisms and factors contributing to lower CRF in this population. Both exercise interventions and strategies to improve CRF are considered. The review advocates for more robust clinical research and exercise interventions to improve CRF with the goal of reducing comorbidities and competing CVD risk among childhood cancer survivors into adolescence and young adulthood.

  8. Impact of body mass index, physical activity, and other clinical factors on cardiorespiratory fitness (from the Cooper Center longitudinal study).

    Science.gov (United States)

    Lakoski, Susan G; Barlow, Carolyn E; Farrell, Stephen W; Berry, Jarett D; Morrow, James R; Haskell, William L

    2011-07-01

    Cardiorespiratory fitness (CRF) is widely accepted as an important reversible cardiovascular risk factor. In the present study, we examined the nonmodifiable and modifiable determinants of CRF within a large healthy Caucasian population of men and women. The study included 20,239 patients presenting to Cooper Clinic (Dallas, Texas) for a comprehensive medical examination from 2000 through 2010. CRF was determined by maximal treadmill exercise testing. Physical activity categories were 0 metabolic equivalent tasks (METs)/min/week (no self-reported moderate or vigorous intensity physical activity), 1 to 449 METs/min/week (not meeting physical activity guideline), 450 to 749 METs/min/week (meeting guideline), and ≥750 METs/min/week (exceeding guideline). Linear regression modeling was used to determine the most robust clinical factors associated with achieved treadmill time. Age, gender, body mass index (BMI), and physical activity were the most important factors associated with CRF, explaining 56% of the variance (R(2) = 0.56). The addition of all other factors combined (current smoking, systolic blood pressure, blood glucose, high-density and low-density lipoprotein cholesterol, health status) were associated with CRF (p physical activity on CRF, such that normal-weight (BMI physical activity compared to obese subjects (BMI ≥30 kg/m(2)). Percent body fat, not lean body mass, was the key factor driving this interaction. In conclusion, BMI was the most important clinical risk factor associated with CRF other than nonmodifiable risk factors age and gender. For a similar amount of physical activity, normal-weight subjects achieved a higher CRF level compared to obese subjects. These data suggest that obesity may offset the benefits of physical activity on achieved CRF, even in a healthy population of men and women.

  9. Genetic characterization of three CRF01_AE full-length HIV type 1 sequences from Fujian Province, China

    Institute of Scientific and Technical Information of China (English)

    HUANG Hai-long; YAN Yan-sheng; YAN Ping-ping; ZHENG Jian; WU Shou-li; CHENG Ge; LIN Xun; ZHENG Wu-xiong; XIE Mei-rong; ZHANG Jian-ming

    2006-01-01

    Background One of the major characteristics of the human immunodeficiency virus type 1 (HIV-1) is its unusually high degree of genetic variability, which involves in genetic diagnosis, subtyping, vaccine design, and epidemiology. HIV-1 CRF01_AE is a main prevalent HIV-1 recombinant strain in China. In this study, three full-length CRF01_AE genomes from Fujian Province, China were cloned, sequenced, and analyzed; and the further genetic diversity defining and epidemiologic analysis were carried out.Methods Proviral DNA was extracted from non-cultured peripheral blood mononuclear cells, the near full-length HIV-1 genome was amplified and the PCR products were cloned into Pcr-XL-TOPO vector and sequenced. 5'-long terminal repeat (LTR) and 3'-LTRs were amplified by additional independent PCR and cloned into Pmd18t vector. Gene-based phylogenic tree was constructed and genetic distances were calculated by MEGA 3.1. Simplot was used for Bootscan analysis.Results The phylogeny and genetic distance analysis of the three near full-length sequences confirmed that these three samples clustered with CRF01_AE isolates, more close to Thailand CRF01_AE strain CM240, and were distantly related to African CRF01_AE strain 90CF402. Analysis of their genomic organization revealed the presence of nine potential open reading frames. There were no major deletions, rearrangements, or insertions in the three sequences, but an in-frame stop codon was found in tat gene of Fj051. LTRs of the three sequences contained a few nucleotides mutation. We did not find new mosaic recombinant in the three sequences. The V3 motif was GPGQ in all the three sequences, and there were only few amino acids differences in all three V3 loop sequences.Conclusion This report reveals the background of the three full-length CRF01_AE genomes, the most dominantly circulating HIV-1 strain in Fujian Province, China. The work is essential for the design and development of an effective AIDS vaccine for the region.

  10. Factorization Method in Oscillator with the Aharonov-Casher System

    Directory of Open Access Journals (Sweden)

    J. Sadeghi

    2014-01-01

    mathematical foundation about factorization method. The factorization method helps us to obtain the energy spectrum and general wave function for the corresponding system in some spin condition. The factorization method leads us to obtain the raising and lowering operators for the Aharonov-Casher system. The corresponding operators give us the generators of the algebra.

  11. 76 FR 32243 - Federal Employees' Retirement System; Present Value Factors

    Science.gov (United States)

    2011-06-03

    ... MANAGEMENT Federal Employees' Retirement System; Present Value Factors AGENCY: Office of Personnel Management... conform the present value factors to changes in the economic assumptions adopted by the Board of Actuaries of the Civil Service Retirement System. DATES: The revised present value factors apply to...

  12. 75 FR 35093 - Civil Service Retirement System; Present Value Factors

    Science.gov (United States)

    2010-06-21

    ... MANAGEMENT Civil Service Retirement System; Present Value Factors AGENCY: Office of Personnel Management... instrumentalities. ] This notice is necessary to conform the present value factors to changes in demographic factors... revised present value factors apply to survivor reductions or employee annuities that commence on or...

  13. Underlying Factors for Practicality of the Production Control Systems

    DEFF Research Database (Denmark)

    Arica, Emrah; Strandhagen, Jan Ola; Hvolby, Hans-Henrik

    2012-01-01

    This paper gives indications to important factors that must be considered for effectiveness of the production control systems under uncertainty. Five key factors have been identified by the literature study. Production schedule generation and execution approach under uncertainty, information...

  14. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Science.gov (United States)

    Cheong, Hui Ting; Chow, Wei Zhen; Takebe, Yutaka; Chook, Jack Bee; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-01-01

    In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  15. Food intake inhibition in rainbow trout induced by activation of serotonin 5-HT2C receptors is associated with increases in POMC, CART and CRF mRNA abundance in hypothalamus.

    Science.gov (United States)

    Pérez-Maceira, Jorge J; Otero-Rodiño, Cristina; Mancebo, María J; Soengas, José L; Aldegunde, Manuel

    2016-04-01

    In rainbow trout, the food intake inhibition induced by serotonin occurs through 5-HT2C and 5-HT1A receptors, though the mechanisms involved are still unknown. Therefore, we assessed if a direct stimulation of 5-HT2C and 5-HT1A serotonin receptors (resulting in decreased food intake in rainbow trout), affects gene expression of neuropeptides involved in the control of food intake, such as pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), corticotrophin releasing factor (CRF), and agouti-related peptide (AgRP). In a first set of experiments, the injection of the 5-HT2C receptor agonists MK212 (60 μg kg(-1) icv) and WAY 161503 (1 mg kg(-1) ip), and of the 5-HT1A receptor agonist 8-OH-DPAT (1 mg kg(-1) ip and 30 μg kg(-1) icv) induced food intake inhibition. In a second set of experiments, we observed that the injection of MK212 or WAY 161503 (1 and 3 mg kg(-1)) significantly increased hypothalamic POMC mRNA abundance. CART mRNA abundance in hypothalamus was enhanced by treatment with MK212 and unaffected by WAY 161503. The administration of the 5-HT1A receptor agonist 8-OH-DPAT did not induce any significant variation in the hypothalamic POMC or CART mRNA levels. CRF mRNA abundance was only affected by MK212 that increased hypothalamic values. Finally, hypothalamic AgRP mRNA abundance was only evaluated with the agonist 5-HT2C MK212 resulting in no significant effects. The results show that the reduction in food intake mediated by 5-HT2C receptors is associated with increases in hypothalamic POMC, CART and CRF mRNA abundance.

  16. Integrating factors and conservation theorems of constrained Birkhoffian systems

    Institute of Scientific and Technical Information of China (English)

    Qiao Yong-Fen; Zhao Shu-Hong; Li Ren-Jie

    2006-01-01

    In this paper the conservation theorems of the constrained Birkhoffian systems are studied by using the method of integrating factors. The differential equations of motion of the system are written. The definition of integrating factors is given for the system. The necessary conditions for the existence of the conserved quantity for the system are studied.The conservation theorem and its inverse for the system are established. Finally, an example is given to illustrate the application of the results.

  17. Construction and characterization of HIV type 1 CRF07_BC infectious molecular clone from men who have sex with men.

    Science.gov (United States)

    Jiang, Yan-Ling; Bai, Wen-Wei; Qu, Fan-Wei; Ma, Hua; Jiang, Run-Sheng; Shen, Bao-Sheng

    2016-03-01

    This study aimed to investigate the biological characterization of HIV type 1 (HIV-1) CRF07_BC infection among men who have sex with men (MSM). From November 2011 to November 2013, a total of 66 blood samples were collected from MSM with acute HIV-1 infection with CRF07_BC subgroup strains. Deletion in the gag p6 region was detected by sequence alignment and comparative analysis. Peripheral blood mononuclear cells (PBMCs) of HNXX1301-1307 samples were separated by density gradient centrifugation. Nested polymerase chain reaction (nPCR) was used to amplify the viral DNA. The near full-length HIV-1 DNA products were ligated to the long terminal repeat (LTR) vector plasmid (07BCLTR) to construct a full-length HIV clone. The molecular clone was transfected into HEK-293T cells, TZM-b1 cells and patients' PBMCs. The pregenome of an infectious molecular clone of HIV-1 (pNL4-3) was amplified, and a subclone with CRF07_BC was developed to construct the full-length chimeric molecular clone pNL4-3/07BCLTR. Detection of p24 antigen and luciferase activity was used to measure the in vitro infectivity of pNL4-3/07BCLTR. Among the 66 MSM patients infected with CRF07_BC strains, deletion mutations of the Gag P6 proteins were found in 7 of 18CRF07_BC strains; deletion mutations of 2-13 amino acids in different regions were discovered in 6 strains; and the remaining 42 strains did not show deletions. Seven strains with amino acids deficiency in the P6 protein accounted for 27% of all strains and 75% of all deletion genotype strains. A total of 186 full-length molecular clones of CRF07_BC were constructed. There were 5, 9, 10 and 11 clones of HNXX1302, HNXX1304, HNXX1305 and HNXX1306 that resulted in p24-positive supernatant when transfected into HEK-293T cells. Full-length clones of HNXX1302, HNXX1304, HNXX1305 and HNXX1306 showed slight infection in the transfected TZM-b1 cells, as judged by the fluorescence values of TZM-b1 cells 48h post-transfection. However, we were unable to

  18. Treatment of CRF Patients with Severe Secondary Hyperparathyroidism by Parathyroidectomy Combined with Parathyroid Tissue Transplantation in Forearm(Report of 10 Cases)

    Institute of Scientific and Technical Information of China (English)

    WuHF; WangXY

    2002-01-01

    Objective To investigate the efficacy of parathyroidectomy combined with parathyroid tissue transplantation in forearm in treatment of CRF patients with severe secondary hyperparathyroidism(SHP).Methods 10 cases of CRF with SHP were treated with parathyroidectomy combined with parathyroid tissue transplantation in forearm from 1995 to 2001.The diagnosis,operation indication and peri-operation management of ten patients were discussed.Results The hypertrophy parathyroids were totally resected in 10 CRF cases with SHP.All grafts were alive after transplantation.Symptoms of hyperparathyroidism disappeared and the various laboratory test turned to normal after operation.Conclusion That surgical manipulation is safe and effective in those CRF patients with severe SHP who failed in medical therapy.

  19. Net positive charge of HIV-1 CRF01_AE V3 sequence regulates viral sensitivity to humoral immunity.

    Directory of Open Access Journals (Sweden)

    Satoshi Naganawa

    Full Text Available The third variable region (V3 of the human immunodeficiency virus type 1 (HIV-1 envelope gp120 subunit participates in determination of viral infection coreceptor tropism and host humoral immune responses. Positive charge of the V3 plays a key role in determining viral coreceptor tropism. Here, we examined by bioinformatics, experimental, and protein modelling approaches whether the net positive charge of V3 sequence regulates viral sensitivity to humoral immunity. We chose HIV-1 CRF01_AE strain as a model virus to address the question. Diversity analyses using CRF01_AE V3 sequences from 37 countries during 1984 and 2005 (n = 1361 revealed that reduction in the V3's net positive charge makes V3 less variable due to limited positive selection. Consistently, neutralization assay using CRF01_AE V3 recombinant viruses (n = 30 showed that the reduction in the V3's net positive charge rendered HIV-1 less sensitive to neutralization by the blood anti-V3 antibodies. The especially neutralization resistant V3 sequences were the particular subset of the CCR5-tropic V3 sequences with net positive charges of +2 to +4. Molecular dynamics simulation of the gp120 monomers showed that the V3's net positive charge regulates the V3 configuration. This and reported gp120 structural data predict a less-exposed V3 with a reduced net positive charge in the native gp120 trimer context. Taken together, these data suggest a key role of the V3's net positive charge in the immunological escape and coreceptor tropism evolution of HIV-1 CRF01_AE in vivo. The findings have molecular implications for the adaptive evolution and vaccine design of HIV-1.

  20. Hierarchical Higher Order Crf for the Classification of Airborne LIDAR Point Clouds in Urban Areas

    Science.gov (United States)

    Niemeyer, J.; Rottensteiner, F.; Soergel, U.; Heipke, C.

    2016-06-01

    We propose a novel hierarchical approach for the classification of airborne 3D lidar points. Spatial and semantic context is incorporated via a two-layer Conditional Random Field (CRF). The first layer operates on a point level and utilises higher order cliques. Segments are generated from the labelling obtained in this way. They are the entities of the second layer, which incorporates larger scale context. The classification result of the segments is introduced as an energy term for the next iteration of the point-based layer. This framework iterates and mutually propagates context to improve the classification results. Potentially wrong decisions can be revised at later stages. The output is a labelled point cloud as well as segments roughly corresponding to object instances. Moreover, we present two new contextual features for the segment classification: the distance and the orientation of a segment with respect to the closest road. It is shown that the classification benefits from these features. In our experiments the hierarchical framework improve the overall accuracies by 2.3% on a point-based level and by 3.0% on a segment-based level, respectively, compared to a purely point-based classification.

  1. CRF-Based Model for Instrument Detection and Pose Estimation in Retinal Microsurgery

    Directory of Open Access Journals (Sweden)

    Mohamed Alsheakhali

    2016-01-01

    Full Text Available Detection of instrument tip in retinal microsurgery videos is extremely challenging due to rapid motion, illumination changes, the cluttered background, and the deformable shape of the instrument. For the same reason, frequent failures in tracking add the overhead of reinitialization of the tracking. In this work, a new method is proposed to localize not only the instrument center point but also its tips and orientation without the need of manual reinitialization. Our approach models the instrument as a Conditional Random Field (CRF where each part of the instrument is detected separately. The relations between these parts are modeled to capture the translation, rotation, and the scale changes of the instrument. The tracking is done via separate detection of instrument parts and evaluation of confidence via the modeled dependence functions. In case of low confidence feedback an automatic recovery process is performed. The algorithm is evaluated on in vivo ophthalmic surgery datasets and its performance is comparable to the state-of-the-art methods with the advantage that no manual reinitialization is needed.

  2. Near Full-Length Identification of a Novel HIV-1 CRF01_AE/B/C Recombinant in Northern Myanmar.

    Science.gov (United States)

    Zhou, Yan-Heng; Chen, Xin; Liang, Yue-Bo; Pang, Wei; Qin, Wei-Hong; Zhang, Chiyu; Zheng, Yong-Tang

    2015-08-01

    The Myanmar-China border appears to be the "hot spot" region for the occurrence of HIV-1 recombination. The majority of the previous analyses of HIV-1 recombination were based on partial genomic sequences, which obviously cannot reflect the reality of the genetic diversity of HIV-1 in this area well. Here, we present a near full-length characterization of a novel HIV-1 CRF01_AE/B/C recombinant isolated from a long-distance truck driver in Northern Myanmar. It is the first description of a near full-length genomic sequence in Myanmar since 2003, and might be one of the most complicated HIV-1 chimeras ever detected in Myanmar, containing four CRF01_AE, six B segments, and five C segments separated by 14 breakpoints throughout its genome. The discovery and characterization of this new CRF01_AE/B/C recombinant indicate that intersubtype recombination is ongoing in Myanmar, continuously generating new forms of HIV-1. More work based on near full-length sequence analyses is urgently needed to better understand the genetic diversity of HIV-1 in these regions.

  3. Antidepressant-like effects of the CRF family peptides, urocortin 1, urocortin 2 and urocortin 3 in a modified forced swimming test in mice.

    Science.gov (United States)

    Tanaka, Masaru; Telegdy, Gyula

    2008-03-28

    Most of the evidence suggests that corticotropin-releasing hormone (CRH) is involved in mood disorders. The CRF receptors type 1 (CRF(1) receptors) elicit a stress response, and their natural and synthetic antagonists have been studied as possible drugs against depression, whereas CRF receptors type 2 (CRF(2) receptors) appear to alleviate the stress response and mediate anxiolytic action. Other CRF family peptides are urocortin 1 (Ucn 1), urocortin 2 (Ucn 2) and urocortin 3 (Ucn 3). Little is known about the action of Ucn 1, Ucn 2 and Ucn 3 on depressive disorders. Antidepressant-like effects of Ucn 1, Ucn 2 and Ucn 3 (0.13, 0.25 and 0.5 microg/2 microl, i.c.v.) were assayed in mice in a modified forced swimming test (FST). This modified FST predicts the clinical efficacy of an antidepressant drug through the scoring of immobility, climbing and swimming behavior. The study demonstrated that Ucn 1 had no action on any of parameters studied in the modified FST. Ucn 2 elicited antidepressive-like action by shortening the immobility time. Additionally Ucn 2 significantly increased the climbing and swimming times. Ucn 3 likewise displayed an antidepressive-like effect by shortening the immobility time, and increasing the climbing and swimming times. The results suggest that CRF(2) receptor stimulation by Ucn 2 or Ucn 3 leads to antidepressant-like action, but dual stimulation of the CRF(1) and CRF(2) receptors by Ucn 1 does not trigger antidepressant-like action in the modified mouse FST.

  4. System Identification by Dynamic Factor Models

    NARCIS (Netherlands)

    C. Heij (Christiaan); W. Scherrer; M. Destler

    1996-01-01

    textabstractThis paper concerns the modelling of stochastic processes by means of dynamic factor models. In such models the observed process is decomposed into a structured part called the latent process, and a remainder that is called noise. The observed variables are treated in a symmetric way, so

  5. Hypothalamic corticotropin-releasing factor is centrally involved in learning under moderate stress.

    Science.gov (United States)

    Lucas, Morgan; Chen, Alon; Richter-Levin, Gal

    2013-08-01

    The corticotropin-releasing factor (CRF) neuropeptide is found to have a pivotal role in the regulation of the behavioral and neuroendocrine responses to stressful challenges. Here, we studied the involvement of the hypothalamic CRF in learning under stressful conditions. We have used a site-specific viral approach to knockdown (KD) CRF expression in the paraventricular nucleus of the hypothalamus (PVN). The two-way shuttle avoidance (TWSA) task was chosen to assess learning and memory under stressful conditions. Control animals learned to shuttle from one side to the other to avoid electrical foot shock by responding to a tone. Novel object and social recognition tasks were used to assess memory under less stressful conditions. KD of PVN-CRF expression decreased the number of avoidance responses in a TWSA session under moderate (0.8 mA), but not strong (1.5 mA), stimulus intensity compared to control rats. On the other hand, KD of PVN-CRF had no effect on memory performance in the less stressful novel object or social recognition tasks. Interestingly, basal or stress-induced corticosterone levels in CRF KD rats were not significantly different from controls. Taken together, the data suggest that the observed impairment was not a result of alteration in HPA axis activity, but rather due to reduced PVN-CRF activity on other brain areas. We propose that hypothalamic CRF is centrally involved in learning under moderate stressful challenge. Under 'basal' (less stressful) conditions or when the intensity of the stress is more demanding, central CRF ceases to be the determinant factor, as was indicated by performances in the TWSA with higher stimulus intensity or in the less stressful tasks of object and social recognition.

  6. Genomic Characterization of Two Novel HIV-1 Unique (CRF01_AE/B) Recombinant Forms Among Men Who Have Sex with Men in Beijing, China

    Science.gov (United States)

    Li, Zheng; Li, Jia; Feng, Yi; Kalish, Marcia L.; Lu, Hongyan; Yin, Lu; Liao, Lingjie; Qian, Han-Zhu; Frost, Simon D.W.; Ruan, Yuhua; Vermund, Sten H.; Shao, Yiming

    2015-01-01

    Abstract We report here two novel HIV-1 recombinant forms (CRF01_AE/B) isolated from two HIV-positive male subjects infected through homosexual contact in Beijing, China. Recombination contributes substantially to the genetic diversity of HIV-1, and is likely to occur in populations in which multiple subtypes circulate. Molecular epidemiological studies showed that subtype B, CRF01_AE, and CRF07_BC are currently cocirculating in parallel among men who have sex with men (MSM) in China, providing the opportunity for the emergence of new recombinants. Phylogenetic analysis of near full-length genome (NFLG) sequences showed that the unique recombinant forms (URFs) were composed of gene regions from CRF01_AE and subtype B. The CRF01_AE region of the recombinants clustered together with a previously described cluster 4 lineage of CRF01_AE. The B regions of both the recombinants clustered within the B strains. The two recombinants were quite similar with six breakpoints in common. These data highlight the importance of continuous surveillance of the dynamic change of HIV-1 subtypes and new recombinants among the MSM population. PMID:26058342

  7. The crystal structure of HIV CRF07 B′/C gp41 reveals a hyper-mutant site in the middle of HR2 heptad repeat

    Energy Technology Data Exchange (ETDEWEB)

    Du, Jiansen; Xue, Hailing; Ma, Jing; Liu, Fang [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Zhou, Jianhua [Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Shao, Yiming [State Key Laboratory for Infectious Disease Prevention and Control, and National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Qiao, Wentao, E-mail: wentaoqiao@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2013-11-15

    HIV CRF07 B′/C is a strain circulating mainly in northwest region of China. The gp41 region of CRF07 is derived from a clade C virus. In order to compare the difference of CRF07 gp41 with that of typical clade B virus, we solved the crystal structure of the core region of CRF07 gp41. Compared with clade B gp41, CRF07 gp41 evolved more basic and hydrophilic residues on its helix bundle surface. Based on sequence alignment, a hyper-mutant cluster located in the middle of HR2 heptads repeat was identified. The mutational study of these residues revealed that this site is important in HIV mediated cell–cell fusion and plays critical roles in conformational changes during viral invasion. - Highlights: • We solved the crystal structure of HIV CRF07 gp41 core region. • A hyper-mutant cluster in the middle of HR2 heptads repeat was identified. • The hyper-mutant site is important in HIV-cell fusion. • The model will help to understand the HIV fusion process.

  8. The predominance of Human Immunodeficiency Virus type 1 (HIV-1 circulating recombinant form 02 (CRF02_AG in West Central Africa may be related to its replicative fitness

    Directory of Open Access Journals (Sweden)

    Butel Christelle

    2006-07-01

    Full Text Available Abstract Background CRF02_AG is the predominant HIV strain circulating in West and West Central Africa. The aim of this study was to test whether this predominance is associated with a higher in vitro replicative fitness relative to parental subtype A and G viruses. Primary HIV-1 isolates (10 CRF02_AG, 5 subtype A and 5 subtype G were obtained from a well-described Cameroonian cohort. Growth competition experiments were carried out at equal multiplicity of infection in activated T cells and monocyte-derived dendritic cells (MO-DC in parallel. Results Dual infection/competition experiments in activated T cells clearly indicated that CRF02_AG isolates had a significant replication advantage over the subtype A and subtype G viruses. The higher fitness of CRF02_AG was evident for isolates from patients with CD4+ T cell counts >200 cells/μL (non-AIDS or CD4+ T cell counts Conclusion We observed a higher ex vivo replicative fitness of CRF02_AG isolates compared to subtype A and G viruses from the same geographic region and showed that this was independent of the co-receptor tropism and irrespective of high or low CD4+ T cell count. This advantage in replicative fitness may contribute to the dominant spread of CRF02_AG over A and G subtypes in West and West Central Africa.

  9. Combining Personality Traits with Traditional Risk Factors for Coronary Stenosis: An Artificial Neural Networks Solution in Patients with Computed Tomography Detected Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Angelo Compare

    2013-01-01

    Full Text Available Background. Coronary artery disease (CAD is a complex, multifactorial disease in which personality seems to play a role but with no definition in combination with other risk factors. Objective. To explore the nonlinear and simultaneous pathways between traditional and personality traits risk factors and coronary stenosis by Artificial Neural Networks (ANN data mining analysis. Method. Seventy-five subjects were examined for traditional cardiac risk factors and personality traits. Analyses were based on a new data mining method using a particular artificial adaptive system, the autocontractive map (AutoCM. Results. Several traditional Cardiovascular Risk Factors (CRF present significant relations with coronary artery plaque (CAP presence or severity. Moreover, anger turns out to be the main factor of personality for CAP in connection with numbers of traditional risk factors. Hidden connection map showed that anger, hostility, and the Type D personality subscale social inhibition are the core factors related to the traditional cardiovascular risk factors (CRF specifically by hypertension. Discussion. This study shows a nonlinear and simultaneous pathway between traditional risk factors and personality traits associated with coronary stenosis in CAD patients without history of cardiovascular disease. In particular, anger seems to be the main personality factor for CAP in addition to traditional risk factors.

  10. Human factors systems approach to healthcare quality and patient safety

    Science.gov (United States)

    Carayon, Pascale; Wetterneck, Tosha B.; Rivera-Rodriguez, A. Joy; Hundt, Ann Schoofs; Hoonakker, Peter; Holden, Richard; Gurses, Ayse P.

    2013-01-01

    Human factors systems approaches are critical for improving healthcare quality and patient safety. The SEIPS (Systems Engineering Initiative for Patient Safety) model of work system and patient safety is a human factors systems approach that has been successfully applied in healthcare research and practice. Several research and practical applications of the SEIPS model are described. Important implications of the SEIPS model for healthcare system and process redesign are highlighted. Principles for redesigning healthcare systems using the SEIPS model are described. Balancing the work system and encouraging the active and adaptive role of workers are key principles for improving healthcare quality and patient safety. PMID:23845724

  11. Corticotropin-releasing factor secretion from dendritic cells stimulated by commensal bacteria

    Institute of Scientific and Technical Information of China (English)

    Mariko Hojo; Toshifumi Ohkusa; Harumi Tomeoku; Shigeo Koido; Daisuke Asaoka; Akihito Nagahara; Sumio Watanabe

    2011-01-01

    AIM: To study the production and secretion of corticotropin-releasing factor (CRF) by dendritic cells and the influence of commensal bacteria.METHODS: JAWSⅡ cells (ATCC CRL-11904), a mouse dendritic cell line, were seeded into 24-well culture plates and grown for 3 d. Commensal bacterial strains of Clostridium clostrodiiforme (JCM1291), Bacteroides vulgatus (B. vulgatus) (JCM5856), Escherichia coli (JCM1649), or Fusobacterium varium (F. varium) (ATCC8501) were added to the cells except for the control well, and incubated for 2 h. After incubation, we performed enzyme-linked immunosorbent assay for the cultured medium and reverse transcription polymerase chain reaction for the dendritic cells, and compared these values with controls.RESULTS: The level of CRF secretion by control dendritic cells was 40.4 ± 6.2 pg/mL. The CRF levels for cells incubated with F. varium and B. vulgatus were significantly higher than that of the control (P < 0.0001). CRF mRNA was present in the control sample without bacteria, and CRF mRNA levels in all samples treated with bacteria were above that of the control sample.F. varium caused the greatest increase in CRF mRNA expression. CONCLUSION: Our results suggest that dendritic cells produce CRF, a process augmented by commensal bacteria.

  12. Molecular Recognition of Corticotropin releasing Factor by Its G protein-coupled Receptor CRFR1

    Energy Technology Data Exchange (ETDEWEB)

    Pioszak, Augen A.; Parker, Naomi R.; Suino-Powell, Kelly; Xu, H. Eric (Van Andel)

    2009-01-15

    The bimolecular interaction between corticotropin-releasing factor (CRF), a neuropeptide, and its type 1 receptor (CRFR1), a class B G-protein-coupled receptor (GPCR), is crucial for activation of the hypothalamic-pituitary-adrenal axis in response to stress, and has been a target of intense drug design for the treatment of anxiety, depression, and related disorders. As a class B GPCR, CRFR1 contains an N-terminal extracellular domain (ECD) that provides the primary ligand binding determinants. Here we present three crystal structures of the human CRFR1 ECD, one in a ligand-free form and two in distinct CRF-bound states. The CRFR1 ECD adopts the alpha-beta-betaalpha fold observed for other class B GPCR ECDs, but the N-terminal alpha-helix is significantly shorter and does not contact CRF. CRF adopts a continuous alpha-helix that docks in a hydrophobic surface of the ECD that is distinct from the peptide-binding site of other class B GPCRs, thereby providing a basis for the specificity of ligand recognition between CRFR1 and other class B GPCRs. The binding of CRF is accompanied by clamp-like conformational changes of two loops of the receptor that anchor the CRF C terminus, including the C-terminal amide group. These structural studies provide a molecular framework for understanding peptide binding and specificity by the CRF receptors as well as a template for designing potent and selective CRFR1 antagonists for therapeutic applications.

  13. 76 FR 32241 - Civil Service Retirement System; Present Value Factors

    Science.gov (United States)

    2011-06-03

    ... MANAGEMENT Civil Service Retirement System; Present Value Factors AGENCY: Office of Personnel Management... instrumentalities. This notice is necessary to conform the present value factors to changes in the economic...: The revised present value factors apply to survivor reductions or employee annuities that commence...

  14. Cooling factor for magnetic refrigeration systems

    Directory of Open Access Journals (Sweden)

    Mohammadreza Ghahremani

    2014-12-01

    Full Text Available The adiabatic temperature change (ΔTad during the magnetization process of polycrystalline gadolinium and Ni51Mn33.4In15.6 Heusler alloy is directly measured near the Curie temperature. The cooling factor (CF is introduced as the area under the curve of adiabatic temperature change versus ambient temperature. The CF provides more representative measure of cooling performance in the operational temperature range. Selecting different temperature abscissas qualitatively changes the interpretation of the cooling performance of a magnetocaloric material. In particular, plotting ΔTad versus initial temperature gives a measurably different CF compared to that given by plotting ΔTad versus average temperature.

  15. Factors in Management Information System Failures.

    Science.gov (United States)

    1980-12-08

    Last, but most important, my thanks to my wife, Barbara , for putting up with me during the often traumatic experience of preparing this report. E. W...does little to aid an executive in making a decision. What he does need is information in 4 Derman, p. 59. sWilliam B. Carper , "Human Factors in MIS... Carper , who believes that many CEOs1 2 only pay lip service 9Derman, p. 56. 1"William A. Jones, III, "The Manager’s Role in Design of an Integrated

  16. Model correction factor method for system analysis

    DEFF Research Database (Denmark)

    Ditlevsen, Ove Dalager; Johannesen, Johannes M.

    2000-01-01

    The Model Correction Factor Method is an intelligent response surface method based on simplifiedmodeling. MCFM is aimed for reliability analysis in case of a limit state defined by an elaborate model. Herein it isdemonstrated that the method is applicable for elaborate limit state surfaces on which...... severallocally most central points exist without there being a simple geometric definition of the corresponding failuremodes such as is the case for collapse mechanisms in rigid plastic hinge models for frame structures. Taking as simplifiedidealized model a model of similarity with the elaborate model...... surface than existing in the idealized model....

