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Sample records for corticotropin-releasing factor insights

  1. Distribution of corticotropin-releasing factor receptors in primate brain

    International Nuclear Information System (INIS)

    Millan, M.A.; Jacobowitz, D.M.; Hauger, R.L.; Catt, K.J.; Aguilera, G.

    1986-01-01

    The distribution and properties of receptors for corticotropin-releasing factor (CRF) were analyzed in the brain of cynomolgus monkeys. Binding of [ 125 I]tyrosine-labeled ovine CRF to frontal cortex and amygdala membrane-rich fractions was saturable, specific, and time- and temperature-dependent, reaching equilibrium in 30 min at 23 0 C. Scatchard analysis of the binding data indicated one class of high-affinity sites with a K/sub d/ of 1 nM and a concentration of 125 fmol/mg. As in the rat pituitary and brain, CRF receptors in monkey cerebral cortex and amygdala were coupled to adenylate cyclase. Autoradiographic analysis of specific CRF binding in brain sections revealed that the receptors were widely distributed in the cerebral cortex and limbic system. Receptor density was highest in the pars tuberalis of the pituitary and throughout the cerebral cortex, specifically in the prefrontal, frontal, orbital, cingulate, insular, and temporal areas, and in the cerebellar cortex. A low binding density was present in the superior colliculus, locus coeruleus, substantia gelatinosa, preoptic area, septal area, and bed nucleus of the stria terminalis. These data demonstrate that receptors for CRF are present within the primate brain at areas related to the central control of visceral function and behavior, suggesting that brain CRF may serve as a neurotransmitter in the coordination of endocrine and neural mechanisms involved in the response to stress

  2. 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.

    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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

  4. 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.

  5. Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum

    NARCIS (Netherlands)

    Swinny, JD; Kalicharan, D; Blaauw, EH; Ijkema-Paassen, J; Shi, F; Gramsbergen, A; van der Want, JJL

    Corticotropin-releasing factor (CRF)-like proteins act via two G-protein-coupled receptors (CRF-R1 and CRF-R2) playing important neuromodulatory roles in stress responses and synaptic plasticity. The cerebellar expression of corticotropin-releasing factor-like ligands has been well documented, but

  6. Expression and Regulation of Corticotropin-Releasing Factor Receptor Type 2 beta in Developing and Mature Mouse Skeletal Muscle

    NARCIS (Netherlands)

    Kuperman, Yael; Issler, Orna; Vaughan, Joan; Bilezikjian, Louise; Vale, Wylie; Chen, Alon

    Corticotropin-releasing factor receptor type 2 (CRFR2) is highly expressed in skeletal muscle (SM) tissue where it is suggested to inhibit interactions between insulin signaling pathway components affecting whole-body glucose homeostasis. However, little is known about factors regulating SM CRFR2

  7. Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.

    Science.gov (United States)

    Rivier, Jean E; Rivier, Catherine L

    2014-04-01

    Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Corticotropin-Releasing Factor (CRF) Neurocircuitry and Neuropharmacology in Alcohol Drinking.

    Science.gov (United States)

    Schreiber, Allyson L; Gilpin, Nicholas W

    2018-01-28

    Alcohol use is pervasive in the United States. In the transition from nonhazardous drinking to hazardous drinking and alcohol use disorder, neuroadaptations occur within brain reward and brain stress systems. One brain signaling system that has received much attention in animal models of excessive alcohol drinking and alcohol dependence is corticotropin-releasing factor (CRF). The CRF system is composed of CRF, the urocortins, CRF-binding protein, and two receptors - CRF type 1 and CRF type 2. This review summarizes how acute, binge, and chronic alcohol dysregulates CRF signaling in hypothalamic and extra-hypothalamic brain regions and how this dysregulation may contribute to changes in alcohol reinforcement, excessive alcohol consumption, symptoms of negative affect during withdrawal, and alcohol relapse. In addition, it summarizes clinical work examining CRF type 1 receptor antagonists in humans and discusses why the brain CRF system is still relevant in alcohol research.

  9. Corticotropin-Releasing Factor Mediates Pain-Induced Anxiety through the ERK1/2 Signaling Cascade in Locus Coeruleus Neurons

    Science.gov (United States)

    Borges, Gisela Patrícia; Micó, Juan Antonio; Neto, Fani Lourença

    2015-01-01

    Background: The corticotropin-releasing factor is a stress-related neuropeptide that modulates locus coeruleus activity. As locus coeruleus has been involved in pain and stress-related patologies, we tested whether the pain-induced anxiety is a result of the corticotropin-releasing factor released in the locus coeruleus. Methods: Complete Freund’s adjuvant-induced monoarthritis was used as inflammatory chronic pain model. α-Helical corticotropin-releasing factor receptor antagonist was microinjected into the contralateral locus coeruleus of 4-week-old monoarthritic animals. The nociceptive and anxiety-like behaviors, as well as phosphorylated extracellular signal-regulated kinases 1/2 and corticotropin-releasing factor receptors expression, were quantified in the paraventricular nucleus and locus coeruleus. Results: Monoarthritic rats manifested anxiety and increased phosphorylated extracellular signal-regulated kinases 1/2 levels in the locus coeruleus and paraventricular nucleus, although the expression of corticotropin-releasing factor receptors was unaltered. α-Helical corticotropin-releasing factor antagonist administration reversed both the anxiogenic-like behavior and the phosphorylated extracellular signal-regulated kinases 1/2 levels in the locus coeruleus. Conclusions: Pain-induced anxiety is mediated by corticotropin-releasing factor neurotransmission in the locus coeruleus through extracellular signal-regulated kinases 1/2 signaling cascade. PMID:25716783

  10. Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin.

    Science.gov (United States)

    Bisagno, Verónica; Cadet, Jean Lud

    2014-09-01

    Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

  11. Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    Mahanand Chatoo

    2018-02-01

    Full Text Available Irritable bowel syndrome (IBS is a common functional gastrointestinal disorder defined by ROME IV criteria as pain in the lower abdominal region, which is associated with altered bowel habit or defecation. The underlying mechanism of IBS is not completely understood. IBS seems to be a product of interactions between various factors with genetics, dietary/intestinal microbiota, low-grade inflammation, and stress playing a key role in the pathogenesis of this disease. The crosstalk between the immune system and stress in IBS mechanism is increasingly recognized. Corticotropin-releasing factor (CRF, a major mediator in the stress response, is involved in altered function in GI, including inflammatory processes, colonic transit time, contractile activity, defecation pattern, pain threshold, mucosal secretory function, and barrier functions. This mini review focuses on the recently establish local GI-CRF system, its involvement in modulating the immune response in IBS, and summarizes current IBS animal models and mapping of CRF, CRFR1, and CRFR2 expression in colon tissues. CRF and receptors might be a key molecule involving the immune and movement function via brain–gut axis in IBS.

  12. Elevated CSF Corticotropin-Releasing Factor Concentrations in Posttraumatic Stress Disorder

    Science.gov (United States)

    Bremner, J. Douglas; Licinio, Julio; Darnell, Adam; Krystal, John H.; Owens, Michael J.; Southwick, Steven M.; Nemeroff, Charles B.; Charney, Dennis S.

    2011-01-01

    Objective Corticotropin-releasing factor (CRF) and somatostatin both play important roles in mediating responses to acute and chronic stress. The purpose of this study was to measure CSF concentrations of CRF and somatostatin in patients with chronic combat-related post-traumatic stress disorder (PTSD) and comparison subjects. Method Lumbar punctures for collection of CSF were performed in Vietnam combat veterans with PTSD (N=11) and comparison subjects (N=17). CSF concentrations of CRF and somatostatin were compared between the two groups. Results CSF concentrations of CRF were higher in the PTSD patients than in the comparison subjects (mean=29.0 pg/ml, SD=7.8, versus mean=21.9 pg/ml, SD=6.0). This group difference remained significant after covariance for age. CSF somatostatin concentrations in PTSD patients were higher than those of the comparison subjects (mean=19.9 pg/ml, SD=5.4, versus mean=13.7 pg/ml, SD=8.0). However, covarying for age reduced the level of significance. Conclusions Higher CSF CRF concentrations in patients with PTSD may reflect alterations in stress-related neurotransmitter systems. The higher CSF CRF concentrations may play a role in disturbances of arousal in patients with PTSD. PMID:9137116

  13. Radioautographic study of binding and internalization of corticotropin-releasing factor by rat anterior pituitary corticotrophs

    International Nuclear Information System (INIS)

    Leroux, P.; Pelletier, G.

    1984-01-01

    In order to identify the anterior pituitary cell type(s) containing corticotropin-releasing factor (CRF) receptors and to study the internalization processes of this peptide by the target cells, radioautography was performed on rat anterior pituitaries removed at specific intervals (2-60 min) after intracarotid injection of [ 125 I]iodo-CRF into intact and adrenalectomized female rats. In intact animals, all corticotrophs were labeled, whereas in the adrenalectomized animals about 80% of the hypertrophied corticotrophs (adrenalectomy cells) were. In control animals injected with both iodinated CRF and an excess of unlabeled peptide, no specific reaction could be detected. The time-course study in intact animals showed that 2 min after injection most silver grains were found over or within 160 nm of the plasma membrane. At the 5-min time intervals, grains were observed both over the plasma membrane and within the cytoplasm, associated with lysosomes, and the Golgi apparatus. Fifteen minutes after injection, grains were mostly found over lysosomes and the Golgi apparatus, whereas at the longest time intervals (30 and 60 min) almost no labeling could be detected. The results obtained in this study indicate that in the anterior pituitary CRF receptors are restricted to corticotrophs (as identified by electron microscopy) and that, after binding to the plasma membrane, CRF is rapidly internalized to Golgi elements and lysosomes

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Sex differences in stress responses: a critical role for corticotropin-releasing factor.

    Science.gov (United States)

    Bangasser, Debra A; Wiersielis, Kimberly R

    2018-03-01

    Rates of post-traumatic stress disorder, panic disorder, and major depression are higher in women than in men. Another shared feature of these disorders is that dysregulation of the stress neuropeptide, corticotropin-releasing factor (CRF), is thought to contribute to their pathophysiology. Therefore, sex differences in responses to CRF could contribute to this sex bias in disease prevalence. Here, we review emerging data from non-human animal models that reveal extensive sex differences in CRF functions ranging from its presynaptic regulation to its postsynaptic efficacy. Specifically, detailed are sex differences in the regulation of CRF-containing neurons and the amount of CRF that they produce. We also describe sex differences in CRF receptor expression, distribution, trafficking, and signaling. Finally, we highlight sex differences in the processes that mitigate the effects of CRF. In most cases, the identified sex differences can lead to increased stress sensitivity in females. Thus, the relevance of these differences for the increased risk of depression and anxiety disorders in women compared to men is also discussed.

  16. GHRELIN ACTIVATES HYPOPHYSIOTROPIC CORTICOTROPIN-RELEASING FACTOR NEURONS INDEPENDENTLY OF THE ARCUATE NUCLEUS

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    Cabral, Agustina; Portiansky, Enrique; Sánchez-Jaramillo, Edith; Zigman, Jeffrey M.; Perello, Mario

    2016-01-01

    Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin’s orexigenic action vs. its role as a stress signal are anatomically dissociated. PMID:26874559

  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.

    2015-01-01

    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. PMID:25926444

  18. 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. Copyright © 2015 the authors 0270-6474/15/356639-15$15.00/0.

  19. 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.

  20. Design and Synthesis of Benzimidazoles As Novel Corticotropin-Releasing Factor 1 Receptor Antagonists.

    Science.gov (United States)

    Mochizuki, Michiyo; Kori, Masakuni; Kobayashi, Katsumi; Yano, Takahiko; Sako, Yuu; Tanaka, Maiko; Kanzaki, Naoyuki; Gyorkos, Albert C; Corrette, Christopher P; Cho, Suk Young; Pratt, Scott A; Aso, Kazuyoshi

    2016-03-24

    Benzazole derivatives with a flexible aryl group bonded through a one-atom linker as a new scaffold for a corticotropin-releasing factor 1 (CRF1) receptor antagonist were designed, synthesized, and evaluated. We expected that structural diversity could be expanded beyond that of reported CRF1 receptor antagonists. In a structure-activity relationship study, 4-chloro-N(2)-(4-chloro-2-methoxy-6-methylphenyl)-1-methyl-N(7),N(7)-dipropyl-1H-benzimidazole-2,7-diamine 29g had the most potent binding activity against a human CRF1 receptor and the antagonistic activity (IC50 = 9.5 and 88 nM, respectively) without concerns regarding cytotoxicity at 30 μM. Potent CRF1 receptor-binding activity in brain in an ex vivo test and suppression of stress-induced activation of the hypothalamus-pituitary-adrenocortical (HPA) axis were also observed at 138 μmol/kg of compound 29g after oral administration in mice. Thus, the newly designed benzimidazole 29g showed in vivo CRF1 receptor antagonistic activity and good brain penetration, indicating that it is a promising lead for CRF1 receptor antagonist drug discovery research.

  1. Neurobiology of stress adaptation in the mouse: Roles of corticotropin-releasing factor and urocortin 1

    NARCIS (Netherlands)

    Körösi, Anikó

    2006-01-01

    The body's ability to adapt to stressors is essential for survival. Failure of stress adaptation may lead to the development of stress-related disorders. The traditionally known adaptation system in vertebrates, is the hypothalamo-pituitary-adrenal (HPA-) axis, in which corticotropin-releasing

  2. Expression and hypophysiotropic actions of corticotropin-releasing factor in Xenopus laevis.

    Science.gov (United States)

    Boorse, Graham C; Denver, Robert J

    2004-07-01

    Members of the corticotropin-releasing factor (CRF) family of peptides play pivotal roles in the regulation of neuroendocrine, autonomic, and behavioral responses to physical and emotional stress. In amphibian tadpoles, CRF-like peptides stimulate both thyroid and interrenal (adrenal) hormone secretion, and can thereby modulate the rate of metamorphosis. To better understand the regulation of expression and actions of CRF in amphibians we developed a homologous radioimmunoassay (RIA) for Xenopus laevis CRF (xCRF). We validated this RIA and tissue extraction procedure for the measurement of brain CRF content in tadpoles and juveniles. We show that the CRF-binding protein, which is highly expressed in X. laevis brain, is largely removed by acid extraction and does not interfere in the RIA. We analyzed CRF peptide content in five microdissected brain regions in prometamorphic tadpoles and juveniles. CRF was detected throughout the brain, consistent with its role as both a hypophysiotropin and a neurotransmitter/neuromodulator. CRF content was highest in the region of the preoptic area (POa) and increased in all brain regions after metamorphosis. Exposure to 4h of handling/shaking stress resulted in increased CRF peptide content in the POa in juvenile frogs. Injections of xCRF into prometamorphic tadpoles increased whole body corticosterone and thyroxine content, thus supporting findings in other anuran species that this peptide functions as both a corticotropin- and a thyrotropin (TSH)-releasing factor. Furthermore, treatment of cultured tadpole pituitaries with xCRF (100nM for 24h) resulted in increased medium content, but decreased pituitary content of TSHbeta-immunoreactivity. Our results support the view that CRF functions as a stress neuropeptide in X. laevis as in other vertebrates. Furthermore, we provide evidence for a dual hypophysiotropic action of CRF on the thyroid and interrenal axes in X. laevis as has been shown previously in other amphibian species.

  3. Effect of corticotropin-releasing factor receptor antagonist on psychologically suppressed masculine sexual behavior in rats.

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    Miwa, Yoshiji; Nagase, Keiko; Oyama, Nobuyuki; Akino, Hironobu; Yokoyama, Osamu

    2011-03-01

    Corticotropin-releasing factor (CRF) coordinates various responses of the body to stress, and CRF receptors are important targets of treatment for stress-related disorders. To investigate the effect of a nonselective CRF receptor antagonist, astressin, on suppression of masculine sexual behavior by psychological stress in rats. First, we investigated the influence of psychological stress, induced 2 hours per day for three consecutive days, on sexual behavior. Then, rats were divided into 4 groups: a control group, an astressin administration group (A), a psychological stress loading group (PS), and a psychological stress loading and astressin administration group (PS + A). The rats were exposed to sham or psychological stress for three consecutive days. After the last stress loading, the rats were injected with vehicle or astressin, and their sexual behavior was observed. We also measured serum levels of adrenocorticotropic hormone (ACTH). The effects of astressin on sexual behavior and serum levels of ACTH in rats affected by psychological stress were determined. Sexual behavior was reduced after psychological stress loading. The PS rats had significantly longer mount, intromission, and ejaculation latencies and lower ejaculation frequency than did the control, A, and PS + A rats. The intromission latency and ejaculation frequency in the PS + A rats did not achieve the level observed in the controls. There was no significant difference in these parameters between the control and A rats. Serum ACTH levels were significantly lower in PS + A rats than in PS rats. Psychologically suppressed masculine sexual behavior could be partially recovered with astressin administration in rats. These data provide a rationale for the further study of CRF receptor antagonists as novel agents for treating psychological sexual disorders. © 2010 International Society for Sexual Medicine.