  17. J-Inner-Outer Factorization, J-Spectral Factorization, and Robust Control for Nonlinear Systems

    NARCIS (Netherlands)

    Ball, Joseph A.; Schaft, Arjan J. van der

    1996-01-01

    The problem of expressing a given nonlinear state-space system as the cascade connection of a lossless system and a stable, minimum-phase system (inner-outer factorization) is solved for the case of a stable system having state-space equations affine in the inputs. The solution is given in terms of

  18. Integrating Factors and Conservation Laws for Relativistic Mechanical System

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yi

    2005-01-01

    In this paper, we present a new method to construct the conservation laws for relativistic mechanical systems by finding corresponding integrating factors. First, the Lagrange equations of relativisticmechanical systems are established, and the definition of integrating factors of the systems is given; second, the necessary conditions for the existence of conserved quantities of the relativistic mechanical systems are studied in detail, and the relation between the conservation laws and the integrating factors of the systems is obtained and the generaized Killing equations for the determination of the integrating factors are given; finally, the conservation theorem and its inverse for the systems are established, and an example is given to illustrate the application of the results.

  19. Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substrates

    Directory of Open Access Journals (Sweden)

    Sajoy Purathumuriyil Varghese

    2015-01-01

    Full Text Available Background: Early Life Stress (ELS can profoundly influence an individual′s genotype and phenotype. Effects of ELS can manifest in the short-term, late life and even in subsequent generations. ELS activate corticotrophin releasing factor (CRF; CRF influences drug seeking and addiction. The aim of this study was to examine the effects of endogenous elevated levels of CRF on addiction. Materials and Methods: Inducible forebrain over-expression of CRF mice (tetop-CRH x CaMKII-tTA was used for this study. Morphine (10 mg/kg was administered every other day for 10 days or with increasing doses of morphine: 20, 40, 60, 80, 100, and 100 mg/kg. The behavioral trials including morphine sensitization, Somatic Opiate Withdrawal Symptoms (SOWS were conducted in a single, open field, activity. After behavioral trial, animals were perfused for immunohistochemistry analysis. Results: CRF-over expressed (CRF-OE mice showed increase in morphine sensitization and withdrawal symptoms after morphine administration compared to wild type (WT mice. The two-way ANOVA in the morphine sensitization study showed a significant effect of treatment (P<0.05 and genotype for distance traveled (P<0.01. In the SOWS study, opiate withdrawal symptoms such as rearings, circling behavior, grooming, and jump in CRF-OE were amplified in parallel to WT mice. In the immunohistochemistry study, pro-dynorphine (PDYN expression was increased after morphine administration in both amygdala and nucleus accumbens (NAcc. Conclusions: CRF-OE in the forebrain increases the sensitization and withdrawal symptoms in morphine treated mice. On exposure to morphine, in CRF-OE mice the PDYN protein expression was increased as compared to WT mice in the amygdala and NAcc.

  20. Patient safety - the role of human factors and systems engineering.

    Science.gov (United States)

    Carayon, Pascale; Wood, Kenneth E

    2010-01-01

    Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety.

  1. RELATIONSHIP BETWEEN ORGANIZATIONAL FACTORS, TECHNOLOGICAL FACTORS AND ENTERPRISE RESOURCE PLANNING SYSTEM IMPLEMENTATION

    Directory of Open Access Journals (Sweden)

    Suha Afaneh

    2015-02-01

    Full Text Available There are three stages of Enterprise Resource planning System (ERP Implementation; which are preimplementation, mid- implementation and post-implementation. In pre-implementation stage the pervious researchers found that it fail in Organizational and Technological factors. Therefore, this research studies the Technological Factors availability and the Organizational Factor readiness at Greater Amman Municipality (GAM Case study. The statistical results showed that there are availability of the Organizational factor (Organizational Objectives and Services, Organization culture, and Business process for success of ERP system, and indicate the technological infrastructure is available og GAM

  2. Corticotropin-releasing factor-overexpressing mice exhibit reduced neuronal activation in the arcuate nucleus and food intake in response to fasting.

    Science.gov (United States)

    Stengel, Andreas; Goebel, Miriam; Million, Mulugeta; Stenzel-Poore, Mary P; Kobelt, Peter; Mönnikes, Hubert; Taché, Yvette; Wang, Lixin

    2009-01-01

    Corticotropin-releasing factor (CRF) overexpressing (OE) mice are a genetic model that exhibits features of chronic stress. We investigated whether the adaptive feeding response to a hypocaloric challenge induced by food deprivation is impaired under conditions of chronic CRF overproduction. Food intake response to a 16-h overnight fast and ip injection of gut hormones regulating food intake were compared in CRF-OE and wild type (WT) littermate mice along with brain Fos expression, circulating ghrelin levels, and gastric emptying of a nonnutrient meal. CRF-OE mice injected ip with saline showed a 47 and 44% reduction of 30-min and 4-h cumulative food intake response to an overnight fast, respectively, compared with WT. However, the 30-min food intake decrease induced by ip cholecystokinin (3 microg/kg) and increase by ghrelin (300 microg/kg) were similar in CRF-OE and WT mice. Overnight fasting increased the plasma total ghrelin to similar levels in CRF-OE and WT mice, although CRF-OE mice had a 2-fold reduction of nonfasting ghrelin levels. The number of Fos-immunoreactive cells induced by fasting in the arcuate nucleus was reduced by 5.9-fold in CRF-OE compared with WT mice whereas no significant changes were observed in other hypothalamic nuclei. In contrast, fasted CRF-OE mice displayed a 5.6-fold increase in Fos-immunoreactive cell number in the dorsal motor nucleus of the vagus nerve and a 34% increase in 20-min gastric emptying. These findings indicate that sustained overproduction of hypothalamic CRF in mice interferes with fasting-induced activation of arcuate nucleus neurons and the related hyperphagic response.

  3. Inhibition of corticotropin releasing factor expression in the central nucleus of the amygdala attenuates stress-induced behavioral and endocrine responses

    Directory of Open Access Journals (Sweden)

    Leah B. Callahan

    2013-10-01

    Full Text Available Corticotropin releasing factor (CRF is a primary mediator of endocrine, autonomic and behavioral stress responses. Studies in both humans and animal models have implicated CRF in a wide-variety of psychiatric conditions including anxiety disorders such as post-traumatic stress disorder (PTSD, depression, sleep disorders and addiction among others. The central nucleus of the amygdala (CeA, a key limbic structure with one of the highest concentrations of CRF-producing cells outside of the hypothalamus, has been implicated in anxiety-like behavior and a number of stress-induced disorders. This study investigated the specific role of CRF in the CeA on both endocrine and behavioral responses to stress. We used RNA Interference (RNAi techniques to locally and specifically knockdown CRF expression in CeA. Behavior was assessed using the elevated plus maze (EPM and open field test (OF. Knocking down CRF expression in the CeA had no significant effect on measures of anxiety-like behavior in these tests. However, it did have an effect on grooming behavior, a CRF-induced behavior. Prior exposure to a stressor sensitized an amygdalar CRF effect on stress-induced HPA activation. In these stress-challenged animals silencing CRF in the CeA significantly attenuated corticosterone responses to a subsequent behavioral stressor. Thus, it appears that while CRF projecting from the CeA does not play a significant role in the expression stress-induced anxiety-like behaviors on the EPM and OF it does play a critical role in stress-induced HPA activation.

  4. Acute stress modulates the histamine content of mast cells in the gastrointestinal tract through interleukin-1 and corticotropin-releasing factor release in rats.

    Science.gov (United States)

    Eutamene, Helene; Theodorou, Vassilia; Fioramonti, Jean; Bueno, Lionel

    2003-12-15

    Stress results in activation of the hypothalamic pituitary adrenal axis and affects illnesses such as neuroinflammatory syndrome. In vivo acute stress (restraint stress) induces gastrointestinal function disturbances through colonic mast cell activation. This study investigated the effect of acute stress in histamine content of colonic mast cells, and the central role of interleukin-1 (IL-1) and corticotropin-releasing factor (CRF) in this effect. After a restraint stress session colonic segments were isolated and submitted to three protocols: (i) determination of histamine levels by radioimmunoassay (RIA) after incubation with 48/80 compound, (ii) evaluation by histology of mucosal mast cell (MMC) number and (iii) determination of histamine immunoreactivity of MMC. These procedures were conducted (1) in sham or stressed rats, (2) in stressed rats previously treated with intracerebroventricular (I.C.V.) IL-1ra or alpha-helical CRF9-41, (3) in naive rats pretreated with I.C.V. rhIL-1beta or CRF and (4) in rats treated with central IL-1beta and CRF plus alpha-helical CRF and IL-1ra, respectively (cross-antagonism reaction). Acute stress increases histamine content in colonic mast cells, without degranulation. I.C.V. pretreatment with IL-1ra or alpha-helical CRF9-41 blocked stress-induced mast cell histamine content increase. Both I.C.V. rhIL-1beta and CRF injections reproduced the stress-linked changes. I.C.V. treatment with CRF antagonist blocked I.C.V. rhIL-1beta-induced mast cell histamine content increase, whereas central IL-1ra did not affect stress events induced by I.C.V. CRF administration. These results suggest that in rats acute stress increases colonic mast cell histamine content. This effect is mediated by the release in cascade in the brain first of IL-1 and secondly of CRF.

  5. Surveying the critical success factors of BPM-systems implementation.

    NARCIS (Netherlands)

    Ravesteyn, P.; Batenburg, R.

    2010-01-01

    Purpose – The purpose of this paper is to explore if there is a common ground for the definition of business process management (BPM) and BPM-systems, as well as the critical success factors (CSFs) for BPM-system implementation. A BPM-system implementation framework is validated that classifies the

  6. Surveying the critical success factors of BPM-systems implementation.

    NARCIS (Netherlands)

    Ravesteyn, P.; Batenburg, R.

    2010-01-01

    Purpose – The purpose of this paper is to explore if there is a common ground for the definition of business process management (BPM) and BPM-systems, as well as the critical success factors (CSFs) for BPM-system implementation. A BPM-system implementation framework is validated that classifies the

  7. Economic growth factors system: theoretical and methodological aspect

    Directory of Open Access Journals (Sweden)

    H.Ya. Hlukha

    2014-03-01

    Full Text Available The aim of the article. The main objective of the article is to create theoretical grounds to build the system of economic growth factors, to modernize their classification, to define exogenous and endogenous factors, to analyze them within the state economic policy structure. The results of the analysis. The article focuses on economic growth factors theoretical studies: - economic growth factors classification characteristics have been highlighted; - various approaches to determine exogenous and endogenous factors have been analyzed; - reflexive and elastic economic growth factors have been determined; - economic policy was given the role of reflective element within the system to ensure economic growth. The system of factors should be considered within the system that ensures economic growth. It comprises two important elements which enlist the economic growth factors system, economic growth rates system and two reflexive elements – the state economic policy and economic growth models system. While analyzing the economic growth factors, their quality and impact upon the economy should be considered. Economic growth depends on the factors, consideration of which is one of the most important aspects of the economic growth theory. Economic growth reasons are the factors that cause this growth. These are phenomena and processes that can increase the production output, improve efficiency and quality. Factors classification completeness and their diversity do not necessarily mean the dead end of the study. Any classification has the sense only if it fulfills the certain function. If we take into account economic growth modeling, factors diversification and their characteristics classification it implies that models are becoming more complex, the range of their parameters expands, however it does not necessarily lead to more accurate prognosis. All the factors have different impact upon the economic development. Their first type is elastic ones

  8. Tissue plasminogen activator promotes the effects of corticotropin-releasing factor on the amygdala and anxiety-like behavior.

    Science.gov (United States)

    Matys, Tomasz; Pawlak, Robert; Matys, Elzbieta; Pavlides, Constantine; McEwen, Bruce S; Strickland, Sidney

    2004-11-16

    Stress-induced plasticity in the brain requires a precisely orchestrated sequence of cellular events involving novel as well as well known mediators. We have previously demonstrated that tissue plasminogen activator (tPA) in the amygdala promotes stress-induced synaptic plasticity and anxiety-like behavior. Here, we show that tPA activity in the amygdala is up-regulated by a major stress neuromodulator, corticotropin-releasing factor (CRF), acting on CRF type-1 receptors. Compared with WT, tPA-deficient mice responded to CRF treatment with attenuated expression of c-fos (an indicator of neuronal activation) in the central and medial amygdala but had normal c-fos responses in paraventricular nuclei. They exhibited reduced anxiety-like behavior to CRF but had a sustained corticosterone response after CRF administration. This effect of tPA deficiency was not mediated by plasminogen, because plasminogen-deficient mice demonstrated normal behavioral and hormonal changes to CRF. These studies establish tPA as an important mediator of cellular, behavioral, and hormonal responses to CRF.

  9. Cerebrospinal fluid corticotropin-releasing factor and perceived early-life stress in depressed patients and healthy control subjects.

    Science.gov (United States)

    Carpenter, Linda L; Tyrka, Audrey R; McDougle, Christopher J; Malison, Robert T; Owens, Michael J; Nemeroff, Charles B; Price, Lawrence H

    2004-04-01

    Previous studies have reported elevated concentrations of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) in patients with major depression. Elevations of CSF CRF have also been reported in adult laboratory animals exposed to the stress of brief maternal deprivation or maternal neglect in the neonatal or preweaning period. The present study was designed to determine whether major depression and a history of perceived early adversity in childhood are independently associated with elevated CSF CRF concentrations in adults. In this case-control study, 27 medication-free adults with major depression and 25 matched controls underwent standardized lumbar puncture for collection of a single CSF sample at 1200. Subjects provided data about significant adverse early-life experiences and rated their global perceived level of stress during pre-school and preteen years on a six-point Likert scale. The mean difference in CSF CRF between depressed patients and controls did not reach statistical significance. In a regression model, perceived early-life stress was a significant predictor of CSF CRF, but depression was not. Perinatal adversity and perceived adversity in the preteen adversity years (ages 6-13 years) were both independently associated with decreasing CSF CRF concentrations. The relationship observed between perceived early-life stress and adult CSF CRF concentrations in this study closely parallels recent preclinical findings. More work is needed to elucidate the critical nature and timing of early events that may be associated with enduring neuroendocrine changes in humans.

  10. Noradrenergic inhibition of canine gallbladder contraction and murine pancreatic secretion during stress by corticotropin-releasing factor.

    Science.gov (United States)

    Lenz, H J; Messmer, B; Zimmerman, F G

    1992-02-01

    Gastrointestinal secretory and motor responses are profoundly altered during stress; but the effects of stress and its mediator(s) on the two major gut functions, exocrine pancreatic secretion and gallbladder motility, are unknown. We therefore developed two animal models that allowed us to examine the effects of acoustic stress on canine gallbladder contraction and restraint stress on rat exocrine pancreatic secretion. Acoustic stress inhibited cholecystokinin-8 (CCK)- and meal-induced gallbladder contraction, and restraint stress inhibited basal and CCK/secretin-stimulated pancreatic secretion. These inhibitory responses were mimicked by cerebral injection of corticotropin-releasing factor (CRF) and abolished by the CRF antagonist, alpha-helical CRF-(9-41). The effects of stress and exogenous CRF were simulated by intravenous infusion of norepinephrine but prevented by ganglionic, noradrenergic, and alpha-adrenergic but not beta-adrenergic receptor blockade. Vagotomy, adrenalectomy, and--in rats--hypophysectomy did not alter the effects produced by stress and CRF. These results indicate that endogenous CRF released in response to different stressors in distinct species inhibits canine gallbladder contraction and murine exocrine pancreatic secretion via activation of sympathetic efferents. Release of norepinephrine appears to be the final common pathway producing inhibition of biliary and pancreatic digestive function during stress mediated by cerebral CRF.

  11. Antepartum cardiorespiratory fitness (CRF) quantification by estimation of maximal oxygen consumption (Vo2 max) in pregnant South Indian women.

    Science.gov (United States)

    Chakaravertty, Biswajit; Parkavi, K; Coumary, Sendhil A; Felix, A J W

    2012-04-01

    The aim of the study was to calculate the maximal oxygen consumption (Vo2max) for pregnant women of varying trimesters and to quantify the cardiorespiratory fitness (CRF)with the objective of being able to determine the exercise dose for antenatal women which can be prescribed to achieve optimal exercise benefits during various trimesters. A study group comprising 64 pregnant women with uncomplicated singleton pregnancy and control group with 77 non-pregnant women were subjected to Cooper's 12 minutes walk test. From the distance covered in 12 minutes, Vo2max was calculated. The Vo2max values were statistically analysed between the non-pregnant and pregnant and also its variability among the trimesters. Percentile tables of Vo2max were drawn and multiple comparisons were applied. Results show that the Vo2max values among non-pregnant and first trimester ranges between 18 and 22 ml/kg/minute. Trimesters II and III had a range of Vo2max values between 16-20 and 14-18 ml/kg/minute respectively. The CRF of pregnant women significantly reduced to 6%, 9% and 18% in each trimester respectively when compared with the reference table framed out of non-pregnant Vo2max values. Among the study group the reduction in Vo2max values had no statistical significance between first 2 trimesters but trimester III significantly differs from other trimesters. The exercise prescription cannot be the same for pregnant and non-pregnant women. Even among the pregnant women, III trimester needs separate exercise prescription from the other two trimesters as CRF is markedly compromised towards term.

  12. Factors affecting goat production in a communal farming system in ...

    African Journals Online (AJOL)

    Factors affecting goat production in a communal farming system in the Eastern ... and for cash sales (23%), and only 15% kept goats for home meat consumption. ... is likely to increase to the detriment of other ruminant species in the future.

  13. Nutrition, Physical Activity, and Obesity - Behavioral Risk Factor Surveillance System

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes data on adult's diet, physical activity, and weight status from Behavioral Risk Factor Surveillance System. This data is used for DNPAO's Data,...

  14. The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains

    Directory of Open Access Journals (Sweden)

    Guimarães Monick L

    2012-01-01

    Full Text Available Abstract Background Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time. Materials and methods Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005. These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt and env regions. Alignment and neighbor-joining (NJ phylogenetic analyses were established from partial env (n = 37 and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay. The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples. Results Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5% samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%. Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005. Conclusion HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70

  15. The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains.

    Science.gov (United States)

    Guimarães, Monick L; Velarde-Dunois, Ketty G; Segurondo, David; Morgado, Mariza G

    2012-01-16

    Molecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time. Fifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005). These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt) and env regions. Alignment and neighbor-joining (NJ) phylogenetic analyses were established from partial env (n = 37) and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay). The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples. Phylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5%) samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%). Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005. HIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70.0%) or BF1 recombinant (23.8% vs 30.0%) samples from Bolivia.

  16. Neutralization pattern of HIV-1 subtype B' and CRF07_BC virus chronically infected individuals%HIV-1B'亚型及CRF07_BC重组毒株感染者中和反应特征分析

    Institute of Scientific and Technical Information of China (English)

    胡新韬; 洪坤学; 赵春红; 郝晓培; 郑扬; 任莉; 阮玉华; 邵一鸣

    2011-01-01

    目的 探讨我国主要流行的HIV-1 B'和CRF07 BC重组毒株感染者中和反应特征.方法 采用基于Env假病毒的以表达CD4及CCR5/CXCR4的TZM-b1细胞系为靶细胞的中和抗体测定方法,测定40例感染时间在3年左右的HIV-1 CRF07_BC重组毒株感染者及31例感染时间在10年以上的HIV-1 B'亚型毒株感染者血浆对11株包括B(4株)、CRF07_BC(3株)、CRF01_AE(3株)及中和敏感毒株(1株)Env假病毒的中和反应,并分析感染者血浆的中和宽度和中和强度.结果 B'亚型毒株感染者在中和宽度及亚型交叉中和强度方面均高于感染时间相对较短的CRF07_BC重组毒株感染者,B'亚型感染者对CRF01_AE亚型病毒的中和活性显著高于CRF07_Bc重组型感染者;而CRF07_BC重组型感染者对同亚型病毒的中和强度则显著高于B'亚型感染者.结论 HIV-1感染者中和抗体宽度以及对异源病毒的中和活性与感染时间正相关.适度的病毒抗原刺激有助于广谱中和活性的产生.%Aim To analyze the neutralizing antibody (Nab) responses to HIV-1 subtype B' and CRF07_BC virus in chronically infected individuals in China.Methods Total 71 anti-retroviral therapy-naive HIV-1 infected individuals were recruited in this study.Among them,40 cases were infected with CRF07_BC virus with infected time around 3 years and 31 cases were infected with subtype B' virus with infected time over 10 years at the sampling time.The standardized Nab assay using Env pseudoviruses and TZM-bl cell-line expressing CD4 and CCR5/CXCR4 was performed against a panel of pseudoviruses composed of subtypes B(4),CRF07_BC(3) and CRF01_AE strains and 1 neutalization-sensitive SF162.LS virus as control.Results The breadth and potency of Nab responses in subtype B' virus chronically infected individuals against inter-subtype viruses were higher than that of CRF07_BC virus chronically infected individuals with shorter infected time.Subtype B' virus chronical infection also

  17. Factorization approach to superintegrable systems: Formalism and applications

    Science.gov (United States)

    Ballesteros, Á.; Herranz, F. J.; Kuru, Ş.; Negro, J.

    2017-03-01

    The factorization technique for superintegrable Hamiltonian systems is revisited and applied in order to obtain additional (higher-order) constants of the motion. In particular, the factorization approach to the classical anisotropic oscillator on the Euclidean plane is reviewed, and new classical (super) integrable anisotropic oscillators on the sphere are constructed. The Tremblay-Turbiner-Winternitz system on the Euclidean plane is also studied from this viewpoint.

  18. Factorization approach to superintegrable systems: Formalism and applications

    Energy Technology Data Exchange (ETDEWEB)

    Ballesteros, Á., E-mail: angelb@ubu.es; Herranz, F. J., E-mail: fjherranz@ubu.es [Universidad de Burgos, Departamento de Física (Spain); Kuru, Ş., E-mail: kuru@science.ankara.edu.tr [Ankara University, Department of Physics, Faculty of Science (Turkey); Negro, J., E-mail: jnegro@fta.uva.es [Universidad de Valladolid, Departamento de Física Teórica, Atómica y Óptica (Spain)

    2017-03-15

    The factorization technique for superintegrable Hamiltonian systems is revisited and applied in order to obtain additional (higher-order) constants of the motion. In particular, the factorization approach to the classical anisotropic oscillator on the Euclidean plane is reviewed, and new classical (super) integrable anisotropic oscillators on the sphere are constructed. The Tremblay–Turbiner–Winternitz system on the Euclidean plane is also studied from this viewpoint.

  19. Theory of ground state factorization in quantum cooperative systems.

    Science.gov (United States)

    Giampaolo, Salvatore M; Adesso, Gerardo; Illuminati, Fabrizio

    2008-05-16

    We introduce a general analytic approach to the study of factorization points and factorized ground states in quantum cooperative systems. The method allows us to determine rigorously the existence, location, and exact form of separable ground states in a large variety of, generally nonexactly solvable, spin models belonging to different universality classes. The theory applies to translationally invariant systems, irrespective of spatial dimensionality, and for spin-spin interactions of arbitrary range.

  20. Global Dispersal Pattern of HIV Type 1 Subtype CRF01_AE: A Genetic Trace of Human Mobility Related to Heterosexual Sexual Activities Centralized in Southeast Asia.

    Science.gov (United States)

    Angelis, Konstantinos; Albert, Jan; Mamais, Ioannis; Magiorkinis, Gkikas; Hatzakis, Angelos; Hamouda, Osamah; Struck, Daniel; Vercauteren, Jurgen; Wensing, Annemarie M J; Alexiev, Ivailo; Åsjö, Birgitta; Balotta, Claudia; Camacho, Ricardo J; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Andrzej; Kostrikis, Leondios G; Lepej, Snjezana; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Schmit, Jean-Claude; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Boucher, Charles A B; Kaplan, Lauren; Vandamme, Anne-Mieke; Paraskevis, Dimitrios

    2015-06-01

    Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01_AE, little is known about its subsequent dispersal pattern. We assembled a global data set of 2736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap trees estimated by the maximum likelihood method. We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 of 20 sampled countries in Europe. Japan, Singapore, Vietnam, and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported strains from neighboring Asian countries, North America, and Africa without any significant viral exportation. The central role of Thailand in the global spread of CRF01_AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sex tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01_AE, the only globally distributed non-B clade whose global dispersal did not originate in Africa. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Advances in Study on Corticotropin-releasing Factor in Inflammatory Bowel Disease%促肾上腺皮质激素释放因子在炎症性肠病中的研究进展

    Institute of Scientific and Technical Information of China (English)

    马俊方; 张予蜀; 孔超美

    2013-01-01

    近年来,越来越多的证据表明应激可干扰神经系统,进而通过脑-肠轴的交互作用引起免疫紊乱,在炎症性肠病(IBD)的发病中起重要作用.促肾上腺皮质激素释放因子(CRF)是一种与应激反应密切相关的神经内分泌肽,其家族成员通过与受体结合,调节机体在应激状态下的下丘脑-垂体-肾上腺(HPA)轴功能,在协调应激相关内分泌、自主神经、免疫、行为等反应中起重要作用.在慢性肠道炎症中,脑和肠黏膜中的CRF系统成员被激活以调节肠道局部和中枢免疫反应.本文对CRF在IBD中作用的研究进展作一综述.%It has become increasingly evident that stress is implicated in the development of inflammatory bowel disease (IBD) via initial nervous disturbance and subsequent immune dysfunction through brain-gut interaction. Being a principal neuroendocrine coordinator of stress responses, corticotropin-releasing factor ( CRF) and its related peptides regulate the hypothalamic-pituitary-adrenal (HPA) axis and coordinate the endocrine, autonomic, immune and behavioral responses to stress through its receptors. In chronic intestinal inflammation, the members of CRF system in brain and colonic mucosa are activated, regulating both the local and central immune response. This article reviewed the advances in study on the role of CRF in IBD.

  2. Degranulation of mast cells located in median eminence in response to compound 48/80 evokes adrenocortical secretion via histamine and CRF in dogs.

    Science.gov (United States)

    Matsumoto, Itsuro; Inoue, Yasuhisa; Tsuchiya, Katsuhiko; Shimada, Toshio; Aikawa, Tadaomi

    2004-10-01

    The effect of intracerebroventricular infusion of compound 48/80 (C48/80), a mast cell secretagogue, on adrenal cortisol secretion was investigated in dogs under pentobarbital sodium anesthesia. A marked increase in adrenal cortisol secretion was elicited by C48/80 along with a concomitant increase in the plasma levels of cortisol and immunoreactive ACTH, but neither arterial blood pressure and heart rate nor the plasma histamine level altered significantly. Pretreatment with either anti-CRF antiserum or pyrilamine maleate (H(1) histamine-receptor antagonist) significantly attenuated the C48/80-evoked increase in cortisol secretion, but pretreatment with metiamide (H(2)-receptor antagonist) significantly potentiated it. Significant attenuation of the C48/80-evoked increase in cortisol also occurred in dogs given ketotifen, a mast cell stabilizing drug, before pharmacologic challenge. In the pars tuberalis and median eminence (ME), mast cells were highly concentrated in close association with the primary plexus of the hypophysial portal system. Degranulated mast cells were extensively found in the ME of C48/80-treated animals. These results suggest that mast cells located in these regions liberated histamine within the brain as a result of degranulation induced by C48/80 and that this led to activation of the hypothalamic-pituitary-adrenocortical axis.

  3. Oestradiol modulates the effects of leptin on energy homeostasis by corticotrophin-releasing factor type 2 receptor.

    Science.gov (United States)

    Marangon, P B; Silva, L E C M; Rorato, R; Gomiero Alves, P; Antunes-Rodrigues, J; Elias, L L K

    2014-11-01

    In addition to its action in the control of the hypothalamic-pituitary-adrenal axis, corticotrophin-releasing factor (CRF) has been described as an anorexigenic neuropeptide, modulating food intake and energy expenditure. CRF synthesis is influenced by leptin, which would act to increase CRF neurone activation in the paraventricular nucleus (PVN). Gonadal hormones also participate in the regulation of energy homeostasis. The reduction of food intake and body weight gain in ovariectomised (OVX) rats treated with oestradiol is associated with an increase in CRF mRNA expression in the PVN. The present study aimed to investigate the role of CRF as a mediator of leptin responsiveness in the presence of oestradiol. Wistar female rats were bilaterally OVX and divided into three groups: OVX, OVX+E (i.e. treated with oestradiol) and OVX+PF (i.e. OVX pairfed with OVX+E). The rats received daily s.c. injections of either oestradiol cypionate or vehicle for 8 days. To evaluate the role of CRF on the effects of leptin, we performed an i.c.v. leptin injection (10 μg/5 μl) with or without previous i.c.v. treatment with an CRF-R2 antagonist. We observed that oestradiol replacement in OVX rats reduced body weight gain and food intake. The effects of exogenous leptin administration with respect to decreasing food intake and body weight, and increasing uncoupling protein-1 expression in the brown adipose tissue and neuronal activation in the arcuate nucleus, were reversed by previous administration of a CRF-R2 antagonist only in oestradiol-treated OVX rats. These effects appear to be mediated by CRF-2 receptor because the antagonist of this receptor reversed the action of oestradiol on the effects of leptin. © 2014 British Society for Neuroendocrinology.

  4. Realization of Lossless Systems Via Constant Matrix Factorizations

    NARCIS (Netherlands)

    Rapisarda, Paolo; Rao, Shodhan

    2013-01-01

    We study the realization problem for linear time-invariant systems described by higher-order differential equations, which are J-lossless with constant J. Our approach is based on the factorization of a constant matrix obtained in a straightforward way from the storage function of the system. State

  5. Normalized doubly coprime factorizations for infinite-dimensional linear systems

    NARCIS (Netherlands)

    Curtain, RF; Opmeer, MR

    2006-01-01

    We obtain explicit formulas for normalized doubly coprime factorizations of the transfer functions of the following class of linear systems: the input and output operators are vector-valued, but bounded, and the system is input and output stabilizable. Moreover, we give explicit formulas for the Bez

  6. The unresolved role of systemic factors in bone metastasis

    Directory of Open Access Journals (Sweden)

    Jessalyn M. Ubellacker

    2016-09-01

    Full Text Available Systemic factors including cytokines, cell-free nucleic acids, microvesicles, and platelets are appreciated as important regulators of adenocarcinoma progression. Research findings using pre-clinical mouse models have revealed that many such systemically acting factors are either secreted by or responsive to peripheral tumors and impact bone and bone marrow (collectively referred to as the bone microenvironment to initiate processes that ultimately govern disease progression, even in the absence of detectable bone metastases. In some cases, cancer-driven modulation of the bone microenvironment involves mobilization of bone marrow hematopoietic and mesenchymal cells into the circulation that are subsequently recruited into peripheral tissues and tumors. In other cases, systemic factors alter bone marrow cell (BMC differentiation and/or gene expression to render the BMCs pro-tumorigenic even prior to their mobilization into the circulation. Given their effect on the bone microenvironment, it stands to reason that such systemic factors might also influence metastases in the bone; however, this hypothesis remains to be comprehensively tested. Here, we briefly review what is known, and not known, about systemic factors that regulate the bone microenvironment and thereby influence bone metastases. We also pose a number of currently unanswered questions in this active area of research. A better understanding of systemic processes that influence bone metastasis should aid discovery of therapeutic approaches that aim to eradicate or reduce disease burden in the bone, which is the cause of significant patient mortality and morbidity and is currently incurable.

  7. Functional upregulation of system xc- by fibroblast growth factor-2.

    Science.gov (United States)

    Liu, Xiaoqian; Resch, Jon; Rush, Travis; Lobner, Doug

    2012-02-01

    The cystine/glutamate antiporter (system xc-) is a Na(+)-independent amino acid transport system. Disruption of this system may lead to multiple effects in the CNS including decreased cellular glutathione. Since multiple neurological diseases involve glutathione depletion, and disruption of growth factor signaling has also been implicated in these diseases, it is possible that some growth factors effects are mediated by regulation of system xc-. We tested the growth factors fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1), neuregulin-1 (NRG), neurotrophin-4 (NT-4), and brain derived neurotrophic factor (BDNF) on system xc- mediated 14C-cystine uptake in mixed neuronal and glial cortical cultures. Only FGF-2 significantly increased cystine uptake. The effect was observed in astrocyte-enriched cultures, but not in cultures of neurons or microglia. The increase was blocked by the system xc- inhibitor (s)-4-carboxyphenylglycine, required at least 12 h FGF-2 treatment, and was prevented by the protein synthesis inhibitor cycloheximide. Kinetic analysis indicated FGF-2 treatment increased the V(max) for cystine uptake while the K(m) remained the same. Quantitative PCR showed an increase in mRNA for xCT, the functional subunit of system xc-, beginning at 3 h of FGF-2 treatment, with a dramatic increase after 12 h. Blocking FGFR1 with PD 166866 blocked the FGF-2 effect. Treatment with a PI3-kinase inhibitor (LY-294002) or a MEK/ERK inhibitor (U0126) for 1 h prior to and during the FGF-2 treatment, each partially blocked the increased cystine uptake. The upregulation of system xc- by FGF-2 may be responsible for some of the known physiological actions of FGF-2. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

  8. Stress and the gastrointestinal tract III. Stress-related alterations of gut motor function: role of brain corticotropin-releasing factor receptors.