  4. Common and divergent structural features of a series of corticotropin releasing factor-related peptides.

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    Grace, Christy Rani R; Perrin, Marilyn H; Cantle, Jeffrey P; Vale, Wylie W; Rivier, Jean E; Riek, Roland

    2007-12-26

    Members of the corticoliberin family include the corticotropin releasing factors (CRFs), sauvagine, the urotensins, and urocortin 1 (Ucn1), which bind to both the CRF receptors CRF-R1 and CRF-R2, and the urocortins 2 (Ucn2) and 3 (Ucn3), which are selective agonists of CRF-R2. Structure activity relationship studies led to several potent and long-acting analogues with selective binding to either one of the receptors. NMR structures of six ligands of this family (the antagonists astressin B and astressin2-B, the agonists stressin1, and the natural ligands human Ucn1, Ucn2, and Ucn3) were determined in DMSO. These six peptides show differences in binding affinities, receptor-selectivity, and NMR structure. Overall, their backbones are alpha-helical, with a small kink or a turn around residues 25-27, resulting in a helix-loop-helix motif. The C-terminal helices are of amphipathic nature, whereas the N-terminal helices vary in their amphipathicity. The C-terminal helices thereby assume a conformation very similar to that of astressin bound to the ECD1 of CRF-R2 recently reported by our group.1 On the basis of an analysis of the observed 3D structures and relative potencies of [Ala]-substituted analogues, it is proposed that both helices could play a crucial role in receptor binding and selectivity. In conclusion, the C-terminal helices may interact along their hydrophobic faces with the ECD1, whereas the entire N-terminal helical surface may be involved in receptor activation. On the basis of the common and divergent features observed in the 3D structures of these ligands, multiple binding models are proposed that may explain their plurality of actions.

  5. Alterations in the corticotropin-releasing hormone (CRH) neurocircuitry: Insights into post stroke functional impairments.

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    Barra de la Tremblaye, P; Plamondon, H

    2016-07-01

    Although it is well accepted that changes in the regulation of the hypothalamic-pituitary adrenal (HPA) axis may increase susceptibility to affective disorders in the general population, this link has been less examined in stroke patients. Yet, the bidirectional association between depression and cardiovascular disease is strong, and stress increases vulnerability to stroke. Corticotropin-releasing hormone (CRH) is the central stress hormone of the HPA axis pathway and acts by binding to CRH receptors (CRHR) 1 and 2, which are located in several stress-related brain regions. Evidence from clinical and animal studies suggests a role for CRH in the neurobiological basis of depression and ischemic brain injury. Given its importance in the regulation of the neuroendocrine, autonomic, and behavioral correlates of adaptation and maladaptation to stress, CRH is likely associated in the pathophysiology of post stroke emotional impairments. The goals of this review article are to examine the clinical and experimental data describing (1) that CRH regulates the molecular signaling brain circuit underlying anxiety- and depression-like behaviors, (2) the influence of CRH and other stress markers in the pathophysiology of post stroke emotional and cognitive impairments, and (3) context and site specific interactions of CRH and BDNF as a basis for the development of novel therapeutic targets. This review addresses how the production and release of the neuropeptide CRH within the various regions of the mesocorticolimbic system influences emotional and cognitive behaviors with a look into its role in psychiatric disorders post stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Potent and long-acting corticotropin releasing factor (CRF) receptor 2 selective peptide competitive antagonists.

    Science.gov (United States)

    Rivier, J; Gulyas, J; Kirby, D; Low, W; Perrin, M H; Kunitake, K; DiGruccio, M; Vaughan, J; Reubi, J C; Waser, B; Koerber, S C; Martinez, V; Wang, L; Taché, Y; Vale, W

    2002-10-10

    We present evidence that members of the corticotropin releasing factor (CRF) family assume distinct structures when interacting with the CRF(1) and CRF(2) receptors. Predictive methods, physicochemical measurements, and structure-activity relationship studies have suggested that CRF, its family members, and competitive antagonists such as astressin [cyclo(30-33)[DPhe(12),Nle(21),Glu(30),Lys(33),Nle(38)]hCRF((12-41))] assume an alpha-helical conformation when interacting with their receptors. We had shown that alpha-helical CRF((9-41)) and sauvagine showed some selectivity for CRF receptors other than that responsible for ACTH secretion(1) and later for CRF2.(2) More recently, we suggested the possibility of a helix-turn-helix motif around a turn encompassing residues 30-33(3) that would confer high affinity for both CRF(1) and CRF(2)(2,4) in agonists and antagonists of all members of the CRF family.(3) On the other hand, the substitutions that conferred ca. 100-fold CRF(2) selectivity to the antagonist antisauvagine-30 [[DPhe(11),His(12)]sauvagine((11-40))] did not confer such property to the corresponding N-terminally extended agonists. We find here that a Glu(32)-Lys(35) side chain to side chain covalent lactam constraint in hCRF and the corresponding Glu(31)-Lys(34) side chain to side chain covalent lactam constraint in sauvagine yield potent ligands that are selective for CRF(2). Additionally, we introduced deletions and substitutions known to increase duration of action to yield antagonists such as cyclo(31-34)[DPhe(11),His(12),C(alpha)MeLeu(13,39),Nle(17),Glu(31),Lys(34)]Ac-sauvagine((8-40)) (astressin(2)-B) with CRF(2) selectivities greater than 100-fold. CRF receptor autoradiography was performed in rat tissue known to express CRF(2) and CRF(1) in order to confirm that astressin(2)-B could indeed bind to established CRF(2) but not CRF(1) receptor-expressing tissues. Extended duration of action of astressin(2)-B vs that of antisauvagine-30 is demonstrated in

  7. The Pseudo signal peptide of the corticotropin-releasing factor receptor type 2A prevents receptor oligomerization.

    Science.gov (United States)

    Teichmann, Anke; Rutz, Claudia; Kreuchwig, Annika; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

    2012-08-03

    N-terminal signal peptides mediate the interaction of native proteins with the translocon complex of the endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) possesses an N-terminal pseudo signal peptide, which represents a so far unique domain within the large protein family of G protein-coupled receptors (GPCRs). In contrast to a conventional signal peptide, the pseudo signal peptide remains uncleaved and consequently forms a hydrophobic extension at the N terminus of the receptor. The functional consequence of the presence of the pseudo signal peptide is not understood. Here, we have analyzed the significance of this domain for receptor dimerization/oligomerization in detail. To this end, we took the CRF(2(a))R and the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R) possessing a conventional cleaved signal peptide and conducted signal peptide exchange experiments. Using single cell and single molecule imaging methods (fluorescence resonance energy transfer and fluorescence cross-correlation spectroscopy, respectively) as well as biochemical experiments, we obtained two novel findings; we could show that (i) the CRF(2(a))R is expressed exclusively as a monomer, and (ii) the presence of the pseudo signal peptide prevents its oligomerization. Thus, we have identified a novel functional domain within the GPCR protein family, which plays a role in receptor oligomerization and which may be useful to study the functional significance of this process in general.

  8. Inhibitory effect of ramosetron on corticotropin releasing factor- and soybean oil-induced delays in gastric emptying in rats.

    Science.gov (United States)

    Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Sengoku, Takanori; Seki, Nobuo

    2012-09-01

    Symptoms of functional dyspepsia (FD) are highly prevalent in patients with irritable bowel syndrome (IBS). However, the effects of therapeutic agents for IBS on the pathophysiology of FD are unclear. In this study, therefore, we examined the effects of ramosetron, a serotonin 5-HT(3) receptor antagonist, on corticotropin releasing factor (CRF)- and soybean oil-induced delays in gastric emptying of rats, in comparison with anti-diarrheal agent and spasmolytics. The involvement of 5-HT and the 5-HT(3) receptor in delayed gastric emptying was also evaluated. Corticotropin releasing factor was administered intravenously to rats 10min before oral administration of 0.05% phenol red solution, and the amount remaining in the stomach was measured after 30min. Soybean oil was administered orally with glass beads, and the number of residual beads in the stomach was counted 1h later. Both CRF and soybean oil inhibited gastric emptying dose-dependently. Ramosetron and itopride, a gastro-prokinetic agent, significantly reduced both CRF- and soybean oil-induced delays in gastric emptying, while an anti-diarrheal agent and spasmolytics aggravated them. Pretreatment with p-chlorophenylalanine for 2days to reduced the synthesis of endogenous 5-HT diminished the effects of both CRF and soybean oil on gastric emptying. A 5-HT(3) receptor agonist m-chlorophenylbiguanide suppressed gastric emptying of both phenol red and glass beads, and those effects were reversed by ramosetron. These results suggest that CRF and soybean oil suppress gastric emptying in rats by activating 5-HT(3) receptors, and that by antagonizing these receptors, ramosetron may ameliorate symptoms of FD in clinical settings. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  9. Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

    Science.gov (United States)

    Bhakta, Ami; Gavini, Kartheek; Yang, Euitaek; Lyman-Henley, Lani; Parameshwaran, Kodeeswaran

    2017-09-29

    Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1β protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Residues remote from the binding pocket control the antagonist selectivity towards the corticotropin-releasing factor receptor-1

    Science.gov (United States)

    Sun, Xianqiang; Cheng, Jianxin; Wang, Xu; Tang, Yun; Ågren, Hans; Tu, Yaoquan

    2015-01-01

    The corticotropin releasing factors receptor-1 and receptor-2 (CRF1R and CRF2R) are therapeutic targets for treating neurological diseases. Antagonists targeting CRF1R have been developed for the potential treatment of anxiety disorders and alcohol addiction. It has been found that antagonists targeting CRF1R always show high selectivity, although CRF1R and CRF2R share a very high rate of sequence identity. This has inspired us to study the origin of the selectivity of the antagonists. We have therefore built a homology model for CRF2R and carried out unbiased molecular dynamics and well-tempered metadynamics simulations for systems with the antagonist CP-376395 in CRF1R or CRF2R to address this issue. We found that the side chain of Tyr6.63 forms a hydrogen bond with the residue remote from the binding pocket, which allows Tyr6.63 to adopt different conformations in the two receptors and results in the presence or absence of a bottleneck controlling the antagonist binding to or dissociation from the receptors. The rotameric switch of the side chain of Tyr3566.63 allows the breaking down of the bottleneck and is a perquisite for the dissociation of CP-376395 from CRF1R.

  11. Corticotropin-releasing factor critical for zebrafish camouflage behavior is regulated by light and sensitive to ethanol.

    Science.gov (United States)

    Wagle, Mahendra; Mathur, Priya; Guo, Su

    2011-01-05

    The zebrafish camouflage response is an innate "hard-wired" behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both adenylyl cyclase 5 and extracellular signal-regulated kinase (ERK) is required for such ethanol-induced or light-induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP-dependent and ERK-dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol.

  12. Identification of corticotropin-releasing factor (CRF) target cells and effects of dexamethasone on binding in anterior pituitary using a fluorescent analog of CRF

    DEFF Research Database (Denmark)

    Schwartz, J; Billestrup, Nils; Perrin, M

    1986-01-01

    A fluorescein-conjugated bioactive analog of corticotropin-releasing factor (CRF) was synthesized and used to label cells that have high affinity CRF-binding sites. Of cultured bovine anterior pituitary cells, 6.1 +/- 0.6% were visible by fluorescence microscopy after incubation with the analog......-binding sites and suggest that binding of CRF to anterior pituitary cells is altered by glucocorticoids....

  13. Emerging Role for Corticotropin Releasing Factor Signaling in the Bed Nucleus of the Stria Terminalis at the Intersection of Stress and Reward

    Directory of Open Access Journals (Sweden)

    Yuval eSilberman

    2013-05-01

    Full Text Available Stress and anxiety play an important role in the development and maintanence 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. The BNST is a complex brain region with multiple afferent and efferent systems and a variety of cell types and there has only been limited work trying to understand how CRF modulates this complex neuronal system. 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 BNST CRF signaling in drug addiction and reinstatment with an emphasis on critical neurocircuitry within the BNST that may offer new insights into treatments for addiction.

  14. 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.

  15. Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor.

    Science.gov (United States)

    Bryce, Courtney A; Floresco, Stan B

    2016-07-01

    Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression.

  16. Involvement of serotonergic pathways in mediating the neuronal activity and genetic transcription of neuroendocrine corticotropin-releasing factor in the brain of systemically endotoxin-challenged rats

    Energy Technology Data Exchange (ETDEWEB)

    Laflamme, N.; Feuvrier, E.; Richard, D.; Rivest, S. [Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, 2705 boul. Laurier, Ste-Foy Quebec (Canada)

    1999-01-01

    The present study investigated the effect of serotonin depletion on the neuronal activity and transcription of corticotropin-releasing factor in the rat brain during the acute-phase response. Conscious male rats received an intraperitoneal (i.p.) injection with the immune activator lipopolysaccaride (25 {mu}g/100 g body wt) after being treated for three consecutive days with para-chlorophenylalanine (30 mg/100 g/day). This irreversible inhibitor of tryptophane-5-hydroxylase decreased hypothalamic serotonin levels by 96%. One, 3 and 6 h after a single i.p. injection of lipopolysaccharide or vehicle solution, rats were killed and their brains cut in 30-{mu}m coronal sections. Messenger RNAs encoding c-fos, nerve-growth factor inducible-B gene, corticotropin-releasing factor and the heteronuclear RNA encoding corticotropin-releasing factor primary transcript were assayed by in situ hybridization using {sup 35}S-labeled riboprobes, whereas Fos-immunoreactive nuclei were labeled by immunocytochemistry. Lipopolysaccharide induced a wide neuronal activation indicated by the expression of both immediate-early gene transcripts and Fos protein in numerous structures of the brain. The signal for both immediate-early gene transcripts was low to moderate 1 h after lipopolysaccharide administration, maximal at 3 h and decline at 6 h post-injection, whereas at that time, Fos-immunoreactive nuclei were still detected in most of the c-fos messenger RNA-positive structures. Interestingly, the strong and widespread induction of both immediate-early gene transcripts was almost totally inhibited by para-chlorophenylalanine treatment; in the hypothalamic paraventricular nucleus for example, c-fos messenger RNA signal and the number of Fos-immunoreactive positive cells were reduced by 80 and 48%, respectively, in serotonin-depleted rats treated with the bacterial endotoxin. This blunted neuronal response was also associated with an attenuated stimulation of neuroendocrine corticotropin-releasing

  17. Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

    Science.gov (United States)

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-01-01

    Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

  18. Sex differences in corticotropin-releasing factor receptor-1 action within the dorsal raphe nucleus in stress responsivity.

    Science.gov (United States)

    Howerton, Alexis R; Roland, Alison V; Fluharty, Jessica M; Marshall, Anikò; Chen, Alon; Daniels, Derek; Beck, Sheryl G; Bale, Tracy L

    2014-06-01

    Women are twice as likely as men to suffer from stress-related affective disorders. Corticotropin-releasing factor (CRF) is an important link between stress and mood, in part through its signaling in the serotonergic dorsal raphe (DR). Development of CRF receptor-1 (CRFr1) antagonists has been a focus of numerous clinical trials but has not yet been proven efficacious. We hypothesized that sex differences in CRFr1 modulation of DR circuits might be key determinants in predicting therapeutic responses and affective disorder vulnerability. Male and female mice received DR infusions of the CRFr1 antagonist, NBI 35965, or CRF and were evaluated for stress responsivity. Sex differences in indices of neural activation (cFos) and colocalization of CRFr1 throughout the DR were examined. Whole-cell patch-clamp electrophysiology assessed sex differences in serotonin neuron membrane characteristics and responsivity to CRF. Males showed robust behavioral and hypothalamic-pituitary-adrenal axis responses to DR infusion of NBI 35965 and CRF, whereas females were minimally responsive. Sex differences were also found for both CRF-induced DR cFos and CRFr1 co-localization throughout the DR. Electrophysiologically, female serotonergic neurons showed blunted membrane excitability and divergent inhibitory postsynaptic current responses to CRF application. These studies demonstrate convincing sex differences in CRFr1 activity in the DR, where blunted female responses to NBI 35965 and CRF suggest unique stress modulation of the DR. These sex differences might underlie affective disorder vulnerability and differential sensitivity to pharmacologic treatments developed to target the CRF system, thereby contributing to a current lack of CRFr1 antagonist efficacy in clinical trials. © 2013 Published by Society of Biological Psychiatry on behalf of Society of Biological Psychiatry.

  19. Behavioral and physiological responses to central administration of corticotropin-releasing factor in the bluebanded goby (Lythrypnus dalli).

    Science.gov (United States)

    Solomon-Lane, Tessa K; Grober, Matthew S

    2012-07-16

    Central manipulation of neuromodulators is critical to establishing causal links between brain function and behavioral output. The absence of a rigorous method of evaluating intracerebroventricular (i.c.v.) injection efficacy in small model organisms is one reason why peripheral administration of neuroactive substances is more common. We use the bluebanded goby (Lythrypnus dalli), a small, highly social fish, to 1) validate our method of i.c.v. injection by testing the hypothesis that corticotropin-releasing factor (CRF) elevates ventilation rate (VR) and 2) propose a novel bioassay using basal physiology and behavior during recovery from anesthesia/i.c.v. administration to assess injection efficacy, neuromodulator activity, and procedural confounds. Central CRF administration significantly increased ventilation rate, demonstrating successful delivery of CRF to the brain. There were no significant differences in cortisol among treatments. The injection procedure did, however, decouple the temporal relationship between the initiation of ventilation and time to regain equilibrium present in control fish. Importantly, neither i.c.v. vehicle nor CRF injection affected the initiation of ventilation, disrupted the stereotyped recovery pattern following anesthesia, or initiated an endocrine stress response. Taken together, we suggest that 1) i.c.v. injection can be effectively used to manipulate central levels of CRF in L. dalli and 2) physiological and behavioral recovery from anesthesia may be used to evaluate injection/technique efficacy. We will use these data in future studies as a measure of effective CRF delivery, to allow for appropriate recovery from i.c.v. injection, and to better evaluate independent effects of CRF on social and/or sexual behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Eosinophils express muscarinic receptors and corticotropin-releasing factor to disrupt the mucosal barrier in ulcerative colitis.