    Science.gov (United States)

    Taché, Y; Martinez, V; Million, M; Wang, L

    2001-02-01

    Alterations of gastrointestinal (GI) motor function are part of the visceral responses to stress. Inhibition of gastric emptying and stimulation of colonic motor function are the commonly encountered patterns induced by various stressors. Activation of brain corticotropin-releasing factor (CRF) receptors mediates stress-related inhibition of upper GI and stimulation of lower GI motor function through interaction with different CRF receptor subtypes. CRF subtype 1 receptors are involved in the colonic and anxiogenic responses to stress and may have clinical relevance in the comorbidity of anxiety/depression and irritable bowel syndrome.

  9. Elastic Enhancement Factor: from Mesoscopic Systems to Macroscopic Analogous Devices

    CERN Document Server

    Sokolov, Valentin V

    2014-01-01

    Excess of probabilities of the elastic processes over the inelastic ones is a common feature of the resonance phenomena, described in the framework of the random matrix theory. This phenomenon is quantitatively characterized by the elastic enhancement factor $F^{(\\beta)}$ that is a typical ratio of elastic and inelastic cross sections. Being measured experimentally, this quantity can supply us with information on the character of dynamics of the intermediate complicated open system. We discuss properties of the enhancement factor in a wide scope from mesoscopoic systems to macroscopic analogous devices and demonstrate essential qualitative distinction between the elastic enhancement factor's peculiarities in these two cases. Complete analytical solution is found for the case of systems without time-reversal symmetry and only a few open equivalent scattering channels.

  10. An Integrated Simulation System for Human Factors Study

    CERN Document Server

    Wang, Ying; Bennis, Fouad; Chablat, Damien

    2007-01-01

    It has been reported that virtual reality can be a useful tool for ergonomics study. The proposed integrated simulation system aims at measuring operator's performance in an interactive way for 2D control panel design. By incorporating some sophisticated virtual reality hardware/software, the system allows natural human-system and/or human-human interaction in a simulated virtual environment; enables dynamic objective measurement of human performance; and evaluates the quality of the system design in human factors perspective based on the measurement. It can also be for operation training for some 2D control panels.

  11. Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF) 33_01B and emergence of multiple unique recombinant clusters.

    Science.gov (United States)

    Chow, Wei Zhen; Ong, Lai Yee; Razak, Siti Humaira; Lee, Yeat Mei; Ng, Kim Tien; Yong, Yean Kong; Azmel, Azureen; Takebe, Yutaka; Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Tee, Kok Keng

    2013-01-01

    Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating

  12. Corticotropin-releasing factor: a possible key to gut dysfunction in the critically ill.

    Science.gov (United States)

    Hill, Lauren T; Kidson, Susan H; Michell, William L

    2013-01-01

    Critically ill patients frequently display unexplained or incompletely explained features of gastrointestinal (GI) dysfunction, including gastric stasis, ileus, and diarrhea. This makes nutrition delivery challenging, and may contribute to poor outcomes. The typical bowel dysfunction seen in severely ill patients includes retarded gastric emptying, unsynchronized intestinal motility, and intestinal hyperpermeability. These functional changes appear similar to the corticotropin-releasing factor (CRF)-mediated bowel dysfunctions associated with stress of various types and some GI disorders and diseases. CRF has been shown to be present within the GI tract and its action on CRF receptors within the gut have been shown to reduce gastric emptying, alter intestinal motility, and increase intestinal permeability. However, the precise role of CRF in the GI dysfunction in critical illness remains unclear. In this short review, we provide an update on GI dysfunction during stress and review the possible role of CRF in the aetiology of gut dysfunction. We suggest that activation of CRF signaling pathways in critical illness might be key to understanding the mechanisms underlying the gut dysfunction that impairs enteral feeding in the intensive care unit.

  13. Critical factors in the implementation process of integrated management systems

    Directory of Open Access Journals (Sweden)

    Ademir Antonio Ferreira

    2015-09-01

    Full Text Available This study is the result of research whose purpose was to study the implementation process of integrated management systems, called ERP Enterprise Resource Planning in the business environment. This study, more specifically, tried to identify the variables in this process and that, somehow, made it easy or caused some type of difficulty implementing the system. Based on the mixed method approach (Creswell, 2003, the study was performed by means of the content analysis of technical and scientific publications about this theme and by means of a field research for data collection from primary sources. The content analysis was based on the per mile procedure by Bardin (1977, making it possible to identify critical factors that may be found in the implementation of ERP system projects. Primary data was collected from structured interviews with the managers in charge of the implementation of the system, in each of the 12 companies in different sectors of the economy and based in Brazil. Based on this information, it was possible to test the factors extracted from the content analysis and then develop a list of factors that may effectively influence the implementation process of the system. In order to recognize the possible relations between the selected factors, the Spearman (rsp correlation coefficient was applied and the multiple regression analysis was performed by means of the stepwise procedure. The purpose of the regression analysis was to determine the relation of the “Assessment of the Implementation” dependent variable with other dependent variables in the selected categories. The results of these analyses showed that the support of the top management, the communication process for the clear evidence of this support, the technical support of the ERP program provider together with the project team expertise, training and qualification processes of the team in the system operation are significantly correlated and relevant factors for a

  14. Enduring, Handling-Evoked Enhancement of Hippocampal Memory Function and Glucocorticoid Receptor Expression Involves Activation of the Corticotropin-Releasing Factor Type 1 Receptor

    Science.gov (United States)

    Fenoglio, Kristina A.; Brunson, Kristen L.; Avishai-Eliner, Sarit; Stone, Blake A.; Kapadia, Bhumika J.; Baram, Tallie Z.

    2011-01-01

    Early-life experience, including maternal care, influences hippocampus-dependent learning and memory throughout life. Handling of pups during postnatal d 2–9 (P2–9) stimulates maternal care and leads to improved memory function and stress-coping. The underlying molecular mechanisms may involve early (by P9) and enduring reduction of hypothalamic corticotropin-releasing factor (CRF) expression and subsequent (by P45) increase in hippocampal glucocorticoid receptor (GR) expression. However, whether hypothalamic CRF levels influence changes in hippocampal GR expression (and memory function), via reduced CRF receptor activation and consequent lower plasma glucocorticoid levels, is unclear. In this study we administered selective antagonist for the type 1 CRF receptor, NBI 30775, to nonhandled rats post hoc from P10–17 and examined hippocampus-dependent learning and memory later (on P50–70), using two independent paradigms, compared with naive and vehicle-treated nonhandled, and naive and antagonist-treated handled rats. Hippocampal GR and hypothalamic CRF mRNA levels and stress-induced plasma corticosterone levels were also examined. Transient, partial selective blockade of CRF1 in nonhandled rats improved memory functions on both the Morris watermaze and object recognition tests to levels significantly better than in naive and vehicle-treated controls and were indistinguishable from those in handled (naive, vehicle-treated, and antagonist-treated) rats. GR mRNA expression was increased in hippocampal CA1 and the dentate gyrus of CRF1-antagonist treated nonhandled rats to levels commensurate with those in handled cohorts. Thus, the extent of CRF1 activation, probably involving changes in hypothalamic CRF levels and release, contributes to the changes in hippocampal GR expression and learning and memory functions. PMID:15932935

  15. Customer Service: A Critical Factor in Library System Selection.

    Science.gov (United States)

    Machovec, George S.

    1993-01-01

    Describes factors in successful customer service programs that are pertinent to libraries choosing an integrated online library system. Topics discussed include quick response time; easy access to information; well-trained client representatives; low costs; cooperation with customers and vendors; and anticipating customer needs. (LRW)

  16. Factors Critical to the Adoption of Career Guidance Systems.

    Science.gov (United States)

    Kester, Ralph J.; Howard, John, Jr.

    The study endeavors to describe, assess, and trace the progress of six high schools as the faculty and staff responded to the adoption of an innovative career guidance system. The study provides a model, a method, and some generalizations about factors influencing the process. The document is organized according to: (1) definitions of basic…

  17. FACTORS OF STEADY AND BALANCED DEVELOPMENT OF REGIONAL ECONOMIC SYSTEMS

    Directory of Open Access Journals (Sweden)

    Polidi A. A.

    2016-03-01

    Full Text Available The article proves the need of identification and classification of the most relevant factors of the sustainable balanced development of the regional economic system (RES. Substantial filling of the category "sustainable balanced development" which is accepted within the real research is designated. On the basis of the analysis of the classifications of factors of the sustainable balanced development of economy of the region presented in scientific literature their discrepancy modern is established to conditions of globalization of the economy causing increase of a role of foreign economic activity of territorial subjects of the Russian Federation in ensuring their long-term competitiveness. Proceeding from the last, within the classification of factors of the sustainable balanced development of RES offered by authors the following their groups are allocated: global, national, regional. For each of the designated groups we substantiated the set of relevant factors

  18. Human Factors Interface with Systems Engineering for NASA Human Spaceflights

    Science.gov (United States)

    Wong, Douglas T.

    2009-01-01

    This paper summarizes the past and present successes of the Habitability and Human Factors Branch (HHFB) at NASA Johnson Space Center s Space Life Sciences Directorate (SLSD) in including the Human-As-A-System (HAAS) model in many NASA programs and what steps to be taken to integrate the Human-Centered Design Philosophy (HCDP) into NASA s Systems Engineering (SE) process. The HAAS model stresses systems are ultimately designed for the humans; the humans should therefore be considered as a system within the systems. Therefore, the model places strong emphasis on human factors engineering. Since 1987, the HHFB has been engaging with many major NASA programs with much success. The HHFB helped create the NASA Standard 3000 (a human factors engineering practice guide) and the Human Systems Integration Requirements document. These efforts resulted in the HAAS model being included in many NASA programs. As an example, the HAAS model has been successfully introduced into the programmatic and systems engineering structures of the International Space Station Program (ISSP). Success in the ISSP caused other NASA programs to recognize the importance of the HAAS concept. Also due to this success, the HHFB helped update NASA s Systems Engineering Handbook in December 2007 to include HAAS as a recommended practice. Nonetheless, the HAAS model has yet to become an integral part of the NASA SE process. Besides continuing in integrating HAAS into current and future NASA programs, the HHFB will investigate incorporating the Human-Centered Design Philosophy (HCDP) into the NASA SE Handbook. The HCDP goes further than the HAAS model by emphasizing a holistic and iterative human-centered systems design concept.

  19. Increased depression-like behaviors in corticotropin-releasing factor receptor-2-deficient mice: sexually dichotomous responses.

    Science.gov (United States)

    Bale, Tracy L; Vale, Wylie W

    2003-06-15

    Depressive disorders affect nearly 19 million American adults, making depression and the susceptibility for developing depression a critical focus of mental health research today. Females are twice as likely to develop depression as males. Stress is a known risk factor for developing depression, and recent hypotheses suggest an involvement of an overactive stress axis. As mediators of the stress response, corticotropin-releasing factor (CRF) and its receptors (CRFR1 and CRFR2) have been implicated in the propensity for developing stress-related mood disorders. Mice deficient in CRFR2 display increased anxiety-like behaviors and a hypersensitive stress response. As a possible animal model of depression, these mice were tested for depression-like behaviors in the forced swim test. Comparisons were made between wild-type and mutant animals, as well as between sexes. Male and female CRFR2-mutant mice showed increased immobility as an indicator of depression compared with wild-type mice of the same sex. In addition, mutant and wild-type female mice demonstrated increased immobile time compared with males of the same genotype. Treatment of CRFR2-deficient mice with the CRFR1 antagonist antalarmin decreased immobile time and increased swim time in both sexes. We found a significant effect of sex for both time spent immobile and swimming after antalarmin treatment. Because differences in behaviors in the forced swim test are good indicators of serotonergic and catecholaminergic involvement, our results may reveal an interaction of CRF pathways with other known antidepressant systems and may also support an involvement of CRF receptors in the development of depression such that elevated CRFR1 activity, in the absence of CRFR2, increases depression-like behaviors.

  20. Parental LTRs are important in a construct of a stable and efficient replication-competent infectious molecular clone of HIV-1 CRF08_BC.

    Science.gov (United States)

    Zhang, Qiwei; Zhang, Xiaomin; Wu, Hao; Seto, Donald; Zhang, Hao-Jie; Chen, Zhiwei; Wan, Chengsong; Zheng, Bo-Jian

    2012-01-01

    Circulating recombinant forms (CRFs) of HIV-1 have been identified in southern China in recent years. CRF08_BC is one of the most predominant subtypes circulating in China. In order to study HIV subtype biology and to provide a tool for biotechnological applications, the first full-length replication-competent infectious molecular clone harboring CRF08_BC is reported. The construction of this clone pBRGX indicates that a moderate-copy number vector is required for its amplification in E. coli. In addition, it is shown that the parental CRF08_BC LTRs are important for generating this efficient replication-competent infectious clone. These observations may aid in the construction of infectious clones from other subtypes. Both the pBRGX-derived virus and its parental isolate contain CCR5 tropism. Their full-length genomes were also sequenced, analyzed, compared and deposited in GenBank (JF719819 and JF719818, respectively). The availability of pBRGX as the first replication-competent molecular clone of CRF08_BC provides a useful tool for a wide range of studies of this newly emergent HIV subtype, including the development of HIV vaccine candidates, antiviral drug screening and drug resistance analysis.

  1. Characterization of the Drug Resistance Profiles of Patients Infected with CRF07_BC Using Phenotypic Assay and Ultra-Deep Pyrosequencing.

    Science.gov (United States)

    Huang, Szu-Wei; Li, Wei-You; Wang, Wen-Hung; Lin, Yu-Ting; Chou, Chih-Hung; Chen, Marcelo; Huang, Hsien-Da; Chen, Yen-Hsu; Lu, Po-Liang; Wang, Sheng-Fan; Oka, Shinichi; Chen, Yi-Ming Arthur

    2017-01-01

    The usefulness of ultra-deep pyrosequencing (UDPS) for the diagnosis of HIV-1 drug resistance (DR) remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004-2005) and 3 from late epidemic (collected in 2008) were obtained from treatment-naïve patient's peripheral blood mononuclear cells. Viral RNA was extracted directly from patient's plasma or from cultural supernatant and the pol sequences were determined using RT-PCR sequencing or UDPS. For comparison, phenotypic drug susceptibility assay using MAGIC-5 cells (in-house phenotypic assay) and Antivirogram were performed. In-house phenotypic assay showed that all the early epidemic and none of the late epidemic CRF07_BC isolates were resistant to most protease inhibitors (PIs) (4.4-47.3 fold). Neither genotypic assay nor Antivirogram detected any DR mutations. UDPS showed that early epidemic isolates contained 0.01-0.08% of PI DR major mutations. Furthermore, the combinations of major and accessory PI DR mutations significantly correlated with the phenotypic DR. The in-house phenotypic assay is superior to other conventional phenotypic assays in the detection of DR variants with a frequency as low as 0.01%.

  2. Controlled-release fertilizer(CRF):A green fertilizer for controlling non-point contamination in agriculture

    Institute of Scientific and Technical Information of China (English)

    MAO Xiao-yun; SUN Ke-jun; WANG De-han; LIAO Zong-wen

    2005-01-01

    Fertilizers contribute greatly to high yields but also result in environmental non-point contamination, including the emission of greenhouse gas(N2O) and eutrophication of water bodies. How to solve this problem has become a serious challenge, especially for China as its high ecological pressure. Controlled-release fertilizer(CRF) has been developed to minimize the contamination while keeping high yield and has become a green fertilizer for agriculture. Several CRFs made with special coating technology were used for testing the fertilizer effects in yield and environment through pot experiment and field trial. The result indicated that the CRFs had higher N use efficiency, thus reducing N loss through leaching and volatilization while keeping higher yields. Comparing with imported standard CRFs,the test on CRFs showed similar fertilizer effect but with much lower cost. CRFs application is becoming a new approach for minimizing non-point contamination in agriculture.

  3. Recombinant expression of placental growth factor in baculovirus expression system

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    Narges Arbabi

    2016-12-01

    Full Text Available Background: Angiogenesis or formation of new blood vessels is the most important factor in physiological and pathological conditions. Human Placental growth factor (hPLGF protein in is one of the most important proteins which stimulate angiogenesis. Baculovirus expression system has been used successfully to over express eukaryotic proteins in insect cells. This system uses a very strong viral promoter, AcNPV polyhedrin, for high level of protein expression. Methods: hPLGF gene cloned in pFastBac-HT vector and transformed in DH10Bac.The recombinant bacmid was extracted and used in SF9 insect cells and transfected by cellfectin method. Target protein expression was confirmed with Western blot. Results: Transferring of the recombinant vector into Bacmid was successful and the PLGF gene sequence was confirmed. PLGF and recombinant protein expression by Western blotting was confirmed. Conclusion: Baculovirus protein expression system expresses PLGF strongly and recombinant protein can be used in different tests.

  4. Effects of CB1 and CRF1 receptor antagonists on binge-like eating in rats with limited access to a sweet fat diet: lack of withdrawal-like responses.

    Science.gov (United States)

    Parylak, Sarah L; Cottone, Pietro; Sabino, Valentina; Rice, Kenner C; Zorrilla, Eric P

    2012-09-10

    Positive reinforcement (e.g., appetitive, rewarding properties) has often been hypothesized to maintain excessive intake of palatable foods. Recently, rats receiving intermittent access to high sucrose diets showed binge-like intake with withdrawal-like signs upon cessation of access, suggesting negative reinforcement mechanisms contribute as well. Whether intermittent access to high fat diets also produces withdrawal-like syndromes is controversial. The present study therefore tested the hypothesis that binge-like eating and withdrawal-like anxiety would arise in a novel model of binge eating based on daily 10-min access to a sweet fat diet (35% fat kcal, 31% sucrose kcal). Within 2-3 weeks, female Wistar rats developed binge-like intake comparable to levels seen previously for high sucrose diets (~40% of daily caloric intake within 10 min) plus excess weight gain and adiposity, but absent increased anxiety-like behavior during elevated plus-maze or defensive withdrawal tests after diet withdrawal. Binge-like intake was unaffected by pretreatment with the corticotropin-releasing factor type 1 (CRF(1)) receptor antagonist R121919, and corticosterone responses to restraint stress did not differ between sweet-fat binge rats and chow-fed controls. In contrast, pretreatment with the cannabinoid type 1 (CB(1)) receptor antagonist SR147778 dose-dependently reduced binge-like intake, albeit less effectively than in ad lib chow or sweet fat controls. A priming dose of the sweet fat diet did not precipitate increased anxiety-like behavior, but rather increased plus-maze locomotor activity. The results suggest that CB(1)-dependent positive reinforcement rather than CRF(1)-dependent negative reinforcement mechanisms predominantly maintain excessive intake in this limited access model of sweet-fat diet binges.

  5. Broad antibody mediated cross-neutralization and preclinical immunogenicity of new codon-optimized HIV-1 clade CRF02_AG and G primary isolates.

    Directory of Open Access Journals (Sweden)

    Simon M Agwale

    Full Text Available Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary "street strain" isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G. Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G and consensus tat (CRF02_AG and G antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G.

  6. Characterization of HIV-1 CRF90_BF1 and putative novel CRFs_BF1 in Central West, North and Northeast Brazilian regions.

    Science.gov (United States)

    Reis, Mônica Nogueira da Guarda; Bello, Gonzalo; Guimarães, Monick Lindenmeyer; Stefani, Mariane Martins Araújo

    2017-01-01

    The Brazilian AIDS epidemic has been characterized by an increasing rate of BF1 recombinants and so far eight circulating recombinant forms/CRFs_BF1 have been described countrywide. In this study, pol sequences (protease/PR, reverse transcriptase/RT) of 87 BF1 mosaic isolates identified among 828 patients living in six Brazilian States from three geographic regions (Central West, North, Northeast) were analyzed. Phylogenetic and bootscan analyses were performed to investigate the evolutionary relationship and mosaic structure of BF1 isolates. Those analyses showed that 20.7% of mosaics (18 out of 87) were CRFs-like isolates, mostly represented by CRF28/CRF29_BF-like viruses (14 out of 18). We also identified five highly supported clusters that together comprise 42 out of 87 (48.3%) BF1 sequences, each cluster containing at least five sequences sharing a similar mosaic structure, suggesting possible new unidentified CRFs_BF1. The divergence time of these five potential new CRFs_BF1 clusters was estimated using a Bayesian approach and indicate that they probably originated between the middle 1980s and the middle 1990s. DNA was extracted from whole blood and four overlapping fragments were amplified by PCR providing full/near full length genomes (FLG/NFLG) and partial genomes. Eleven HIV-1 isolates from Cluster # 5 identified in epidemiologically unlinked individuals living in Central West and North regions provided FLG/NFLG/partial genome sequences with identical mosaic structure. These viruses differ from any known CRF_BF1 reported to date and were named CRF90_BF1 by the Los Alamos National Laboratory. This is the 9th CRF_BF1 described in Brazil and the first one identified in Central West and North regions. Our results highlight the importance of continued molecular screening and surveillance studies, especially of full genome sequences to understand the evolutionary dynamics of the HIV-1 epidemic in a country of continental dimensions as Brazil.

  7. Transient gastric irritation in the neonatal rats leads to changes in hypothalamic CRF expression, depression- and anxiety-like behavior as adults.

    Directory of Open Access Journals (Sweden)

    Liansheng Liu

    Full Text Available AIMS: A disturbance of the brain-gut axis is a prominent feature in functional bowel disorders (such as irritable bowel syndrome and functional dyspepsia and psychological abnormalities are often implicated in their pathogenesis. We hypothesized that psychological morbidity in these conditions may result from gastrointestinal problems, rather than causing them. METHODS: Functional dyspepsia was induced by neonatal gastric irritation in male rats. 10-day old male Sprague-Dawley rats received 0.1% iodoacetamide (IA or vehicle by oral gavage for 6 days. At 8-10 weeks of age, rats were tested with sucrose preference and forced-swimming tests to examine depression-like behavior. Elevated plus maze, open field and light-dark box tests were used to test anxiety-like behaviors. ACTH and corticosterone responses to a minor stressor, saline injection, and hypothalamic CRF expression were also measured. RESULTS: Behavioral tests revealed changes of anxiety- and depression-like behaviors in IA-treated, but not control rats. As compared with controls, hypothalamic and amygdaloid CRF immunoreactivity, basal levels of plasma corticosterone and stress-induced ACTH were significantly higher in IA-treated rats. Gastric sensory ablation with resiniferatoxin had no effect on behaviors but treatment with CRF type 1 receptor antagonist, antalarmin, reversed the depression-like behavior in IA-treated rats CONCLUSIONS: The present results suggest that transient gastric irritation in the neonatal period can induce a long lasting increase in depression- and anxiety-like behaviors, increased expression of CRF in the hypothalamus, and an increased sensitivity of HPA axis to stress. The depression-like behavior may be mediated by the CRF1 receptor. These findings have significant implications for the pathogenesis of psychological co-morbidity in patients with functional bowel disorders.

  8. Challenges and Success Factors of ERP Systems in Australian SMEs

    Directory of Open Access Journals (Sweden)

    Sitalakshmi Venkatraman

    2016-05-01

    Full Text Available Today, great potential is envisaged for ERP systems in small and medium-sized enterprises (SMEs, and software vendors have been repackaging their ERP systems for SMEs with a recent focus on cloud-based systems. While cloud ERP offers the best solution for SMEs without the overheads of the huge investment and management costs that are associated with traditional ERP systems, the SME sector faces many challenges in their adoption. Traditional ERP studies have predominantly focused on large organizations, and gaps in the literature indicate that both vendor and consumer perspectives require more understanding with new technology offerings for SMEs. This paper describes some of the common challenges, such as cost effectiveness, alignment between software and business processes, customized governance and training, which form the major SME constraints for ERP system adoption. Due to the dynamic nature of SME businesses, best practice guidelines for an SME’s ERP implementation could be arrived at through closer investigation of its business requirements in order to avoid misfits. This forms the main objective of the study. We identify key success factors of ERP implementation in an Australian SME as a case study. These target success factors are then compared to the actual outcomes achieved. Factors such as business process alignment with the ERP system, meeting customer and stakeholder needs and reducing recurring and maintenance costs were key to the success of ERP implementation for the Australian SME. In particular, the IT and business strategy alignment with a customer focus and flexible reporting features of ERP systems has resulted in business agility.

  9. Nutrition and the insulin-like growth factor system.

    Science.gov (United States)

    Estívariz, C F; Ziegler, T R

    1997-08-01

    Nutritional status is a key regulator of the circulating and tissue insulin-like growth factor (IGF) system. IGF-I mRNA and protein levels decrease in tissues such as liver and intestine with fasting and are restored with refeeding. Additional studies suggest that the level of protein and calorie intake independently regulate plasma IGF-I concentrations in man. The level of nutrition effects the biological actions of recombinant growth hormone (GH) and IGF-I administration in humans. Limited data demonstrate that plasma and tissue levels of the insulin-like growth factor binding proteins (IGFBPs) are also sensitive to nutrient intake. Specific micronutrients, such as potassium, magnesium and zinc also appear to be important for optimal IGF-I synthesis and anabolic effects in animal models. Malnutrition is common in elderly patients, however, the interaction between specific nutrients, general nutritional status and the aging process on the IGF system is incompletely understood. Mechanisms of nutrient-IGF system interactions which may affect the biological actions of IGF-I, IGF-II, and the IGFBPs are increasingly being determined in basic studies. The effects of underlying nutritional status and responses to dietary intake will be important to evaluate in clinical studies of the IGF system and exogenous growth factor therapy.

  10. Exercise protects the cardiovascular system: effects beyond traditional risk factors.

    Science.gov (United States)

    Joyner, Michael J; Green, Daniel J

    2009-12-01

    In humans, exercise training and moderate to high levels of physical activity are protective against cardiovascular disease. In fact they are 40% more protective than predicted based on the changes in traditional risk factors (blood lipids, hypertension, diabetes etc.) that they cause. In this review, we highlight the positive effects of exercise on endothelial function and the autonomic nervous system. We also ask if these effects alone, or in combination, might explain the protective effects of exercise against cardiovascular disease that appear to be independent of traditional risk factor modification. Our goal is to use selected data from our own work and that of others to stimulate debate on the nature and cause of the 'risk factor gap' associated with exercise and physical activity.

  11. Role of a genetic polymorphism in the corticotropin-releasing factor receptor 1 gene in alcohol drinking and seeking behaviors of Marchigian Sardinian alcohol-preferring (msP rats

    Directory of Open Access Journals (Sweden)

    Lydia Ojonemile Ayanwuyi

    2013-04-01

    Full Text Available Marchigian Sardinian alcohol-preferring (msP rats exhibit innate preference for alcohol, are highly sensitive to stress and stress-induced alcohol seeking. Genetic analysis showed that over-expression of the corticotropin-releasing factor (CRF system of msP rats is correlated with the presence of two single nucleotide polymorphisms (SNPs occurring in the promoter region (position -1836 and -2097 of the CRF1 receptor (CRF1-R gene. Here we examined whether these point mutations were associated to the innate alcohol preference, stress-induced drinking and seeking.We have recently re-derived the msP rats to obtain two distinct lines carrying the wild type (GG and the point mutations (AA, respectively. The phenotypic characteristics of these two lines were compared with those of unselected Wistar rats. Both AA and GG rats showed similar patterns of voluntary alcohol intake and preference. Similarly, the pharmacological stressor yohimbine (0.0, 0.625, 1.25 and 2.5 mg/kg elicited increased operant alcohol self-administration under fixed and progressive ratio reinforcement schedules in all three lines. Following extinction, yohimbine (0.0, 0.625, 1.25 and 2.5 mg/kg significantly reinstated alcohol seeking in the three groups. However, at the highest dose this effect was no longer evident in AA rats. Treatment with the CRF1-R antagonist antalarmin (0, 5, 10 and 20 mg/kg significantly reduced alcohol-reinforced lever pressing in the AA line (10 and 20 mg/kg while a weaker or no effect was observed in the Wistar and the GG group, respectively. Finally, antalarmin significantly reduced yohimbine-induced increase in alcohol drinking in all three groups.In conclusion, these specific SNPs in the CRF1-R gene do not seem to play a primary role in the expression of the msP excessive-drinking phenotype or stress-induced drinking but may be associated with a decreased threshold for stress-induced alcohol seeking and an increased sensitivity to the effects of

  12. Depressive symptoms and associated factors in systemic lupus erythematosus.

    Science.gov (United States)

    Karol, David E; Criscione-Schreiber, Lisa G; Lin, Min; Clowse, Megan E B

    2013-01-01

    Depressive symptoms affect anywhere from 11% to 71% of patients with systemic lupus erythematosus (SLE), which may be related to SLE disease activity, other clinical variables, or sociodemographic factors. We aimed to measure the rate of depressive symptoms in our cohort of patients with SLE and to identify modifiable factors associated with depressive symptoms. Patients in our university-based SLE registry completed the Beck Depression Inventory-II (BDI-II), pain scores, and demographic information. Disease activity was measured using the physician's global assessment (PGA) and Selena-SLE disease activity index (Selena-systemic lupus erythematosus disease activity index (SLEDAI)). Patients were identified as having moderate or severe depressive symptoms (BDI-II ≥ 18) or not (BDI-II lupus arthritis (P lupus arthritis, may result in alleviation of depressive symptoms in patients with SLE. Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  13. Probing quantum frustrated systems via factorization of the ground state.

    Science.gov (United States)

    Giampaolo, Salvatore M; Adesso, Gerardo; Illuminati, Fabrizio

    2010-05-21

    The existence of definite orders in frustrated quantum systems is related rigorously to the occurrence of fully factorized ground states below a threshold value of the frustration. Ground-state separability thus provides a natural measure of frustration: strongly frustrated systems are those that cannot accommodate for classical-like solutions. The exact form of the factorized ground states and the critical frustration are determined for various classes of nonexactly solvable spin models with different spatial ranges of the interactions. For weak frustration, the existence of disentangling transitions determines the range of applicability of mean-field descriptions in biological and physical problems such as stochastic gene expression and the stability of long-period modulated structures.

  14. Factor Analysis of Enterprise Internet+ Impetus Based on System Dynamics

    Directory of Open Access Journals (Sweden)

    Cao Haiwang

    2017-01-01

    Full Text Available Internet+ plays an important role in the transition and upgrading of enterprises in this era. To promote enterprise Internet+ implementation, this paper studies the influencing factors in enterprise Internet+ impetus. First, based on system dynamics, the influencing factors of enterprise Internet+ impetus are analyzed as well as their relationships. Then, a system dynamics model is established and Vensim PLE is utilized to simulate the model. Finally, some suggestions about the Internet+ implementation are given. The simulation results show that technological environment, government policy and information asymmetry all have different influence on the enterprise Internet+ impetus and different strategies can be taken to change their influence. This study is helpful for enterprises to understand the Internet+ impetus mechanism thus promote Internet+ implementation.

  15. PERIODONTAL INFECTION AS A POTENTIAL RISK FACTOR FOR SYSTEMIC DISEASE

    Directory of Open Access Journals (Sweden)

    Sumintarti Sumintarti

    2015-06-01

    Full Text Available Oral infection can have an adverse effect on other organs of the body. Oral infections, especially periodontitis, may affect the course and pathogenesis of a number of systemic diseases, such as diabetes mellitus, cardiovascular disease, pre-term low birth weight infant and respiratory disease. The purpose of this article is to evaluate the current status of oral infection especially periodontitis as a potential risk factor of systemic diseases. Three main pathways linking oral infection to secondary systemic effects have been proposed: metastatic infection, metastatic injury and metastatic inflammation. Periodontitis can cause bacteria to enter the blood stream and activate immune cells. These activated cells produce inflammatory cytokines that have a destructive effect throughout the entire body. Therefore, periodontitis as a major oral infection may affect the host’s susceptibility to systemic disease.