    Science.gov (United States)

    Wallon, Conny; Persborn, Mats; Jönsson, Maria; Wang, Arthur; Phan, Van; Lampinen, Maria; Vicario, Maria; Santos, Javier; Sherman, Philip M; Carlson, Marie; Ericson, Ann-Charlott; McKay, Derek M; Söderholm, Johan D

    2011-05-01

    Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropin-releasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers ((51)Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), α-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Dissociation of corticotropin-releasing factor receptor subtype involvement in sensitivity to locomotor effects of methamphetamine and cocaine.

    Science.gov (United States)

    Giardino, William J; Mark, Gregory P; Stenzel-Poore, Mary P; Ryabinin, Andrey E

    2012-02-01

    Enhanced sensitivity to the euphoric and locomotor-activating effects of psychostimulants may influence an individual's predisposition to drug abuse and addiction. While drug-induced behaviors are mediated by the actions of several neurotransmitter systems, past research revealed that the corticotropin-releasing factor (CRF) system is important in driving the acute locomotor response to psychostimulants. We previously reported that genetic deletion of the CRF type-2 receptor (CRF-R2), but not the CRF type-1 receptor (CRF-R1) dampened the acute locomotor stimulant response to methamphetamine (1 mg/kg). These results contrasted with previous studies implicating CRF-R1 in the locomotor effects of psychostimulants. Since the majority of previous studies focused on cocaine, rather than methamphetamine, we set out to test the hypothesis that these drugs differentially engage CRF-R1 and CRF-R2. We expanded our earlier findings by first replicating our previous experiments at a higher dose of methamphetamine (2 mg/kg), and by assessing the effects of the CRF-R1-selective antagonist CP-376,395 (10 mg/kg) on methamphetamine-induced locomotor activity. Next, we used both genetic and pharmacological tools to examine the specific components of the CRF system underlying the acute locomotor response to cocaine (5-10 mg/kg). While genetic deletion of CRF-R2 dampened the locomotor response to methamphetamine (but not cocaine), genetic deletion and pharmacological blockade of CRF-R1 dampened the locomotor response to cocaine (but not methamphetamine). These findings highlight the differential involvement of CRF receptors in acute sensitivity to two different stimulant drugs of abuse, providing an intriguing basis for the development of more targeted therapeutics for psychostimulant addiction.

  2. 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.

  3. Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

    Science.gov (United States)

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

    2013-09-01

    Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

  4. A role for corticotropin-releasing factor signaling in the lateral habenula and its modulation by early-life stress.

    Science.gov (United States)

    Authement, Michael E; Langlois, Ludovic D; Shepard, Ryan D; Browne, Caroline A; Lucki, Irwin; Kassis, Haifa; Nugent, Fereshteh S

    2018-03-06

    Centrally released corticotropin-releasing factor or hormone (extrahypothalamic CRF or CRH) in the brain is involved in the behavioral and emotional responses to stress. The lateral habenula (LHb) is an epithalamic brain region involved in value-based decision-making and stress evasion. Through its inhibition of dopamine-mediated reward circuitry, the increased activity of the LHb is associated with addiction, depression, schizophrenia, and behavioral disorders. We found that extrahypothalamic CRF neurotransmission increased neuronal excitability in the LHb. Through its receptor CRFR1 and subsequently protein kinase A (PKA), CRF application increased the intrinsic excitability of LHb neurons by affecting changes in small-conductance SK-type and large-conductance BK-type K + channels. CRF also reduced inhibitory γ-aminobutyric acid-containing (GABAergic) synaptic transmission onto LHb neurons through endocannabinoid-mediated retrograde signaling. Maternal deprivation is a severe early-life stress that alters CRF neural circuitry and is likewise associated with abnormal mental health later in life. LHb neurons from pups deprived of maternal care exhibited increased intrinsic excitability, reduced GABAergic transmission, decreased abundance of SK2 channel protein, and increased activity of PKA, without any substantial changes in Crh or Crhr1 expression. Furthermore, maternal deprivation blunted the response of LHb neurons to subsequent, acute CRF exposure. Activating SK channels or inhibiting postsynaptic PKA activity prevented the effects of both CRF and maternal deprivation on LHb intrinsic excitability, thus identifying potential pharmacological targets to reverse central CRF circuit dysregulation in patients with associated disorders. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. Corticotropin-releasing factor: effect on cerebral blood flow in physiologic and ischaemic conditions.

    Science.gov (United States)

    De Michele, Manuela; Touzani, Omar; Foster, Alan C; Fieschi, Cesare; Sette, Giuliano; McCulloch, James

    2005-09-01

    The expression of corticotrophin-releasing factor (CRF) receptors in cerebral arteries and arterioles suggests that CRF may modulate cerebral blood flow (CBF). In the present study, the effects of CRF, CRF-like peptides and the CRF broad spectrum antagonist DPhe-CRF on CBF have been investigated under normal physiologic conditions and in the margins of focal ischaemic insult. The experiments were carried out in anaesthetised and ventilated rats. Changes in CBF after subarachnoid microapplication of CRF and related peptides were assessed with a laser-Doppler flowmetry (LDF) probe. In the ischaemic animals, agents were injected approximately 60 minutes after permanent middle cerebral artery occlusion (MCAo). Microapplication of CRF and related peptides in normal rats into the subarachnoid space produced sustained concentration-dependent increases in CBF. This effect was attenuated by co-application with DPhe-CRF, which did not alter CBF itself. A second microapplication of CRF 30 min after the first failed to produce increases in CBF in normal animals. Microapplication of CRF in the subarachnoid space overlying the ischaemic cortex effected minor increases in CBF whereas D-Phe-CRF had no significant effect on CBF. Activation of the CRF peptidergic system increases CBF in the rat. Repeated activation of CRF receptors results in tachyphylaxis of the vasodilator response. CRF vasodilator response is still present after MCAo in the ischaemic penumbra, suggesting that the CRF peptidergic system may modulate CBF in ischaemic stroke.

  6. 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

  7. 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

    2006-04-13

    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 microl) or amphetamine (20 microg/0.2 microl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 microg) 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 attempts to

  8. Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption.

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    Pucci, Mariangela; Micioni Di Bonaventura, Maria Vittoria; Giusepponi, Maria Elena; Romano, Adele; Filaferro, Monica; Maccarrone, Mauro; Ciccocioppo, Roberto; Cifani, Carlo; D'Addario, Claudio

    2016-11-01

    Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin-releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF-1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF-1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge-eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds. © 2015 Society for the Study of Addiction.

  9. The specific monomer/dimer equilibrium of the corticotropin-releasing factor receptor type 1 is established in the endoplasmic reticulum.

    Science.gov (United States)

    Teichmann, Anke; Gibert, Arthur; Lampe, André; Grzesik, Paul; Rutz, Claudia; Furkert, Jens; Schmoranzer, Jan; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

    2014-08-29

    G protein-coupled receptors (GPCRs) represent the most important drug targets. Although the smallest functional unit of a GPCR is a monomer, it became clear in the past decades that the vast majority of the receptors form dimers. Only very recently, however, data were presented that some receptors may in fact be expressed as a mixture of monomers and dimers and that the interaction of the receptor protomers is dynamic. To date, equilibrium measurements were restricted to the plasma membrane due to experimental limitations. We have addressed the question as to where this equilibrium is established for the corticotropin-releasing factor receptor type 1. By developing a novel approach to analyze single molecule fluorescence cross-correlation spectroscopy data for intracellular membrane compartments, we show that the corticotropin-releasing factor receptor type 1 has a specific monomer/dimer equilibrium that is already established in the endoplasmic reticulum (ER). It remains constant at the plasma membrane even following receptor activation. Moreover, we demonstrate for seven additional GPCRs that they are expressed in specific but substantially different monomer/dimer ratios. Although it is well known that proteins may dimerize in the ER in principle, our data show that the ER is also able to establish the specific monomer/dimer ratios of GPCRs, which sheds new light on the functions of this compartment. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. [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.

  11. Enduring sensorimotor gating abnormalities following predator exposure or corticotropin-releasing factor in rats: a model for PTSD-like information-processing deficits?

    Science.gov (United States)

    Bakshi, Vaishali P; Alsene, Karen M; Roseboom, Patrick H; Connors, Elenora E

    2012-02-01

    A deficit in prepulse inhibition (PPI) can be one of the clinically observed features of post-traumatic stress disorder (PTSD) that is seen long after the acute traumatic episode has terminated. Thus, reduced PPI may represent an enduring psychophysiological marker of this illness in some patients. PPI is an operational measure of sensorimotor gating and refers to the phenomenon in which a weak stimulus presented immediately before an intense startling stimulus inhibits the magnitude of the subsequent startle response. The effects of stress on PPI have been relatively understudied, and in particular, there is very little information on PPI effects of ethologically relevant psychological stressors. We aimed to develop a paradigm for evaluating stress-induced sensorimotor gating abnormalities by comparing the effects of a purely psychological stressor (predator exposure) to those of a nociceptive physical stressor (footshock) on PPI and baseline startle responses in rats over an extended period of time following stressor presentation. Male Sprague-Dawley rats were exposed (within a protective cage) to ferrets for 5 min or left in their homecage and then tested for PPI immediately, 24 h, 48 h, and 9 days after the exposure. The effects of footshock were evaluated in a separate set of rats. The effects seen with stressor presentation were compared to those elicited by corticotropin-releasing factor (CRF; 0.5 and 3 μg/6 μl, intracerebroventricularly). Finally, the effects of these stressors and CRF administration on plasma corticosterone were measured. PPI was disrupted 24 h after ferret exposure; in contrast, footshock failed to affect PPI at any time. CRF mimicked the predator stress profile, with the lowdose producing a PPI deficit 24 h after infusion. Interestingly, the high dose also produced a PPI deficit 24 h after infusion, but with this dose, the PPI deficit was evident even 9d later. Plasma corticosterone levels were elevated acutely (before PPI deficits

  12. Fecal pellet output does not always correlate with colonic transit in response to restraint stress and corticotropin-releasing factor in rats

    International Nuclear Information System (INIS)

    Nakade, Yukiomi; Mantyh, C.; Pappas, T.N.; Takahashi, Toku

    2007-01-01

    Fecal pellet output has been assessed as a colonic motor activity because of its simplicity. However, it remains unclear whether an acceleration of colonic transit correlates well with an increase in fecal pellet output. We examined the causal relationship between colonic transit and fecal pellet output stimulated by the central application of corticotropin-releasing factor (CRF) and restraint stress. Immediately after intracisternal injection of CRF, 51 Cr was injected via a catheter positioned in the proximal colon. Ninety minutes after 51 Cr injection, the total number of excreted feces was counted, and then the rats were killed. The radioactivity of each colonic segment was evaluated, and the geometric center (GC) of the distribution of 51 Cr was calculated. For the restraint stress study, after administration of 51 Cr into the proximal colon, rats were submitted to wrapping restraint stress for 90 min. Then they were killed, and GC was calculated. Both restraint stress and CRF significantly accelerated colonic transit. There was a positive correlation observed between fecal pellet output and GC of colonic transit in response to restraint stress, but not CRF, when the number of excreted feces was more than three. In contrast, there was no significant correlation observed between the two in stress and CRF when the number of excreted feces was less than two. The acceleration of colonic transit in response to restraint stress and central administration of CRF does not always correlate with an increase in fecal pellet output. (author)

  13. Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

    Science.gov (United States)

    Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

    2016-10-05

    A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor.

    Science.gov (United States)

    Turner, Laura H; Lim, Chen E; Heinrichs, Stephen C

    2007-02-01

    Social interaction phenotyping is an unexplored niche in animal modeling of epilepsy despite the sensitivity of affiliative behaviors to emotionality and stress, which are known seizure triggers. Thus, the present studies examined the social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in untreated animals and following preexposure to a handling stressor. The second aim of the present studies was to evaluate the dependence of sociability in El mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively reduced CRF peptide levels in the basolateral amygdala of El mice. El mice exhibited lower social investigation times than ddY counterparts, whereas central administration of CRF-SAP normalized social investigation times relative to ddY controls. Moreover, handling-induced seizures in El mice were reduced by 50% following treatment with CRF-SAP relative to saporin alone-injected El controls. The results of this study suggest that tonically activated CRF systems in the El mouse brain suppress affiliative behavior and facilitate evoked seizures.

  15. Differential effects of stress and amphetamine administration on Fos-like protein expression in corticotropin releasing factor-neurons of the rat brain.

    Science.gov (United States)

    Rotllant, David; Nadal, Roser; Armario, Antonio

    2007-05-01

    Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine.

  16. Activation of corticotropin-releasing factor receptors from the basolateral or central amygdala increases the tonic immobility response in guinea pigs: an innate fear behavior.

    Science.gov (United States)

    Donatti, Alberto Ferreira; Leite-Panissi, Christie Ramos Andrade

    2011-11-20

    The tonic immobility (TI) behavior is an innate response associated with extreme threat situations such as a predator attack. Several studies have provided evidence suggesting an important role for corticotropin-releasing factor (CRF) in the regulation of the endocrine system, defensive behaviors and behavioral responses to stress. TI has been shown to be positively correlated with the basal plasma levels of corticosterone. CRF receptors and neurons that are immunoreactive to CRF are found in many cerebral regions, especially in the amygdaloid complex. Previous reports have demonstrated the involvement of the basolateral amygdaloid (BLA) and central amygdaloid (CeA) nuclei in the TI response. In this study, we evaluated the CRF system of the BLA and the CeA in the modulation of the TI response in guinea pigs. The activation of CRF receptors in the BLA and in the CeA promoted an increase in the TI response. In contrast, the inhibition of these receptors via alpha-helical-CRF(9-41) decreased the duration of the TI response. Moreover, neither the activation nor inhibition of CRF receptors in the BLA or the CeA altered spontaneous motor activity in the open-field test. These data suggest that the activation of the CRF receptors in the BLA or the CeA probably potentiates fear and anxiety, which may be one of the factors that promote an increase in the TI behavior. Therefore, these data support the role of the CRF system in the control of emotional responses, particularly in the modulation of innate fear. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Corticotropin-releasing Factor in the Rat Dorsal Raphe Nucleus Promotes Different Forms of Behavioral Flexibility Depending on Social Stress History.

    Science.gov (United States)

    Snyder, Kevin P; Hill-Smith, Tiffany E; Lucki, Irwin; Valentino, Rita J

    2015-10-01

    The stress-related neuropeptide, corticotropin-releasing factor (CRF) regulates the dorsal raphe nucleus-serotonin (DRN-5-HT) system during stress and this may underlie affective and cognitive dysfunctions that characterize stress-related psychiatric disorders. CRF acts on both CRF1 and CRF2 receptor subtypes in the DRN that exert opposing inhibitory and excitatory effects on DRN-5-HT neuronal activity and 5-HT forebrain release, respectively. The current study first assessed the cognitive effects of intra-DRN microinfusion of CRF or the selective CRF2 agonist, urocortin II in stress-naive rats on performance of an operant strategy set-shifting task that is mediated by the medial prefrontal cortex (mPFC). CRF (30 ng) facilitated strategy set-shifting performance, whereas higher doses of CRF and urocortin II that would interact with CRF2 were without effect, consistent with a CRF1-mediated action. This dose decreased 5-HT extracellular levels in the mPFC, further supporting a role for CRF1. The effects of CRF were then assessed in rats exposed to repeated social stress using the resident-intruder model. Repeated social stress shifted the CRF effect from facilitation of strategy set shifting to facilitation of reversal learning and this was most prominent in a subpopulation of rats that resist defeat. Notably, in this subpopulation of rats 5-HT neuronal responses to CRF have been demonstrated to shift from CRF1-mediated inhibition to CRF2-mediated excitation. Because 5-HT facilitates reversal learning, the present results suggest that stress-induced changes in the cellular effects of CRF in the DRN translate to changes in cognitive effects of CRF. Together, the results underscore the potential for stress history to shift cognitive processing through changes in CRF neurotransmission in the DRN and the association of this effect with coping strategy.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Corticotropin-Releasing Factor Receptors Modulate Oxytocin Release in the Dorsolateral Bed Nucleus of the Stria Terminalis (BNST in Male Rats

    Directory of Open Access Journals (Sweden)

    Daisy Martinon

    2018-03-01

    Full Text Available The neuropeptide oxytocin (OT plays an important role in the regulation of social and anxiety-like behavior. Our previous studies have shown that OT neurons send projections from the hypothalamus to the dorsolateral bed nucleus of the stria terminalis (BNSTdl, a forebrain region critically involved in the modulation of anxiety-like behavior. Importantly, these OT terminals in the BNSTdl express presynaptic corticotropin releasing factor (CRF receptor type 2 (CRFR2. This suggests that CRFR2 might be involved in the modulation of OT release. To test this hypothesis, we measured OT content in microdialysates collected from the BNSTdl of freely-moving male Sprague-Dawley rats following the administration of a selective CRFR2 agonist (Urocortin 3 or antagonist (Astressin 2B, As2B. To determine if type 1 CRF receptors (CRFR1 are also involved, we used selective CRFR1 antagonist (NBI35965 as well as CRF, a putative ligand of both CRFR1 and CRFR2. All compounds were delivered directly into the BNSTdl via reverse dialysis. OT content in the microdialysates was measured with highly sensitive and selective radioimmunoassay. Blocking CRFR2 with As2B caused an increase in OT content in BNSTdl microdialysates, whereas CRFR2 activation by Urocortin 3 did not have an effect. The As2B-induced increase in OT release was blocked by application of the CRFR1 antagonist demonstrating that the effect was dependent on CRFR1 transmission. Interestingly, CRF alone caused a delayed increase in OT content in BNSTdl microdialysates, which was dependent on CRF2 but not CRF1 receptors. Our results suggest that members of the CRF peptide family modulate OT release in the BNSTdl via a fine-tuned mechanism that involves both CRFR1 and CRFR2. Further exploration of mechanisms by which endogenous OT system is modulated by CRF peptide family is needed to better understand the role of these neuropeptides in the regulation of anxiety and the stress response.