  16. Risk factors of systemic lupus erythematosus flares during pregnancy.

    Science.gov (United States)

    Jara, Luis J; Medina, Gabriela; Cruz-Dominguez, Pilar; Navarro, Carmen; Vera-Lastra, Olga; Saavedra, Miguel A

    2014-12-01

    This review examines the risk factors for the development of systemic lupus erythematosus (SLE) flares during pregnancy. In preconception, anti-DNA, hypocomplementemia, previous thrombosis, triple antiphospholipid (aPL) antibody positivity, active lupus nephritis and discontinuation of medications such as hydroxychloroquine and azathioprine are factors associated with pregnancy failure. During pregnancy, SLE flares are associated with aPL antibodies, synergic changes of pregnancy on Th1 and TH2 cytokines, other cytokines and chemokines that interact with hormones such as estrogen and prolactin that amplify the inflammatory effect. From the clinical point of view, SLE activity at pregnancy onset, thrombocytopenia, lupus nephritis, arterial hypertension, aPL syndromes, preeclampsia is associated with lupus flares and fetal complications. In puerperium, the risk factors of flares are similar to pregnancy. Hyperactivity of immune system, autoantibodies, hyperprolactinemia, active lupus nephritis, decrease in TH2 cytokines with increase in TH1 cytokines probably participate in SLE flare. The SLE flares during pregnancy make the difference between an uncomplicated pregnancy and pregnancy with maternal and fetal complications. Therefore, the knowledge of risk factors leads the best treatment strategies to reduce flares and fetal complications in SLE patients.

  17. Yang-Baxter Systems, Algebra Factorizations and Braided Categories

    Directory of Open Access Journals (Sweden)

    Florin F. Nichita

    2013-09-01

    Full Text Available The Yang-Baxter equation first appeared in a paper by the Nobel laureate, C.N. Yang, and in R.J. Baxter’s work. Later, Vladimir Drinfeld, Vaughan F. R. Jones and Edward Witten were awarded Fields Medals for their work related to the Yang-Baxter equation. After a short review on this equation and the Yang-Baxter systems, we consider the problem of constructing algebra factorizations from Yang-Baxter systems. Our sketch of proof uses braided categories. Other problems are also proposed.

  18. Yang-Baxter Systems, Algebra Factorizations and Braided Categories

    OpenAIRE

    2013-01-01

    The Yang-Baxter equation first appeared in a paper by the Nobel laureate, C.N. Yang, and in R.J. Baxter’s work. Later, Vladimir Drinfeld, Vaughan F. R. Jones and Edward Witten were awarded Fields Medals for their work related to the Yang-Baxter equation. After a short review on this equation and the Yang-Baxter systems, we consider the problem of constructing algebra factorizations from Yang-Baxter systems. Our sketch of proof uses braided categories. Other problems are also proposed.

  19. Determination of selectivity of HPLC systems by correspondence factor analysis

    Institute of Scientific and Technical Information of China (English)

    Yuan Wang; Jun Yang; Xin Lu; Guo Wang Xu

    2007-01-01

    Correspondence factor analysis (CFA) was employed to study the selectivity of 14 HPLC systems, The tested LC systems were classified as reversed-phase (RP), ion-exchange (IE) and hydrophilic interaction chromatography (HILIC) modes. It was found that the retentions of the hydrophilic solutes on HILIC column were significantly influenced by the second-order effects besides their hydrophilic properties. Organic modifiers and residue silanol groups on silica surface both participated in retention. HypersilTM amino column performed separation in the HILIC mode at appropriate conditions, and its retention mechanism was more similar to that of HILIC silica column than that of HILIC column coating poly(aspartamide) groups.

  20. Corticotropin-releasing factor antagonist attenuates stress-induced inhibition of seasonal ovarian recrudescence in the lizard Mabuya carinata.

    Science.gov (United States)

    Ganesh, C B; Yajurvedi, H N

    2002-04-01

    Whether administration of the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF(9-41) (hCRF) prevents stress response of the ovary, the oviduct, the adrenals, and the spleen was studied in the lizard Mabuya carinata. Stressors (handling, chasing, and noise) applied randomly, five times a day, for 1 month to lizards during the recrudescence phase of the ovarian cycle caused a significant increase in mean nuclear diameter of the adrenal cortical cells and a significant reduction in mean number of islands of white pulp in the spleen. These results, albeit indirectly, indicated an activation of the adrenal gland and immune suppression. There was a significant decrease in the mean relative weight of the ovary and the oviduct and in the mean number of oocytes and the primordial follicles compared to those of controls. Furthermore, vitellogenic follicles were absent in the ovary of lizards exposed to stressors in contrast to their presence in controls. However, administration of hCRF to the lizards exposed to stressors (stress + hCRF) resulted in vitellogenesis and follicular growth. The mean relative weight of the ovary and the oviduct and the mean number of oocytes and the primordial follicles in stress + hCRF-treated lizards were significantly higher than those in the lizards exposed to stressors, whereas they did not significantly differ from those of controls. The results indicate that hCRF attenuates stress-induced inhibition of ovarian follicular and oviductal development in M. carinata. To the best of our knowledge, this is the first report revealing that CRF antagonist can prevent ovarian stress response in lower vertebrates.

  1. Analytic system problems and J-lossless coprime factorization for infinite-dimensional linear systems

    NARCIS (Netherlands)

    Curtain, R

    1997-01-01

    This paper extends the coprime factorization approach to the synthesis of internally stabilizing controllers satisfying an H-infinity-norm bound to a class of systems with irrational transfer matrices. Using the coprime factorization description, the H-infinity-control problem can be reduced to two

  2. Analytic system problems and J-lossless coprime factorization for infinite-dimensional linear systems

    NARCIS (Netherlands)

    Curtain, R

    This paper extends the coprime factorization approach to the synthesis of internally stabilizing controllers satisfying an H-infinity-norm bound to a class of systems with irrational transfer matrices. Using the coprime factorization description, the H-infinity-control problem can be reduced to two

  3. Isolation and characterisation of the corticotropin releasing factor receptor 1 (CRFR1) gene in a teleost fish, Fugu rubripes.

    Science.gov (United States)

    Cardoso, João C; Power, Deborah M; Elgar, Greg; Clark, Melody S

    2003-06-01

    Corticotropin releasing factor receptor (CRF) is a member of the secretin family of the G-protein coupled receptor superfamily. These are characterised by the presence of seven transmembrane domains and six conserved cysteines that are important for receptor conformation and ligand binding. IN vertebrates two CRF receptors (CRF1 and CRF2) have been isolated and characterised. In this study the complete structure of the CRF1 receptor was isolated and partially characterised for the first time in a vertebrate using the compact genome of the Japanese pufferfish, Fugu rubripes as a model. The Fugu CRF1 receptor gene is composed of 14 exons is approximately 27 kb in length. A tissue distribution of this receptor in Fugu reveals that it is expressed mainly in liver, gonads, heart and brain, however, expression in the kidney, gut and gills was also detected. In vertebrates this receptor appears to have a different tissue distribution and its presence in the gills may indicate a new role in osmoregulatory processes.

  4. HIV-1 CRF07_BC毒株gp41重组DNA-蛋白疫苗的制备及免疫%Preparation and application of HIV-1 CRF07_BC recombinant gp41 DNA-protein vaccine

    Institute of Scientific and Technical Information of China (English)

    王妮丹; 罗振武; 孙红岩; 何彦平; 邵一鸣; 郝彦玲

    2014-01-01

    目的 制备中国HIV-1流行株CRF07_BC膜蛋白gp41重组DNA-蛋白疫苗,并观察其在BALB/c小鼠中的免疫效果.方法 从CRF07_BC毒株(CN54)中扩增gp41胞外段,删除抗原决定环loop区(the immune dominant loop region),引入T569A和I675V两个突变位点,制备含N-端七价重复序列(N-terminal heptad repeat,NHR)、C-端七价 重复序列(C-terminal heptad repeat,CHR)和近膜区(membrane proximal external region,MPER)的重组疫苗,以未改造的gp41相应区域为对照免疫原.使用DNA疫苗初免-蛋白疫苗加强的方式免疫BALB/c小鼠,最后一针免疫后4周,经小鼠眼眶采血,分离血清,检测结合抗体水平、中和抗体水平、线性表位抗体水平.结果 CN54 gp41野生型及改造型重组DNA疫苗质粒和原核蛋白表达质粒经双酶切及测序鉴定均构建正确;CN54 gp41W和CN54 gp41M表达蛋白相对分子质量约在12 000 ~ 15 000之间,纯化的重组蛋白可被豚鼠抗gp140阳性血清识别.CN54M组(CN54 gp41改造抗原组)诱导出较高的结合抗体水平,而线性表位抗体水平明显低于CN54W组(CN54 gp41未改造组),两组均未检测出具有保护性的中和抗体水平.结论 CN54 gp41改造抗原经DNA疫苗初免-蛋白疫苗加强免疫小鼠,可产生较高的结合抗体,且主要是针对空间构象表位,但不具有中和能力.

  5. Environmental Factor{trademark} system: RCRA hazardous waste handler information

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    Environmental Factor{trademark} RCRA Hazardous Waste Handler Information on CD-ROM unleashes the invaluable information found in two key EPA data sources on hazardous waste handlers and offers cradle-to-grave waste tracking. It`s easy to search and display: (1) Permit status, design capacity and compliance history for facilities found in the EPA Resource Conservation and Recovery Information System (RCRIS) program tracking database; (2) Detailed information on hazardous wastes generation, management and minimization by companies who are large quantity generators, and (3) Data on the waste management practices of treatment, storage and disposal (TSD) facilities from the EPA Biennial Reporting System which is collected every other year. Environmental Factor`s powerful database retrieval system lets you: (1) Search for RCRA facilities by permit type, SIC code, waste codes, corrective action or violation information, TSD status, generator and transporter status and more; (2) View compliance information -- dates of evaluation, violation, enforcement and corrective action; (3) Lookup facilities by waste processing categories of marketing, transporting, processing and energy recovery; (4) Use owner/operator information and names, titles and telephone numbers of project managers for prospecting; and (5) Browse detailed data on TSD facility and large quantity generators` activities such as onsite waste treatment, disposal, or recycling, offsite waste received, and waste generation and management. The product contains databases, search and retrieval software on two CD-ROMs, an installation diskette and User`s Guide. Environmental Factor has online context-sensitive help from any screen and a printed User`s Guide describing installation and step-by-step procedures for searching, retrieving and exporting. Hotline support is also available for no additional charge.

  6. The role of tissue factor in systemic inflammatory response syndrome.

    Science.gov (United States)

    Egorina, Elena M; Sovershaev, Mikhail A; Hansen, John-Bjarne

    2011-09-01

    Tissue factor (TF) is a major initiator of extrinsic pathway of blood coagulation. A dual role of TF in the extensive crosstalk between blood coagulation and inflammation has recently become apparent. The majority of the cases of systemic inflammatory response syndrome, disseminated intravascular coagulation, and sepsis are accompanied by hyperactivation of TF in circulating monocytes and damaged tissue. Systemic Gram-negative infection induces expression of TF by vascular cells. In addition to extrinsic coagulation pathway, TF induces proinflammatory signaling cascade originating from activation of protease-activated receptors. Because TF-activated proteolytic cascade is placed in a nexus between coagulation and inflammation, early modulation of TF activity presently becomes a tempting experimental therapeutic strategy in systemic inflammatory response syndrome patients.

  7. The insulin-like growth factor system in Multiple Myeloma

    DEFF Research Database (Denmark)

    Bieghs, Liesbeth; Johnsen, Hans E; Maes, Ken;

    2016-01-01

    , increased IGF-I receptor (IGF-IR) expression on MM cells correlates with a poor prognosis in MM patients. Despite the prominent role of the IGF system in MM, strategies targeting the IGF-IR using blocking antibodies or small molecule inhibitors have failed to translate into the clinic. However, increasing......Multiple myeloma (MM) is a highly heterogeneous plasma cell malignancy. The MM cells reside in the bone marrow (BM), where reciprocal interactions with the BM niche foster MM cell survival, proliferation, and drug resistance. As in most cancers, the insulin-like growth factor (IGF) system has been...... demonstrated to play a key role in the pathogenesis of MM. The IGF system consists of IGF ligands, IGF receptors, IGF binding proteins (IGFBPs), and IGFBP proteases and contributes not only to the survival, proliferation, and homing of MM cells, but also MM-associated angiogenesis and osteolysis. Furthermore...

  8. An Illumination Modeling System for Human Factors Analyses

    Science.gov (United States)

    Huynh, Thong; Maida, James C.; Bond, Robert L. (Technical Monitor)

    2002-01-01

    Seeing is critical to human performance. Lighting is critical for seeing. Therefore, lighting is critical to human performance. This is common sense, and here on earth, it is easily taken for granted. However, on orbit, because the sun will rise or set every 45 minutes on average, humans working in space must cope with extremely dynamic lighting conditions. Contrast conditions of harsh shadowing and glare is also severe. The prediction of lighting conditions for critical operations is essential. Crew training can factor lighting into the lesson plans when necessary. Mission planners can determine whether low-light video cameras are required or whether additional luminaires need to be flown. The optimization of the quantity and quality of light is needed because of the effects on crew safety, on electrical power and on equipment maintainability. To address all of these issues, an illumination modeling system has been developed by the Graphics Research and Analyses Facility (GRAF) and Lighting Environment Test Facility (LETF) in the Space Human Factors Laboratory at NASA Johnson Space Center. The system uses physically based ray tracing software (Radiance) developed at Lawrence Berkeley Laboratories, a human factors oriented geometric modeling system (PLAID) and an extensive database of humans and environments. Material reflectivity properties of major surfaces and critical surfaces are measured using a gonio-reflectometer. Luminaires (lights) are measured for beam spread distribution, color and intensity. Video camera performances are measured for color and light sensitivity. 3D geometric models of humans and the environment are combined with the material and light models to form a system capable of predicting lighting conditions and visibility conditions in space.

  9. Patients infected with CRF07_BC have significantly lower viral loads than patients with HIV-1 subtype B: mechanism and impact on disease progression.

    Directory of Open Access Journals (Sweden)

    Szu-Wei Huang

    Full Text Available The circulating recombinant form (CRF 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less than patients with subtype B infection (p = 0.002. The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag.

  10. System-related factors contributing to diagnostic errors.

    Science.gov (United States)

    Thammasitboon, Satid; Thammasitboon, Supat; Singhal, Geeta

    2013-10-01

    Several studies in primary care, internal medicine, and emergency departments show that rates of errors in test requests and result interpretations are unacceptably high and translate into missed, delayed, or erroneous diagnoses. Ineffective follow-up of diagnostic test results could lead to patient harm if appropriate therapeutic interventions are not delivered in a timely manner. The frequency of system-related factors that contribute directly to diagnostic errors depends on the types and sources of errors involved. Recent studies reveal that the errors and patient harm in the diagnostic testing loop have occurred mainly at the pre- and post-analytic phases, which are directed primarily by clinicians who may have limited expertise in the rapidly expanding field of clinical pathology. These errors may include inappropriate test requests, failure/delay in receiving results, and erroneous interpretation and application of test results to patient care. Efforts to address system-related factors often focus on technical errors in laboratory testing or failures in delivery of intended treatment. System-improvement strategies related to diagnostic errors tend to focus on technical aspects of laboratory medicine or delivery of treatment after completion of the diagnostic process. System failures and cognitive errors, more often than not, coexist and together contribute to the incidents of errors in diagnostic process and in laboratory testing. The use of highly structured hand-off procedures and pre-planned follow-up for any diagnostic test could improve efficiency and reliability of the follow-up process. Many feedback pathways should be established so that providers can learn if or when a diagnosis is changed. Patients can participate in the effort to reduce diagnostic errors. Providers should educate their patients about diagnostic probabilities and uncertainties. The patient-safety strategies focusing on the interface between diagnostic system and therapeutic

  11. Factors affecting economies of scale in combined sewer systems.

    Science.gov (United States)

    Maurer, Max; Wolfram, Martin; Anja, Herlyn

    2010-01-01

    A generic model is introduced that represents the combined sewer infrastructure of a settlement quantitatively. A catchment area module first calculates the length and size distribution of the required sewer pipes on the basis of rain patterns, housing densities and area size. These results are fed into the sewer-cost module in order to estimate the combined sewer costs of the entire catchment area. A detailed analysis of the relevant input parameters for Swiss settlements is used to identify the influence of size on costs. The simulation results confirm that an economy of scale exists for combined sewer systems. This is the result of two main opposing cost factors: (i) increased construction costs for larger sewer systems due to larger pipes and increased rain runoff in larger settlements, and (ii) lower costs due to higher population and building densities in larger towns. In Switzerland, the more or less organically grown settlement structures and limited land availability emphasise the second factor to show an apparent economy of scale. This modelling approach proved to be a powerful tool for understanding the underlying factors affecting the cost structure for water infrastructures.

  12. Stress, gender, and addiction: potential roles of CRF, oxytocin and argininevasopressin

    OpenAIRE

    Bisagno, Verónica; Lud Cadet, Jean

    2014-01-01

    Stress sensitivity and gender are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but they are also triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, because this understanding may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations ...

  13. Influencing Factors on Farming System Development in Shandong Province

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The developmental situation of the farming system in Shandong Province is introduced.At present,Shandong Province is at the semi-intensive,semi-commercial and semi-sufficiency level of farming system.Eastern coast and central Shandong agricultural zones are moving in the direction of modern farming system,having formed a preliminary new pattern of the coordinated development of grain,feedstuff,economic and other crops.Influencing factors on the development of farming system in Shandong Province is analyzed,which are agricultural production condition and input level,population and food,policy measures,development of natural resources and regions,agricultural industrialization and urbanization level,and scientific and technological level.Total population will be within 100 million at the year 2020;per capita annual share of grain will be 475 kilograms;and there is great pressure on grain production.Therefore,we must change the pattern of agricultural development and accelerate the establishment of modern farming system.Agricultural machinery,water conservancy projects,and chemical fertilizer application have greatly affected the development of farming system.Improvement of production conditions has promoted the adjustment of agricultural structure,increased the planting ratio of winter wheat-summer maize,and improved multiple-cropping index.Development of agricultural industrialization has promoted the transfer of rural labor force and the establishment of modern farming system;while the unbalanced development of cities has restricted the establishment of modern farming system.Therefore,the appropriate policy,scientific and rational regional distribution,and advanced science and technology can help to set up the modern farming system in Shandong Province.

  14. CRF及其受体在胃肠疾病中的研究进展%Corticotropin-releasing factor and its receptor in gastrointestinal disease

    Institute of Scientific and Technical Information of China (English)

    马宝庆; 白光

    2008-01-01

    促肾上腺皮质激素释放因子(crticotropin releasing factor,CRF)是一种重要的神经内分泌肽.CRF在体内分布广泛,主要作用为促进腺垂体合成与释放促肾上腺皮质激素,与内分泌、神经化学、行为等多种生理反应有关,广泛参与消化管生理和病理活动的调控.CRF引起胃肠动力功能改变最常见的类型是胃排空延迟、延缓小肠蠕动及结肠运转加快.CRF通过CRFR2作用抑制胃排空,而刺激结肠动力是通过CRFRI调节的.CRF受体拮抗剂的研发为治疗应激相关胃肠疾病可能开辟新方向.%Corticotropin-releasing factor (CRF)is a neuroendoerine peptide that stimulates the synthesis and release of adrenecortieotropic hormone from the pituitary. CRF widely distributed in the body has been implicated in the regulation of endocrine, neural, behavioral responses and has relevance in the the physio- logical effects and pathophysiology of gut. The delayed gastric emptying, inhibited small intestinal transit and stimulated colonic transit are the most common responses evoked by CRF. CRF delay gastric emptying by ac- tivating CRF2 receptor while the stimulation of colonic motility is mediated by the activation of CRF1 recep- tor. Development of antagonists of CRF receptor may treat a new therapeutic strategy for treatment of stress- related gastrointestinal disease.

  15. Genetic Factors in Systemic Lupus Erythematosus: Contribution to Disease Phenotype

    Science.gov (United States)

    Ceccarelli, Fulvia; Perricone, Carlo; Borgiani, Paola; Ciccacci, Cinzia; Rufini, Sara; Cipriano, Enrica; Alessandri, Cristiano; Spinelli, Francesca Romana; Sili Scavalli, Antonio; Novelli, Giuseppe; Valesini, Guido; Conti, Fabrizio

    2015-01-01

    Genetic factors exert an important role in determining Systemic Lupus Erythematosus (SLE) susceptibility, interplaying with environmental factors. Several genetic studies in various SLE populations have identified numerous susceptibility loci. From a clinical point of view, SLE is characterized by a great heterogeneity in terms of clinical and laboratory manifestations. As widely demonstrated, specific laboratory features are associated with clinical disease subset, with different severity degree. Similarly, in the last years, an association between specific phenotypes and genetic variants has been identified, allowing the possibility to elucidate different mechanisms and pathways accountable for disease manifestations. However, except for Lupus Nephritis (LN), no studies have been designed to identify the genetic variants associated with the development of different phenotypes. In this review, we will report data currently known about this specific association. PMID:26798662

  16. Factors related to adherence to treatment for systemic hypertension

    Directory of Open Access Journals (Sweden)

    Silvana Maria Coelho Leite Fava

    2014-06-01

    Full Text Available This study aimed to seek the evidence available in the literature regarding the factors related to adherence to treatment for systemic hypertension. It used the method of integrative review in the databases MEDLINE, CINAHL, and LILACS, using the keywords: hypertension, compliance, non-compliance, adherence, non-adherence, patient compliance, in the period 2004 – 2008, and articles in Portuguese, English and Spanish, with the use of a validated instrument and content analysis. 28 studies were selected, 64.3% of which had level of evidence VI. The following were identified as factors related to adherence to treatment: treatment costs, educational activities, sex, physician-patient relationship, physiological and behavioral aspects, drug therapy, attending checkups and lifestyle. The use of combined strategies is suggested in order to increase the individuals’ adherence to the treatment. Gaps point to the valorization of dialogic relationships for integrated and more efficacious health practices.

  17. Risk factors for chronic renal failure in Ivory coast: A prospective study of 280 patients

    Directory of Open Access Journals (Sweden)

    Ackoundou-N′Guessan K

    2011-01-01

    Full Text Available Chronic renal failure (CRF represents the major cause of mortality in the nephro-logy unit in Ivory Coast because the means for appropriate management are lacking. The present study was performed to investigate the risk factors for CRF so that strategies for prevention could be elaborated. A case-control study was performed prospectively at the Yopougon Teaching Hos-pital in Abidjan from January 2006 to December 2006. Factors known to cause CRF were investigated in patients and controls. Their prevalence rates were compared with the general population. A total of 280 patients and 113 controls were recruited. The mean age of the patients was 37.88 ± 13.33 years and that of the controls was 41.5 ± 9.72 years. Both genders were equally represented. The main causes of CRF were chronic glomerulonephritis (47.48%, with HIV infec-tion accounting for 15% of them, and essential hypertension (HTA (25%. Essential HTA repre-sented the only factor which, if untreated, inevitably leads to CRF. Thus, our study indicates that HTA is a major public health concern. All efforts should be implemented to reduce the high prevalence of HTA and the deleterious effect of this disorder in Ivory Coast.

  18. Risk factors for chronic renal failure in Ivory Coast: a prospective study of 280 patients.

    Science.gov (United States)

    Ackoundou-N'Guessan, K C; Lagou, D A; Tia, M W; Gnionsahe, D A; Guei, M C

    2011-01-01

    Chronic renal failure (CRF) represents the major cause of mortality in the nephrology unit in Ivory Coast because the means for appropriate management are lacking. The present study was performed to investigate the risk factors for CRF so that strategies for prevention could be elaborated. A case-control study was performed prospectively at the Yopougon Teaching Hospital in Abidjan from January 2006 to December 2006. Factors known to cause CRF were investigated in patients and controls. Their prevalence rates were compared with the general population. A total of 280 patients and 113 controls were recruited. The mean age of the patients was 37.88 ± 13.33 years and that of the controls was 41.5 ± 9.72 years. Both genders were equally represented. The main causes of CRF were chronic glomerulonephritis (47.48%), with HIV infection accounting for 15% of them, and essential hypertension (HTA) (25%). Essential HTA represented the only factor which, if untreated, inevitably leads to CRF. Thus, our study indicates that HTA is a major public health concern. All efforts should be implemented to reduce the high prevalence of HTA and the deleterious effect of this disorder in Ivory Coast.

  19. Expert System Diagnosis Dental Disease Using Certainty Factor Method

    Directory of Open Access Journals (Sweden)

    Whisnu Ulinnuha Setiabudi

    2017-05-01

    Full Text Available Technological development is growing rapidly among with the increasing of human needs especially in mobile technology where the technology that often be used is android. The existence of this android facilitates the user in access of information. This android can be used for healthy needs, for example is detecting dental disease. One of the branches of computer science that can help society in detecting dental disease is expert system. In this research, making expert system to diagnosis dental disease by using certainty factor method. Dental disease diagnosis application can diagnose the patient based on griping of the patient about dental disease so it can be obtained diseases possibility of the patient itself. This application is an expert system application that operates on android platform. Furthermore, in the measurement accuracy of the system test performed by 20 patients, there were 19 cases of corresponding and 1 cases that do not fit. So, from system testing performed by 20 patients resulted in a 95% accuracy rate. 

  20. Immunocytochemical demonstration of proopiomelanocortin- and other opioid-related substances and a CRF-like peptide in the gut of the american cockroach, Periplaneta americana L.

    Science.gov (United States)

    Schols, D; Verhaert, P; Huybrechts, R; Vaudry, H; Jégou, S; De Loof, A

    1987-01-01

    Using the peroxidase-antiperoxidase technique, we showed the presence of peptides which are immunologically resembling mammalian corticotropin releasing hormone (CRF)-, adrenocorticotropic hormone (ACTH)-, beta-endorphin (beta-END)-, alpha-melanocyte stimulating hormone (alpha-MSH)-, methionine-enkephalin (met-ENK)- and leucine enkephalin (leu-ENK)- like immunoreactivity in hundreds to thousands of endocrine cells and nerve fibers in the midgut of the American cockroach Periplaneta americana. In the cockroach hindgut no immunoreactive cell bodies could be observed, although nerve fibers were clearly noticed to be recognized by antisera to CRF, ACTH1-24, ACTH11-24 and beta-END. Nothing is exactly known as to the function(s) of the demonstrated materials, but one can speculate that these numerous immunoreactive cells, might have important paracrine and/or endocrine functions in the insect physiology.

  1. THE INSPECTION LIKE QUALITY FACTOR IN THE EDUCATIONAL SYSTEM

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    Joaquín Oliver Pozo

    2016-07-01

    Full Text Available The Inspection, along with other educational sectors, shapes from complementarity, coordination and communication between them, the architecture of the educational system. Each has its specificity and its own space in Education. The aim of this study is simply identify and define the location of the inspection into the education system, between educational administration and schools, and the "why" (their mission, and consistent with it, "which makes" (its functions and assignations. Mission and functions that take place in schools, at the sight of the Educational Administration and the society, through the Inspectorate as organization. Of the principles underlying this organization and of the communication, training, and technical and professional exchange that drives through their organizational structures, will depend its leadership in Education and to be seen as a quality factor.

  2. Nucleic acid amplification of HIV-1 integrase sequence subtypes CRF01_AE and B for development of HIV anti-integrase drug resistance genotyping assay

    Science.gov (United States)

    Adlar, F. R.; Bela, B.

    2017-08-01

    To anticipate the potential use of anti-integrase drugs in Indonesia for treatment of HIV-1 infection, the development of a drug resistance genotyping assay for anti-integrase is crucial in identifying the genetic drug resistance profile of Indonesian HIV-1 strains. This experiment aimed to amplify a target region in the integrase gene of Indonesian HIV-1 subtypes CRF01_AE and B that contain genetic mutations known to confer resistance to anti-integrase drug. Eleven archived plasma samples from individuals living with HIV-1 were obtained from the Virology and Cancer Pathobiology Research Center for Health Service (VCPRC FKUI-RSCM) laboratory. One of the plasma samples contained HIV-1 subtype B, and the remaining plasma samples contained subtype CRF01_AE. The target regions for all samples were amplified through RT-PCR, with an annealing temperature of 55 °C, using the primer pair AE_POL 4086F and AE_POL 5232R that were designed by VCPRC FKUI-RSCM. The results of this experiment show that 18.2% (2/11) of the samples were successfully amplified using the one-step RT-PCR. While the primer pair was effective in amplifying the target region in the integrase gene sequence for subtype B (100%; 1/1), it had a low efficacy (10%, 1/10) for subtype CRF01_AE. In conclusion, the primer pair can be used to amplify the target region in Indonesian HIV-1 strain subtypes CRF01_AE and B. However, optimization of the PCR condition and an increased number of samples would help to determine an accurate representation of the efficacy of the primer pair.

  3. Recent HIV-1 Outbreak Among Intravenous Drug Users in Romania: Evidence for Cocirculation of CRF14_BG and Subtype F1 Strains.

    Science.gov (United States)

    Niculescu, Iulia; Paraschiv, Simona; Paraskevis, Dimitrios; Abagiu, Adrian; Batan, Ionelia; Banica, Leontina; Otelea, Dan

    2015-05-01

    Since 2011, Romania has faced an HIV outbreak among injecting drug users (IDUs). Our aim was to identify and describe clinical and epidemiological patterns of this outbreak. A cross-sectional study enrolled 138 IDUs diagnosed with HIV infection between 2011 and 2013 with 58 sexually infected individuals included as the control group. The IDUs had a long history of heroin abuse (10 years) and a recent history of new psychostimulant injection (3-4 years). Classical epidemiological data and molecular techniques were used to describe the transmission dynamics. A high prevalence of hepatitis C virus (HCV) coinfection was noted (98.6%) compared to the control group (10.3%) (p<0.001). IDUs had initially been infected with HCV. HIV infection was more recent, linked to starting injecting stimulants. HIV subtype analysis showed a predominance of the local F1 strain in both IDUs and sexually infected patients; in IDUs it also identified 28 CRF14_BG recombinants and six unique recombinant forms (URFs) between F1 and CRF14_BG. A few patients from both risk groups were infected with subtype B. Among IDUs, CRF14_BG was associated with a lower CD4 cell count and more advanced stages of disease, which correlated with CXCR4 tropism. Phylogenetic analysis revealed the spread of HIV through three major IDU clusters of recent date. Among IDUs with CRF14_BG, some reported travel abroad (Spain, Greece). By identifying clusters of IDUs with related viruses, molecular epidemiologic methods provide valuable information on patterns of HIV transmission that can be useful in planning appropriate harm reduction interventions.

  4. An Improved Reinforcement Learning System Using Affective Factors

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    Takashi Kuremoto

    2013-07-01

    Full Text Available As a powerful and intelligent machine learning method, reinforcement learning (RL has been widely used in many fields such as game theory, adaptive control, multi-agent system, nonlinear forecasting, and so on. The main contribution of this technique is its exploration and exploitation approaches to find the optimal solution or semi-optimal solution of goal-directed problems. However, when RL is applied to multi-agent systems (MASs, problems such as “curse of dimension”, “perceptual aliasing problem”, and uncertainty of the environment constitute high hurdles to RL. Meanwhile, although RL is inspired by behavioral psychology and reward/punishment from the environment is used, higher mental factors such as affects, emotions, and motivations are rarely adopted in the learning procedure of RL. In this paper, to challenge agents learning in MASs, we propose a computational motivation function, which adopts two principle affective factors “Arousal” and “Pleasure” of Russell’s circumplex model of affects, to improve the learning performance of a conventional RL algorithm named Q-learning (QL. Compared with the conventional QL, computer simulations of pursuit problems with static and dynamic preys were carried out, and the results showed that the proposed method results in agents having a faster and more stable learning performance.

  5. Pre- and postnatally administered ACTH, Organon 2766 and CRF facilitate or inhibit active avoidance task performance in young adult mice.

    Science.gov (United States)

    Honour, L C; White, M H

    1988-01-01

    This study investigated the effect of learning/memory-related neuropeptides on behavioral task performance in later life. A 1 mg/kg dosage of adrenocorticotropic hormone 4-9, Organon 2766, ACTH/MSH 4-10, ACTH 1-24, CRF, or diluent was subcutaneously injected into either pregnant females or into newborn pups during specific neural developmental windows. Each of the progeny was trained in an active-avoidance task and tested for acquisition on postpartum days 35-37. The mice were then tested for memory task performance and reacquisition on days 42-44 postpartum using the identical experimental paradigm as that used in the training sessions. Prenatal treatment with these memory-related neuropeptides resulted in significant facilitation of learning/memory task performance in male and female mice treated with Organon 2766 (p less than 0.001), and a significant inhibition of learning/memory task performance in males and females treated with ACTH 1-24 (p less than 0.01). Additional sex-specific performance facilitations and inhibitions resulted from the pre- or postnatal administration of the various neuropeptides used in this study. These results suggest that neuropeptides, when available in increased amounts during specific neural developmental windows, can significantly improve or suppress related behavioral performance capability in later life.