  20. Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala

    Science.gov (United States)

    Flandreau, Elizabeth I.; Bourke, Chase H.; Ressler, Kerry J.; Vale, Wylie W.; Nemeroff, Charles B.; Owens, Michael J.

    2013-01-01

    Summary We have previously demonstrated that viral-mediated overexpression of corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) reproduces many of the behavioral and endocrine consequences of chronic stress. The present experiment sought to determine whether administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram reverses the adverse effects of CeA CRF overexpression. In a 2 × 2 design, adult male rats received bilateral infusions of a control lentivirus or a lentivirus in which a portion of the CRF promoter is used to drive increased expression of CRF peptide. Four weeks later, rats were then implanted with an Alzet minipump to deliver vehicle or 10 mg/kg/day escitalopram for a 4-week period of time. The defensive withdrawal (DW) test of anxiety and the sucrose-preference test (SPT) of anhedonia were performed both before and after pump implantation. Additional post-implant behavioral tests included the elevated plus maze (EPM) and social interaction (SI) test. Following completion of behavioral testing, the dexamethasone/CRF test was performed to assess HPA axis reactivity. Brains were collected and expression of HPA axis-relevant transcripts were measured using in situ hybridization. Amygdalar CRF overexpression increased anxiety-like behavior in the DW test at week eight, which was only partially prevented by escitalopram. In both CRF-overexpressing and control groups, escitalopram decreased hippocampal CRF expression while increasing hypothalamic and hippocampal expression of the glucocorticoid receptor (GR). These gene expression changes were associated with a significant decrease in HPA axis reactivity in rats treated with escitalopram. Interestingly, escitalopram increased the rate of weight gain only in rats overexpressing CRF. Overall these data support our hypothesis that amygdalar CRF is critical in anxiety-like behavior; because the antidepressant was unable to reverse behavioral

  1. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor.

    Science.gov (United States)

    Lewis, K; Li, C; Perrin, M H; Blount, A; Kunitake, K; Donaldson, C; Vaughan, J; Reyes, T M; Gulyas, J; Fischer, W; Bilezikjian, L; Rivier, J; Sawchenko, P E; Vale, W W

    2001-06-19

    The corticotropin-releasing factor (CRF) family of neuropeptides includes the mammalian peptides CRF, urocortin, and urocortin II, as well as piscine urotensin I and frog sauvagine. The mammalian peptides signal through two G protein-coupled receptor types to modulate endocrine, autonomic, and behavioral responses to stress, as well as a range of peripheral (cardiovascular, gastrointestinal, and immune) activities. The three previously known ligands are differentially distributed anatomically and have distinct specificities for the two major receptor types. Here we describe the characterization of an additional CRF-related peptide, urocortin III, in the human and mouse. In searching the public human genome databases we found a partial expressed sequence tagged (EST) clone with significant sequence identity to mammalian and fish urocortin-related peptides. By using primers based on the human EST sequence, a full-length human clone was isolated from genomic DNA that encodes a protein that includes a predicted putative 38-aa peptide structurally related to other known family members. With a human probe, we then cloned the mouse ortholog from a genomic library. Human and mouse urocortin III share 90% identity in the 38-aa putative mature peptide. In the peptide coding region, both human and mouse urocortin III are 76% identical to pufferfish urocortin-related peptide and more distantly related to urocortin II, CRF, and urocortin from other mammalian species. Mouse urocortin III mRNA expression is found in areas of the brain including the hypothalamus, amygdala, and brainstem, but is not evident in the cerebellum, pituitary, or cerebral cortex; it is also expressed peripherally in small intestine and skin. Urocortin III is selective for type 2 CRF receptors and thus represents another potential endogenous ligand for these receptors.

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

    International Nuclear Information System (INIS)

    Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L.

    2014-01-01

    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

  3. The effect of short moderate stress on the midbrain corticotropin-releasing factor system in a macaque model of functional hypothalamic amenorrhea.

    Science.gov (United States)

    Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

    2013-10-01

    To study the effect of moderate stress on corticotropin-releasing factor (CRF) components in the serotonergic midbrain region in a monkey model of functional hypothalamic amenorrhea. After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days before euthanasia. Primate research center. Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n = 5), medium stress resilient (n = 4), or stress sensitive (SS, n = 4). Five days of diet in a novel room with unfamiliar conspecifics. Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of urocortin 1 (UCN1) cells; the density of UCN1 axons; the expression of CRF receptor 1 (CRF-R1) and CRF-R2 in the dorsal raphe nucleus. The CRF innervation was higher in HSR than in SS animals; UCN1 cell number was higher in HSR than in SS animals and UCN1 axon bouton density was not different; all opposite of nonstressed animals. The CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than in SS animals. The relative expression of CRF-R1 and CRF-R2 was similar to nonstressed animals. The HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. The CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Adolescent binge drinking leads to changes in alcohol drinking, anxiety, and amygdalar corticotropin releasing factor cells in adulthood in male rats.

    Directory of Open Access Journals (Sweden)

    Nicholas W Gilpin

    Full Text Available Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (~postnatal days 28-42 in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF cell in the lateral portion of the central amygdala (CeA, a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity, an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects

  5. Is it really a matter of simple dualism? Corticotropin-releasing factor receptors in body and mental health.

    Science.gov (United States)

    Janssen, Donny; Kozicz, Tamás

    2013-01-01

    Physiological responses to stress coordinated by the hypothalamo-pituitary-adrenal axis are concerned with maintaining homeostasis in the presence of real or perceived challenges. Regulators of this axis are corticotrophin releasing factor (CRF) and CRF related neuropeptides, including urocortins 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.

  6. Corticotropin Releasing Factor in the Bed Nucleus of the Stria Terminalis in Socially Defeated and Non-stressed Mice with a History of Chronic Alcohol Intake.

    Science.gov (United States)

    Albrechet-Souza, Lucas; Viola, Thiago W; Grassi-Oliveira, Rodrigo; Miczek, Klaus A; de Almeida, Rosa M M

    2017-01-01

    Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated use to the development of alcohol dependence. Preclinical studies have shown that dysregulation of the corticotropin releasing factor (CRF) neurotransmission has been implicated in stress-related psychopathologies such as depression and anxiety, and may affect alcohol consumption. The bed nucleus of the stria terminalis (BNST) contains CRF-producing neurons which seem to be sensitive to stress. In this study, adult male C57BL/6 mice previously defeated in resident-intruder confrontations were evaluated in the elevated plus-maze and tail suspension test. Mice were also tested for sweet solution intake before and after social stress. After having had continuous access to ethanol (20% weight/volume) for 4 weeks, control and stressed mice had CRF type 1 (CRFR1) or type 2 (CRFR2) receptor antagonists infused into the BNST and then had access to ethanol for 24 h. In separate cohorts of control and stressed mice, we assessed mRNA levels of BNST CRF, CRFR1 and CRFR2 . Stressed mice increased their intake of sweet solution after ten sessions of social defeat and showed reduced activity in the open arms of the elevated plus-maze. When tested for ethanol consumption, stressed mice persistently drank significantly more than controls during the 4 weeks of access. Also, social stress induced higher BNST CRF mRNA levels. The selective blockade of BNST CRFR1 with CP376,395 effectively reduced alcohol drinking in non-stressed mice, whereas the selective CRFR2 antagonist astressin2B produced a dose-dependent increase in ethanol consumption in both non-stressed controls and stressed mice. The 10-day episodic defeat stress used here elicited anxiety- but not depressive-like behaviors, and promoted an increase in ethanol drinking. CRF-CRFR1 signaling in the BNST seems to underlie ethanol intake in non-stressed mice, whereas CRFR2 modulates alcohol

  7. Corticotropin Releasing Factor in the Bed Nucleus of the Stria Terminalis in Socially Defeated and Non-stressed Mice with a History of Chronic Alcohol Intake

    Directory of Open Access Journals (Sweden)

    Lucas Albrechet-Souza

    2017-10-01

    Full Text Available Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated use to the development of alcohol dependence. Preclinical studies have shown that dysregulation of the corticotropin releasing factor (CRF neurotransmission has been implicated in stress-related psychopathologies such as depression and anxiety, and may affect alcohol consumption. The bed nucleus of the stria terminalis (BNST contains CRF-producing neurons which seem to be sensitive to stress. In this study, adult male C57BL/6 mice previously defeated in resident-intruder confrontations were evaluated in the elevated plus-maze and tail suspension test. Mice were also tested for sweet solution intake before and after social stress. After having had continuous access to ethanol (20% weight/volume for 4 weeks, control and stressed mice had CRF type 1 (CRFR1 or type 2 (CRFR2 receptor antagonists infused into the BNST and then had access to ethanol for 24 h. In separate cohorts of control and stressed mice, we assessed mRNA levels of BNST CRF, CRFR1 and CRFR2. Stressed mice increased their intake of sweet solution after ten sessions of social defeat and showed reduced activity in the open arms of the elevated plus-maze. When tested for ethanol consumption, stressed mice persistently drank significantly more than controls during the 4 weeks of access. Also, social stress induced higher BNST CRF mRNA levels. The selective blockade of BNST CRFR1 with CP376,395 effectively reduced alcohol drinking in non-stressed mice, whereas the selective CRFR2 antagonist astressin2B produced a dose-dependent increase in ethanol consumption in both non-stressed controls and stressed mice. The 10-day episodic defeat stress used here elicited anxiety- but not depressive-like behaviors, and promoted an increase in ethanol drinking. CRF-CRFR1 signaling in the BNST seems to underlie ethanol intake in non-stressed mice, whereas CRFR2 modulates

  8. Corticotropin-releasing factor in the basolateral amygdala enhances memory consolidation via an interaction with the beta-adrenoceptor-cAMP pathway: dependence on glucocorticoid receptor activation.

    Science.gov (United States)

    Roozendaal, Benno; Schelling, Gustav; McGaugh, James L

    2008-06-25

    Extensive evidence indicates that stress hormone effects on the consolidation of emotionally influenced memory involve noradrenergic activation of the basolateral complex of the amygdala (BLA). The present experiments examined whether corticotropin-releasing factor (CRF) modulates memory consolidation via an interaction with the beta-adrenoceptor-cAMP system in the BLA. In a first experiment, male Sprague Dawley rats received bilateral infusions of the CRF-binding protein ligand inhibitor CRF(6-33) into the BLA either alone or together with the CRF receptor antagonist alpha-helical CRF(9-41) immediately after inhibitory avoidance training. CRF(6-33) induced dose-dependent enhancement of 48 h retention latencies, which was blocked by coadministration of alpha-helical CRF(9-41), suggesting that CRF(6-33) enhances memory consolidation by displacing CRF from its binding protein, thereby increasing "free" endogenous CRF concentrations. In a second experiment, intra-BLA infusions of atenolol (beta-adrenoceptor antagonist) and Rp-cAMPS (cAMP inhibitor), but not prazosin (alpha(1)-adrenoceptor antagonist), blocked CRF(6-33)-induced retention enhancement. In a third experiment, the CRF receptor antagonist alpha-helical CRF(9-41) administered into the BLA immediately after training attenuated the dose-response effects of concurrent intra-BLA infusions of clenbuterol (beta-adrenoceptor agonist). In contrast, alpha-helical CRF(9-41) did not alter retention enhancement induced by posttraining intra-BLA infusions of either cirazoline (alpha(1)-adrenoceptor agonist) or 8-br-cAMP (cAMP analog). These findings suggest that CRF facilitates the memory-modulatory effects of noradrenergic stimulation in the BLA via an interaction with the beta-adrenoceptor-cAMP cascade, at a locus between the membrane-bound beta-adrenoceptor and the intracellular cAMP formation site. Moreover, consistent with evidence that glucocorticoids enhance memory consolidation via a similar interaction with the

  9. Hexa-histidin tag position influences disulfide structure but not binding behavior of in vitro folded N-terminal domain of rat corticotropin-releasing factor receptor type 2a

    OpenAIRE

    Klose, Jana; Wendt, Norbert; Kubald, Sybille; Krause, Eberhard; Fechner, Klaus; Beyermann, Michael; Bienert, Michael; Rudolph, Rainer; Rothemund, Sven

    2004-01-01

    The oxidative folding, particularly the arrangement of disulfide bonds of recombinant extracellular N-terminal domains of the corticotropin-releasing factor receptor type 2a bearing five cysteines (C2 to C6), was investigated. Depending on the position of a His-tag, two types of disulfide patterns were found. In the case of an N-terminal His-tag, the disulfide bonds C2–C3 and C4–C6 were found, leaving C5 free, whereas the C-terminal position of the His-tag led to the disulfide pattern C2–C5 a...

  10. Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans

    International Nuclear Information System (INIS)

    Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G.; Cossett, J.M.; Magdelenat, H.

    1994-01-01

    Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig

  11. Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Berga, S L; Loucks-Daniels, T L; Adler, L J; Chrousos, G P; Cameron, J L; Matthews, K A; Marcus, M D

    2000-04-01

    Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and beta-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. Corticotropin-releasing hormone, vasopressin, and beta-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and beta-endorphin levels were lower in women with functional hypothalamic amenorrhea. In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid corticotropin-releasing hormone, vasopressin, or beta-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea.

  12. Role of innate and drug-induced dysregulation of brain stress and arousal systems in addiction: Focus on corticotropin-releasing factor, nociceptin/orphanin FQ, and orexin/hypocretin

    Science.gov (United States)

    Martin-Fardon, Rémi; Zorrilla, Eric P.; Ciccocioppo, Roberto; Weiss, Friedbert

    2010-01-01

    Stress-like symptoms are an integral part of acute and protracted drug withdrawal, and several lines of evidence have shown that dysregulation of brain stress systems, including the extrahypothalamic corticotropin-releasing factor (CRF) system, following long-term drug use is of major importance in maintaining drug and alcohol addiction. Recently, two other neuropeptide systems have attracted interest, the nociceptin/orphanin FQ (N/OFQ) and orexin/hypocretin (Orx/Hcrt) systems. N/OFQ participates in a wide range of physiological responses, and the hypothalamic Orx/Hcrt system helps regulate several physiological processes, including feeding, energy metabolism, and arousal. Moreover, these two systems have been suggested to participate in psychiatric disorders, including anxiety and drug addiction. Dysregulation of these systems by chronic drug exposure has been hypothesized to play a role in the maintenance of addiction and dependence. Recent evidence demonstrated that interactions between CRF-N/OFQ and CRF-Orx/Hcrt systems may be functionally relevant for the control of stress-related addictive behavior. The present review discusses recent findings that support the hypotheses of the participation and dysregulation of these systems in drug addiction and evaluates the current understanding of interactions among these stress-regulatory peptides. PMID:20026088

  13. Up-regulation of corticotropin releasing hormone is associated with ...

    African Journals Online (AJOL)

    Purpose: To determine the expression of corticotropin-releasing hormone (CRH) in psoriasis and ... Methods: Psoriasis and normal skin biopsy samples were obtained from three psoriatic and ... established in literature that stress signals such.

  14. A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain

    International Nuclear Information System (INIS)

    Moon, Bo-Hyun; Hong, Chang Gwun; Kim, Soo-Young; Kim, Hyun-Ju; Shin, Seung Keon; Kang, Seungwoo; Lee, Kuem-Ju; Kim, Yong-Ku; Lee, Min-Soo; Shin, Kyung-Ho

    2008-01-01

    The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 μg/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 μg/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration

  15. Corticotropin-releasing hormone: Mediator of vertebrate life stage transitions?

    Science.gov (United States)

    Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert

    2016-03-01

    Hormones, particularly thyroid hormones and corticosteroids, play critical roles in vertebrate life stage transitions such as amphibian metamorphosis, hatching in precocial birds, and smoltification in salmonids. Since they synergistically regulate several metabolic and developmental processes that accompany vertebrate life stage transitions, the existence of extensive cross-communication between the adrenal/interrenal and thyroidal axes is not surprising. Synergies of corticosteroids and thyroid hormones are based on effects at the level of tissue hormone sensitivity and gene regulation. In addition, in representative nonmammalian vertebrates, corticotropin-releasing hormone (CRH) stimulates hypophyseal thyrotropin secretion, and thus functions as a common regulator of both the adrenal/interrenal and thyroidal axes to release corticosteroids and thyroid hormones. The dual function of CRH has been speculated to control or affect the timing of vertebrate life history transitions across taxa. After a brief overview of recent insights in the molecular mechanisms behind the synergic actions of thyroid hormones and corticosteroids during life stage transitions, this review examines the evidence for a possible role of CRH in controlling vertebrate life stage transitions. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 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

  17. Corticotropin-releasing factor overexpression in mice abrogates sex differences in body weight, visceral fat, and food intake response to a fast and alters levels of feeding regulatory hormones.