  6. Herpesvirus-mediated systemic delivery of nerve growth factor.

    Science.gov (United States)

    Wolfe, D; Goins, W F; Kaplan, T J; Capuano, S V; Fradette, J; Murphey-Corb, M; Robbins, P D; Cohen, J B; Glorioso, J C

    2001-01-01

    Sustained systemic dissemination of therapeutic proteins from peripheral sites is an attractive prospect for gene therapy applications. Replication-defective genomic herpes simplex virus type 1 (HSV-1) vectors were evaluated for their ability to express nerve growth factor (NGF) as a model gene product both locally and systemically. Intra-articular inoculation of NGF expression vectors in rabbits resulted in significant increases in joint lavage and blood plasma NGF that persisted for 1 year. A rhesus macaque injected intra-articularly displayed a comparable increase in plasma NGF for at least 6 months, at which time the serum NGF levels of this animal were sufficient to cause differentiation of PC12 cells in culture, but not to increase footpad epidermis innervation. Long-term reporter transgene expression was observed primarily in ligaments, a finding confirmed by direct inoculation of patellar ligament. Patellar ligament inoculation with a NGF vector resulted in elevated levels of circulating NGF similar to those observed following intra-articular vector delivery. These results represent the first demonstration of sustained systemic release of a transgene product using HSV vectors, raising the prospect of new applications for HSV-1 vectors in the treatment of systemic disease.

  7. Short Communication Phylogenetic Characterization of HIV Type 1 CRF01_AE V3 Envelope Sequences in Pregnant Women in Northern Vietnam

    Science.gov (United States)

    Caridha, Rozina; Ha, Tran Thi Thanh; Gaseitsiwe, Simani; Hung, Pham Viet; Anh, Nguyen Mai; Bao, Nguyen Huy; Khang, Dinh Duy; Hien, Nguyen Tran; Cam, Phung Dac; Chiodi, Francesca

    2012-01-01

    Abstract Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005–2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology. PMID:21936713

  8. Short communication: phylogenetic characterization of HIV type 1 CRF01_AE V3 envelope sequences in pregnant women in Northern Vietnam.

    Science.gov (United States)

    Caridha, Rozina; Ha, Tran Thi Thanh; Gaseitsiwe, Simani; Hung, Pham Viet; Anh, Nguyen Mai; Bao, Nguyen Huy; Khang, Dinh Duy; Hien, Nguyen Tran; Cam, Phung Dac; Chiodi, Francesca; Ehrnst, Anneka

    2012-08-01

    Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005-2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology.

  9. Characterization of an old complex circulating recombinant form, CRF27_cpx, originating from the Democratic Republic of Congo (DRC) and circulating in France.

    Science.gov (United States)

    Vidal, Nicole; Frange, Pierre; Chaix, Marie-Laure; Mulanga, Claire; Lepira, François; Bazepeo, Samuel Edidi; Goujard, Cecile; Meyer, Laurence; Rouzioux, Christine; Delaporte, Eric; Peeters, Martine

    2008-02-01

    Full-length genomes were characterized for two samples, 02CD-LBR024 from the Democratic Republic of Congo (DRC) and 04FR-CD-KZS from France, that formed a separate subcluster with a previously characterized env subtype E isolate from DRC with a recombinant structure different from CRF01-AE. Since the three viruses are clearly epidemiologically unlinked and share the same complex recombinant structure, they represent a circulating recombinant form, designated as CRF27-cpx. The recombination pattern involves six different HIV-1 subtypes (A, E, G, H, J, and K) and a small unclassified fragment. The genetic distances are relatively high, indicating that CRF27-cpx evolved over a long time. Their prevalence is low (0.75%) and remained stable over time in the DRC. The existence of the 04FR.CD.KZS virus, in a patient who recently seroconverted in France, confirmed that these strains now circulate outside the DRC. Continuous monitoring of HIV-1 strains thus remains important to allow early identification of the introduction of new variants.

  10. Systemic hypertension and associated factors in school adolescents

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    Salma B. Galal

    2011-02-01

    Full Text Available Background: Systemic hypertension is an endemic disease, which causes serious morbidities and mortality in all age groups. Hypertension of adults in Egypt is 26%. It can start in childhood and needs to be assessed in Egyptian children and adolescents.Aim and objectives: This study aims to investigate the prevalence of systemic hypertension in 12-14 year old school children and associated factors. Methods and study design: A cross sectional study was done in some preparatory public and private schools selected from a district of Cairo. The 234 children (167 females, 67males in this study were 12 - 14 year of age. Their weight ranged from 30 – 100 kg Subjects with high blood pressure (BP were identified according to the percentiles of Rosner, et al. Beside characteristics of the sample and blood pressure (BP, associated factors investigated were: - weight and body mass index (BMI, tea / coffee consumption, "added salt before tasting food", sleeping less than 8 hours per day and physical activity. Each student filled out stress and tension level tests. The school health team obtained informed parental consent to include their children in this study. Statistical analysis was done with EPI using chi-square, t-test, odd ratio (OR with 95% confidence limits (Cl and logistic regression with the 5% level for tests. The ethical committee of the faculty approved the study.Results / Finding: The prevalence of systemic hypertension was 10%. Children with high BP (23 were compared to 211 subjects with normotensive BP. High stress and tension score, less sleeping hours / day, adding salt to food and higher BMI were found significantly associated (p<0.05 with high BP. Study limitation: Researchers could assess preparatory schools children. However, primary and secondary school levels are separated in other schools and administrations. We used US standards for hypertension and BMI for children as local standards are not published.Conclusions: One tenth of 12

  11. SISTEMA ENDOCANABINOIDE: MODIFICANDO LOS FACTORES DE RIESGO CARDIOVASCULAR Endocannabinoid system: modifying cardiovascular risk factors

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    John Edwin Feliciano Alfonso

    2006-10-01

    Full Text Available La necesidad de alcanzar un tratamiento óptimo para el tabaquismo, la obesidad y sus comorbilidades, conocidos factores de riesgo cardiovascular, ha fomentado la búsqueda de objetivos terapéuticos novedosos. Es el caso del sistema endocanabinoide, involucrado en diversos fenómenos fisiológicos entre los que se encuentran el refuerzo de ciertos comportamientos y la regulación del apetito. La sobreactivación de este sistema altera la homeostasis corporal predisponiendo a dependencias o a un aumento en la ingesta alimentaria, lo que puede traducirse en tabaquismo u obesidad. La intervención farmacológica sobre el sistema endocanabinoide puede contribuir al manejo de estos factores de riesgo cardiovascular, teniendo en cuenta que a tales beneficios se suman otros independientes de la suspensión del tabaquismo o la reducción de peso, como el aumento del colesterol de alta densidad, la disminución de triglicéridos y la mejoría del control glucémico en pacientes con diabetes. Ensayos clínicos controlados aleatorizados adelantados en poblaciones con diferentes características, han evaluado la utilidad de la regulación farmacológica del sistema endocanabinoide; confirmando su eficacia en personas con factores de riesgo cardiovascular establecidos.The need for an optimal treatment for smoking, obesity and their comorbidities, well-known cardiovascular risk factors; has prompted the search for novel therapeutic targets. This is the case of the endocannabinoid system, involved in several physiological phenomena including the reinforcement of certain behaviors and the regulation of appetite.

  12. A Large-scale Survey of CRF55_01B from Men-Who-Have-Sex-with-Men in China: implying the Evolutionary History and Public Health Impact.

    Science.gov (United States)

    Han, Xiaoxu; Takebe, Yutaka; Zhang, Weiqing; An, Minghui; Zhao, Bin; Hu, Qinghai; Xu, Junjie; Wu, Hao; Wu, Jianjun; Lu, Lin; Chen, Xi; Liang, Shu; Wang, Zhe; Yan, Hongjing; Fu, Jihua; Cai, Weiping; Zhuang, Minghua; Liao, Christina; Shang, Hong

    2015-12-15

    The HIV-1 epidemic among men-who-have-sex-with-men (MSM) continues to expand in China, involving the co-circulation of several different lineages of HIV-1 strains, including subtype B and CRF01_AE. This expansion has created conditions that facilitate the generation of new recombinant strains. A molecular epidemiologic survey among MSM in 11 provinces/cities around China was conducted from 2008 to 2013. Based on pol nucleotide sequences, a total of 19 strains (1.95%) belonged to the CRF55_01B were identified from 975 MSM in 7 provinces, with the prevalence range from 1.5% to 12.5%. Near full length genome (NFLG) sequences from six epidemiologically-unlinked MSM were amplified for analyzing evolutionary history, an identical genome structure composed of CRF01_AE and subtype B with four unique recombination breakpoints in the pol region were identified. Bayesian molecular clock analyses for both CRF01_AE and B segments indicated that the estimated time of the most recent common ancestors of CRF55_01B was around the year 2000. Our study found CRF55_01B has spread throughout the most provinces with high HIV-1 prevalence and highlights the importance of continual surveillance of dynamic changes in HIV-1 strains, the emergence of new recombinants, and the need for implementing effective prevention measures specifically targeting the MSM population in China.

  13. HIV-1 CRF07_BC with a Seven Amino Acid Deletion in the gag p6 Region Dominates in HIV-1-Infected Men Who Have Sex with Men in China.

    Science.gov (United States)

    Wu, Yue; Wang, Haiying; Ren, Xuqi; Wan, Zhengwei; Hu, Guifang; Tang, Shixing

    2017-09-01

    We examined sequence variation in the HIV-1 gag p6 region from 27 individuals infected with HIV-1 CRF07_BC. An additional 269 gag p6 sequences of CRF07_BC from the Los Alamos National Laboratory database were also analyzed. A unique deletion of seven amino acid (aa) (p6Δ7) (aa 30-36, PIDKELY, in the HXB2 genome) was observed to exist exclusively in CRF07_BC. Indeed, 54.1% (160/296) of the CRF07_BC sequences contained the p6Δ7 mutation. The prevalence of the p6Δ7 mutation was 37.2% (29/78) and 92.3% (48/52) in CRF07_BC-infected intravenous drug users and men who have sex with men (MSM), respectively. Our results demonstrate that the p6Δ7 mutation dominates in MSM infected by HIV-1 CRF07_BC in China and suggests that this deletion could serve as a useful marker for monitoring HIV-1 evolution and epidemic. In future studies, it will be of interest to determine whether such genotypic variation influences viral replication capacity and disease progression.

  14. Potato root system development and factors that determine its architecture.

    Science.gov (United States)

    Joshi, Mukul; Fogelman, Edna; Belausov, Eduard; Ginzberg, Idit

    2016-10-20

    The potato root system is often characterized as shallow and inefficient, with poor ability to extract water and minerals from the soil. Potato root system architecture (RSA) refers to its 3-dimensional structure as determined by adventitious root (AR) growth and branching through lateral roots (LR). Understanding how the root system develops holds potential to increase plant yield and optimize agricultural land use. Root system development was monitored in greenhouse-grown potato while a root-on-a-plate assay was developed to explore factors that affect AR and LR development. Expression study of LR-related genes was conducted. Transgenic plants carrying DR5:GFP and CycB1:GUS reporter genes were used to monitor auxin signaling and cell division during root primordia formation, respectively. Maximum root development occurred mainly during the 6-week post seed-tuber planting and slowed during the onset of tuberization. AR and LR development was coordinated - a positive correlation was found between the length of AR and LR and between LR length and number. The expression of LR-related genes was higher in LR than in AR. High nitrate levels reduced LR number and length, however ablation of root-cap by high temperature (33°C) or cutting resulted with enhanced formation of LR. Growth conditions affect AR and LR development in potato, determining the final architecture of its root system. The overall results indicate that LR formation in potato follows similar pattern as in model plants, facilitating study and manipulation of its RSA to improve soil exploitation and yield. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

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    Huang Xu

    2010-08-01

    Full Text Available Abstract Background Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF in breast cancer patients undergoing endocrine therapy in an urban area. Methods Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371 in the study. The 315 women who responded to the questionnaire (84.9%, 54 (17.1% had completed endocrine therapy and 261 (82.9% were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months; the average age was 48 (range, 33 to 72 years. The 11-point scale and Visual Analog Scale (VAS were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF. Results Among the 315 patients, 189 (60% had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF. Conclusions The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF

  16. Systemic factors and mortality in elderly patients with pressure ulcers.

    Science.gov (United States)

    Jaul, Efraim; Calderon-Margalit, Ronit

    2015-06-01

    The aim of this article was to identify specific systemic factors associated with existence of pressure ulcers (PUs) and the effect on survival from the time of admission. Patients admitted to the Skilled Nursing Department of the Herzog Hospital, Jerusalem, between 1 July 2008 and 31 December 2011. Of the 174 admitted patients (mean age: 77·4 ± 13·2 years), 107 (61·5%) had pre-existing PUs and 67 (38·5%) did not have PUs. Major systemic factors were assessed for each patient at the time of admission: sociodemographic characteristics, comorbidities, use of urinary catheter, tube feeding and tracheostomy; nutritional state; Global Deterioration Scale, Glasgow Coma Scale and Norton Scale. Complications such as the number of provided antibiotic courses, and length and outcomes of hospitalisation were identified at the end of the study. In the univariate analysis, patients in the PU group had significantly prevalent characteristics including advanced age, low cognitive and consciousness function, low Norton scale, Parkinson's disease and anaemia due to chronic diseases, low nutritional parameters and higher number of antibiotics provided. Conditions that were associated with PUs in multiple regression analyses included advanced dementia (OR = 3·0, 95% CI: 1·4-6·3; P = 0·002), urinary catheter usage (OR = 2·25, 95% CI: 1·06-4·7; P = 0·03), low body mass index, BMI (OR = 0·92, 95% CI: 0·86-0·99; P = 0·02) and anaemia level (OR = 0·7, 95% CI: 0·58-0·9; P = 0·004). The median survival time of patients with PUs was significantly lower than the non PUs group (94 versus 414 days, respectively) (P = 0·005, log rank test). Length of stay was also significantly lower in the PU group (166 versus 270 days, P = 0·02). The existence of PUs may indicate a final common pathway of various systemic factors (geriatric conditions, diseases and frailty dysfunction).

  17. Construction and characterization of a new simian/human immunodeficiency viruses clone carrying an env gene derived from a CRF07_BC strain

    Institute of Scientific and Technical Information of China (English)

    LI Yue; YANG Gui-bo; CHEN Qi-min; LIU Qiang; MENG Zhe-feng; GENG Yun-qi; QIAO Wen-tao; SHAO Yi-ming

    2009-01-01

    Background The CRF07_BC recombinant strain has been one of the most predominantly circulated HIV-1 strains in China, it is therefore necessary and urgent to develop a relevant animal model to evaluate candidate vaccines targeting HIV-1 CRF07_BC. A highly replication-competent simian/human immunodeficiency viruses (SHIV) construct containing the Chinese CRF07_BC HIV-1 env gene with the ability to infect Chinese rhesus monkeys would serve as an important tool in the development of HIV vaccines. The aim of this study was to examine whether SHIV XJDC6431 with the env fragment from a Chinese HIV-1 isolate virus could infect the human and monkey peripheral blood mononuclear cell (PBMC), establish infection in Chinese rhesus macaque.Methods A SHIV strain was constructed by replacing the rev/env genes of SHIV KB9 with the corresponding fragment derived from the HIV-1 CRF07_BC strain. The infectious activity of the SHIV clones was determined in vitro in PBMCs from both non-human primate animals and humans. Finally, one Chinese rhesus macaques (Macaca mulatto) was infected with one SHIV via intravenous infusion.Results One SHIV clone designated as SHIV XJDC6431, was generated that could infect macaque and human PBMC. The virus produced from this clone also efficiently infected the CCR5-expressing GHOST cell lines, indicating that it uses CCR5 as its coreceptor. Finally, the virus was intravenously inoculated into one Chinese rhesus macaque. Eventually, the animal became infected as shown by the occurrence of viremia within 3 of infection. The viral load reached 10~5 copies of viral RNA per ml of plasma during the acute phase of infection and lasted for 10 weeks post infection. Conclusions We conclude that SHIV XJDC6431 is an R5-tropic chimeric virus, which can establish infection not only in vitro but also in vivo in the Chinese rhesus macaque. Although the animal inoculated with SHIV XJDC6431 became infected without developing a pathologic phenotype, the virus efficiently

  18. A systems biology approach to transcription factor binding site prediction.

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    Xiang Zhou

    Full Text Available BACKGROUND: The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles and cross-species conserved regulatory regions in DNA. Technical challenges faced by these methods include distinguishing between direct and indirect interactions, associating transcription regulators with predicted transcription factor binding sites (TFBSs, identifying non-linearly conserved binding sites across species, and providing realistic accuracy estimates. METHODOLOGY/PRINCIPAL FINDINGS: We address these challenges by closely integrating proven methods for regulatory network reverse engineering from mRNA expression data, linearly and non-linearly conserved regulatory region discovery, and TFBS evaluation and discovery. Using an extensive test set of high-likelihood interactions, which we collected in order to provide realistic prediction-accuracy estimates, we show that a careful integration of these methods leads to significant improvements in prediction accuracy. To verify our methods, we biochemically validated TFBS predictions made for both transcription factors (TFs and co-factors; we validated binding site predictions made using a known E2F1 DNA-binding motif on E2F1 predicted promoter targets, known E2F1 and JUND motifs on JUND predicted promoter targets, and a de novo discovered motif for BCL6 on BCL6 predicted promoter targets. Finally, to demonstrate accuracy of prediction using an external dataset, we showed that sites matching predicted motifs for ZNF263 are significantly enriched in recent ZNF263 ChIP-seq data. CONCLUSIONS/SIGNIFICANCE: Using an integrative framework, we were able to address technical challenges faced by state of the art network reverse engineering methods, leading to significant improvement in direct

  19. Design flow factors for sewerage systems in small arid communities

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    Emad H. Imam

    2014-09-01

    Full Text Available Reliable estimation of sewage flow rates is essential for the proper design of sewers, pumping stations, and treatment plants. The design of the various components of the sewerage system should be based on the most critical flow rates with a focus on extremely low and peak flow rates that would be sustained for a duration related to the acceptable limits of behavior of the components under consideration. The extreme flow conditions and to what extent they differ from the average values are closely related to the size of the community or network, and the socioeconomic conditions. A single pumping station is usually sufficient to pump flow from small community in either flat or non-undulating topography. Therefore, the hydraulic loading on the wastewater treatment plant (WWTP results from the pumped flow from the pumping station rather than the trunk sewer flow. The intermittent operation of the pumping units further accentuates the sewage hydrograph in the final trunk sewer. Accordingly, the design flow for the various components of the WWTP should be determined based on their relevant flow factors. In this study, analysis of one representative small community out of five monitored small communities in Egypt and the Kingdom of Saudi Arabia is presented. Pumped sewage flow rates were measured and the sewer incoming flows were hydraulically derived. The hourly and daily sewer and pumped flow records were analyzed to derive the relationship between the flow factors that would be sustained for various durations (instantaneously, 1 h, 2 h, etc. and their probability of non-exceedance. The resulting peaking factors with a consideration for their sustained flow duration and specified probability would permit the design of the various components of the treatment plant using more accurate critical flows.

  20. Design flow factors for sewerage systems in small arid communities.

    Science.gov (United States)

    Imam, Emad H; Elnakar, Haitham Y

    2014-09-01

    Reliable estimation of sewage flow rates is essential for the proper design of sewers, pumping stations, and treatment plants. The design of the various components of the sewerage system should be based on the most critical flow rates with a focus on extremely low and peak flow rates that would be sustained for a duration related to the acceptable limits of behavior of the components under consideration. The extreme flow conditions and to what extent they differ from the average values are closely related to the size of the community or network, and the socioeconomic conditions. A single pumping station is usually sufficient to pump flow from small community in either flat or non-undulating topography. Therefore, the hydraulic loading on the wastewater treatment plant (WWTP) results from the pumped flow from the pumping station rather than the trunk sewer flow. The intermittent operation of the pumping units further accentuates the sewage hydrograph in the final trunk sewer. Accordingly, the design flow for the various components of the WWTP should be determined based on their relevant flow factors. In this study, analysis of one representative small community out of five monitored small communities in Egypt and the Kingdom of Saudi Arabia is presented. Pumped sewage flow rates were measured and the sewer incoming flows were hydraulically derived. The hourly and daily sewer and pumped flow records were analyzed to derive the relationship between the flow factors that would be sustained for various durations (instantaneously, 1 h, 2 h, etc.) and their probability of non-exceedance. The resulting peaking factors with a consideration for their sustained flow duration and specified probability would permit the design of the various components of the treatment plant using more accurate critical flows.

  1. Activating Transcription Factor 3 (ATF3 and the Nervous System

    Directory of Open Access Journals (Sweden)

    Patrick Norval Anderson

    2012-02-01

    Full Text Available It has been recognised for over a century that the ability of axons to regenerate in peripheral nerves is fundamentally greater than that of axons in the brain, spinal cord or optic nerves [early literature was reviewed in (Ramon y Cajal, 1928]. One factor that contributes to the successful regeneration of the axons in peripheral nerves is the complex cell body response the neurons show to axotomy. That transcription factors must play an important role in enabling neurons to regrow their axons is implicit to the observation that several hundred genes are regulated in neurons during axonal regeneration (Costigan et al., 2002; Boeshore et al., 2004. In addition, similarly large numbers of genes are regulated in the non-neuronal cells present in injured peripheral nerves [especially Schwann cells (Barrette et al., 2010] and CNS tissue. Of the transcription factors that regulate these changes in gene expression, the function of c-jun is best understood but ATF-3 (also known as LRF-1, LRG-21, CRG-5 and TI-241 is also upregulated in most of the neurons (Fig. 1 and Schwann cells that express c-jun. Indeed, ATF-3 has become a standard marker for neurons axotomised by peripheral nerve injury (Tsuzuki et al., 2001; Yamanaka et al., 2005; Yano et al., 2008; Linda et al., 2011 and its expression by injured neurons is closely correlated with a regenerative response. None the less, surprisingly little is known about the functions of ATF3 in neurons or glia within the injured nervous system, especially when compared with those of its potential binding partner, c-Jun.

  2. Axiological crisis among the factors of development of political system

    Directory of Open Access Journals (Sweden)

    R. M. Kliuchnyk

    2015-12-01

    Full Text Available The article is dedicated to axiological crisis as one of the factors of development of political system. Intergeneration and civilization crises are separated. It is shown that contradictions between survival and self-expressionpolitical values often lead to political crises. The Arabic Spring is proved to have been a consequence of a deep generation crisis. Dangerous consequences of cultural and civilization crisis within globalization are underlined. The influence of illegal migration, extremism and intolerance on axiological crises is considered. A special attention is paid to modernization possibilities of high school within axiological crisis. The necessity of reforming of high school in order to avoid negative consequences of axiological crises is underlined. International experience in high school reforms is analyzed. The perspectives of its implementation in Ukraine are considered.

  3. Compulsive drug-seeking behavior and relapse. Neuroadaptation, stress, and conditioning factors.

    Science.gov (United States)

    Weiss, F; Ciccocioppo, R; Parsons, L H; Katner, S; Liu, X; Zorrilla, E P; Valdez, G R; Ben-Shahar, O; Angeletti, S; Richter, R R

    2001-06-01

    The development of addiction and vulnerability to relapse following withdrawal is proposed to be the result of neuroadaptive processes within the central nervous system that oppose the acute reinforcing actions of drugs of abuse. These changes lead to impairment in the mechanisms that mediate positive reinforcement and the emergence of affective changes such as anxiety, dysphoria, and depression during withdrawal. Considerable evidence exists implicating perturbations in DA and 5-HT transmission in the nucleus accumbens--neurochemical systems that are activated by cocaine and ethanol self-administration and deficient during withdrawal--as potential substrates for these affective changes. In addition, growing evidence suggests that enhanced CRF release in the central nucleus of the amygdala represents a mechanism underlying the anxiogenic and stress-like consequences of withdrawal that are common to all drugs of abuse. A growing body of evidence also implicates dysregulation of the non-neuroendocrine CRF stress system within the central nucleus of the amygdala as a common factor in the anxiogenic and aversive consequences of withdrawal from drugs of abuse. Moreover, a possible link may exist between long-lasting abnormalities in CRF function in the CeA and vulnerability to relapse during protracted abstinence. Another presumably critical element contributing to the chronic relapsing nature of drug addiction is the learned responses to drug-related stimuli. The long-lasting efficacy of drug- and alcohol-associated contextual stimuli in eliciting drug-seeking behavior in animal models of relapse resembles the endurance of conditioned cue reactivity and cue-induced cocaine craving in humans and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. With cocaine, D1-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala may be important substrates for the motivating effects of drug

  4. Evaluation of prognostic factors and scoring system in colonic perforation

    Institute of Scientific and Technical Information of China (English)

    Atsushi Horiuchi; Yuji Watanabe; Takashi Doi; Kouichi Sato; Syungo Yukumi; Motohira Yoshida; Yuji Yamamoto; Hiroki Sugishita; Kanji Kawachi

    2007-01-01

    AIM: To study the significance of scoring systems assessing severity and prognostic factors in patients with colonic perforation.METHODS: A total of 26 patients (9 men, 17 women;mean age 72.7±11.6 years) underwent emergency operation for colorectal perforation in our institution between 1993 and 2005. Several clinical factors were measured preoperatively and 24 h postoperatively. Acute physiology and chronic health evaluationⅡ (APACHE Ⅱ),Mannheim peritonitis index (MPI) and peritonitis index of Altona (PIA Ⅱ) scores were calculated preoperatively.RESULTS: Overall postoperative mortality rate was 23.1% (6 patients). Compared with survivors, nonsurvivors displayed low blood pressure, low serum protein and high serum creatinine preoperatively, and low blood pressure, low white blood cell count, low pH,low PaO2/FiO2, and high serum creatinine postoperatively.APACHE Ⅱ score was significantly lower in survivors than in non-survivors (10.4±3.84 vs19.3±2.87, P= 0.00003). Non-survivors tended to display high MPI score and low PIA Ⅱ score, but no significant difference was identified.CONCLUSION: Pre- and postoperative blood pressure and serum creatinine level appear related to prognosis of colonic perforation. APACHE Ⅱ score is most associated with prognosis and scores ≥ 20 are associated with significantly increased mortality rate.

  5. Risk factors for systemic inflammatory response after congenital cardiac surgery.

    Science.gov (United States)

    Güvener, Murat; Korun, Oktay; Demirtürk, Orhan Saim

    2015-01-01

    This study aims to assess the frequency of systemic inflammatory response syndrome (SIRS) following congenital heart surgery and risk factors associated with this clinical syndrome. Charts of all patients undergoing surgery for congenital heart disease in a single institution over a five-year period were analyzed retrospectively. The presence of SIRS was evaluated based on the criteria of the International Pediatric Sepsis Consensus Conference. Of the 246 patients included in the study 22 (8.9%) had clinical parameters indicating SIRS. The patients in the SIRS group had significantly longer cardiopulmonary bypass time (105.14 ± 27.27 vs. 66.86 ± 26.64 min; p SIRS group. Binary logistic regression revealed cardiopulmonary bypass time (OR: 1.05, p SIRS. SIRS was also found to be a strong independent predictor of mortality (OR: 10.13, p SIRS after congenital heart surgery is associated with increased mortality. Independent risk factors for SIRS in the patient population of the study were cardiopulmonary bypass time, body weight below 10 kg and preoperative diagnosis of right to left shunt congenital heart disease. © 2014 Wiley Periodicals, Inc.

  6. A Study of Evaluation System of Restricting Factors in Training Students' Qualities

    Institute of Scientific and Technical Information of China (English)

    MA Xiao-yan

    2002-01-01

    This paper studies evaluation system of restricting factors in training students' qualities by modern mathematical method of analysis hierarchy process and principal factor analysis, and to build up a mathematical model of evaluation system.

  7. High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

    Directory of Open Access Journals (Sweden)

    Tomohiro Kotaki

    Full Text Available BACKGROUND: Human immunodeficiency virus (HIV infection and acquired immune deficiency syndrome (AIDS cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs, we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs. METHODOLOGY/PRINCIPAL FINDINGS: The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1 and the prevalence of other blood-borne viruses, hepatitis B virus (HBV, hepatitis C virus (HCV and GB virus C (GBV-C, were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients. CONCLUSIONS/SIGNIFICANCE: The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%. In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.

  8. High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

    Science.gov (United States)

    Kotaki, Tomohiro; Khairunisa, Siti Qamariyah; Sukartiningrum, Septhia Dwi; Arfijanto, M Vitanata; Utsumi, Takako; Normalina, Irine; Handajani, Retno; Widiyanti, Prihartini; Rusli, Musofa; Rahayu, Retno Pudji; Lusida, Maria Inge; Hayashi, Yoshitake; Nasronudin; Kameoka, Masanori

    2013-01-01

    Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs), we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs. The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1) and the prevalence of other blood-borne viruses, hepatitis B virus (HBV), hepatitis C virus (HCV) and GB virus C (GBV-C), were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients. The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%). In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.

  9. 21 CFR 864.7280 - Factor V Leiden DNA mutation detection systems.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Factor V Leiden DNA mutation detection systems....7280 Factor V Leiden DNA mutation detection systems. (a) Identification. Factor V Leiden deoxyribonucleic acid (DNA) mutation detection systems are devices that consist of different reagents...

  10. Role of Corticotropin Releasing Factor 1 Signaling in Cocaine Seeking during Early Extinction in Female and Male Rats.

    Directory of Open Access Journals (Sweden)

    Angie M Cason

    Full Text Available Locus coeruleus norepinephrine (LC-NE and corticotropin releasing factor (CRF neurons are involved in stress responses, including stress's ability to drive drug relapse. Previous animal studies indicate that female rats exhibit greater drug seeking than male rats during initial drug abstinence. Moreover, females are more sensitive to the effect of stress to drive drug seeking than males. Finally, LC-NE neurons are more sensitive to CRF in females compared to males. We hypothesized that increased drug seeking in females on extinction day one (ED1 is due to increased response to the stress of early withdrawal and is dependent upon the increased response of LC in females to CRF. We predicted that LC-NE neurons would exhibit Fos activation on ED1, and that blocking CRF1 signaling would decrease drug seeking on ED1 measured by responding on an active lever previously associated with cocaine self- administration. After chronic cocaine self-administration, female and male rats underwent a test for initial extinction responding by measuring lever pressing in the absence of cocaine. Prior to this Extinction Day 1 (ED1 session, rats were injected with vehicle or the selective CRF1 antagonist (CP to measure effects of CRF antagonism on drug seeking during early abstinence. ED1 increased corticosterone in female rats, in proportion to lever responding in male and female, indicating that ED1 was stressful. Pretreatment with CP decreased cocaine seeking on ED1 more effectively in female compared to male rats. This increase in responding was associated with an increase in activation of LC NE neurons. Together, these findings indicate that stress, and signaling at CRF receptors in LC, may be involved in the increased drug seeking during initial abstinence.

  11. Suppression of piriform cortex activity in rat by corticotropin-releasing factor 1 and serotonin 2A/C receptors.

    Science.gov (United States)

    Narla, Chakravarthi; Dunn, Henry A; Ferguson, Stephen S G; Poulter, Michael O

    2015-01-01

    The piriform cortex (PC) is richly innervated by corticotropin-releasing factor (CRF) and serotonin (5-HT) containing axons arising from central amygdala and Raphe nucleus. CRFR1 and 5-HT2A/2CRs have been shown to interact in manner where CRFR activation subsequently potentiates the activity of 5-HT2A/2CRs. The purpose of this study was to determine how the activation of CRFR1 and/or 5-HT2Rs modulates PC activity at both the circuit and cellular level. Voltage sensitive dye imaging showed that CRF acting through CRFR1 dampened activation of the Layer II of PC and interneurons of endopiriform nucleus. Application of the selective 5-HT2A/CR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) following CRFR1 activation potentiated this effect. Blocking the interaction between CRFR1 and 5-HT2R with a Tat-CRFR1-CT peptide abolished this potentiation. Application of forskolin did not mimic CRFR1 activity but instead blocked it, while a protein kinase A antagonist had no effect. However, activation and antagonism of protein kinase C (PKC) either mimicked or blocked CRF modulation, respectively. DOI had no effect when applied alone indicating that the prior activation of CRFR1 receptors was critical for DOI to show significant effects similar to CRF. Patch clamp recordings showed that both CRF and DOI reduced the synaptic responsiveness of Layer II pyramidal neurons. CRF had highly variable effects on interneurons within Layer III, both increasing and decreasing their excitability, but DOI had no effect on the excitability of this group of neurons. These data show that CRF and 5-HT, acting through both CRFR1 and 5-HT2A/CRs, reduce the activation of the PC. This modulation may be an important blunting mechanism of stressor behaviors mediated through the olfactory cortex.

  12. Suppression of piriform cortex activity in rat by corticotropin-releasing factor 1 and serotonin 2A/C receptors

    Directory of Open Access Journals (Sweden)

    Chakravarthi eNarla

    2015-05-01

    Full Text Available The piriform cortex (PC is richly innervated by Corticotropin-releasing factor (CRF and Serotonin (5-HT containing axons arising from central amygdala and Raphe nucleus. CRFR1 and 5-HT2A/2CRs have been shown to interact in manner where CRFR activation subsequently potentiates the activity of 5-HT2A/2CRs. The purpose of this study was to determine how the activation of CRFR1 and/or 5-HT2Rs modulates PC activity at both the circuit and cellular level. Voltage sensitive dye imaging showed that CRF acting through CRFR1 dampened activation of the layer II of PC and interneurons of endopiriform nucleus. Application of the selective 5-HT2A/CR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI following CRFR1 activation potentiated this effect. Blocking the interaction between CRFR1 and 5-HT2R with a Tat-CRFR1-CT peptide abolished this potentiation. Application of forskolin did not mimic CRFR1 activity but instead blocked it, while a protein kinase A antagonist had no effect. However, activation and antagonism of protein kinase C (PKC either mimicked or blocked CRF modulation respectively. DOI had no effect when applied alone indicating that the prior activation of CRFR1 receptors was critical for DOI to show significant effects similar to CRF. Patch clamp recordings showed that both CRF and DOI reduced the synaptic responsiveness of layer II pyramidal neurons. CRF had highly variable effects on interneurons within layer III, both increasing and decreasing their excitability, but DOI had no effect on the excitability of this group of neurons. These data show that CRF and serotonin, acting through both CRFR1 and 5-HT2A/CRs, reduce the activation of the PC. This modulation may be an important blunting mechanism of stressor behaviours mediated through the olfactory cortex.

  13. HANS SELYE AND THE STRESS RESPONSE: FROM "THE FIRST MEDIATOR" TO THE IDENTIFICATION OF THE HYPOTHALAMIC CORTICOTROPIN-RELEASING FACTOR.

    Science.gov (United States)

    Tachè, Yvette

    2014-03-30

    Selye pioneered the stress concept that is ingrained in the vocabulary of daily life. This was originally build on experimental observations that divers noxious agents can trigger a similar triad of endocrine (adrenal enlargement), immune (involution of thymus) and gut (gastric erosion formation) responses as reported in a letter to Nature in 1936. Subsequently, he articulated the underlying mechanisms and hypothesized the existence of a "first mediator" in the hypothalamus able to orchestrate this bodily changes. However he took two generations to identify this mediator. The Nobel Laureate, Roger Guillemin, a former Selye's PhD student, demonstrated in 1955 the existence of a hypothalamic factor that elicited adrenocorticotropic hormone release from the rat pituitary and named it corticotropin releasing factor (CRF). In 1981, Wylie Vale, a former Guillemin's Ph Student, characterized CRF as 41 amino acid and cloned the CRF1 and CRF2 receptors. This paves the way to experimental studies establishing that the activation of the CRF signaling pathways in the brain plays a key role in mediating the stress-related endocrine, behavioral, autonomic and visceral responses. The unraveling of the biochemical coding of stress is rooted in Selye legacy continues to have increasing impact on the scientific community.

  14. Nomenclature for factors of the SLA system, update 2008.

    Science.gov (United States)

    Ho, C-S; Lunney, J K; Ando, A; Rogel-Gaillard, C; Lee, J-H; Schook, L B; Smith, D M

    2009-04-01

    This report summarizes the new swine leukocyte antigen (SLA) allele sequences and haplotypes designated by the SLA Nomenclature Committee of the International Society for Animal Genetics. There have been 74 new SLA alleles, comprising 18 SLA-1 alleles, 11 SLA-2 alleles, six SLA-3 alleles, two SLA-6 alleles, one SLA-DRA allele, 20 SLA-DRB1 alleles, three SLA-DQA alleles and 13 SLA-DQB1 alleles. Twelve new SLA class I and four new class II haplotypes have also been designated. This is the first official update since the 2005 reports on the nomenclature for factors of the SLA class I and II systems. This report also summarizes recent updates to the Immunopolymorphism Database-Major Histocompatibility Complex (IPD-MHC) website (http://www.ebi.ac.uk/ipd/mhc/sla/). All information has now been integrated to the SLA section of the IPD-MHC database, which serves as the repository for maintaining a list of all recognized SLA genes and their allelic sequences.

  15. Systems lifecycle cost-effectiveness the commercial, design and human factors of systems engineering

    CERN Document Server

    Pica, Massimo

    2014-01-01

    The pressure to minimize expenditure and provide value for money from reduced resources means that complex projects have to encompass a wide range of often conflicting issues and interests. Systems Lifecycle Cost-Effectiveness shows how to manage the difficulties that can arise. Massimo Pica presents a variety of models for calculating cost, benefits and risk in projects, and explains how the human factors associated with a system's design and consequent value are as important as the technical costs associated with its construction or creation. This comprehensive text can be used by students,

  16. Independent associations of physical activity and cardiorespiratory fitness with metabolic risk factors in children: the European youth heart study

    DEFF Research Database (Denmark)

    Ekelund, U; Anderssen, S A; Froberg, K

    2007-01-01

    of Europe (n = 1709). We examined the independent associations of subcomponents of PA and CRF with metabolic risk factors (waist circumference, BP, fasting glucose, insulin, triacylglycerol and HDL-cholesterol levels). Clustered metabolic risk was expressed as a continuously distributed score calculated...... circumference from the summary score and further adjustment for waist circumference as a confounding factor, the magnitude of the association between CRF and clustered metabolic risk was attenuated (standardised beta = -0.05, 95% CI -0.08, -0.02), whereas the association with total PA was unchanged...... as the average of the standardised values of the six subcomponents. RESULTS: CRF (standardised beta = -0.09, 95% CI -0.12, -0.06), total PA (standardised beta = -0.08, 95% CI -0.10, -0.05) and all other subcomponents of PA were significantly associated with clustered metabolic risk. After excluding waist...

  17. THE PLACE AND ROLE OF OUTSIDE FORMAL INSTITUTIONAL FACTORS IN THE DEVELOPMENT OF REGIONAL ECONOMIC SYSTEM

    Directory of Open Access Journals (Sweden)

    Елена Федоровна Волошина

    2014-05-01

    Full Text Available This article investigates formal external institutional factors affecting the development of the regional economic system.Purpose: To determine the effect of external factors on the formal institutional development of the regional economic system.Methodology: We used scientific methods: analysis and synthesis, comparison, generalization, systematic approach.Results: A concept of foreign institutional factors in the development of the regional economic system. Three main external formal institutional factors: the law and the legal system, the system of governance at the national and regional levels; judicial system.DOI: http://dx.doi.org/10.12731/2218-7405-2014-2-18

  18. Estudios del rol modulador de ghrelina sobre la actividad neuroendocrina: circuitos neuronales implicados en la activación de las neuronas CRF hipofisiotrópicas

    OpenAIRE

    2014-01-01

    En la presente Tesis Doctoral estudiamos los circuitos neuronales que median los efectos de la ghrelina sobre las neuronas CRF hipofisiotrópicas del NPV y el eje HHA. Esperamos que el esclarecimiento de estos circuitos pueda ayudar a entender cómo funcionan y cómo se integran la homeostasis energética y el estrés. Así como también, contribuir al desarrollo de futuras terapias que intenten manipular las acciones de la ghrelina. Facultad de Ciencias Exactas

  19. Recent Transmission Clustering of HIV-1 C and CRF17_BF Strains Characterized by NNRTI-Related Mutations among Newly Diagnosed Men in Central Italy.

    Directory of Open Access Journals (Sweden)

    Lavinia Fabeni

    Full Text Available Increased evidence of relevant HIV-1 epidemic transmission in European countries is being reported, with an increased circulation of non-B-subtypes. Here, we present two recent HIV-1 non-B transmission clusters characterized by NNRTI-related amino-acidic mutations among newly diagnosed HIV-1 infected men, living in Rome (Central-Italy.Pol and V3 sequences were available at the time of diagnosis for all individuals. Maximum-Likelihood and Bayesian phylogenetic-trees with bootstrap and Bayesian-probability supports defined transmission-clusters. HIV-1 drug-resistance and V3-tropism were also evaluated.Among 534 new HIV-1 non-B cases, diagnosed from 2011 to 2014, in Central-Italy, 35 carried virus gathering in two distinct clusters, including 27 HIV-1 C and 8 CRF17_BF subtypes, respectively. Both clusters were centralized in Rome, and their origin was estimated to have been after 2007. All individuals within both clusters were males and 37.1% of them had been recently-infected. While C-cluster was entirely composed by Italian men-who-have-sex-with-men, with a median-age of 34 years (IQR:30-39, individuals in CRF17_BF-cluster were older, with a median-age of 51 years (IQR:48-59 and almost all reported sexual-contacts with men and women. All carried R5-tropic viruses, with evidence of atypical or resistance amino-acidic mutations related to NNRTI-drugs (K103Q in C-cluster, and K101E+E138K in CRF17_BF-cluster.These two epidemiological clusters provided evidence of a strong and recent circulation of C and CRF17_BF strains in central Italy, characterized by NNRTI-related mutations among men engaging in high-risk behaviours. These findings underline the role of molecular epidemiology in identifying groups at increased risk of HIV-1 transmission, and in enhancing additional prevention efforts.

  20. [Nitrogen uptake rate and use efficiency by rice under different levels of the controlled-release N fertilizers (CRF) in the Nansi Lake basin].

    Science.gov (United States)

    Zhang, Qing-Wen; Du, Chun-Xiang; Li, Xiao-Wei; Li, Gui-Chun; Wang, Ming

    2011-07-01

    The nitrogen (N) fertilizers overused or misused are the main contributors for water eutrophication of the Nansi Lake in eastern China. A field experiment with different application levels of controlled-release N fertilizer (CRF) was carried out at a rice field in the Nansi lake basin to provide information on the nitrogen uptake rate and use efficiency by rice with CRF application at different growth stages of rice. The fertilization levels for the controlled fertilizer in this study were 0, 300, 337.5 and 375 kg/hm2, respectively, and 375 kg/hm2 for conventional urea (CU). We estimated the N uptake rate in different growing season and apparent recovery of fertilizer in root, stover and grain of rice. The result showed that grain yield increased by higher N rate. However, the N uptake rate did not increase linearly with the nitrogen application amount. The highest N uptake rate was 22.48 mg/(plant x d) under the fertilization amount of 337.5 kg/hm2 during the young panicle differentiation stage. Apparent N recovery efficiency for CU with traditional application amount of 375 kg/hm2 was 21.86%. Apparent N recovery efficiency for CRF with application amount of 337.5 kg/hm2 was highest with 37.17%. Based on the statistical data, with CU of traditional urea application amount of 375 kg/hm2, nitrogen loss and soil N residue at one growing season are 130.07 x 10(3) t for Jining city and 11.4 x 10(3) t for Yutai county of the Nansi Lake basin. If using CRF with the optimized application amount of 337.5 kg/hm2, nitrogen loss and soil residual at one growing season is 10.46 x 10(4) t for Jining city. It could reduce losses of 2.55 x 10(4) t N for Jining city and 2 235.26 t N for Yutai county per year. Because of releasing patterns more closely matched to crop N uptake patterns, controlled release N fertilizer could be a good way to prevent water eutrophication due to nitrogen fertilizer overused or misused in the Nansi Lake.

  1. Modified Framingham Risk Factor Score for Systemic Lupus Erythematosus.

    Science.gov (United States)

    Urowitz, Murray B; Ibañez, Dominique; Su, Jiandong; Gladman, Dafna D

    2016-05-01

    The traditional Framingham Risk Factor Score (FRS) underestimates the risk for coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE). We aimed to determine whether an adjustment to the FRS would more accurately reflect the higher prevalence of CAD among patients with SLE. Patients with SLE without a previous history of CAD or diabetes followed regularly at the University of Toronto Lupus Clinic were included. A modified FRS (mFRS) was calculated by multiplying the items by 1.5, 2, 3, or 4. In the first part of the study, using one-third of all eligible patients, we evaluated the sensitivity and specificity of the FRS and the different multipliers for the mFRS. In the second part of the study, using the remaining 2/3 of the eligible patients, we compared the predictive ability of the FRS to the mFRS. In the third part of the study, we assessed the prediction for CAD in a time-dependent analysis of the FRS and mFRS. There were 905 women (89.3%) with a total of 95 CAD events included. In part 1, we determined that a multiplier of 2 provided the best combination of sensitivity and specificity. In part 2, 2.4% of the patients were classified as moderate/high risk based on the classic FRS and 17.3% using the 2FRS (the FRS with a multiplier of 2). In part 3, a time-dependent covariate analysis for the prediction of the first CAD event revealed an HR of 3.22 (p = 0.07) for the classic FRS and 4.37 (p mFRS in which each item is multiplied by 2 more accurately predicts CAD in patients with SLE.

  2. Effect of fluoxetine on depression-induced changes in the expression of vasoactive intestinal polypeptide and corticotrophin releasing factor in rat duodenum

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate changes in vasoactive intestinal polypeptide (VIP) and corticotrophinreleasing factor (CRF) in the plasma and duodenum of chronic stressinduced depressed rats and the effects of fluoxetine hydrochloride (fluoxetine) treatment on depressioninduced changes in VIP and CRF.METHODS: A Sprague-Dawley rat model of chronic stress-induced depression was produced. Thirty experimental rats were randomly divided into the following groups: control group, saline-treated depressed group, and fluoxetine-treated depressed group. Openfield testing was performed to assess the rats' behavior.VIP and CRF levels in plasma were measured by ELISA.Immunofluorescence techniques combined with laser scanning confocal microscopy (LSCM) were used to investigate VIP and CRF expression in the duodenum.RESULTS: The open-field behavior, both crossing and rearing, of depression model rats, decreased significantly compared with those of normal control rats over 5 min.Defecation times increased significantly. Compared to the control group, FITC fluorescence of duodenal CRF expression and plasma CRF levels in the depressed rats increased significantly (fluorescence intensity of duodenal CRF: 11.82 ± 2.54 vs 25.17 ± 4.63; plasma CRF: 11.82 ± 2.54 ng/L vs 25.17 ± 4.63 ng/L, P<0.01),whereas duodenal VIP expression and plasma VIP levels decreased significantly (fluorescence intensity of duodenal VIP: 67.37 ± 18.90 vs 44.51 ± 16.37; plasma VIP: 67.37 ± 18.90 ng/L vs 44.51±16.37 ng/L, P < 0.01).Fluoxetine improved depressed behavior, increased VIP expression and decreased CRF expression in plasma and the duodenal tissue of depressed rats.CONCLUSION: Chronic stress can induce injury to the duodenum, accompanied by increasing CRF and decreasing VIP in the plasma and duodenum. Treatment with fluoxetine can ameliorate pathological changes in the duodenum of depressed rats, which suggests that antidepressants are an effective therapeutic agent for some duodenal diseases caused by

  3. 1992—2008年深圳HIV-1CRF01_AE重组株的流行趋势与进化规律%Epidemic trend and evolution of HIV-1 CRF01 _AE strains isolated from 1992 through 2008 in Shenzhen district

    Institute of Scientific and Technical Information of China (English)

    于微; 赵广录; 张娟娟; 陈琳; 冯铁建

    2011-01-01

    目的 了解HIV-1 CRF01_AE重组株在深圳地区的流行情况,并分析其流行趋势及进化规律.方法 收集深圳地区1992-2008年HIV确认阳性血液样本489份,应用巢式聚合酶链反应(Nested-PCR)技术,对样本膜蛋白(Env)基因进行扩增,并对其基因区核苷酸序列进行测定,判定亚型结果.对获得的CRF01_AE重组株核酸序列进行系统进化分析,并计算基因离散率.结果 共有465份样本获得分型结果,其中CRF01 _AE重组株样本300份(占64.5%).1992-1999、2000-2005和2006-2008年3个时间段CRF01_AE重组株所占比例分别为56.8%( 21/37)、68.4%(78/114)和64.0% (201/314);在这3个时间段内,经异性性传播的比例分别为52.4%( 11/21)、43.6%( 34/78)和45.8% (92/201),经同性性传播的比率上升明显,分别为4.8%( 1/21)、0.0%( 0/78)和22.4% (45/201),经吸毒传播的比例分别为19.0% (4/21)、51.3% (40/78)和30.8%(62/210).系统进化分析发现,不同时间段的样本出现明显的时间聚集现象,并伴有传播途径的聚集及交叉感染现象.各时间段CRF01 _AE重组株组内基因离散率分别为(8.783 +4.717)%、(11.054±7.141)%、(13.218±4.080)%,有明显的增大趋势.结论 HIV-1 CRF01_AE重组株是深圳地区的主要流行株,主要经异性性行为、同性恋和吸毒人群传播,随着时间的推移毒株变异程度逐渐增大.%Objective To study the prevalent status of CRF01_AE strains of recombinant HIV-1 in Shenzhen and their source of infection in order to predict the epidemic trend and evolution.Methods A total of 489 samples of HIV-1 positive plasma were collected from 1992 to 2008 in Shenzhen.HIV-1 Env genes were amplified by nested-PCR from RNA.Subtype analysis were performed on the nucleotide sequence data.CRF01 _AE sequences were analyzed by phylogenetic methods and characterized by calculating the genetic distance.Results A total of 300 CRF01_AE strain sequences were amplified,accounting for 64

  4. Power factor control system for ac induction motors

    Science.gov (United States)

    Nola, F. J. (Inventor)

    1981-01-01

    A power control circuit for an induction motor is disclosed in which a servo loop is used to control power input by controlling the power factor of motor operation. The power factor is measured by summing the voltage and current derived square wave signals.

  5. Insulin-like growth factor system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Wilczak, N; de Keyser, J; Cianfarani, S; Clemmons, DR; Savage, MO

    2005-01-01

    Insulin-like growth factor-I (IGF-I) is a neurotrophic factor with insulin-like metabolic activities, and possesses potential clinical applications, particularly in neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is a chronic progressive devastating disorder of the central nervous s

  6. 21 CFR 866.5330 - Factor XIII, A, S, immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Factor XIII, A, S, immuno-logical test system. 866.5330 Section 866.5330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....5330 Factor XIII, A, S, immuno-logical test system. (a) Identification. A factor XIII, A,...

  7. Cardiorespiratory Fitness, Adiposity, and Cardiometabolic Risk Factors in Schoolchildren.

    Science.gov (United States)

    Ramírez-Vélez, Robinson; Daza, Fernando; González-Jiménez, Emilio; Schmidt-RioValle, Jacqueline; González-Ruíz, Katherine; Correa-Bautista, Jorge E

    2016-08-01

    The aim of this study was to investigate the association between cardiorespiratory fitness (CRF) and cardiovascular risk factors (CVRF) in schoolchildren. A secondary aim was to evaluate the degree of association between overall and abdominal adiposity and CRF in a total of 1,875 children and adolescents attending public schools. We expressed CRF performance as the nearest stage (minute) completed and the estimated peak oxygen consumption. A CVRF ( Z score) was calculated and participants were divided into tertiles according to low and high levels of overall (sum of the skinfold thicknesses) and abdominal adiposity. Schoolchildren with a high-level of overall adiposity demonstrated significant differences in seven of the 10 variables analyzed (i.e., systolic and diastolic blood pressure, triglycerides, triglycerides/high density lipoproteins [HDL-c] ratio, total cholesterol, glucose, C-reactive protein [usCRP], HDL-c, low density lipoproteins [LDL-c], and cardiovascular risk score). Schoolchildren with high levels of both overall and abdominal adiposity and low CRF had the least favorable CVRF score.

  8. Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear.

    Science.gov (United States)

    Hurt, R C; Garrett, J C; Keifer, O P; Linares, A; Couling, L; Speth, R C; Ressler, K J; Marvar, P J

    2015-09-01

    Although generally associated with cardiovascular regulation, angiotensin II receptor type 1a (AT1a R) blockade in mouse models and humans has also been associated with enhanced fear extinction and decreased post-traumatic stress disorder (PTSD) symptom severity, respectively. The mechanisms mediating these effects remain unknown, but may involve alterations in the activities of corticotropin-releasing factor (CRF)-expressing cells, which are known to be involved in fear regulation. To test the hypothesis that AT1a R signaling in CRFergic neurons is involved in conditioned fear expression, we generated and characterized a conditional knockout mouse strain with a deletion of the AT1a R gene from its CRF-releasing cells (CRF-AT1a R((-/-)) ). These mice exhibit normal baseline heart rate, blood pressure, anxiety and locomotion, and freeze at normal levels during acquisition of auditory fear conditioning. However, CRF-AT1a R((-/-)) mice exhibit less freezing than wild-type mice during tests of conditioned fear expression-an effect that may be caused by a decrease in the consolidation of fear memory. These results suggest that central AT1a R activity in CRF-expressing cells plays a role in the expression of conditioned fear, and identify CRFergic cells as a population on which AT1 R antagonists may act to modulate fear extinction. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  9. The epidermal growth factor system in Caenorhabditis elegans.

    Science.gov (United States)

    Moghal, Nadeem; Sternberg, Paul W

    2003-03-10

    The single known epidermal growth factor-like growth factor and single epidermal growth factor receptor in Caenorhabditis elegans mediate two types of processes, each via a distinct signal transduction pathway. Several instances of cell fate specification during organogenesis require the RAS-MAP kinase pathway, as well as multiple nuclear factors. By contrast, appropriate myoepithelial contractions during ovulation involve IP3-mediated signal transduction. Positive modulators of the RAS pathway include KSR, SUR-8, phosphatase PP2A, and a zinc cation diffusion facilitator. Negative regulators of the RAS pathway include homologs of CBL, GAP-1, ACK, and MAP kinase phosphatase, while negative regulators of the IP3 pathway are enzymes that modify IP3. In addition to its stimulation of RAS activity, the GRB2 homolog SEM-5 acts negatively on both signaling pathways, as does the Ack-related kinase ARK-1.

  10. Dynamics of competitive systems with a single common limiting factor.

    Science.gov (United States)

    Kon, Ryusuke

    2015-02-01

    The concept of limiting factors (or regulating factors) succeeded in formulating the well-known principle of competitive exclusion. This paper shows that the concept of limiting factors is helpful not only to formulate the competitive exclusion principle, but also to obtain other ecological insights. To this end, by focusing on a specific community structure, we study the dynamics of Kolmogorov equations and show that it is possible to derive an ecologically insightful result only from the information about interactions between species and limiting factors. Furthermore, we find that the derived result is a generalization of the preceding work by Shigesada, Kawasaki, and Teramoto (1984), who examined a certain Lotka-Volterra equation in a different context.

  11. Matrix factorization method for the Hamiltonian structure of integrable systems

    Indian Academy of Sciences (India)

    S Ghosh; B Talukdar; S Chakraborti

    2003-07-01

    We demonstrate that the process of matrix factorization provides a systematic mathematical method to investigate the Hamiltonian structure of non-linear evolution equations characterized by hereditary operators with Nijenhuis property.

  12. Determinant Factors of Morbidity in Patients with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Margarida Jacinto

    2017-05-01

    Discussion and Conclusion: Disease duration and number of American College of Rheumatology criteria predict Systemic Lupus International Collaborating Clinics/ Systemic Damage Index. neuropsychiatric disease has an impact on damage accrual.

  13. Genetic characterization of eight full-length HIV type 1 genomes from the Democratic Republic of Congo (DRC) reveal a new subsubtype, A5, in the A radiation that predominates in the recombinant structure of CRF26_A5U.

    Science.gov (United States)

    Vidal, Nicole; Bazepeo, Samuel Edidi; Mulanga, Claire; Delaporte, Eric; Peeters, Martine

    2009-08-01

    In this study, we characterized HIV-1 strains from the Democratic Republic of Congo (DRC), previously described as divergent subtype A (n = 1, 97CD.KMST91) or untypable (n = 7) in the V3-V5 env region. Four strains had the same structure over the entire genome, including alternating fragments of a new subsubtype, A5, within the subtype A radiation and fragments that remain unclassified. Therefore, the cluster of new viruses represents a new circulating recombinant, CRF26_A5U. Three additional strains were unique recombinants with the newly described CRF26_A5U and subtype C. Finally, the nearly full-length sequence of 97CD.KMST91 showed that this strain also consisted of alternating fragments of a divergent subtype A lineage and unclassified fragments, although different from previously reported A and U sequences. The high genetic distances among the different CRF26-A5U strains suggest their longstanding presence in the DRC.

  14. [Determinant Factors of Morbidity in Patients with Systemic Lupus Erythematosus].

    Science.gov (United States)

    Jacinto, Margarida; Silva, Eliana; Riso, Nuno; Moraes-Fontes, Maria Francisca

    2017-05-31

    Severity in systemic lupus erythematosus may vary from mild to even fatal consequences. There are no biomarkers to predict the disease's prognosis. The Systemic Lupus International Collaborating Clinics/ Systemic Damage Index defines systemic lupus erythematosus disease severity and is found to predict prognosis. To test damage determinants in a single-centre systemic lupus erythematosus cohort. Retrospectively followed systemic lupus erythematosus female patients (defined by the identification of at least four systemic lupus erythematosus American College of Rheumatology criteria - fulfillment 100%, n = 76) over the past five years. Age of onset, ethnicity, disease duration, number of American College of Rheumatology criteria at the end of follow-up, cumulative: renal, neuropsychiatric and articular phenotypes, hypertension, dyslipidaemia, smoking and Systemic Lupus Erythematosus Disease Activity Index 2K were correlated to the presence and degree of irreversible damage (Systemic Lupus International Collaborating Clinics Damage Index). Accumulation of American College of Rheumatology criteria was measured in a sub-group of patients followed from disease onset (within a year of the first symptom ascribed to systemic lupus erythematosus) (n = 39 - 51%); Systemic Lupus Erythematosus Disease Activity Index and Systemic Lupus International Collaborating Clinics Damage Index were performed. Statistical analysis was performed using Chi-square, Wilcoxon Mann-Whitney tests and Spearman correlation rho (Sig. 2-tailed p Systemic Lupus International Collaborating Clinics/Systemic Damage Index > 0 was present in 56.6% and significantly associated to a longer duration, a higher number of American College of Rheumatology criteria and a neuropsychiatric phenotype when compared with those with no damage. The final number of American College of Rheumatology criteria accrued was positively correlated to a higher disease activity over the past five years of follow-up (Spearman´s rho

  15. Contextual Factors Impacting Battered Women's Intentions to Reuse the Criminal Legal System

    Science.gov (United States)

    Fleury-Steiner, Ruth E.; Bybee, Deborah; Sullivan, Cris M.; Belknap, Joanne; Melton, Heather C.

    2006-01-01

    While a small number of past studies have examined either situational, relational, or systems-level factors that influence battered women's use of either the police, prosecutorial, or court systems, no study to date has examined how these factors each influence women's intentions to reuse these systems. To address this gap, in-person interviews…

  16. HFE (Human Factors Engineering) Technology for Navy Weapon System Acquisition.

    Science.gov (United States)

    1979-07-01

    uncovering of improved propulsion systems, sensors , weapons, etc., by industry or governr-ient agencies, may in.tiate the development of a new weapon system...needs. (No. A-109) _L a f. Tailor an acquisition stratagy for each program, as soon as the agency decides to solict alternative system design concepto

  17. Favorable therapeutic response with an antiretroviral salvage regimen in an HIV-1-positive subject infected with a CRF11-cpx virus.

    Science.gov (United States)

    Tau, Pamela; Mancon, Alessandro; Mileto, Davide; Di Nardo Stuppino, Silvia; Bottani, Giulia; Gismondo, Maria Rita; Galli, Massimo; Micheli, Valeria; Rusconi, Stefano

    2014-05-01

    HIV drug resistance still represents a crucial problem in antiretroviral therapy. We report a case of a naive patient, harboring a CRF11-cpx virus, which showed drug resistance mutations in the reverse transcriptase. A drug resistance genotyping test was performed for the pol (protease, reverse transcriptase, and integrase) and V3 regions. The initial clinical parameter results showed a 4 log level of HIV-RNA (12,090 cp/ml) and a very low CD4(+) cell count (35 cells/μl). We designed an initial highly active antiretroviral therapy (HAART) regimen including lamivudine (3TC)+abacavir (ABC)+booster ritonavir (DRV/r). The virus was highly resistant to all nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) except for ABC, tenofovir (TDF), and efavirenz (EFV) and was susceptible to all protease inhibitors (PIs) and integrase inhibitors (INIs). A salvage regimen including raltegravir (RAL)+DRV/r was started. Ten months later, the immunovirological status shows CD4(+) 142/μl and HIV-RNA <37 cp/ml. Our results demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r in a patient infected with a complex X4-tropic CRF11-cpx virus.

  18. Cardiovascular risk factors in cognitively impaired nursing home patients: A relationship with pain?

    NARCIS (Netherlands)

    Achterberg, W.P.; Scherder, E.J.A.; Pot, A.M.; Ribbe, M.W.

    2007-01-01

    Cardiovascular risk factors (CRF) such as hypertension and diabetes mellitus favour the development of both vascular dementia (VaD) and Alzheimer’s disease (AD). The resulting deafferentation may increase the experience of pain in VaD and in AD. The goal of the present study was to examine the relat

  19. Treatment with a corticotrophin releasing factor 2 receptor agonist modulates skeletal muscle mass and force production in aged and chronically ill animals

    Directory of Open Access Journals (Sweden)

    Ferreira Leonardo F

    2011-01-01

    Full Text Available Abstract Background Muscle weakness is associated with a variety of chronic disorders such as emphysema (EMP and congestive heart failure (CHF as well as aging. Therapies to treat muscle weakness associated with chronic disease or aging are lacking. Corticotrophin releasing factor 2 receptor (CRF2R agonists have been shown to maintain skeletal muscle mass and force production in a variety of acute conditions that lead to skeletal muscle wasting. Hypothesis We hypothesize that treating animals with a CRF2R agonist will maintain skeletal muscle mass and force production in animals with chronic disease and in aged animals. Methods We utilized animal models of aging, CHF and EMP to evaluate the potential of CRF2R agonist treatment to maintain skeletal muscle mass and force production in aged animals and animals with CHF and EMP. Results In aged rats, we demonstrate that treatment with a CRF2R agonist for up to 3 months results in greater extensor digitorum longus (EDL force production, EDL mass, soleus mass and soleus force production compared to age matched untreated animals. In the hamster EMP model, we demonstrate that treatment with a CRF2R agonist for up to 5 months results in greater EDL force production in EMP hamsters when compared to vehicle treated EMP hamsters and greater EDL mass and force in normal hamsters when compared to vehicle treated normal hamsters. In the rat CHF model, we demonstrate that treatment with a CRF2R agonist for up to 3 months results in greater EDL and soleus muscle mass and force production in CHF rats and normal rats when compared to the corresponding vehicle treated animals. Conclusions These data demonstrate that the underlying physiological conditions associated with chronic diseases such as CHF and emphysema in addition to aging do not reduce the potential of CRF2R agonists to maintain skeletal muscle mass and force production.