    Science.gov (United States)

    Wang, Lixin; Goebel-Stengel, Miriam; Yuan, Pu-Qing; Stengel, Andreas; Taché, Yvette

    2017-01-01

    Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. Male and female CRF-OE mice and WT littermates (4-6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals. Under fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females. These data indicate that CRF-OE mice have abnormal basal and fasting

  18. Up-regulation of corticotropin releasing hormone is associated with ...

    African Journals Online (AJOL)

    Purpose: To determine the expression of corticotropin-releasing hormone (CRH) in psoriasis and normal skin biopsy samples, and to correlate the expression of CRH with the expression of CRHBP and inflammatory cytokines IL-8 and IL-33. Methods: Psoriasis and normal skin biopsy samples were obtained from three ...

  19. Genetic moderation of child maltreatment effects on depression and internalizing symptoms by serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter (NET), and corticotropin releasing hormone receptor 1 (CRHR1) genes in African American children.

    Science.gov (United States)

    Cicchetti, Dante; Rogosch, Fred A

    2014-11-01

    Genetic moderation of the effects of child maltreatment on depression and internalizing symptoms was investigated in a sample of low-income maltreated and nonmaltreated African American children (N = 1,096). Lifetime child maltreatment experiences were independently coded from Child Protective Services records and maternal report. Child depression and internalizing problems were assessed in the context of a summer research camp by self-report on the Children's Depression Inventory and adult counselor report on the Teacher Report Form. DNA was obtained from buccal cell or saliva samples and genotyped for polymorphisms of the following genes: serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter, and corticotropin releasing hormone receptor 1. Analyses of covariance with age and gender as covariates were conducted, with maltreatment status and respective polymorphism as main effects and their Gene × Environment (G × E) interactions. Maltreatment consistently was associated with higher Children's Depression Inventory and Teacher Report Form symptoms. The results for child self-report symptoms indicated a G × E interaction for BDNF and maltreatment. In addition, BDNF and triallelic 5-HTTLPR interacted with child maltreatment in a G × G × E interaction. Analyses for counselor report of child anxiety/depression symptoms on the Teacher Report Form indicated moderation of child maltreatment effects by triallelic 5-HTTLPR. These effects were elaborated based on variation in developmental timing of maltreatment experiences. Norepinephrine transporter was found to further moderate the G × E interaction of 5-HTTLPR and maltreatment status, revealing a G × G × E interaction. This G × G × E was extended by consideration of variation in maltreatment subtype experiences. Finally, G × G × E effects were observed for the co-action of BDNF and the corticotropin releasing hormone receptor 1

  20. Regulation of feeding behavior and psychomotor activity by corticotropin-releasing hormone (CRH in fish

    Directory of Open Access Journals (Sweden)

    Kouhei eMatsuda

    2013-05-01

    Full Text Available Corticotropin-releasing hormone (CRH is a hypothalamic neuropeptide belonging to a family of neuropeptides that includes urocortins, urotensin I and sauvagine in vertebrates. CRH and urocortin act as anorexigenic factors for satiety regulation in fish. In a goldfish model, intracerebroventricular (ICV administration of CRH has been shown to affect not only food intake, but also locomotor and psychomotor activities. In particular, CRH elicits anxiety-like behavior as an anxiogenic neuropeptide in goldfish, as is the case in rodents. This paper reviews current knowledge of CRH and its related peptides derived from studies of teleost fish, as representative non-mammals, focusing particularly on the role of the CRH system, and examines its significance from a comparative viewpoint.

  1. Endocrinology and the brain: corticotropin-releasing hormone signaling.

    Science.gov (United States)

    Inda, Carolina; Armando, Natalia G; Dos Santos Claro, Paula A; Silberstein, Susana

    2017-08-01

    Corticotropin-releasing hormone (CRH) is a key player of basal and stress-activated responses in the hypothalamic-pituitary-adrenal axis (HPA) and in extrahypothalamic circuits, where it functions as a neuromodulator to orchestrate humoral and behavioral adaptive responses to stress. This review describes molecular components and cellular mechanisms involved in CRH signaling downstream of its G protein-coupled receptors (GPCRs) CRHR1 and CRHR2 and summarizes recent findings that challenge the classical view of GPCR signaling and impact on our understanding of CRHRs function. Special emphasis is placed on recent studies of CRH signaling that revealed new mechanistic aspects of cAMP generation and ERK1/2 activation in physiologically relevant contexts of the neurohormone action. In addition, we present an overview of the pathophysiological role of the CRH system, which highlights the need for a precise definition of CRHRs signaling at molecular level to identify novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. © 2017 The authors.

  2. Human fear acquisition deficits in relation to genetic variants of the corticotropin releasing hormone receptor 1 and the serotonin transporter.

    Directory of Open Access Journals (Sweden)

    Ivo Heitland

    Full Text Available The ability to identify predictors of aversive events allows organisms to appropriately respond to these events, and failure to acquire these fear contingencies can lead to maladaptive contextual anxiety. Recently, preclinical studies demonstrated that the corticotropin-releasing factor and serotonin systems are interactively involved in adaptive fear acquisition. Here, 150 healthy medication-free human subjects completed a cue and context fear conditioning procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex (FPS was measured to assess both uninstructed fear acquisition and instructed fear expression. All participants were genotyped for polymorphisms located within regulatory regions of the corticotropin releasing hormone receptor 1 (CRHR1 - rs878886 and the serotonin transporter (5HTTLPR. These polymorphisms have previously been linked to panic disorder and anxious symptomology and personality, respectively. G-allele carriers of CRHR1 (rs878886 showed no acquisition of fear conditioned responses (FPS to the threat cue in the uninstructed phase, whereas fear acquisition was present in C/C homozygotes. Moreover, carrying the risk alleles of both rs878886 (G-allele and 5HTTLPR (short allele was associated with increased FPS to the threat context during this phase. After explicit instructions regarding the threat contingency were given, the cue FPS and context FPS normalized in all genotype groups. The present results indicate that genetic variability in the corticotropin-releasing hormone receptor 1, especially in interaction with the 5HTTLPR, is involved in the acquisition of fear in humans. This translates prior animal findings to the human realm.

  3. Corticotropin releasing hormone and imaging, rethinking the stress axis

    International Nuclear Information System (INIS)

    Contoreggi, Carlo

    2015-01-01

    The stress system provides integration of both neurochemical and somatic physiologic functions within organisms as an adaptive mechanism to changing environmental conditions throughout evolution. In mammals and primates the complexity and sophistication of these systems have surpassed other species in triaging neurochemical and physiologic signaling to maximize chances of survival. Corticotropin releasing hormone (CRH) and its related peptides and receptors have been identified over the last three decades and are fundamental molecular initiators of the stress response. They are crucial in the top down regulatory cascade over a myriad of neurochemical, neuroendocrine and sympathetic nervous system events. From neuroscience, we've seen that stress activation impacts behavior, endocrine and somatic physiology and influences neurochemical events that one can capture in real time with current imaging technologies. To delineate these effects one can demonstrate how the CRH neuronal networks infiltrate critical cognitive, emotive and autonomic regions of the central nervous system (CNS) with somatic effects. Abundant preclinical and clinical studies show inter-regulatory actions of CRH with multiple neurotransmitters/peptides. Stress, both acute and chronic has epigenetic effects which magnify genetic susceptibilities to alter neurochemistry; stress system activation can add critical variables in design and interpretation of basic and clinical neuroscience and related research. This review will attempt to provide an overview of the spectrum of known functions and speculative actions of CRH and stress responses in light of imaging technology and its interpretation. Metabolic and neuroreceptor positron emission/single photon tomography (PET/SPECT), functional magnetic resonance imaging (fMRI), anatomic MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (pMRS) are technologies that can delineate basic mechanisms of neurophysiology and

  4. Paraventricular nucleus of the human hypothalamus in primary hypertension: Activation of corticotropin-releasing hormone neurons

    NARCIS (Netherlands)

    Goncharuk, Valeri D.; van Heerikhuize, Joop; Swaab, Dick F.; Buijs, Ruud M.

    2002-01-01

    By using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin-releasing hormone (CRH)-producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control

  5. Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

    Science.gov (United States)

    Warren, W B; Gurewitsch, E D; Goland, R S

    1995-02-01

    We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

  6. Corticotropine-releasing hormone and/or corticosterone differentially affect behavior of rat

    Czech Academy of Sciences Publication Activity Database

    Valeš, Karel; Řezáčová, Lenka; Stuchlík, Aleš

    2008-01-01

    Roč. 11, Suppl.1 (2008), s. 118-118 ISSN 1461-1457. [CINP Congress /26./. 13.07.2008-17.07.2008, Munich] R&D Projects: GA MŠk(CZ) 1M0517; GA MZd NR9180; GA ČR(CZ) GA309/07/0341 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * corticotropine-releasing hormone * corticosterone * behavior Subject RIV: FH - Neurology

  7. Sexual dimorphism of stress response and immune/ inflammatory reaction: the corticotropin releasing hormone perspective

    OpenAIRE

    Vamvakopoulos, Nicholas V.

    1995-01-01

    This review higlghts key aspects of corticotropin releasing hormone (CRH) biology of potential relevance to the sexual dimorphism of the stress response and immune/inflammatory reaction, and introduces two important new concepts based on the regulatory potential of the human (h) CRH gene: (1) a proposed mechanism to account for the tissue-specific antithetical responses of hCRH gene expression to glucocorticolds, that may also explain the frequently observed antithetical effects of chronic gl...

  8. Characterization of brn1.2 and corticotropin-releasing hormone genes in zebrafish

    OpenAIRE

    Chandrasekar, Gayathri

    2007-01-01

    The zebrafish (Danio rerio), a tropical fresh water fish originally found in the rivers of India and Bangladesh has become a popular vertebrate model system over the last decade. The rapid sequencing of the zebrafish genome together with the latest advances in forward and reverse genetics has made this model organism more fascinating as it can be used to decipher the genetic mechanisms involved in the vertebrate development. Corticotropin-releasing hormone (CRH) regulates t...

  9. Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta

    International Nuclear Information System (INIS)

    Robinson, B.G.; Emanuel, R.L.; Frim, D.M.; Majzoub, J.A.

    1988-01-01

    Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. The authors report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery

  10. Sexual dimorphism of stress response and immune/ inflammatory reaction: the corticotropin releasing hormone perspective

    Directory of Open Access Journals (Sweden)

    Nicholas V. Vamvakopoulos

    1995-01-01

    Full Text Available This review higlghts key aspects of corticotropin releasing hormone (CRH biology of potential relevance to the sexual dimorphism of the stress response and immune/inflammatory reaction, and introduces two important new concepts based on the regulatory potential of the human (h CRH gene: (1 a proposed mechanism to account for the tissue-specific antithetical responses of hCRH gene expression to glucocorticolds, that may also explain the frequently observed antithetical effects of chronic glucocorticoid administration in clinical practice and (2 a heuristic diagram to illustrate the proposed modulation of the stress response and immune/ inflammatory reaction by steroid hormones, from the perspective of the CRH system.

  11. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

    Science.gov (United States)

    Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2011-01-01

    Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

  12. CORTICOTROPIN-RELEASING HORMONE MICROINFUSION IN THE CENTRAL AMYGDALA DIMINISHES A CARDIAC PARASYMPATHETIC OUTFLOW UNDER STRESS-FREE CONDITIONS

    NARCIS (Netherlands)

    WIERSMA, A; BOHUS, B; KOOLHAAS, JM

    1993-01-01

    The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH) cell bodies. Neuroanatomical studies revealed that the majority of

  13. Differential contribution of CBP:CREB binding to corticotropin-releasing hormone expression in the infant and adult hypothalamus

    NARCIS (Netherlands)

    Cope, J.L.; Regev, L.; Chen, Y.; Korosi, A.; Rice, C.J.; Ji, S.; Rogge, G.A.; Wood, M.A.; Baram, T.Z.

    2014-01-01

    Corticotropin-releasing hormone (CRH) contributes crucially to the regulation of central and peripheral responses to stress. Because of the importance of a finely-tuned stress system, CRH expression is tightly regulated in an organ- and brain region-specific manner. Thus, in hypothalamus, CRH is

  14. Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome

    OpenAIRE

    Sagami, Y; Shimada, Y; Tayama, J; Nomura, T; Satake, M; Endo, Y; Shoji, T; Karahashi, K; Hongo, M; Fukudo, S

    2004-01-01

    Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of α-helical CRH (αhCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patient...

  15. The interaction of corticotropin-releasing hormone receptor gene and early life stress on emotional empathy.

    Science.gov (United States)

    Grimm, Simone; Wirth, Katharina; Fan, Yan; Weigand, Anne; Gärtner, Matti; Feeser, Melanie; Dziobek, Isabel; Bajbouj, Malek; Aust, Sabine

    2017-06-30

    Early life stress (ELS) is associated with increased vulnerability for depression, changes to the corticotropin-releasing hormone (CRH) system and structural and functional changes in hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS to predict depression, cognitive functions and hippocampal activity. Social cognition has been related to hippocampal function and might be crucial for maintaining mental health. However, the interaction of CRHR1 gene variation and ELS on social cognition has not been investigated yet. We assessed social cognition in 502 healthy subjects to test effects of ELS and the CRHR1 gene. Participants were genotyped for rs110402 and rs242924. ELS was assessed by Childhood Trauma Questionnaire, social cognition was measured via Multifaceted Empathy Test and Empathy Quotient. Severity of ELS was associated with decreased emotional, but not cognitive empathy. Subjects with the common homozygous GG GG genotype showed decreased implicit emotional empathy after ELS exposure regardless of its severity. The results reveal that specific CRHR1 polymorphisms moderate the effect of ELS on emotional empathy. Exposure to ELS in combination with a vulnerable genotype results in impaired emotional empathy in adulthood, which might represent an early marker of increased vulnerability after ELS. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Corticotropin-releasing hormone induces depression-like changes of sleep electroencephalogram in healthy women.

    Science.gov (United States)

    Schüssler, P; Kluge, M; Gamringer, W; Wetter, T C; Yassouridis, A; Uhr, M; Rupprecht, R; Steiger, A

    2016-12-01

    We reported previously that repetitive intravenous injections of corticotropin-releasing hormone (CRH) around sleep onset prompt depression-like changes in certain sleep and endocrine activity parameters (e.g. decrease of slow-wave sleep during the second half of the night, blunted growth hormone peak, elevated cortisol concentration during the first half of the night). Furthermore a sexual dimorphism of the sleep-endocrine effects of the hormones growth hormone-releasing hormone and ghrelin was observed. In the present placebo-controlled study we investigated the effect of pulsatile administration of 4×50μg CRH on sleep electroencephalogram (EEG) and nocturnal cortisol and GH concentration in young healthy women. After CRH compared to placebo, intermittent wakefulness increased during the total night and the sleep efficiency index decreased. During the first third of the night, REM sleep and stage 2 sleep increased and sleep stage 3 decreased. Cortisol concentration was elevated throughout the night and during the first and second third of the night. GH secretion remained unchanged. Our data suggest that after CRH some sleep and endocrine activity parameters show also depression-like changes in healthy women. These changes are more distinct in women than in men. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats

    Directory of Open Access Journals (Sweden)

    Ricardo Borges Machado

    2010-01-01

    Full Text Available Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical CRH9−41, a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis—at least at the hypothalamic level—is capable to reduce the sleep rebound induced by sleep deprivation.

  18. Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity.

    Science.gov (United States)

    Liu, Hui-Rong; Fang, Xiao-Yi; Wu, Huan-Gan; Wu, Lu-Yi; Li, Jing; Weng, Zhi-Jun; Guo, Xin-Xin; Li, Yu-Guang

    2015-06-21

    To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity. A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7(th) week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus. The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P 0.05). Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.

  19. Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse brain

    Directory of Open Access Journals (Sweden)

    Ribeiro Ana C

    2009-04-01

    Full Text Available Abstract Background Gap junction proteins, connexins, are expressed in most endocrine and exocrine glands in the body and are at least in some glands crucial for the hormonal secretion. To what extent connexins are expressed in neurons releasing hormones or neuropeptides from or within the central nervous system is, however, unknown. Previous studies provide indirect evidence for gap junction coupling between subsets of neuropeptide-containing neurons in the paraventricular nucleus (PVN of the hypothalamus. Here we employ double labeling and retrograde tracing methods to investigate to what extent neuroendocrine and neuropeptide-containing neurons of the hypothalamus and brainstem express the neuronal gap junction protein connexin 36. Results Western blot analysis showed that connexin 36 is expressed in the PVN. In bacterial artificial chromosome transgenic mice, which specifically express the reporter gene Enhanced Green Fluorescent Protein (EGFP under the control of the connexin 36 gene promoter, EGFP expression was detected in magnocellular (neuroendocrine and in parvocellular neurons of the PVN. Although no EGFP/connexin36 expression was seen in neurons containing oxytocin or vasopressin, EGFP/connexin36 was found in subsets of PVN neurons containing corticotropin-releasing hormone (CRH, and in somatostatin neurons located along the third ventricle. Moreover, CRH neurons in brainstem areas, including the lateral parabrachial nucleus, also expressed EGFP/connexin 36. Conclusion Our data indicate that connexin 36 is expressed in subsets of neuroendocrine and CRH neurons in specific nuclei of the hypothalamus and brainstem.

  20. Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders.