  20. Novel oscillator model with damping factor for plasmon induced transparency in waveguide systems.

    Science.gov (United States)

    Zhao, Mingzhuo; Li, Hongjian; He, Zhihui; Chen, Zhiquan; Xu, Hui; Zheng, Mingfei

    2017-09-06

    We introduce a novel two-oscillator model with damping factor to describe the plasmon induced transparency (PIT) in a bright-dark model plasmonic waveguide system. The damping factor γ in the model can be calculated from metal conductor damping factor γ c and dielectric damping factor γ d . We investigate the influence of geometry parameters and damping factor γ on transmission spectra as well as slow-light effects in the plasmonic waveguide system. We can find an obvious PIT phenomenon and realize a considerable slow-light effect in the double-cavities system. This work may provide guidance for optical switching and plasmon-based information processing.

  1. Over-expression of corticotropin-releasing factor mRNA in inferior olivary neurons of rolling mouse Nagoya.

    Science.gov (United States)

    Sawada, Kazuhiko; Kawano, Michihiro; Tsuji, Hiroshi; Sakata-Haga, Hiromi; Hisano, Setsuji; Fukui, Yoshihiro

    2003-10-01

    Expression of corticotropin-releasing factor (CRF) mRNA was examined in the inferior olivary nucleus (ION) of an ataxic mutant, rolling mouse Nagoya (RMN) by semi-quantitative in situ hybridization. The most marked difference in the level of CRF mRNA signals between RMN and non-ataxic littermates (control mice) was observed in the beta-subnucleus and ventrolateral protrusion of the ION. The level of signals in these subnuclei was about twofold higher in RMN than in the controls. Signal levels in the dorsal nucleus, principal nucleus and subnucleus A were slightly but significantly higher in RMN than in the controls. In the other subnuclei, there were no differences in signal level between RMN and controls. These results suggest a region-related over-expression of CRF mRNA in the ION of RMN. This may be responsible for the increased sensitivity of some Purkinje cells to glutamate, resulting in ataxic symptoms of RMN.

  2. Three-year changes in fitness and adiposity are independently associated with cardiovascular risk factors among young danish children

    DEFF Research Database (Denmark)

    Jago, Russell; Froberg, Karsten; Cooper, Ashley R

    2010-01-01

    , sum of skinfolds (SSF), and blood pressure were assessed. Fasting blood samples were used to calculate total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C & LDL-C), triglycerides, insulin, glucose, and HOMA-IR. Regression models examined whether CRF change or SSF change were...... independently or interactively associated with risk variables. RESULTS: Change in SSF was independently associated with change in TC (z = 4.83, P blood pressure. CRF change was independently associated...... with change in TC (z = -3.86, P blood pressure (z = 2.06, P = .040). CONCLUSIONS: Change in fitness and adiposity were independently associated with the development of cardiovascular risk factors among young children suggesting a need to increase CRF...

  3. Extracellular matrix-inspired growth factor delivery systems for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Martino, Mikaël M. [Osaka Univ. (Japan). Immunology Frontier Research Center; Briquez, Priscilla S. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Maruyama, Kenta [Osaka Univ. (Japan). Immunology Frontier Research Center; Hubbell, Jeffrey A. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Univ. of Chicago, IL (United States). Inst. for Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-04-17

    Growth factors are very promising molecules to enhance bone regeneration. However, their translation to clinical use has been seriously limited, facing issues related to safety and cost-effectiveness. These problems derive from the vastly supra-physiological doses of growth factor used without optimized delivery systems. Therefore, these issues have motivated the development of new delivery systems allowing better control of the spatio-temporal release and signaling of growth factors. Because the extracellular matrix (ECM) naturally plays a fundamental role in coordinating growth factor activity in vivo, a number of novel delivery systems have been inspired by the growth factor regulatory function of the ECM. After introducing the role of growth factors during the bone regeneration process, this review exposes different issues that growth factor-based therapies have encountered in the clinic and highlights recent delivery approaches based on the natural interaction between growth factor and the ECM.

  4. Factors affecting goat production in a communal farming system in ...

    African Journals Online (AJOL)

    Unknown

    The mean flock size was 16 head, of which 76.7% consisted of does, 15.8% castrates .... The migration of younger people to urban areas might also be a factor ... ranking are expressed as a percentage of the total for all rankings within that ...

  5. A novel latent factor model for recommender system

    National Research Council Canada - National Science Library

    Kumar, Bipul

    2016-01-01

    ... a latent factor model that caters to both accuracy and efficiency by reducing the number of latent features of either users or items making it less complex than Funk-SVD, where latent features of both users and items are equal and often larger. A comprehensive empirical evaluation of accuracy on two publicly available, amazon and ml-100 k datasets rev...

  6. Is it really a matter of simple dualism? Corticotropin-releasing factor receptors in body and mental health

    Directory of Open Access Journals (Sweden)

    Donny eJanssen

    2013-03-01

    Full Text Available Physiological responses to stress coordinated by the hypothalamo-pituitary-adrenal (HPA- axis are concerned with maintaining homeostasis in the presence of real or perceived challenges. Regulators of this axis are corticotrophin releasing hormone (CRF and CRF related neuropeptides, including urocortins (Ucn 1, 2 and 3. They mediate their actions by binding to CRF receptors (CRFR 1 and 2, which are located in several stress related brain regions. The prevailing theory has been that the initiation of and the recovery from an elicited stress response is coordinated by two elements, viz. the (mainly opposing, but well balanced actions of CRFR1 and CRFR2. Such a dualistic view suggests that CRF/CRFR1 controls the initiation of, and urocortins/CRFR2 mediate the recovery from stress to maintain body and mental health. Consequently, failed adaptation to stress can lead to neuropathology, including anxiety and depression. Recent literature, however, challenges such dualistic and complementary actions of CRFR1 and CRFR2, and suggests that stress recruits CRF system components in a brain area and neuron specific manner to promote adaptation as conditions dictate.

  7. Synthesis and evaluation of carbamate and aryl ether substituted pyrazinones as corticotropin releasing factor-1 (CRF₁) receptor antagonists.

    Science.gov (United States)

    Ahuja, Vijay T; Hartz, Richard A; Molski, Thaddeus F; Mattson, Gail K; Lentz, Kimberley A; Grace, James E; Lodge, Nicholas J; Bronson, Joanne J; Macor, John E

    2016-05-01

    A series of pyrazinone-based compounds incorporating either carbamate or aryl ether groups was synthesized and evaluated as corticotropin-releasing factor-1 (CRF1) receptor antagonists. Structure-activity relationship studies led to the identification of highly potent CRF1 receptor antagonists 14a (IC50=0.74 nM) and 14b (IC50=1.9 nM). The synthesis, structure-activity relationships and in vitro metabolic stability properties of compounds in this series will be described. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Determination of OB/OD/SF Emission Factors using Unmanned Aerial Systems

    Science.gov (United States)

    Instrumented, unmanned aerial systems (UASs) have been used successfully in eight campaigns since 2010 to determine emission factors from open burning (OB), open detonation (OD), and static firing (SF) demilitarization activities. These systems have sampled directly from the plu...

  9. New factors influencing G protein coupled receptors’ system ...

    African Journals Online (AJOL)

    Abdelaziz Ghanemi

    2012-11-24

    Nov 24, 2012 ... system functions. Abdelaziz .... systems. Such factors will be added to those already known including ..... crossroad between cell biology and physics. Nat Cell ... classification of receptors for 5-hydroxytryptamine (Serotonin).

  10. Behavioral Risk Factor Surveillance System (BRFSS) Historical Questions

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1984-2014. Centers for Disease Control and Prevention (CDC). BRFSS Survey Data. The BRFSS is a continuous, state-based surveillance system that collects information...

  11. Human Factors Engineering and Ergonomics in Systems Engineering

    Science.gov (United States)

    Whitmore, Mihriban

    2017-01-01

    The study, discovery, and application of information about human abilities, human limitations, and other human characteristics to the design of tools, devices, machines, systems, job tasks and environments for effective human performance.

  12. High Quality Factor Resonators for Inductive Power Transfer Systems

    Science.gov (United States)

    Etemadrezaei, Mohammad

    In this dissertation, the Inductive Power Transfer (IPT) systems for multi-MHz frequency of operation are investigated, and new ideas for magnetic link inductive coils are presented. (Abstract shortened by ProQuest.).

  13. Behavioral Risk Factor Surveillance System (BRFSS) Historical Questions

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1984-2016. Centers for Disease Control and Prevention (CDC). BRFSS Survey Data. The BRFSS is a continuous, state-based surveillance system that collects information...

  14. Studying the factors affecting solar power generation systems performance ( SPGSP)

    OpenAIRE

    Jalal A Al-Tabtabaei

    2014-01-01

    Solar energy is a huge, clean and renewable source of energy. It is also available everywhere on the earth. However, there are many technical and economic difficulties need to be solved so that solar energy becomes a strong competition against the traditional energy sources. Energy from the sun can be used successfully in electric power generation systems. Depending on the climate conditions and the use of a properly designed, installing and maintained system can meet a large dema...

  15. Human performance modeling for system of systems analytics: combat performance-shaping factors.

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, Craig R.; Miller, Dwight Peter

    2006-01-01

    The US military has identified Human Performance Modeling (HPM) as a significant requirement and challenge of future systems modeling and analysis initiatives. To support this goal, Sandia National Laboratories (SNL) has undertaken a program of HPM as an integral augmentation to its system-of-system (SoS) analytics capabilities. The previous effort, reported in SAND2005-6569, evaluated the effects of soldier cognitive fatigue on SoS performance. The current effort began with a very broad survey of any performance-shaping factors (PSFs) that also might affect soldiers performance in combat situations. The work included consideration of three different approaches to cognition modeling and how appropriate they would be for application to SoS analytics. This bulk of this report categorizes 47 PSFs into three groups (internal, external, and task-related) and provides brief descriptions of how each affects combat performance, according to the literature. The PSFs were then assembled into a matrix with 22 representative military tasks and assigned one of four levels of estimated negative impact on task performance, based on the literature. Blank versions of the matrix were then sent to two ex-military subject-matter experts to be filled out based on their personal experiences. Data analysis was performed to identify the consensus most influential PSFs. Results indicate that combat-related injury, cognitive fatigue, inadequate training, physical fatigue, thirst, stress, poor perceptual processing, and presence of chemical agents are among the PSFs with the most negative impact on combat performance.

  16. Factors affecting the environmental carrying capacity of a freshwater tropical lake system.

    Science.gov (United States)

    Mullakkezhil Reghunathan, Vishnuprasad; Joseph, Sabu; Warrier, C Unnikrishnan; Hameed, A Shahul; Albert Moses, Sheela

    2016-11-01

    Environmental carrying capacity is a measure of competence of a lake to accommodate pollution inputs without degrading water quality. In the research reported here, we identified the factors influencing the environmental carrying capacity of Vellayani Lake or VL (a typical tropical freshwater lake), Thiruvananthapuram, Kerala State, India. R-mode factor analysis is used to identify the factors controlling the carrying capacity of the lake, whereas hierarchical cluster analysis (HCA) helped to classify the lake. The carrying capacity of the lake is low with respect to alkalinity, due to ion deficiency, and is potentially reactive to sudden changes in pH. Eutrophic condition exists in the entire lake system. Acidic factor, mineralization factor, fertilizer factor (P & K), evaporation factor and organic pollution factor are the controllers of VL water quality during the pre-monsoon period. The same factors (but not evaporation factor) and an additional runoff factor control the water quality during monsoon. In the post-monsoon, the aforesaid factors (other than runoff, alkalinity) and soil erosion factor influence the water quality. Hence, managers of the lake system need to also focus on combating acidic factor during pre- and post-monsoons and runoff during monsoon. Smaller areal extent and shallow depth of VL, reduced outflow from it, less rainfall, presence of lateritic rock and soil and absence of limestone strata in the catchment are the chief elements affecting the acidic factor of Vellayani Lake.

  17. Factor B structure provides insights into activation of the central protease of the complement system

    NARCIS (Netherlands)

    Milder, F.J.; Gomes, L.; Schouten, A.; Janssen, B.J.C.; Huizinga, E.G.; Romijn, R.A.; Hemrika, W.; Roos, A; Daha, M.R.; Gros, P.

    2007-01-01

    Factor B is the central protease of the complement system of immune defense. Here, we present the crystal structure of human factor B at 2.3-A° resolution, which reveals how the five-domain proenzyme is kept securely inactive. The canonical activation helix of the Von Willebrand factor A (VWA) domai

  18. Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC

    Directory of Open Access Journals (Sweden)

    Yu Xu G

    2007-08-01

    Full Text Available Abstract Background The characterization of HIV-1-specific T cell responses in people infected with locally circulating HIV-1 strain will facilitate the development of HIV-1 vaccine. Sixty intravenous drug users infected with HIV-1 circulating recombinant form 07_BC (CRF07_BC, which has been spreading rapidly in western China from north to south, were recruited from Xinjiang, China to assess the HIV-1-specific T cell responses at single peptide level with overlapping peptides (OLP covering the whole concensus clades B and C proteome. Results The median of the total magnitude and total number of OLPs recognized by CTL responses were 10925 SFC/million PBMC and 25 OLPs, respectively, when tested by clade C peptides, which was significantly higher than when tested by clade B peptides. The immunodominant regions, which cover 14% (58/413 of the HIV-1 proteome, are widely distributed throughout the HIV-1 proteome except in Tat, Vpu and Pol-PR, with Gag, Pol-RT, Pol-Int and Nef being most frequently targeted. The subdominant epitopes are mostly located in p24, Nef, integrase, Vpr and Vif. Of the responses directed to clade C OLPs, 61.75% (972/1574 can be observed when tested with corresponding clade B OLPs. However, Pol-PR and Vpu tend to be targeted in the clade B sequence rather than the clade C sequence, which is in line with the recombinant pattern of CRF07_BC. Stronger and broader CTL responses in subjects with CD4 cell counts ranging from 200 to 400/mm3 were observed when compared to those with less than 200/mm3 or more than 400/mm3, though there have been no significant correlations identified between the accumulative CTL responses or overall breadth and CD4 cell count or plasma viral load. Conclusion This is the first study conducted to comprehensively address T cell responses in Chinese subjects infected with HIV-1 CRF07_BC in which subtle differences in cross-reactivity were observed, though similar patterns of overall immune responses were

  19. Evaluating immunologic response and clinical deterioration in treatment-naïve patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

    Science.gov (United States)

    Oyomopito, Rebecca A.; Li, Patrick CK.; Sungkanuparph, Somnuek; Phanuphak, Praphan; Tee, Kok Keng; Sirisanthana, Thira; Kantipong, Pacharee; Oka, Shinichi; Lee, Chris KC.; Kamarulzaman, Adeeba; Choi, Jun Yong; Sohn, Annette H.; Law, Matthew; Chen, Yi-Ming A.

    2012-01-01

    Background HIV-1 group M viruses diverge 25%–35% in envelope, important for viral attachment during infection, and 10–15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunologic or virologic treatment responses differed by genotype in treatment-naïve patients initiating first-line therapy. Methods Prospectively collected, longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of CDC category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post-therapy, evaluated by linear and logistic regression, respectively. Results Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median:413 days, IQR:169–672 days). Patients >40 years demonstrated smaller immunological increases (p=0.002) and higher risk of clinical deterioration (HR=2.17; p=0.008). Patients with baseline CD4 cell counts >200 cells/μL had lower risk of clinical deterioration (HR=0.373; p=0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post-therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (p=0.024). A total of 530 patients (48.0% of eligible) were included in virologic analyses with no differences in response found between genotypes. Conclusions Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared to

  20. Analysis of Factors Affecting Testing in Object oriented systems

    Directory of Open Access Journals (Sweden)

    Mrs. Sujata Khatri,

    2011-03-01

    Full Text Available Software testing is an important software quality assurance activity to ensure that the benefits of Object oriented programming will be realized. Testing object oriented systems is little bit challenging ascomplexity shifted from functions and procedures as in traditional procedural systems to the interconnections among its components. Object oriented development has presented a numerous variety of new challenges due to its features like encapsulation, inheritance, polymorphism and dynamic binding. Earlier the faults used to bein the software units, whereas the problem now is primarily in the way in which we connect the software. Development is writing the code, testing is finding out whether or not the code runs the way you expect it to. A major challenge to the software developers remains how to reduce the cost while improving the quality of software testing. Software testing is difficult and expensive, and testing object oriented system is even more difficult. A tester often needs to spend significant time in developing lengthy testing code to ensure that system under test is reasonably well tested. Substantial research has been carried out in object oriented analysis, design.However relatively less attention has been paid to testing of object oriented programs. This paper describes the various features of object oriented programming and how they effect testing of object oriented systems.

  1. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rheumatoid factor immuno-logical test system. 866.5775 Section 866.5775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid...

  2. Steroid-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF, and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system

    Directory of Open Access Journals (Sweden)

    Aloe Luigi

    2003-04-01

    Full Text Available Abstract Previous studies on the effect of repeated electro-acupuncture (EA treatments in rats with steriod-induced polycystic ovaries (PCO, EA has been shown to modulate nerve growth factor (NGF concentration in the ovaries as well as corticotropin releasing factor (CRF in the median eminence (ME. In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1, a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p p p p

  3. Control of the renal renin system by local factors

    DEFF Research Database (Denmark)

    Wagner, C; Jensen, B L; Krämer, B K

    1998-01-01

    prostanoid, both stimulate renin secretion and renin gene expression by activating cAMP formation in JG cells. Although the direct effect of NO on JG cells is less clear, its overall effect in vivo seems to be to stimulate the renin system. Evidence is emerging that stimulation by NO is related to the c......AMP pathway, and cGMP-induced inhibition of cAMP-phosphodiesterase III (PDE-III) may mediate this effect. ETs, on the other hand, appear to inhibit the renin system, in particular in those pathways activated by cAMP, acting via Ca2+- and protein kinase C-related mechanisms. There is increasing evidence...... that both NO and PGs could be involved in the physiological regulatory mechanisms by which salt intake affects the renin system....

  4. Urine macrophage migration inhibitory factor in pediatric systemic lupus erythematosus.

    Science.gov (United States)

    Otukesh, Hasan; Chalian, Majid; Hoseini, Rozita; Chalian, Hamid; Hooman, Nakysa; Bedayat, Arash; Yazdi, Reza Salman; Sabaghi, Saeed; Mahdavi, Saeed

    2007-12-01

    We reported a series of ten patients with lupus nephritis (five patients in the relapse phase and five in the remission phase) and measured the macrophage migration inhibitory factor (MIF), an important pro-inflammatory cytokine with probable role in the pathogenesis of many inflammatory diseases, in their urine samples. MIF/creatinine (Cr) ratio directly correlated with disease activity and it does not have any significant difference between inactive disease and normal ones. We found that the urine MIF/Cr ratio not only differentiates active disease from inactive disease and normal ones but also correlates with the activity indices of renal pathology.

  5. Factors that influence the acceptance of integrated community energy systems

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, A. S.; Tschanz, J. F.; Mosena, D.; Erley, D.; Gil, E.; Slovak, P.; Lenth, C. S.

    1977-01-01

    This report is part of a series of studies designed to analyze the commercialization potential of various concepts of community-scale energy systems that have been termed Integrated Community Energy Systems (ICES). The study reported here concerns ways that affected individuals and organizations will respond to proposed ICES development projects. The intent is an initial examination of several institutional sectors that will: (1) anticipate responses that could impede ICES proposals and (2) provide an information base from which strategies to address adverse responses can be formulated.

  6. What Factors Affect the Prices of Low-Priced U.S. Solar PV Systems?

    Energy Technology Data Exchange (ETDEWEB)

    Nemet, Gregory F.; O' Shaughnessy, Eric; Wiser, Ryan; Darghouth, Naïm R.; Barbose, Galen; Gillingham, Ken; Rai, Varun

    2017-09-06

    The price of solar PV systems has declined rapidly, yet there are some much lower-priced systems than others. This study explores the factors leading some systems to be so much lower priced than others. Using a data set of 42,611 residential-scale PV systems installed in the U.S. in 2013, we use quantile regressions to estimate the importance of factors affecting the installed prices for low-priced (LP) systems (those at the 10th percentile) in comparison to median-priced systems. We find that the value of solar to consumers–a variable that accounts for subsidies, electric rates, and PV generation levels–is associated with lower prices for LP systems but higher prices for median priced systems. Conversely, systems installed in new home construction are associated with lower prices at the median but higher prices for LP. Other variables have larger cost-reducing effects on LP than on median priced systems: systems installed in Arizona and Florida, as well as commercial and thin film systems. In contrast, the following have a smaller effect on prices for LP systems than median priced systems: tracking systems, self-installations, systems installed in Massachusetts, the system size, and installer experience. These results highlight the complex factors at play that lead to LP systems and shed light into how such LP systems can come about.

  7. What Factors Affect the Prices of Low-Priced U.S. Solar PV Systems?

    Energy Technology Data Exchange (ETDEWEB)

    OShaughnessy, Eric J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Nemet, Greg [University of Wisconsin-Madison; Wiser, Ryan [Lawrence Berkeley National Laboratory; Darghouth, Naim [Lawrence Berkeley National Laboratory; Barbose, Galen [Lawrence Berkeley National Laboratory; Gillingham, Ken [Lawrence Berkeley National Laboratory; Rai, Varun [Lawrence Berkeley National Laboratory

    2017-08-09

    The price of solar PV systems has declined rapidly, yet there are some much lower-priced systems than others. This study explores the factors that determine prices in these low-priced (LP) systems. Using a data set of 42,611 residential-scale PV systems installed in the U.S. in 2013, we use quantile regressions to estimate the importance of factors affecting the installed prices for LP systems (those at the 10th percentile) in comparison to median-priced systems. We find that the value of solar to consumers-a variable that accounts for subsidies, electric rates, and PV generation levels-is associated with lower prices for LP systems but higher prices for median priced systems. Conversely, systems installed in new home construction are associated with lower prices at the median but higher prices for LP. Other variables have larger price-reducing effects on LP than on median priced systems: systems installed in Arizona and Florida, as well as commercial and thin film systems. In contrast, the following have a smaller effect on prices for LP systems than median priced systems: tracking systems, self-installations, systems installed in Massachusetts, the system size, and installer experience. These results highlight the complex factors at play that lead to LP systems and shed light into how such LP systems can come about.

  8. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    Directory of Open Access Journals (Sweden)

    Karim MAMDOUH ABBAS

    2014-04-01

    Full Text Available The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC in Egyptian manufacturing firms.

  9. SISTEMA ENDOCANABINOIDE: MODIFICANDO LOS FACTORES DE RIESGO CARDIOVASCULAR Endocannabinoid system: modifying cardiovascular risk factors

    OpenAIRE

    John Edwin Feliciano Alfonso; Carlos Olimpo Mendivil Anaya; Iván Darío Sierra Ariza

    2006-01-01

    La necesidad de alcanzar un tratamiento óptimo para el tabaquismo, la obesidad y sus comorbilidades, conocidos factores de riesgo cardiovascular, ha fomentado la búsqueda de objetivos terapéuticos novedosos. Es el caso del sistema endocanabinoide, involucrado en diversos fenómenos fisiológicos entre los que se encuentran el refuerzo de ciertos comportamientos y la regulación del apetito. La sobreactivación de este sistema altera la homeostasis corporal predisponiendo a dependencias o a un aum...

  10. The insulin-like growth factor system in multiple sclerosis

    NARCIS (Netherlands)

    Chesik, Daniel; Wilczak, Nadine; De Keyser, Jacques

    2007-01-01

    Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by inflammation, demyelination, and axonal degeneration. Present therapeutic strategies for MS reduce inflammation and its destructive consequences, but are not effective in the progressive phase of the disease

  11. Increased systemic inflammation is a risk factor for COPD exacerbations

    NARCIS (Netherlands)

    K.H. Groenewegen (Karin); D.S. Postma (Dirkje); W.C.J. Hop (Wim); P.L.M.L. Wielders (Pascal); N.J.J. Schlösser (Noel); E.F.M. Wouters (Emiel)

    2008-01-01

    textabstractBackground: COPD is characterized by episodic increases in respiratory symptoms, so-called exacerbations. COPD exacerbations are associated with an increase in local and systemic inflammation. Data of a previously published study in a well-characterized COPD cohort were analyzed to defin

  12. Increased systemic inflammation is a risk factor for COPD exacerbations

    NARCIS (Netherlands)

    Groenewegen, Karin H.; Postma, Dirkje S.; Hop, Wim C. J.; Wielders, Pascal L. M. L.; Schlosser, Noel J. J.; Wouters, Entiel F. M.

    2008-01-01

    Background: COPD is characterized by episodic increases in respiratory symptoms, so-called exacerbations. COPD exacerbations are associated with an increase in local and systemic inflammation. Data of a previously published study in a well-characterized COPD cohort were analyzed to define predictive

  13. Factors Affecting Bacterial Growth in Drinking Water Distribution System

    Institute of Scientific and Technical Information of China (English)

    WEI LU; XIAO-JIAN ZHANG

    2005-01-01

    Objective To define the influence of some parameters, including assimilable organic carbon (AOC), chloramine residual, etc. on the bacterial growth in drinking water distribution systems. Methods Three typical water treatment plants in a northern city (City T) of China and their corresponding distribution systems were investigated. Some parameters of the water samples, such as heterotrophic plate content (HPC), AOC, CODMn, TOC, and phosphate were measured. Results The AOC in most water samples were more than 100 μg/L, or even more than 200 μg/L in some cases. The HPC in distribution systems increased significantly with the decrease of residual chlorine. When the residual chlorine was less than 0.1 mg/L, the magnitude order of HPC was 104 CFU/mL; when it was 0.5-0.7 mg/L, the HPC was about 500 CFU/mL. Conclusion For controlling the biostability of drinking water, the controlling of AOC and residual chlorine should be considered simultaneously. The influence of phosphors on the AOC tests of water is not significant. Phosphors may not be the limiting nutrient in the water distribution systems.

  14. Designing safe road systems : A Human Factors perspective

    NARCIS (Netherlands)

    Theeuwes, J.; Horst, A.R.A. van der; Kuiken, M.

    2012-01-01

    Many books focus on individual differences and how those relate to traffic safety, such as accident proneness, gender differences, age, alcohol, and the effects of drugs. Others focus on the safety effects regarding the vehicle, such as airbags, anti-lock brakes, navigation systems, intelligent crui

  15. Regional difference in corticotropin-releasing factor immunoreactivity in mossy fiber terminals innervating calretinin-immunoreactive unipolar brush cells in vestibulocerebellum of rolling mouse Nagoya.

    Science.gov (United States)

    Ando, Masahiro; Sawada, Kazuhiko; Sakata-Haga, Hiromi; Jeong, Young-Gil; Takeda, Noriaki; Fukui, Yoshihiro

    2005-11-23

    Unipolar brush cells (UBCs), a class of interneurons in the vestibulocerebellum, play roles in amplifying excitatory inputs from vestibulocerebellar mossy fibers. This study aimed to clarify whether corticotropin-releasing factor (CRF)-positive mossy fiber innervation of calretinin (CR)-positive UBCs was altered in rolling mouse Nagoya (RMN). The distribution and the number of CR-positive UBCs in the vestibulocerebellum were not different between RMN and control mice. Double immunofluorescence revealed that some CRF-positive mossy fiber terminals were in close apposition to CR-positive UBCs. In the lobule X of vermis, such mossy fiber terminals were about 5-fold greater in number in RMN than in controls. In contrast, the number of CRF-positive mossy fiber terminals adjoining CR-positive UBCs in the flocculus was not significantly different between RMN and controls. The results suggest increased number of CRF-positive mossy fiber terminals innervating CR-positive UBCs in the lobule X but not in the flocculus of RMN. CRF may alter CR-positive UBC-mediated excitatory pathways in the lobule X of RMN and may disturb functions of the lobule X such as cerebellar adaptation for linear motion of the head.

  16. Somatosensory regulation of serotonin release in the central nucleus of the amygdala is mediated via corticotropin releasing factor and gamma-aminobutyric acid in the dorsal raphe nucleus.

    Science.gov (United States)

    Tokunaga, Ryota; Shimoju, Rie; Shibata, Hideshi; Kurosawa, Mieko

    2016-10-15

    Noxious cutaneous stimulation increases, whereas innocuous cutaneous stimulation decreases serotonin (5-HT) release in the central nucleus of the amygdala (CeA) in anesthetized rats. In the present study, we investigated the contribution of corticotropin releasing factor (CRF) receptors and gamma-aminobutyric acid (GABA) receptors in the dorsal raphe nucleus (DRN) to those responses. Release of 5-HT in the CeA was monitored by microdialysis before and after 10-min stimulation by pinching or stroking. Increased 5-HT release in the CeA in response to pinching was abolished by CRF2 receptor antagonism in the DRN. Decreased 5-HT release in the CeA in response to stroking was abolished by either CRF1 receptor antagonism or GABAA receptor antagonism in the DRN. These results suggest that opposite responses of 5-HT release in the CeA to noxious versus innocuous stimulation of the skin are due to separate contributions of CRF2, CRF1 and GABAA receptors in the DRN.

  17. Nephrogenic systemic fibrosis: risk factors suggested from Japanese published cases

    DEFF Research Database (Denmark)

    Tsushima, Y; Kanal, E; Thomsen, H S

    2010-01-01

    The aim of this article is to review the published cases of nephrogenic systemic fibrosis (NSF) in Japan. The Japanese medical literature database and MedLine were searched using the keywords NSF and nephrogenic fibrosing dermopathy (January 2000 to March 2009). Reports in peer-reviewed journals...... of knowledge about the possible association between GBCA and NSF. NSF is found among Japanese end-stage renal failure patients even after examinations using a single dose....

  18. Knowledge as a Contingency Factor: Achieving Coordination in Interorganizational Systems

    Science.gov (United States)

    2010-09-01

    within the firm, but from the environment as well—especially from other organizations. This makes knowledge research paradigms an apropos lens through...making methods seemed appropriate depending on environmental conditions (e.g., uncertainty). By the early 1960s, a contingency theory paradigm began...coordination among an interorganizational system in a disaster environment. Grounded in an objective, positivistic perspective, the qualitative phase

  19. Studying the factors affecting solar power generation systems performance ( SPGSP

    Directory of Open Access Journals (Sweden)

    Jalal A Al-Tabtabaei

    2014-12-01

    Full Text Available Solar energy is a huge, clean and renewable source of energy. It is also available everywhere on the earth. However, there are many technical and economic difficulties need to be solved so that solar energy becomes a strong competition against the traditional energy sources. Energy from the sun can be used successfully in electric power generation systems. Depending on the climate conditions and the use of a properly designed, installing and maintained system can meet a large demand in this request. Work plane for this research will include many steps, the first step will include an introduction to solar energy. The second step will be a short review of the solar energy availability, geometry, fields of applications and the largest commercial application of solar energy is the solar thermal power generation. In addition, the most common types of solar thermal power plants, the solar field, heat transfer fluid and the power conversion system types will be explained in detail. The third step, a simple analysis for the solar thermal power plant will be explained in order to predict the optimum conditions leading to maximum performance. Discussions of results will be the fourth step. The last step a conclusion and recommendation for future work will also be included.

  20. Structural factors of solar system cluster ground coupled storage rationalization

    Directory of Open Access Journals (Sweden)

    Viktor V. Wysochin

    2015-12-01

    Full Text Available The computational investigations of unsteady heat transfer in seasonal solar heat storage system were conducted. This storage system consists of nine ground heat exchangers. The investigations were made for periodical diurnal cycle charging during summer season. The heat exchanger is presented as vertical probe with concentric tubes arrangement. Aim: The aim of the work is the optimization of cluster ground coupled storage – the probes quantity in cluster, their lengths and interval – using high precision mathematical model. Materials and Methods: The mathematical model of conjugate solar system functioning and ground coupled storage involves differential equations describing the incoming and conversion of solar energy in solar collector. Also it includes the heat exchange in ground heat exchangers and three-dimensional soil mass. Results: The need of mutual influence accounting of the solar collector and the ground heat exchanger size ranges is shown. One more thing – capability of effectiveness improvement of the collector based on reasonable step size selection for cluster and selection of active heat exchangers quantity in requisite construction. Conclusions: The recommendations for organization of heat exchangers of the collector work are offered. The five-probe structure is the most effective one for cluster arrangement of seasonal heat storage. The recommended interval between probes is 4 meters.

  1. EFFECT OF CORTICOTROPIN-RELEASING FACTOR ANTAGONIST ON BEHAVIORAL AND NEUROENDOCRINE RESPONSES DURING EXPOSURE TO DEFENSIVE BURYING PARADIGM IN RATS

    NARCIS (Netherlands)

    KORTE, SM; KORTEBOUWS, GAH; BOHUS, B; KOOB, GF

    1994-01-01

    Defensive burying behavior is a coping strategy in rodents in response to an aversive stimulus where fear will facilitate burying and treatment with anxiolytics will result in less burying. To test the hypothesis that endogenous corticotropin-releasing factor (CRF) is involved in the defensive buryi

  2. Common Mechanisms Underlying the Proconflict Effects of Corticotropin-Releasing Factor, A Benzodiazepine Inverse Agonist and Electric Foot-Shock

    NARCIS (Netherlands)

    Boer, Sietse F. de; Katz, Jonathan L.; Valentino, Rita J.

    1992-01-01

    The effects of corticotropin-releasing factor (CRF), a benzodiazepine inverse agonist (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate; DMCM) and electric foot-shock on rat conflict behavior were characterized and compared. Rats were trained to lever press under a multiple fixed-ratio schedul

  3. Analysis of HIV type 1 BF recombinant sequences from South America dates the origin of CRF12_BF to a recombination event in the 1970s.

    Science.gov (United States)

    Dilernia, Dario A; Jones, Leandro R; Pando, Maria A; Rabinovich, Roberto D; Damilano, Gabriel D; Turk, Gabriela; Rubio, Andrea E; Pampuro, Sandra; Gomez-Carrillo, Manuel; Salomón, Horacio

    2011-05-01

    HIV-1 epidemics in South America are believed to have originated in part from the subtype B epidemic initiated in the Caribbean/North America region. However, circulation of BF recombinants in similar proportions was extensively reported. Information currently shows that many BF recombinants share a recombination structure similar to that found in the CRF12_BF. In the present study, analyzing a set of 405 HIV sequences, we identified the most likely origin of the BF epidemic in an early event of recombination. We found that the subtype B epidemics in South America analyzed in the present study were initiated by a founder event that occurred in the early 1970s, a few years after the introduction of these strains in the Americas. Regarding the F/BF recombinant epidemics, by analyzing a subtype F genomic segment within the viral gene gag present in the majority of the BF recombinants, we found evidence of a geographic divergence very soon after the introduction of subtype F strains in South America. Moreover, through analysis of a subtype B segment present in all the CRF12_BF-like recombination structure, we estimated the circulation of the subtype B strain that gave rise to that recombinant structure around the same time period estimated for the introduction of subtype F strains. The HIV epidemics in South America were initiated in part through a founder event driven by subtype B strains coming from the previously established epidemic in the north of the continent. A second introduction driven by subtype F strains is likely to have encountered the incipient subtype B epidemic that soon after their arrival recombined with them, originating the BF epidemic in the region. These results may explain why in South America the majority of F sequences are found as BF recombinants.

  4. 慢性肾衰竭的四诊客观化研究进展%Objectification Progress of Four Diagnostic Methods of Chronic Renal Failure(CRF)

    Institute of Scientific and Technical Information of China (English)

    张宇; 金亚明; 王忆勤

    2013-01-01

    Traditional Chinese Medicine ( TCM ) four diagnostic methods (inspection, auscultation - olfaction, interrogation and palpation) ,are the basis of syndrome differentiation and treatment, and the objectification of four diagnostic methods is an effective approach to develop the TCM. Nowadays,researchers have observed and summarized significant a-mount of four diagnostic methods information against different types of diseases, and then objectified the four diagnostic methods through the analysis and research by using modern information technology. CRF is one of the late - stage clinical disorders of various types of chronic kidney diseases. This paper summarized the current situation of inspection, auscultation - olfaction, interrogation and palpation objectification researches about chronic renal failure within last two decades, proved the four diagnostic methods objectification development of CRF, which is meaningful for syndrome differentiation and prognosis of chronic renal failure.%中医四诊信息——“望、闻、问、切”是辨证论治的基础,而四诊客观化更是发展中医的一种有效途径.目前,学者们对大量疾病四诊信息进行观察总结,并利用现代信息技术进行分析研究,实现四诊客观化.慢性肾衰竭是各种慢性肾脏疾病后期的一种临床病症,综述了近20年来慢性肾衰竭在中医望闻问切四方面的客观化研究现状,发现慢性肾衰竭的四诊客观化取得了很大的进展,对慢性肾衰竭的辨证及预后产生了一定的意义.

  5. Integrating Factors and Conservation Theorems of Lagrangian Equations for Nonconservative Mechanical System in Generalized Classical Mechanics

    Institute of Scientific and Technical Information of China (English)

    QIAO Yong-Fen; ZHAO Shu-Hong

    2006-01-01

    The conservation theorems of the generalized Lagrangian equations for nonconservative mechanical system are studied by using method of integrating factors. Firstly, the differential equations of motion of system are given, and the definition of integrating factors is given. Next, the necessary conditions for the existence of the conserved quantity are studied in detail. Finally, the conservation theorem and its inverse for the system are established, and an example is given to illustrate the application of the result.

  6. Human factors research problems in electronic voice warning system design

    Science.gov (United States)

    Simpson, C. A.; Williams, D. H.

    1975-01-01

    The speech messages issued by voice warning systems must be carefully designed in accordance with general principles of human decision making processes, human speech comprehension, and the conditions in which the warnings can occur. The operator's effectiveness must not be degraded by messages that are either inappropriate or difficult to comprehend. Important experimental variables include message content, linguistic redundancy, signal/noise ratio, interference with concurrent tasks, and listener expectations generated by the pragmatic or real world context in which the messages are presented.

  7. Cultural Factors in Systems Design Decision Making and Action

    CERN Document Server

    Proctor, Robert W; Yih, Yuehwern

    2011-01-01

    This book brings together an interdisciplinary group of experts to provide increased understanding of the ways in which cultural differences may influence decision making and action. It brings together current knowledge about decision processes, culture and cognition, design of products and interfaces for human interaction with machines and organizational processes culled from a wide variety of sources and puts them into one comprehensive resource. It examines how to design systems used by individuals from different cultures and accommodate the varied backgrounds that affect the users' decisio

  8. Looking under the Bonnet: Factors Affecting Student Adoption of E-Learning Systems in Jordan

    Directory of Open Access Journals (Sweden)

    Muneer Mahmood Abbad, David Morris, Carmel de Nahlik

    2009-04-01

    Full Text Available The primary questions addressed in this paper are the following: what are the factors that affect students’ adoption of an e-learning system and what are the relationships among these factors?This paper investigates and identifies some of the major factors affecting students’ adoption of an e-learning system in a university in Jordan. E-learning adoption is approached from the information systems acceptance point of view. This suggests that a prior condition for learning effectively using e-learning systems is that students must actually use them. Thus, a greater knowledge of the factors that affect IT adoption and their interrelationships is a pre-cursor to a better understanding of student acceptance of e-learning systems. In turn, this will help and guide those who develop, implement, and deliver e-learning systems.In this study, an extended version of the Technology Acceptance Model (TAM was developed to investigate the underlying factors that influence students’ decisions to use an e-learning system. The TAM was populated using data gathered from a survey of 486 undergraduate students using the Moodle based e-learning system at the Arab Open University. The model was estimated using Structural Equation Modelling (SEM. A path model was developed to analyze the relationships between the factors to explain students’ adoption of the e-learning system. Whilst findings support existing literature about prior experience affecting perceptions, they also point to surprising group effects, which may merit future exploration.

  9. Integrating Factors and Conservation Laws of Generalized Birkhoff System Dynamics in Event Space

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yi

    2009-01-01

    In this paper, the conservation laws or generalized Birkhoff system in event space are studied by using the method of integrating factors. Firstly, the generalized Pfaff-Birkhoff principle and the generalized Birkhoff equations are established, and the definition of the integrating factors for the system is given. Secondly, based on the concept of integrating factors, the conservation theorems and their inverse for the generalized Birkhoff system in the event space are presented in detail, and the relation between the conservation laws and the integrating factors of the system is obtained and the generalized Killing equations for the determination of the integrating factors are given. Finally, an example is given to illustrate the application of the results.

  10. [Evaluation factors for CR system introduction using AHP and simulation].

    Science.gov (United States)

    Yokooka, Yuki; Ogasawara, Katsuhiko

    2008-09-20

    Medical institutions usually find it difficult to select computed radiography (CR) equipment because of the involvement of many complicated factors such as operability, processing time, and price. The analytic hierarchy process (AHP) is often applied in complex decision and evaluation situations. This study quantitatively evaluates the institution's selection criteria of equipment using AHP. The AHP model of this study consisted of 3 levels: the goal, 6 evaluations, and 3 alternatives. Processing time, price operability, picture quality, connectivity, and equipment size were considered as the criteria for decision marking. We simulated alteration of priority of evaluations by changing the weight of pricing between 0 and 1. Results showed that price and connectivity accounted for 60% of the total weight. On excluding operability, the difference in weight between equipment was 1.16 times; the priority of processing time was 1.36 times; and the priority of price was 1.37 times. In the same way, when considering operability, the difference in weight between equipment was 0.36 times, the priority of processing time was 0.45 times, and the priority of price was 0.11 times.

  11. Chronic stress induces sex-specific alterations in methylation and expression of corticotropin-releasing factor gene in the rat.

    Directory of Open Access Journals (Sweden)

    Linda Sterrenburg

    Full Text Available BACKGROUND: Although the higher prevalence of depression in women than in men is well known, the neuronal basis of this sex difference is largely elusive. METHODS: Male and female rats were exposed to chronic variable mild stress (CVMS after which immediate early gene products, corticotropin-releasing factor (CRF mRNA and peptide, various epigenetic-associated enzymes and DNA methylation of the Crf gene were determined in the hypothalamic paraventricular nucleus (PVN, oval (BSTov and fusiform (BSTfu parts of the bed nucleus of the stria terminalis, and central amygdala (CeA. RESULTS: CVMS induced site-specific changes in Crf gene methylation in all brain centers studied in female rats and in the male BST and CeA, whereas the histone acetyltransferase, CREB-binding protein was increased in the female BST and the histone-deacetylase-5 decreased in the male CeA. These changes were accompanied by an increased amount of c-Fos in the PVN, BSTfu and CeA in males, and of FosB in the PVN of both sexes and in the male BSTov and BSTfu. In the PVN, CVMS increased CRF mRNA in males and CRF peptide decreased in females. CONCLUSIONS: The data confirm our hypothesis that chronic stress affects gene expression and CRF transcriptional, translational and secretory activities in the PVN, BSTov, BSTfu and CeA, in a brain center-specific and sex-specific manner. Brain region-specific and sex-specific changes in epigenetic activity and neuronal activation may play, too, an important role in the sex specificity of the stress response and the susceptibility to depression.

  12. Heat Shock Factor-1 and Nuclear Factor-kappaB Are Systemically Activated in Human Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Derek A O’Reilly

    2006-03-01

    Full Text Available Context :Nuclear factor-kappa B (NFkappaB is a transcription factor for a wide range of proinflammatory mediators while heat shock factor-1 (HSF-1 transcribes stress proteins that protect against cellular damage. Both are attractive therapeutic targets, undergoing investigation in other acute inflammatory conditions, such as sepsis. Objective :To evaluate the role of the transcription factors NF-kappaB and HSF-1 in human acute pancreatitis and their relationship to cytokine/chemokine production, disease severity and outcome. Patients :Twenty-four patients with acute pancreatitis and 12 healthy controls. Main outcome measures :Peripheral blood mononuclear cells were isolated. NF-kappaB and HSF-1 were measured by electrophoretic mobility shift assay. Soluble tumor necrosis factor (TNF receptor II and interleukin-8 were measured by ELISA. Acute physiology scores (APS, APACHE II scores and final Atlanta designations of severity were also determined. Results: Systemic NF-kappaB activation occurs in acute pancreatitis compared to healthy controls (P=0.004. However, there was no significant difference between those with mild and severe disease (P=0.685. Systemic activation of HSF-1 was observed in acute pancreatitis compared to healthy controls although this did not reach statistical significance (P=0.053. Activation, however, was greatest in those who had a final Atlanta designation of mild pancreatitis compared to those who had a severe attack of acute pancreatitis (P=0.036. Furthermore, HSF-1 was inversely correlated with acute physiology score (APS; r=-0.49, P=0.019 and APACHE II score (r=-0.47, P=0.026. Conclusions: Both NF-kappaB and HSF-1 are systemically activated in human acute pancreatitis. HSF-1 activation may protect against severity of pancreatitis

  13. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    Energy Technology Data Exchange (ETDEWEB)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed.

  14. Research on Assessment Model of Information System Security Based on Various Security Factors

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    With the rapid development of network technology, the meaning of layers and attributes in respect of information system security must be extended based on the understanding of the concept of information system security. The layering model (LM) of information system security and the five-attribute model (FAM) based on security factors were put forward to perfect the description and modeling of the information system security framework. An effective framework system of risk calculation and assessment was proposed, which is based on FAM.

  15. Human factors analysis and design methods for nuclear waste retrieval systems: Human factors design methodology and integration plan

    Science.gov (United States)

    Casey, S. M.

    1980-06-01

    The nuclear waste retrieval system intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository is discussed. The implementation of human factors engineering principles during the design and construction of the retrieval system facilities and equipment is reported. The methodology is structured around a basic system development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Examples of application of the techniques in the analysis of human tasks, and equipment required in the removal of spent fuel canisters is provided. The framework for integrating human engineering with the rest of the system development effort is documented.

  16. Analysis of the Important Factors for the LSDTS System

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Deok; Song, Jae Hoon; Park, Chang Je; Song, Kee Chan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-11-15

    It is confirmed that it is necessary to have domestic experience for measuring fissile material such as U-235, U-238, and Pu-239 in spent fuel or pyro-processed fuel containing TRU and to have technology related with measurement for fissile material. Understanding newly advanced measurement system for fissile material, it indicates the development directions. In this research, it is shown to the basic principle of LSDTS and it is investigated to commercial neutron source generator in order to use appropriated neutron source in the LSDTS. On the other hand, it is understood to the properties for fission chamber as induced neutron detector. It is confirmed to the relationship between slowing-down time and neutron energy in slowing-down medium. Understanding the application of SDTS, the efficiency is broaden, that is, it can help as equipment for real-time, direct, and quantitative measurement of fissile material from fuel assay such as spent fuel or pyro-processed fuel.

  17. Nephrogenic systemic fibrosis: risk factors suggested from Japanese published cases

    DEFF Research Database (Denmark)

    Tsushima, Y; Kanal, E; Thomsen, H S

    2010-01-01

    The aim of this article is to review the published cases of nephrogenic systemic fibrosis (NSF) in Japan. The Japanese medical literature database and MedLine were searched using the keywords NSF and nephrogenic fibrosing dermopathy (January 2000 to March 2009). Reports in peer-reviewed journals...... and meeting abstracts were included, and cases with biopsy confirmation were selected. 14 biopsy-verified NSF cases were found. In seven of eight patients reported after the association between gadolinium-based contrast agent (GBCA) and NSF was proposed, GBCA administration was documented: five received only...... gadodiamide; two received both gadodiamide and gadopentetate dimeglumine. In four cases, the amounts of contrast agent were registered: two received only a single dose (0.1 mmol kg(-1) body weight) whereas the other two received 7-15 ml (the body weight was not disclosed) for each MR examination. Five...

  18. Human Factors Evaluation of the Hidalgo Equivital EQ-02 Physiological Status Monitoring System

    Science.gov (United States)

    2013-10-11

    Equivital™ EQ-02 physiological status monitoring ( PSM ) system. The usability and acceptability of this system has been tested previously and generally...under CBRNE- PPE provided utility and was comfortable to wear. Thermal strain; CBRNE; PPE; physiological status monitoring; PSM ; human factors; chem...real-time physiological monitoring. The Hidalgo, Ltd. (Cambridge, UK) Equivital™ EQ-02 physiological status monitoring ( PSM ) system is a typical

  19. A study to determine influential factors on implementation of management information system

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2013-08-01

    Full Text Available Management information system (MIS plays an important role on sharing necessary information within organization. In this paper, we study to find out important factors influencing the implementation of MIS in banking industry. The study designs a questionnaire in Likert scale and distributes it among 253 randomly selected people. Cronbach alpha has been calculated as 0.82, which is within an acceptable limit. The study uses factor analysis to find important factors and detects six important factors including fear of technology, organizational instability, informal groups, cultural factors, organizational development and understanding that change is always good.

  20. Key success factors for clinical knowledge management systems: Comparing physician and hospital manager viewpoints.

    Science.gov (United States)

    Chang, Sho-Fang; Hsieh, Ping-Jung; Chen, Hui-Fang

    2015-01-01

    The study explores the perceptions of physicians and hospital managers regarding the key success factors (KSFs) of a clinical knowledge management system (CKMS). It aims to eliminate the perception gap and gain more insights for a successful CKMS.A survey was conducted in four medical centers in Taiwan. A total of 340 questionnaires, including 15 for hospital managers and 70 for physicians in each hospital, were administered. The effective response rates are 78.3% and 56.1% respectively. Partial least square (PLS) were used to analyze the data.The results identified six KSFs of CKMS including system software and hardware, knowledge quality, system quality, organizational factors, user satisfaction, and policy factors. User satisfaction and policy factors have direct effects on perceived CKMS performance. Knowledge quality is regarded as an antecedent to user satisfaction, while system quality is the antecedent to both user satisfaction and policy factors. System software and hardware was supported only by managers, and organizational factors were supported only by physicians.Among the factors, this study highlighted the policy factor. Besides, the study provides hospital managers additional insights into physician requirements for organizational support. Third, more physician participation and involvement are recommended when introducing and developing a CKMS.

  1. Tumor interactions with soluble factors and the nervous system

    Directory of Open Access Journals (Sweden)

    Voss Melanie J

    2010-09-01

    Full Text Available Abstract In the genomic era of cancer research, the development of metastases has been attributed to mutations in the tumor that enable the cells to migrate. However, gene analyses revealed that primary tumors and metastases were in some cases genetically identical and the question was raised whether metastasis formation might be an inherent feature of certain tumor cells. In contradiction to this view, the last decade of cancer research has brought to light, that tumor cell migration, similar to leukocyte and fibroblast migration, is a highly regulated process. The nervous system plays an important role in this regulation, at least in two respects: firstly, neurotransmitters are known to regulate the migratory activity of tumor cells, and secondly, nerve fibers are used as routes for perineural invasion. We also summarize here the current knowledge on the innervation of tumors. Such a process might establish a neuro-neoplastic synapse, with the close interaction of tumor cells and nerve cells supporting metastasis formation.

  2. An integrative literature review of contextual factors in perioperative information management systems.

    Science.gov (United States)

    Wilbanks, Bryan A

    2013-12-01

    Perioperative information management systems are used to generate the official documentation of patient care throughout the surgical experience. Successful implementation of perioperative information management systems requires a careful assessment of the contextual factors (ie, the social, cultural, and physical environment) that are present at the site. Failure to sufficiently assess these contextual factors is one of the leading causes of unsuccessful system implementation and can result in decreased patient safety, poor documentation quality, inefficient work processes, and wasted financial resources. Clearly defining and identifying the contextual factors are necessary to improve the performance and utilization of information management systems. The purpose of this article was to provide an integrative review of the empirical and theoretical literature on the contextual factors present in the perioperative environment to help guide future research and clinical practice. Specifically, this review addresses a gap in the literature regarding the descriptions of the contextual factors and how these factors affect implementation practices and system use. By clearly identifying these contextual factors and determining their relationship to successful system implementations, informatics specialists can tailor implementation and assessment tools to both patients and perioperative settings.

  3. Cell autonomous and systemic factors in progeria development.

    Science.gov (United States)

    Osorio, Fernando G; Ugalde, Alejandro P; Mariño, Guillermo; Puente, Xose S; Freije, José M P; López-Otín, Carlos

    2011-12-01

    Progeroid laminopathies are accelerated aging syndromes caused by defects in nuclear envelope proteins. Accordingly, mutations in the LMNA gene and functionally related genes have been described to cause HGPS (Hutchinson-Gilford progeria syndrome), MAD (mandibuloacral dysplasia) or RD (restrictive dermopathy). Functional studies with animal and cellular models of these syndromes have facilitated the identification of the molecular alterations and regulatory pathways involved in progeria development. We have recently described a novel regulatory pathway involving miR-29 and p53 tumour suppressor which has provided valuable information on the molecular components orchestrating the response to nuclear damage stress. Furthermore, by using progeroid mice deficient in ZMPSTE24 (zinc metalloprotease STE24 homologue) involved in lamin A maturation, we have demonstrated that, besides these abnormal cellular responses to stress, dysregulation of the somatotropic axis is responsible for some of the alterations associated with progeria. Consistent with these observations, pharmacological restoration of the somatotroph axis in these mice delays the onset of their progeroid features, significantly extending their lifespan and supporting the importance of systemic alterations in progeria progression. Finally, we have very recently identified a novel progeroid syndrome with distinctive features from HGPS and MAD, which we have designated NGPS (Néstor-Guillermo progeria syndrome) (OMIM #614008). This disorder is caused by a mutation in BANF1, a gene encoding a protein with essential functions in the assembly of the nuclear envelope, further illustrating the importance of the nuclear lamina integrity for human health and providing additional support to the study of progeroid syndromes as a valuable source of information on human aging.

  4. Human factors programs for high-level radioactive waste handling systems

    Energy Technology Data Exchange (ETDEWEB)

    Pond, D.J.

    1992-04-01

    Human Factors is the discipline concerned with the acquisition of knowledge about human capabilities and limitations, and the application of such knowledge to the design of systems. This paper discusses the range of human factors issues relevant to high-level radioactive waste (HLRW) management systems and, based on examples from other organizations, presents mechanisms through which to assure application of such expertise in the safe, efficient, and effective management and disposal of high-level waste. Additionally, specific attention is directed toward consideration of who might be classified as a human factors specialist, why human factors expertise is critical to the success of the HLRW management system, and determining when human factors specialists should become involved in the design and development process.

  5. Structural and Functional Analysis of HIV-1CRF07-BC gp41 HR2 Hyper-mutant Site%HIV-1CRF07-BC gp41 HR2高突变区氨基酸结构和功能分析

    Institute of Scientific and Technical Information of China (English)

    杜建森; 马婧; 刘方; 刘新奇

    2015-01-01

    HIV-1包膜蛋白ENV介导病毒进入靶细胞,这个过程可以作为设计抗艾滋病药物的一个重要靶点,进入抑制剂能够抑制HIV进入靶细胞,从而在感染的最初环节抑制病毒的传播.为了更好地筛选针对中国株CRF07-BC的进入抑制剂,建立了细胞-细胞融合系统.通过比较CRF07-BC gp41和B亚型gp41的序列同源性和融合能力,gp41HR2存在着一个7个氨基酸的高突变区.通过结构生物学对gp41HR2高突变区进行分析发现,高突变区内氨基酸可以在功能上互补,保持了gp41的融合能力.这种功能互补性的研究可以为HIV gp41进化提供理论参考,为HIV-1进入抑制剂的设计提供更准确的靶点.

  6. Corticotropin-releasing factor in ventromedial prefrontal cortex mediates avoidance of a traumatic stress-paired context.

    Science.gov (United States)

    Schreiber, Allyson L; Lu, Yi-Ling; Baynes, Brittni B; Richardson, Heather N; Gilpin, Nicholas W

    2017-02-01

    Post-traumatic stress disorder (PTSD) affects 7.7 million Americans. One diagnostic criterion for PTSD is avoidance of stimuli that are related to the traumatic stress. Using a predator odor stress conditioned place aversion (CPA) model, rats can be divided into groups based on stress reactivity, as measured by avoidance of the odor-paired context. Avoider rats, which show high stress reactivity, exhibit persistent avoidance of stress-paired context and escalated alcohol drinking. Here, we examined the potential role of corticotropin-releasing factor (CRF), a neuropeptide that promotes anxiety-like behavior in mediating avoidance and escalated alcohol drinking after stress. CRF is expressed in the medial prefrontal cortex (mPFC). The dorsal and ventral sub-regions of the mPFC (dmPFC and vmPFC) have opposing roles in stress reactivity and alcohol drinking. We hypothesized that vmPFC CRF-CRFR1 signaling contributes functionally to stress-induced avoidance and escalated alcohol self-administration. In Experiment 1, adult male Wistar rats were exposed to predator odor stress in a CPA paradigm, indexed for avoidance of odor-paired context, and brains processed for CRF-immunoreactive cell density in vmPFC and dmPFC. Post-stress, Avoiders exhibited higher CRF cell density in vmPFC, but not the dmPFC. In Experiment 2, rats were tested for avoidance of a context repeatedly paired with intra-vmPFC CRF infusions. In Experiment 3, rats were stressed and indexed, then tested for the effects of intra-vmPFC CRFR1 antagonism on avoidance and alcohol self-administration. Intra-vmPFC CRF infusion produced avoidance of a paired context, and intra-vmPFC CRFR1 antagonism reversed avoidance of a stress-paired context, but did not alter post-stress alcohol self-administration. These findings suggest that vmPFC CRF-CRFR1 signaling mediates avoidance of stimuli paired with traumatic stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. EFFECT OF CONTROLLED-RELEASE FERTILIZER (CRF) ON NITROUS OXIDE EMISSION DURING THE WHEAT GROWING PERIOD%控释肥施用对小麦生长期N2O排放的影响

    Institute of Scientific and Technical Information of China (English)

    纪洋; 刘刚; 马静; 李小平; 徐华; 蔡祖聪

    2012-01-01

    A field experiment was conducted to study effect of application rate (N O, 100, 200 and 270 kg hm-2) of controlled-release fertilizer (CRF) and urea on N2 O emission from the wheat cropping system. Seven treatments, i. e. CK, U100, U200, U270, C100, C200 and C270, were designed and implemented separately during the wheat growing period. Results indicate that application of either urea and CRF, increased total N, 0 emission during the wheat growing period exponentially from 32% to 164% with increasing N-fertilizer application rate (p 0. 05). Specific N2O emission increased exponentially from 31% to 114% in Treatment Urea with increasing application rate (p0. 05 ).%通过田间试验,采用静态箱法研究不同施氮水平下控释肥和尿素(N 0、100、200、270 kg hm-2)对麦季N2O排放的影响.结果表明,与对照相比,整个小麦生长季N2O排放量均随尿素和控释肥施用量的增加呈指数增加( 32%~164%,p<0.05),但控释肥处理增加程度则较尿素处理缓和;施用控释肥可以有效抑制小麦生长季N2O排放(p<0.05),控释肥对N2O的减排量随着施氮量的增加而增加.小麦产量随尿素施用量的增加呈抛物线增加(24%~43%,p<0.05),随控释肥施用量的增加亦呈抛物线增加(30%~45%,p<0.05);与施用相同水平尿素相比,施用控释肥的小麦产量略有增加,但无显著差异(p>0.05).单位产量N2O排放量随尿素施用量的增加而呈指数增加(31%~114%,p<0.05),随控释肥施用量的增加而呈抛物线增加(2%~50%,p<0.05);施用控释肥可以有效抑制小麦生长季单位产量N2O排放(p<0.05),控释肥对单位产量N2O的减排量随着施氮量的增加而增加.各处理N2O排放量与土壤水分存在显著正相关(p<0.05),与土壤NH4+-N、NO3--N浓度和土温不呈明显线性关系(p>0.05).

  8. Behavioral Risk Factor Surveillance System (BRFSS) Prevalence Data (2010 and prior)

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2010. BRFSS land line only prevalence data. BRFSS is a continuous, state-based surveillance system that collects information about modifiable risk factors for...

  9. 76 FR 55213 - Technical Amendments to Federal Employees' Retirement System; Present Value Conversion Factors...

    Science.gov (United States)

    2011-09-07

    ... RIN 3206-AM29 Technical Amendments to Federal Employees' Retirement System; Present Value Conversion...--Present Value Conversion Factors for Earlier Commencing Date of Annuities of Current and Former Spouses...

  10. Behavioral Risk Factor Surveillance System (BRFSS) Prevalence Data (2010 and prior)

    Data.gov (United States)

    U.S. Department of Health & Human Services — 1995-2010. BRFSS land line only prevalence data. BRFSS is a continuous, state-based surveillance system that collects information about modifiable risk factors for...

  11. Factors Associated with Service Use among Immigrants in the Child Welfare System

    Science.gov (United States)

    Rajendran, Khushmand; Chemtob, Claude M.

    2010-01-01

    This study investigated child, caregiver, and caseworker factors associated with greater use of family support services by immigrant families in the U.S. child welfare system. Among child factors, higher levels of internalizing behavior problems (Odds Ratio (O.R.) = 3.60), externalizing behavior problems (O.R. = 2.62) and a history of neglect…

  12. Examination of Factors Impacting Student Satisfaction with a New Learning Management System

    Science.gov (United States)

    Green, Lucy Santos; Inan, Fethi A.; Denton, Bree

    2012-01-01

    The purpose of this study was to determine factors that influenced student satisfaction with a new learning management system and to identify which of these factors were most important. The data was collected using an an online survey tool that was administered to students enrolled in courses designed and taught by faculty who participated in a…

  13. Market factors feedback system of the pilot program of the Energy Extension Service

    Energy Technology Data Exchange (ETDEWEB)

    None

    1978-04-01

    The market factors feedback system of the pilot program of the Energy Extension Service are described. The description contains the plans of the 10 pilot EES states and the DOE for operating the system between December 1977 and March 1979. Chapter one contains the planned scope of the market factors feedback system during the pilot program: the target audiences, program services, likely topics of market factors feedback, and energy decision makers. Chapter two presents how the market factors feedback system will operate over the pilot program period. Chapter three summarizes the roles and functions of DOE/EXT in supporting state EES market factors feedback operations and in evaluating the program. There are three appendices. Appendix A contains the market factors feedback plans of the pilot EES states. Appendix B describes how DOE/EXT will work with national-level energy decision makers on market factors feedback received from state EESs. Appendix C is the design for the formal evaluation of the market factors feedback component of the pilot EES program. (MCW)

  14. Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas

    DEFF Research Database (Denmark)

    Vinter-Jensen, Lars; Juhl, C O; Teglbjaerg, P S;

    1997-01-01

    Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and the EGF receptor are often overexpressed in chronic pancreatitis and in malignant pancreatic growth. Transgenic mice overexpressing TGF-alpha develop tissue changes in the pancrease resembling changes found in chronic...... pancreatitis. The effects of systemic treatment with EGF on the porcine pancrease were investigated in this study....

  15. Outer-(J1,J2)-lossless factorizations of linear discrete time-varying systems

    NARCIS (Netherlands)

    Yu, Xiaode; Scherpen, Jacqueline M.A.; Veen, Allejan van der; Dewilde, Patrick

    1996-01-01

    In this paper the outer-J-lossless factorization for linear discrete time-varying systems is treated. Lossless operators and its corresponding J-lossless chain-scattering operators are studied. Then the factorization is treated by first 'taking out' the anticausal part, and then considering the

  16. Dysfunction of stress responsive systems as a risk factor for functional somatic syndromes

    NARCIS (Netherlands)

    Tak, Lineke M.; Rosmalen, Judith G. M.

    2010-01-01

    The etiology of functional somatic syndromes or disorders (FSDs) is generally considered to be a multifactorial interplay between psychological, biological, and social factors. One of the most investigated biological factors is stress responsive system dysfunction Despite more than twenty years of r

  17. Outer-(J1,J2)-lossless factorizations of linear discrete time-varying systems

    NARCIS (Netherlands)

    Yu, Xiaode; Scherpen, Jacqueline M.A.; Veen, Allejan van der; Dewilde, Patrick

    1996-01-01

    In this paper the outer-J-lossless factorization for linear discrete time-varying systems is treated. Lossless operators and its corresponding J-lossless chain-scattering operators are studied. Then the factorization is treated by first 'taking out' the anticausal part, and then considering the oute

  18. General Open Systems Theory and the Substrata-Factor Theory of Reading.

    Science.gov (United States)

    Kling, Martin

    This study was designed to extend the generality of the Substrata-Factor Theory by two methods of investigation: (1) theoretically, to est"blish the validity of the hypothesis that an isomorphic relationship exists between the Substrata-Factor Theory and the General Open Systems Theory, and (2) experimentally, to disc"ver through a…

  19. Factors Affecting the Full Use of Library and Information Management Systems by Library Personnel

    Science.gov (United States)

    Skretas, Georgios

    2005-01-01

    Purpose: To provide a general list of factors that affects and determines the full use of library information management systems (LIMS) by library staff. Design/methodology/approach: The factors, which were identified mainly during participation in the implementation of automation projects in Greece, are listed and briefly analysed in categories…

  20. Development of management qua