    Science.gov (United States)

    Contoreggi, Carlo; Rice, Kenner C; Chrousos, George

    2004-01-01

    Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of

  1. Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice

    Science.gov (United States)

    Zhang, Rong; Asai, Masato; Mahoney, Carrie E; Joachim, Maria; Shen, Yuan; Gunner, Georgia; Majzoub, Joseph A

    2016-01-01

    A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, while extra-hypothalamic CRH plays a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma ACTH, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open field, elevated plus maze, holeboard, light-dark box, and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus, and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation. PMID:27595593

  2. Neuroendocrine circuitry and endometriosis: progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro.

    Science.gov (United States)

    Tariverdian, Nadja; Rücke, Mirjam; Szekeres-Bartho, Julia; Blois, Sandra M; Karpf, Eva F; Sedlmayr, Peter; Klapp, Burghard F; Kentenich, Heribert; Siedentopf, Friederike; Arck, Petra C

    2010-03-01

    Clinical symptoms of endometriosis, such as pain and infertility, can be described as persistent stressors. Such continuous exposure to stress may severely affect the equilibrium and bidirectional communication of the endocrine and immune system, hereby further aggravating the progression of endometriosis. In the present study, we aimed to tease apart mediators that are involved in the stress response as well as in the progression of endometriosis. Women undergoing diagnostic laparoscopy due to infertility were recruited (n = 69). Within this cohort, early stage of endometriosis were diagnosed in n = 30 and advanced stage of endometriosis in n = 8. Levels of progesterone in serum were determined. Frequency of progesterone receptor (PR) expression on CD56(+) and CD8(+) peritoneal lymphocytes was analysed by flow cytometry. The production of tumour necrosis factor (TNF) and interleukin (IL)-10 by peritoneal leukocytes upon stimulation with the potent stress mediator corticotropin-releasing hormone (CRH) and the progesterone derivative dydrogesterone, or both, were evaluated. Furthermore, the production of progesterone-induced blocking factor (PIBF) by peritoneal leukocytes and the expression of PR in endometriotic tissue were investigated. Levels of progesterone in serum were decreased in women with endometriosis and inversely correlated to pain scores. Furthermore, an increased frequency of CD56(+)PR(+) and CD8(+)PR(+) peritoneal lymphocytes was present in advanced endometriosis. The TNF/IL-10 ratio, reflecting cytokine secretion by peritoneal cells, was higher in cells derived from endometriosis patients and could be further heightened by CRH stimulation, whereas stimulation with dydrogesterone abrogated the CRH-mediated inflammation. Finally, the expression of PIBF by peritoneal leukocytes was increased in endometriosis. Low levels of progesterone in the follicular phase could be responsible for the progression of endometriosis and related pain. Peripheral CRH

  3. How do the many etiologies of West syndrome lead to excitability and seizures? The corticotropin releasing hormone excess hypothesis.

    Science.gov (United States)

    Brunson, K L; Eghbal-Ahmadi, M; Baram, T Z

    2001-11-01

    West syndrome (WS) is associated with diverse etiological factors. This fact has suggested that there must be a 'final common pathway' for these etiologies, which operates on the immature brain to result in WS only at the maturational state present during infancy. Any theory for the pathogenesis of WS has to account for the unique features of this disorder. For example, how can a single entity have so many etiologies? Why does WS arise only in infancy, even when a known insult had occurred prenatally, and why does it disappear? Why is WS associated with lasting cognitive dysfunction? And, importantly, why do these seizures--unlike most others--respond to treatment by a hormone, ACTH? The established hormonal role of ACTH in human physiology is to function in the neuroendocrine cascade of the responses to all stressful stimuli, including insults to the brain. As part of this function, ACTH is known to suppress the production of corticotropin releasing hormone (CRH), a peptide that is produced in response to diverse insults and stressors.The many etiologies of WS all lead to activation of the stress response, including increased production and secretion of the stress-neurohormone CRH. CRH has been shown, in infant animal models, to cause severe seizures and death of neurons in areas involved with learning and memory. These effects of CRH are restricted to the infancy period because the receptors for CRH, which mediate its action on neurons, are most abundant during this developmental period. ACTH administration is known to inhibit production and release of CRH via a negative feedback mechanism. Therefore, the efficacy of ACTH for WS may depend on its ability to decrease the levels of the seizure-promoting stress-neurohormone CRH.This CRH-excess theory for the pathophysiology of WS is consistent not only with the profile of ACTH effects, but also with the many different 'causes' of WS, with the abnormal ACTH levels in the cerebrospinal fluid of affected infants and

  4. Corticotropin-releasing hormone expression in patients with intrahepatic cholestasis of pregnancy after ursodeoxycholic acid treatment: an initial experience.

    Science.gov (United States)

    Zhou, Fan; Zhang, Li; He, Mao Mao; Liu, Zheng Fei; Gao, Bing Xin; Wang, Xiao Dong

    2014-08-01

    Corticotropin-releasing hormone (CRH) is one of the most potent vasodilatory factors in the human feto-placental circulation. The expression of CRH was significantly down-regulated in patients with intrahepatic cholestasis of pregnancy (ICP). One hundred pregnant women diagnosed with ICP at 34-34(+6) weeks of gestation agreed to participate in this prospective nested case-control study. Thirty ICP patients were finally recruited in this study, with 16 cases in the ursodeoxycholic acid (UDCA) group (UDCA 750 mg/d) and 14 cases in the control group (Transmetil 1000 mg/d or Essentiale 1368 mg/d). Maternal serum samples were obtained in diagnosis and at 37-37(+6) weeks of gestation. Placental tissues were obtained from participants after delivery. ELISA, enzymatic colorimetric and Western blotting were used to evaluate the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and CRH in maternal serum and expression of CRH in placenta tissues. The UDCA group had greater reduction in maternal serum ALT, AST and TBA levels in ICP patients (all p < 0.01). Maternal serum CRH concentrations in the UDCA group after treatment (122.10 ± 44.20) pg/ml was significantly higher than pretreatment (95.45 ± 26.47) pg/ml (p < 0.01). After treatment, maternal serum CRH concentrations of the UDCA group (122.10 ± 44.20) pg/ml was significantly higher than in the control group (80.71 ± 41.10) pg/ml (p < 0.01). Placental CRH expression in the UDCA group (2.79 ± 1.72) was significantly higher than in the control group (0.69 ± 0.36) (p < 0.01). Maternal serum and placental CRH expression in ICP patients were up-regulated after treatment of UDCA. The up-regulation of CRH expression after UDCA treatment may play an important role in the therapeutic mechanism of ICP. All patients recruited in this study had severe cholestasis (TBA ≥ 40 µmol/L). Further studies are warranted in

  5. Corticotropin-releasing hormone and mast cells in the regulation of mucosal barrier function in the human colon.

    Science.gov (United States)

    Wallon, Conny; Söderholm, Johan D

    2009-05-01

    Corticotropin-releasing hormone (CRH) is an important neuro-endocrine mediator of the stress response. Local effects of CRH in the intestinal mucosa have become evident in recent years. We showed that CRH activates CRH receptor subtypes R1 and R2 on subepithelial mast cells, thereby inducing increased transcellular uptake of protein antigens in human colonic biopsies in Ussing chambers. Ongoing studies also implicate local cholinergic signaling in regulation of macromolecular permeability in the human colon. Since increased uptake of antigenic molecules is associated with mucosal inflammation, our findings may have implications for understanding stress-related intestinal disorders.

  6. Corticotropin-Releasing Hormone Receptor 2 Gene Variants in Irritable Bowel Syndrome.

    Directory of Open Access Journals (Sweden)

    Hazuki Komuro

    Full Text Available Corticotropin-releasing hormone (CRH plays an important role in the pathophysiology of irritable bowel syndrome (IBS and regulates the stress response through two CRH receptors (R1 and R2. Previously, we reported that a CRHR1 gene polymorphism (rs110402, rs242924, and rs7209436 and haplotypes were associated with IBS. However, the association between the CRHR2 gene and IBS was not investigated. We tested the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are associated with IBS pathophysiology and negative emotion in IBS patients.A total of 142 IBS patients and 142 healthy controls participated in this study. Seven single nucleotide polymorphisms (SNPs of the CRHR2 gene (rs4722999, rs3779250, rs2240403, rs2267710, rs2190242, rs2284217, and rs2284220 were genotyped. Subjects' psychological states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-Rating Depression Scale.We found that rs4722999 and rs3779250, located in intronic region, were associated with IBS in terms of genotype frequency (rs4722999: P = 0.037; rs3779250: P = 0.017 and that the distribution of the major allele was significantly different between patients and controls. There was a significant group effect (controls vs. IBS, and a CRHR2 genotype effect was observed for three psychological scores, but the interaction was not significant. We found a haplotype of four SNPs (rs4722999, rs3779250, rs2240403, and rs2267710 and two SNPs (rs2284217 and rs2284220 in strong linkage disequilibrium (D' > 0.90. We also found that haplotypes of the CRHR2 gene were significantly different between IBS patients and controls and that they were associated with negative emotion.Our findings support the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are related to IBS. In addition, we found associations between CRHR2 genotypes and haplotypes and negative emotion in IBS patients and controls. Further studies on IBS and the CRH

  7. The relationships among acculturation, biobehavioral risk, stress, corticotropin-releasing hormone, and poor birth outcomes in Hispanic women.

    Science.gov (United States)

    Ruiz, R Jeanne; Dolbier, Christyn L; Fleschler, Robin

    2006-01-01

    To determine the predictive ability of acculturation as an antecedent of stress, biobehavioral risk, corticotropin-releasing hormone levels, and poor birth outcomes in pregnant Hispanic women. A prospective, observational design with data collected at 22-25 weeks of gestation and at birth through medical record review. Public prenatal health clinics in south Texas serving low-income women. Self-identified Hispanic women who had singleton pregnancies, no major medical risk complications, and consented to answer questionnaires as well as a venipuncture and review of their prenatal and birth medical records. Gestational age, Apgar scores, length, weight, percentile size, and head circumference of the infant at birth. Significant differences were seen in infant birth weight, head circumference, and percentile size by acculturation. English acculturation predicted stress, corticotropin-releasing hormone, biobehavioral risk, and decreased gestational age at birth. Investigation must continue to understand the circumstances that give rise to the decline in birth outcomes observed in Hispanics with acculturation to the dominant English culture in the United States.

  8. Corticotropin-Releasing Hormone (CRH Promotes Macrophage Foam Cell Formation via Reduced Expression of ATP Binding Cassette Transporter-1 (ABCA1.

    Directory of Open Access Journals (Sweden)

    Wonkyoung Cho

    Full Text Available Atherosclerosis, the major pathology of cardiovascular disease, is caused by multiple factors involving psychological stress. Corticotropin-releasing hormone (CRH, which is released by neurosecretory cells in the hypothalamus, peripheral nerve terminals and epithelial cells, regulates various stress-related responses. Our current study aimed to verify the role of CRH in macrophage foam cell formation, the initial critical stage of atherosclerosis. Our quantitative real-time reverse transcriptase PCR (qRT-PCR, semi-quantitative reverse transcriptase PCR, and Western blot results indicate that CRH down-regulates ATP-binding cassette transporter-1 (ABCA1 and liver X receptor (LXR-α, a transcription factor for ABCA1, in murine peritoneal macrophages and human monocyte-derived macrophages. Oil-red O (ORO staining and intracellular cholesterol measurement of macrophages treated with or without oxidized LDL (oxLDL and with or without CRH (10 nM in the presence of apolipoprotein A1 (apoA1 revealed that CRH treatment promotes macrophage foam cell formation. The boron-dipyrromethene (BODIPY-conjugated cholesterol efflux assay showed that CRH treatment reduces macrophage cholesterol efflux. Western blot analysis showed that CRH-induced down-regulation of ABCA1 is dependent on phosphorylation of Akt (Ser473 induced by interaction between CRH and CRH receptor 1(CRHR1. We conclude that activation of this pathway by CRH accelerates macrophage foam cell formation and may promote stress-related atherosclerosis.

  9. Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders

    NARCIS (Netherlands)

    Bao, Ai-Min; Hestiantoro, Andon; van Someren, Eus J. W.; Swaab, Dick F.; Zhou, Jiang-Ning

    2005-01-01

    Oestrogens may modulate the activity of the hypothalamic-pituitary-adrenal (HPA) axis. The present study was to investigate whether the activity of the HPA axis in mood disorders might be directly modulated by oestrogens via oestrogen receptors (ORs) in the corticotropin-releasing hormone (CRH)

  10. Isolation and amino acid sequence of corticotropin-releasing factor from pig hypothalami.

    OpenAIRE

    Patthy, M; Horvath, J; Mason-Garcia, M; Szoke, B; Schlesinger, D H; Schally, A V

    1985-01-01

    A polypeptide was isolated from acid extracts of porcine hypothalami on the basis of its high ability to stimulate the release of corticotropin from superfused rat pituitary cells. After an initial separation by gel filtration on Sephadex G-25, further purification was carried out by reversed-phase HPLC. The isolated material was homogeneous chromatographically and by N-terminal sequencing. Based on automated gas-phase sequencing of the intact and CNBr-cleaved peptide and on carboxypeptidase ...

  11. Corticotropin-releasing factor receptors in the pituitary gland and central nervous system: methods and overview

    International Nuclear Information System (INIS)

    De Souza, E.B.; Kuhar, M.J.

    1986-01-01

    Studies with the radioiodinated oCRF analog, Nle21, 125I-Tyr32-oCRF have identified, characterized, and localized high affinity binding sites for CRF in anterior and intermediate lobes of rat pituitary, in anterior lobe of human pituitary, and in rat, monkey, and human brain. The pharmacology and distribution of Nle21, 125I-Tyr32-oCRF binding in the pituitary gland correlate well with the biological potency and sites of action of CRF and suggest that these CRF binding sites represent specific receptors that mediate the well-established actions of CRF on the anterior pituitary and on the intermediate lobe of the pituitary. The studies in adrenalectomized rats demonstrating that endogenous CRF is capable of modulating its receptor density provide additional evidence that the radioligand labels the functional CRF receptor. The areas of distribution of Nle21, 125I-Tyr32-oCRF binding sites in the rat CNS correlate well with the immunohistochemical distribution of CRF pathways and the pharmacological sites of action of CRF. These data confirm the established role of CRF in regulating secretion of POMC-derived peptides from the pituitary gland. In addition, the data support a physiological role for endogenous CRF in regulating CNS activity and suggest the importance of this neuropeptide in integrating endocrine and visceral functions and behavior, especially in response to stress. Studies to characterize CRF receptors and CRF-containing pathways in the brain provide a means for better understanding the various functions of this neuropeptide in different areas of the CNS. Finally, the ability to map CRF receptors in postmortem human tissue provides a basis for studying the role of CRF in a variety of endocrine, neurological, and psychiatric disorders

  12. Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Hashimoto, K.; Hattori, T.; Murakami, K.; Suemaru, S.; Kawada, Y.; Kageyama, J.; Ota, Z.

    1985-01-01

    The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of 125 I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neurointermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR

  13. Effect of in ovo injection of corticotropin-releasing hormone on the timing of hatching in broiler chickens.

    Science.gov (United States)

    Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert

    2017-09-01

    In chicken embryos, intravenous injection of corticotropin-releasing hormone (CRH) causes the release of both corticosteroids and thyroid hormones. These hormones initiate and enhance the hatching process, raising the possibility that CRH treatment of the late chicken embryo could accelerate hatching and/or decrease the spread of hatching. We performed a series of exploratory tests to investigate whether in ovo delivery methods of CRH other than intravenous injection that are more practical in a commercial setting, affect hatching time in broilers. Corticotropin-releasing hormone was injected into the air cell, albumen, or amniotic fluid of broiler breeder eggs, in the last week of embryonic development. Average incubation duration was significantly decreased by 22 h when 2 μg of CRH was injected into the air cell on embryonic day 18 (E18) of Cobb eggs. Acceleration of hatching (but only by 8 h) was also seen for Ross chicks when CRH was injected daily into the albumen between E10 and E18. However, repeats of both experiments did not show consistent effects of CRH on hatching time; in most experiments performed, CRH did not affect hatching time. We speculate that the effectiveness of CRH uptake via these delivery methods and/or the duration and magnitude of the thyroxine and corticosterone response to CRH is not sufficient to have a substantial effect on hatching time. We therefore conclude that in ovo CRH treatment does not seem a feasible option as a practical tool to increase hatchery productivity or to investigate the effects of CRH agonists and antagonists on hatching. © 2017 Poultry Science Association Inc.

  14. Plasma adiponectin levels are increased despite insulin resistance in corticotropin-releasing hormone transgenic mice, an animal model of Cushing syndrome.

    Science.gov (United States)

    Shinahara, Masayuki; Nishiyama, Mitsuru; Iwasaki, Yasumasa; Nakayama, Shuichi; Noguchi, Toru; Kambayashi, Machiko; Okada, Yasushi; Tsuda, Masayuki; Stenzel-Poore, Mary P; Hashimoto, Kozo; Terada, Yoshio

    2009-01-01

    Adiponectin (AdN), an adipokine derived from the adipose tissue, has an insulin-sensitizing effect, and plasma AdN is shown to be decreased in obesity and/or insulin resistant state. To clarify whether changes in AdN are also responsible for the development of glucocorticoid-induced insulin resistance, we examined AdN concentration in plasma and AdN expression in the adipose tissue, using corticotropin-releasing hormone (CRH) transgenic mouse (CRH-Tg), an animal model of Cushing syndrome. We found, unexpectedly, that plasma AdN levels in CRHTg were significantly higher than those in wild-type littermates (wild-type: 19.7+/-2.5, CRH-Tg: 32.4+/-3.1 microg/mL, pAdN mRNA and protein levels were significantly decreased in the adipose tissue of CRH-Tg. Bilateral adrenalectomy in CRH-Tg eliminated both their Cushing's phenotype and their increase in plasma AdN levels (wild-type/sham: 9.4+/-0.5, CRH-Tg/sham: 15.7+/-2.0, CRH-Tg/ADX: 8.5+/-0.4 microg/mL). These results strongly suggest that AdN is not a major factor responsible for the development of insulin resistance in Cushing syndrome. Our data also suggest that glucocorticoid increases plasma AdN levels but decreases AdN expression in adipocytes, the latter being explained possibly by the decrease in AdN metabolism in the Cushing state.

  15. Schizothorax prenanti corticotropin-releasing hormone (CRH): molecular cloning, tissue expression, and the function of feeding regulation.

    Science.gov (United States)

    Wang, Tao; Zhou, Chaowei; Yuan, Dengyue; Lin, Fangjun; Chen, Hu; Wu, Hongwei; Wei, Rongbin; Xin, Zhiming; Liu, Ju; Gao, Yundi; Li, Zhiqiong

    2014-10-01

    Corticotropin-releasing hormone (CRH) is a potent mediator of endocrine, autonomic, behavioral, and immune responses to stress. For a better understanding of the structure and function of the CRH gene and to study its effect on feeding regulation in cyprinid fish, the cDNA of the CRH gene from the brain of Schizothorax prenanti was cloned and sequenced. The full-length CRH cDNA consisted of 1,046 bp with an open reading frame of 489 bp encoding a protein of 162 amino acids. Real-time quantitative PCR analyses revealed that CRH was widely expressed in central and peripheral tissues. In particular, high expression level of CRH was detected in brain. Furthermore, CRH mRNA expression was examined in different brain regions, especially high in hypothalamus. In addition, there was no significant change in CRH mRNA expression in fed group compared with the fasted group in the S. prenanti hypothalamus during short-term fasting. However, CRH gene expression presented significant decrease in the hypothalamus in fasted group compared with the fed group (P < 0.05) on day 7; thereafter, re-feeding could lead to a significant increase in CRH mRNA expression in fasted group on day 9. The results suggest that the CRH may play a critical role in feeding regulation in S. prenanti.

  16. Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Kyllo, J.H.; Collins, M.M.; Vetter, K.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others

    1996-03-29

    Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene of chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes. 25 refs., 5 figs., 2 tabs.

  17. Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome.

    Science.gov (United States)

    Sagami, Y; Shimada, Y; Tayama, J; Nomura, T; Satake, M; Endo, Y; Shoji, T; Karahashi, K; Hongo, M; Fukudo, S

    2004-07-01

    Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg). ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH. Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

  18. Ectopic corticotropin-releasing hormone (CRH syndrome from metastatic small cell carcinoma: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Shahani Sadeka

    2010-08-01

    Full Text Available Abstract Background Cushing's Syndrome (CS which is caused by isolated Corticotropin-releasing hormone (CRH production, rather than adrenocorticotropin (ACTH production, is extremely rare. Methods We describe the clinical presentation, course, laboratory values and pathologic findings of a patient with isolated ectopic CRH causing CS. We review the literature of the types of tumors associated with this unusual syndrome and the behavior of these tumors by endocrine testing. Results A 56 year old woman presented with clinical and laboratory features consistent with ACTH-dependent CS. Pituitary imaging was normal and cortisol did not suppress with a high dose dexamethasone test, consistent with a diagnosis of ectopic ACTH. CT imaging did not reveal any discrete lung lesions but there were mediastinal and abdominal lymphadenopathy and multiple liver lesions suspicious for metastatic disease. Laboratory testing was positive for elevated serum carcinoembryonic antigen and the neuroendocrine marker chromogranin A. Serum markers of carcinoid, medullary thyroid carcinoma, and pheochromocytoma were in the normal range. Because the primary tumor could not be identified by imaging, biopsy of the presumed metastatic liver lesions was performed. Immunohistochemistry was consistent with a neuroendocrine tumor, specifically small cell carcinoma. Immunostaining for ACTH was negative but was strongly positive for CRH and laboratory testing revealed a plasma CRH of 10 pg/ml (normal 0 to 10 pg/ml which should have been suppressed in the presence of high cortisol. Conclusions This case illustrates the importance of considering the ectopic production of CRH in the differential diagnosis for presentations of ACTH-dependent Cushing's Syndrome.

  19. Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

    Science.gov (United States)

    Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

    2000-03-01

    Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

  20. Associations between Single-Nucleotide Polymorphisms in Corticotropin-Releasing Hormone-Related Genes and Irritable Bowel Syndrome.

    Directory of Open Access Journals (Sweden)

    Ayaka Sasaki

    Full Text Available Irritable bowel syndrome (IBS is a common functional disorder with distinct features of stress-related pathophysiology. A key mediator of the stress response is corticotropin-releasing hormone (CRH. Although some candidate genes have been identified in stress-related disorders, few studies have examined CRH-related gene polymorphisms. Therefore, we tested our hypothesis that single-nucleotide polymorphisms (SNPs in CRH-related genes influence the features of IBS.In total, 253 individuals (123 men and 130 women participated in this study. They comprised 111 IBS individuals and 142 healthy controls. The SNP genotypes in CRH (rs28364015 and rs6472258 and CRH-binding protein (CRH-BP (rs10474485 were determined by direct sequencing and real-time polymerase chain reaction. The emotional states of the subjects were evaluated using the State-Trait Anxiety Inventory, Perceived Stress Scale, and the Self-rating Depression Scale.Direct sequencing of the rs28364015 SNP of CRH revealed no genetic variation among the study subjects. There was no difference in the genotype distributions and allele frequencies of rs6472258 and rs10474485 between IBS individuals and controls. However, IBS subjects with diarrhea symptoms without the rs10474485 A allele showed a significantly higher emotional state score than carriers.These results suggest that the CRH and CRH-BP genes have no direct effect on IBS status. However, the CRH-BP SNP rs10474485 has some effect on IBS-related emotional abnormalities and resistance to psychosocial stress.

  1. Alcohol dysregulates corticotropin-releasing-hormone (CRH promoter activity by interfering with the negative glucocorticoid response element (nGRE.

    Directory of Open Access Journals (Sweden)

    Magdalena M Przybycien-Szymanska

    Full Text Available EtOH exposure in male rats increases corticotropin-releasing hormone (CRH mRNA in the paraventricular nucleus of the hypothalamus (PVN, a brain region responsible for coordinating stress and anxiety responses. In this study we identified the molecular mechanisms involved in mediating these effects by examining the direct effects of EtOH on CRH promoter activity in a neuronal cell line derived from the PVN (IVB. In addition, we investigated the potential interactions of EtOH and glucocorticoids on the CRH promoter by concomitantly treating cells with EtOH and the glucocorticoid receptor (GR antagonist RU486, and by sequentially deleting GR binding sites within glucocorticoid response element (GRE on the CRH promoter. Cells were transiently transfected with a firefly luciferase reporter construct containing 2.5 kb of the rat wild type (WT or mutated CRH promoter. Our results showed that EtOH treatment induced a biphasic response in CRH promoter activity. EtOH exposure for 0.5 h significantly decreased promoter activity compared to vehicle treated controls, whereas promoter activity was significantly increased after 2.0 h of EtOH exposure. Treatment with RU486, or deletion of the GR binding sites 1 and 2 within the GRE, abolished the EtOH-induced increase in the promoter activity, however did not affect EtOH-induced decrease in CRH promoter activity at an earlier time point. Overall, our data suggest that alcohol exposure directly regulates CRH promoter activity by interfering with the normal feedback mechanisms of glucocorticoids mediated by GR signaling at the GRE site of the CRH promoter.

  2. Serum blood metabolite response and evaluation of select organ weight, histology and cardiac morphology of beef heifers exposed to a dual corticotropin-releasing hormone and vasopressin challenge following supplementation of

    Science.gov (United States)

    The objective of this study was to: 1) determine if supplementation of Zilpaterol Hydrochloride (ZH) altered select organ weights, histology and cardiac anatomical features at harvest and 2) determine if administration of a corticotropin-releasing hormone (CRH) and vasopressin (VP) challenge followi...

  3. Mapping the human corticotropin releasing hormone binding protein gene (CRHBP) to the long arm of chromosome 5 (5q11.2-q13.3)

    Energy Technology Data Exchange (ETDEWEB)

    Vamvakopoulos, N.C. [Univ. of Thessaly School of Medicine, Larisa (Greece); Sioutopoulou, T.O. [Univ. of Athens Medical School (Greece); Durkin, S.A. [American Type Culture Collection, Rockville, MD (United States)

    1995-01-01

    Unexpected stimulation or stress activates the heat shock protein (hsp) system at the cellular level and the hypothalamic-pituitary-adrenal (HPA) axis at the level of the whole organism. At the molecular level, these two systems communicate through the functional interaction between hsp90 and glucocorticoid receptor (GR). The corticotropin releasing hormone (CRH) system regulates the mammalian stress response by coordinating the activity of the HPA axis. It consists of the 41-amino-acid-long principal hypothalamic secretagogue for pituitary adrenocorticotropic hormone (ACTH), CRH, its receptor (CRHR), and its binding protein (CRHBP). Because of its central role in the coordination of stress response and whole body homeostasis, the CRH system has been implicated in the pathogenesis of neuroendocrine and psychiatric disease. 19 refs., 1 fig.

  4. Water deprivation increases Fos expression in hypothalamic corticotropin-releasing factor neurons induced by right atrial distension in awake rats.

    Science.gov (United States)

    Benedetti, Mauricio; Rorato, Rodrigo; Castro, Margaret; Machado, Benedito H; Antunes-Rodrigues, Jose; Elias, Lucila L K

    2008-11-01

    Atrial mechanoreceptors, sensitive to stretch, contribute in regulating heart rate and intravascular volume. The information from those receptors reaches the nucleus tractus solitarius and then the paraventricular nucleus (PVN), known to have a crucial role in the regulation of cardiovascular function. Neurons in the PVN synthesize CRF, AVP, and oxytocin (OT). Stimulation of atrial mechanoreceptors was performed in awake rats implanted with a balloon at the junction of the superior vena cava and right atrium. Plasma ACTH, AVP, and OT concentrations and Fos, CRF, AVP, and OT immunolabeling in the PVN were determined after balloon inflation in hydrated and water-deprived rats. The distension of the balloon increased the plasma ACTH concentrations, which were higher in water-deprived than in hydrated rats (P neurons in the parvocellular PVN, which was higher in the water-deprived than in the hydrated group (P neurons after distension in hydrated and water-deprived groups, compared with respective controls. In conclusion, parvocellular CRF neurons showed an increase of Fos expression induced by stimulation of right atrial mechanoreceptors, suggesting that CRF participates in the cardiovascular reflex adjustments elicited by volume loading. Activation of CRF neurons in the PVN by cardiovascular reflex is affected by osmotic stimulation.

  5. Identification and characterization of a pituitary corticotropin-releasing factor binding protein by chemical cross-linking

    DEFF Research Database (Denmark)

    Nishimura, E; Billestrup, Nils; Perrin, M

    1987-01-01

    appeared to have a molecular weight of approximately 70,000. The cross-linking was specific since an excess (1 microM) of an unrelated peptide (insulin) did not affect the appearance of the Mr 75,000 band. The concentration of CRF required to inhibit cross-linking by 50% was found to be similar...

  6. Corticotropin-releasing factor (CRF) receptors in intermediate lobe of the pituitary: Biochemical characterization and autoradiographic localization

    International Nuclear Information System (INIS)

    Grigoriadis, D.E.; De Souza, E.B.

    1989-01-01

    CRF receptors were characterized using radioligand binding and chemical affinity cross-linking techniques and localized using autoradiographic techniques in porcine, bovine and rat pituitaries. The binding of 125I-[Tyr0]-ovine CRF (125I-oCRF) to porcine anterior and neurointermediate lobe membranes was saturable and of high affinity with comparable KD values (200-600 pM) and receptor densities (100-200 fmoles/mg protein). The pharmacological rank order of potencies for various analogs and fragments of CRF in inhibiting 125I-oCRF binding in neurointermediate lobe was characteristic of the well-established CRF receptor in anterior pituitary. Furthermore, the binding of 125I-oCRF to both anterior and neurointermediate lobes of the pituitary was guanine nucleotide-sensitive. Affinity cross-linking studies revealed that the molecular weight of the CRF binding protein in rat intermediate lobe was identical to that in rat anterior lobe (Mr = 75,000). While the CRF binding protein in the anterior lobes of porcine and bovine pituitaries had identical molecular weights to CRF receptors in rat pituitary (Mr = 75,000), the molecular weight of the CRF binding protein in porcine and bovine intermediate lobe was slightly higher (Mr = 78,000). Pituitary autoradiograms from the three species showed specific binding sites for 125I-oCRF in anterior and intermediate lobes, with none being apparent in the posterior pituitary. The identification of CRF receptors in the intermediate lobe with comparable characteristics to those previously identified in the anterior pituitary substantiate further the physiological role of CRF in regulating intermediate lobe hormone secretion

  7. 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.

  8. Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partum.

    Science.gov (United States)

    Engineer, Neelam; Darwin, Lucy; Nishigandh, Deole; Ngianga-Bakwin, Kandala; Smith, Steve C; Grammatopoulos, Dimitris K

    2013-09-01

    Women with postnatal depression (PND) appear to have abnormal hypothalamic pituitary adrenal (HPA) axis responses to stress, which might involve a genetic variability component. We investigated association of genetic variants in the glucocorticoid receptor (GR, NR3C1) and corticotropin releasing hormone receptor 1 (CRHR1) genes with increased risk for PND. Two hundred pregnant women were recruited prospectively and PND risk was assessed by the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and again 2-8 weeks post-natally (CW-GAPND study). The BclI and ER22/23EK single nucleotide polymorphisms (SNPs) of the GR and the haplotype-tagged rs1876828, rs242939 and rs242941 SNPs of the CRHR1 associated with genetic risk to depressive disorders were genotyped. A cut-off score of 10 was used to detect increased risk of PND. Association analysis was carried out in 140 patients that completed the study protocol. The BclI and rs242939 SNPs were over-represented in women with postnatal EPDS score ≥10 with significant allele association (p = 0.011 and depression during pregnancy and postpartum. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Corticotropin-releasing hormone-mediated metamorphosis in the neotenic axolotl Ambystoma mexicanum: synergistic involvement of thyroxine and corticoids on brain type II deiodinase.

    Science.gov (United States)

    Kühn, Eduard R; De Groef, Bert; Van der Geyten, Serge; Darras, Veerle M

    2005-08-01

    In the present study, morphological changes leading to complete metamorphosis have been induced in the neotenic axolotl Ambystoma mexicanum using a submetamorphic dose of T(4) together with an injection of corticotropin-releasing hormone (CRH). An injection of CRH alone is ineffective in this regard presumably due to a lack of thyrotropic stimulation. Using this low hormone profile for induction of metamorphosis, the deiodinating enzymes D2 and D3 known to be present in amphibians were measured in liver and brain 24h following an intraperitoneal injection. An injection of T(4) alone did not influence liver nor brain D2 and D3, but dexamethasone (DEX) or CRH alone or in combination with T(4) decreased liver D2 and D3. Brain D2 activity was slightly increased with a higher dose of DEX, though CRH did not have this effect. A profound synergistic effect occurred when T(4) and DEX or CRH were injected together, in the dose range leading to metamorphosis, increasing brain D2 activity more than fivefold. This synergistic effect was not found in the liver. It is concluded that brain T(3) availability may play an important role for the onset of metamorphosis in the neotenic axolotl.

  10. Minimal alteration in the ratio of circulatory fetal DNA to fetal corticotropin-releasing hormone mRNA level in preeclampsia.

    Science.gov (United States)

    Zhong, Xiao Yan; Holzgreve, Wolfgang; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Gupta, Anurag Kumar; Huppertz, Berthold; Hahn, Sinuhe

    2006-01-01

    We have recently observed that fetal DNA and fetal corticotropin-releasing hormone (CRH) mRNA are associated with in vitro generated syncytiotrophoblast-derived microparticles, and that the ratio of fetal DNA to mRNA (CRH) varied according to whether the particles were derived by predominantly apoptotic, apo-necrotic or necrotic pathways. Hence, we examined whether these ratios varied in maternal plasma samples taken from normotensive and preeclamptic pregnancies in vivo. Maternal plasma samples were collected from 18 cases with preeclampsia and 29 normotensive term controls. Circulatory fetal CRH mRNA and DNA levels were quantified by real-time PCR and RT-PCR. Circulatory fetal mRNA and fetal DNA levels were significantly elevated in the preeclampsia study group when compared to normotensive controls. Alterations in the fetal mRNA to DNA ratio between the study and control groups were minimal, even when stratified into early (34 weeks of gestation) onset preeclampsia. Our data suggest that although circulatory fetal DNA and mRNA levels are significantly elevated in preeclampsia, the ratios in maternal plasma are not dramatically altered. Copyright 2006 S. Karger AG, Basel.

  11. Noise stress changes mRNA expressions of corticotropin-releasing hormone, its receptors in amygdala, and anxiety-related behaviors

    Directory of Open Access Journals (Sweden)

    Evren Eraslan

    2015-01-01

    Full Text Available Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON, acute noise exposure (ANE, and chronic noise exposure (CNE. The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR. The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.

  12. Noise stress changes mRNA expressions of corticotropin-releasing hormone, its receptors in amygdala, and anxiety-related behaviors.

    Science.gov (United States)

    Eraslan, Evren; Akyazi, Ibrahim; Erg L-Ekiz, Elif; Matur, Erdal

    2015-01-01

    Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH) system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON), acute noise exposure (ANE), and chronic noise exposure (CNE). The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR). The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB) leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.

  13. Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

    Science.gov (United States)

    Phumsatitpong, Chayarndorn; Moenter, Suzanne M

    2018-01-01

    Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

  14. Corticotropin-Releasing Hormone As the Homeostatic Rheostat of Feto-Maternal Symbiosis and Developmental Programming In Utero and Neonatal Life

    Directory of Open Access Journals (Sweden)

    Viridiana Alcántara-Alonso

    2017-07-01

    Full Text Available A balanced interaction between the homeostatic mechanisms of mother and the developing organism during pregnancy and in early neonatal life is essential in order to ensure optimal fetal development, ability to respond to various external and internal challenges, protection from adverse programming, and safeguard maternal care availability after parturition. In the majority of pregnancies, this relationship is highly effective resulting in successful outcomes. However, in a number of pathological settings, perturbations of the maternal homeostasis disrupt this symbiosis and initiate adaptive responses with unpredictable outcomes for the fetus or even the neonate. This may lead to development of pathological phenotypes arising from developmental reprogramming involving interaction of genetic, epigenetic, and environmental-driven pathways, sometimes with acute consequences (e.g., growth impairment and sometimes delayed (e.g., enhanced susceptibility to disease that last well into adulthood. Most of these adaptive mechanisms are activated and controlled by hormones of the hypothalamo-pituitary adrenal axis under the influence of placental steroid and peptide hormones. In particular, the hypothalamic peptide corticotropin-releasing hormone (CRH plays a key role in feto-maternal communication by orchestrating and integrating a series of neuroendocrine, immune, metabolic, and behavioral responses. CRH also regulates neural networks involved in maternal behavior and this determines efficiency of maternal care and neonate interactions. This review will summarize our current understanding of CRH actions during the perinatal period, focusing on the physiological roles for both mother and offspring and also how external challenges can alter CRH actions and potentially impact on fetus/neonate health.

  15. Corticotropin-Releasing Hormone Receptor Type 1 (CRHR1 Clustering with MAGUKs Is Mediated via Its C-Terminal PDZ Binding Motif.

    Directory of Open Access Journals (Sweden)

    Julia Bender

    Full Text Available The corticotropin-releasing hormone receptor type 1 (CRHR1 plays an important role in orchestrating neuroendocrine, behavioral, and autonomic responses to stress. To identify molecules capable of directly modulating CRHR1 signaling, we performed a yeast-two-hybrid screen using the C-terminal intracellular tail of the receptor as bait. We identified several members of the membrane-associated guanylate kinase (MAGUK family: postsynaptic density protein 95 (PSD95, synapse-associated protein 97 (SAP97, SAP102 and membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2. CRHR1 is co-expressed with the identified MAGUKs and with the additionally investigated PSD93 in neurons of the adult mouse brain and in primary hippocampal neurons, supporting the probability of a physiological interaction in vivo. The C-terminal PDZ (PSD-95, discs large, zona occludens 1 binding motif of CRHR1 is essential for its physical interaction with MAGUKs, as revealed by the CRHR1-STAVA mutant, which harbors a functionally impaired PDZ binding motif. The imitation of a phosphorylation at Thr413 within the PDZ binding motif also disrupted the interaction with MAGUKs. In contrast, distinct PDZ domains within the identified MAGUKs are involved in the interactions. Expression of CRHR1 in primary neurons demonstrated its localization throughout the neuronal plasma membrane, including the excitatory post synapse, where the receptor co-localized with PSD95 and SAP97. The co-expression of CRHR1 and respective interacting MAGUKs in HEK293 cells resulted in a clustered subcellular co-localization which required an intact PDZ binding motif. In conclusion, our study characterized the PDZ binding motif-mediated interaction of CRHR1 with multiple MAGUKs, which directly affects receptor function.

  16. Differential Activation in Amygdala and Plasma Noradrenaline during Colorectal Distention by Administration of Corticotropin-Releasing Hormone between Healthy Individuals and Patients with Irritable Bowel Syndrome.

    Directory of Open Access Journals (Sweden)

    Yukari Tanaka

    Full Text Available Irritable bowel syndrome (IBS often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg or saline (1:1 was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH, serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.

  17. Differential effects of stable elevated levels of corticotropin-releasing hormone and systemic corticosterone on various types of rat learning

    Czech Academy of Sciences Publication Activity Database

    Řezáčová, Lenka; Svoboda, Jan; Stuchlík, Aleš; Valeš, Karel

    2011-01-01

    Roč. 32, č. 1 (2011), s. 64-76 ISSN 0172-780X R&D Projects: GA MZd(CZ) NR9180; GA ČR(CZ) GA309/09/0286; GA ČR(CZ) GCP303/10/J032; GA MŠk(CZ) LC554; GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z50110509 Keywords : corticosterone * CRH * behavior Subject RIV: FH - Neurology Impact factor: 1.296, year: 2011

  18. 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

    epoch consisted of a single daily defeat episode as described above on 3 consecutive days. Between each epoch, there was a time-out period of 3 days...2.5 weeks after the final defeat (data not shown). Treatment with twice daily imipramine (i.p., 2.5 mg/kg) for 2.5 weeks, eliminated the effects of...time course of immediate early gene expression in rat brain following acute stress. Neuroscience 64:477–505. ayas CV, Buller KM, Day TA (1999

  19. 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...

  20. The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Cannell, Elizabeth; Dornan, Anthony J.; Halberg, Kenneth Agerlin

    2016-01-01

    Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin...

  1. Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors

    Science.gov (United States)

    Reyes, T. M.; Lewis, K.; Perrin, M. H.; Kunitake, K. S.; Vaughan, J.; Arias, C. A.; Hogenesch, J. B.; Gulyas, J.; Rivier, J.; Vale, W. W.; Sawchenko, P. E.

    2001-01-01

    Here we describe the cloning and initial characterization of a previously unidentified CRF-related neuropeptide, urocortin II (Ucn II). Searches of the public human genome database identified a region with significant sequence homology to the CRF neuropeptide family. By using homologous primers deduced from the human sequence, a mouse cDNA was isolated from whole brain poly(A)+ RNA that encodes a predicted 38-aa peptide, structurally related to the other known mammalian family members, CRF and Ucn. Ucn II binds selectively to the type 2 CRF receptor (CRF-R2), with no appreciable activity on CRF-R1. Transcripts encoding Ucn II are expressed in discrete regions of the rodent central nervous system, including stress-related cell groups in the hypothalamus (paraventricular and arcuate nuclei) and brainstem (locus coeruleus). Central administration of 1–10 μg of peptide elicits activational responses (Fos induction) preferentially within a core circuitry subserving autonomic and neuroendocrine regulation, but whose overall pattern does not broadly mimic the CRF-R2 distribution. Behaviorally, central Ucn II attenuates nighttime feeding, with a time course distinct from that seen in response to CRF. In contrast to CRF, however, central Ucn II failed to increase gross motor activity. These findings identify Ucn II as a new member of the CRF family of neuropeptides, which is expressed centrally and binds selectively to CRF-R2. Initial functional studies are consistent with Ucn II involvement in central autonomic and appetitive control, but not in generalized behavioral activation. PMID:11226328

  2. Emerging Role for Corticotropin Releasing Factor Signaling in the Bed Nucleus of the Stria Terminalis at the Intersection of Stress and Reward

    OpenAIRE

    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 neurop...

  3. The effects of CRA 1000, a non-peptide antagonist of corticotropin-releasing factor receptor type 1, on adaptive behaviour in the rat.

    Science.gov (United States)

    Harro, J; Tõnissaar, M; Eller, M

    2001-04-01

    Intracerebrally administered CRF has been demonstrated to elicit several behavioural deficits in novel and potentially stressful experimental paradigms, and to promote activity in familiar situations. This study examined the effect of CRA 1000, a novel non-peptide antagonist of CRF(1)receptors, on rat behaviour in tests of anxiolytic and antidepressant activity and novelty-oriented behaviour. CRA 1000 (1.25-10 mg/kg) had no major effect in elevated plus-maze and social interaction tests. However, CRA 1000 (5 mg/kg) significantly reduced immobility in the forced swimming test, suggesting an antidepressant-like effect. In the exploration box test, CRA 1000 (1.25 mg/kg) had an anxiolytic effect on rat exploratory behaviour both in intact rats and after lesioning of the projections of locus coeruleus by DSP-4 (50 mg/kg) treatment. A higher dose of CRA 1000 (5 mg/kg) tended to have anxiolytic-like effects in DSP-4 pretreated rats, but in intact animals this dose prevented the increase in exploration which develops with repeated exposure to initially anxiety-provoking situations. Taken together, these experiments demonstrate that CRF1 receptor blockade by CRA 1000 has antidepressant-like effects, does not have a robust anti-anxiety effect in non-stressed animals, but does have anxiolytic-like effects in more complex tasks, which can be observed also after denervation of the locus coeruleus projections. However, large doses of CRF1 receptor antagonists may reduce motivation of exploratory behaviour in familiar environments. Copyright 2001 Harcourt Publishers Ltd.

  4. Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain

    NARCIS (Netherlands)

    Doelen, R.H.A. van der; Arnoldussen, I.A.C.; Ghareh, H.; Och, L. van; Homberg, J.R.; Kozicz, L.T.

    2015-01-01

    The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene x Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid

  5. The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster.

    Science.gov (United States)

    Cannell, Elizabeth; Dornan, Anthony J; Halberg, Kenneth A; Terhzaz, Selim; Dow, Julian A T; Davies, Shireen-A

    2016-06-01

    Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin (Drome-kinin, DK) in desiccation and starvation tolerance. Gene expression and labelled DH44 ligand binding data, as well as highly selective knockdowns and/or neuronal ablations of DH44 in neurons of the pars intercerebralis and DH44 receptor (DH44-R2) in Malpighian tubule principal cells, indicate that suppression of DH44 signalling improves desiccation tolerance of the intact fly. Drome-kinin receptor, encoded by the leucokinin receptor gene, LKR, is expressed in DH44 neurons as well as in stellate cells of the Malpighian tubules. LKR knockdown in DH44-expressing neurons reduces Malpighian tubule-specific LKR, suggesting interactions between DH44 and LK signalling pathways. Finally, although a role for DK in desiccation tolerance was not defined, we demonstrate a novel role for Malpighian tubule cell-specific LKR in starvation tolerance. Starvation increases gene expression of epithelial LKR. Also, Malpighian tubule stellate cell-specific knockdown of LKR significantly reduced starvation tolerance, demonstrating a role for neuropeptide signalling during starvation stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes.

    Science.gov (United States)

    Ciechanowska, Magdalena; Łapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

    2011-01-01

    There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo-pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo-anterior pituitary unit. © CSIRO 2011 Open Access

  7. A second corticotropin-releasing hormone gene (CRH2) is conserved across vertebrate classes and expressed in the hindbrain of a basal neopterygian fish, the spotted gar (Lepisosteus oculatus).

    Science.gov (United States)

    Grone, Brian P; Maruska, Karen P

    2015-05-01

    To investigate the origins of the vertebrate stress-response system, we searched sequenced vertebrate genomes for genes resembling corticotropin-releasing hormone (CRH). We found that vertebrate genomes possess, in addition to CRH, another gene that resembles CRH in sequence and syntenic environment. This paralogous gene was previously identified only in the elephant shark (a holocephalan), but we find it also in marsupials, monotremes, lizards, turtles, birds, and fishes. We examined the relationship of this second vertebrate CRH gene, which we name CRH2, to CRH1 (previously known as CRH) and urocortin1/urotensin1 (UCN1/UTS1) in primitive fishes, teleosts, and tetrapods. The paralogs CRH1 and CRH2 likely evolved via duplication of CRH during a whole-genome duplication early in the vertebrate lineage. CRH2 was subsequently lost in both teleost fishes and eutherian mammals but retained in other lineages. To determine where CRH2 is expressed relative to CRH1 and UTS1, we used in situ hybridization on brain tissue from spotted gar (Lepisosteus oculatus), a neopterygian fish closely related to teleosts. In situ hybridization revealed widespread distribution of both crh1 and uts1 in the brain. Expression of crh2 was restricted to the putative secondary gustatory/secondary visceral nucleus, which also expressed calcitonin-related polypeptide alpha (calca), a marker of parabrachial nucleus in mammals. Thus, the evolutionary history of CRH2 includes restricted expression in the brain, sequence changes, and gene loss, likely reflecting release of selective constraints following whole-genome duplication. The discovery of CRH2 opens many new possibilities for understanding the diverse functions of the CRH family of peptides across vertebrates. © 2015 Wiley Periodicals, Inc.

  8. Motivational factors for educational tourism: marketing insights

    Directory of Open Access Journals (Sweden)

    Harazneh Ibrahim

    2018-03-01

    Full Text Available Intertwined with other structural changes, are policies to increase the number of international students to diversify tourism activities into what is known as educational tourism (edutourism. Of immediate relevance to this article is the implementation of policies and strategies to attract students from all over the world. Unfortunately, these policies are partially implemented opting out important factors, as such this article attempt to conceptualize the motivational factors associated with edu-tourism. Data garnered from foreign students in North Cyprus suggest that cost, quality, environmental, regulatory, cultural, political, safety and social factors are key factors for edu-tourism. The outcome in this study will help policy makers determine the factors that influence the choice of tertiary institutions in North Cyprus associated with a particular geodemographic setup. This will also enable policy makers to create a tailor made persuasive strategies, policies, adverts and messages to increase their market share.

  9. CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro

    Directory of Open Access Journals (Sweden)

    Colette G. Ngo Ndjom

    2017-06-01

    Full Text Available Sepsis is a life-threatening health condition caused by infectious pathogens of the respiratory tract, and accounts for 28–50% of annual deaths in the US alone. Current treatment regimen advocates the use of corticosteroids as adjunct treatment with antibiotics, for their broad inhibitory effect on the activity and production of pro-inflammatory mediators. However, despite their use, corticosteroids have not proven to be able to reverse the death incidence among septic patients. We have previously demonstrated the potential for neuroendocrine factors to directly influence Streptococcus pneumoniae virulence, which may in turn mediate disease outcome leading to sepsis and septic shock. The current study investigated the role of Corticotropin-releasing hormone (CRH in mediating key markers of pneumococcal virulence as important phenotypic determinants of sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal strain with CRH promoted growth rate, increased capsule thickness and penicillin resistance, as well as induced pneumolysin gene expression. These results thus provide significant insights of CRH–pathogen interactions useful in understanding the underlying mechanisms of neuroendocrine factor's role in the onset of community acquired pneumonias (CAP, sepsis and septic shock.

  10. Dimensions of insight in schizophrenia: Exploratory factor analysis of items from multiple self- and interviewer-rated measures of insight.

    Science.gov (United States)

    Konsztowicz, Susanna; Schmitz, Norbert; Lepage, Martin

    2018-03-10

    Insight in schizophrenia is regarded as a multidimensional construct that comprises aspects such as awareness of the disorder and recognition of the need for treatment. The proposed number of underlying dimensions of insight is variable in the literature. In an effort to identify a range of existing dimensions of insight, we conducted a factor analysis on combined items from multiple measures of insight. We recruited 165 participants with enduring schizophrenia (treated for >3years). Exploratory factor analysis was conducted on itemized scores from two interviewer-rated measures of insight: the Schedule for the Assessment of Insight-Expanded and the abbreviated Scale to assess Unawareness of Mental Disorder; and two self-report measures: the Birchwood Insight Scale and the Beck Cognitive Insight Scale. A five-factor solution was selected as the best-fitting model, with the following dimensions of insight: 1) awareness of illness and the need for treatment; 2) awareness and attribution of symptoms and consequences; 3) self-certainty; 4) self-reflectiveness for objectivity and fallibility; and 5) self-reflectiveness for errors in reasoning and openness to feedback. Insight in schizophrenia is a multidimensional construct comprised of distinct clinical and cognitive domains of awareness. Multiple measures of insight, both clinician- and self-rated, are needed to capture all of the existing dimensions of insight. Future exploration of associations between the various dimensions and their potential determinants will facilitate the development of clinically useful models of insight and effective interventions to improve outcome. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Factoring the car-climate challenge: Insights and implications

    International Nuclear Information System (INIS)

    DeCicco, John M.

    2013-01-01

    Three approaches commonly are identified for controlling automobile greenhouse gas (GHG) emissions: reducing travel demand, improving vehicle efficiency and using alternatively (non-petroleum) fueled vehicles (AFVs). Similarly, sector emissions are factored by travel distance, vehicle fuel intensity and fuel GHG (“carbon”) intensity. Analyzing these factors using US and China data reveals that for a broad range of conditions, stringent GHG emissions limits for the auto sector imply limits of comparable stringency for fuel carbon intensity. However, carbon intensity is a modeled representation of complex energy supply and use systems rather than a measurable property of fuels themselves. Carefully examining the locations and magnitudes of fuel-related emissions indicates that the proper policy focus is on the sectors that supply fuel rather than the choice of fuels in the auto sector. Therefore, beyond fundamental R and D, policies to commercialize AFVs are not necessarily required for climate protection at present. In addition to managing travel demand and improving vehicle efficiency, the implied policy priority is limiting net GHG impacts in the energy and other natural resource sectors that supply fuels. Future work is needed to develop GHG management protocols for liquid fuel supply systems involving fungible commodities and dynamic global supply chains. - Highlights: • Factor analysis offers insights about ways to reduce automotive GHG emissions. • Improving vehicle efficiency and reducing travel demand remain important. • Reducing net GHG impacts in energy sectors that supply motor fuels is also a priority. • Commercialization of alternatively fueled vehicles is not necessarily required at present

  12. The remarkable conservation of corticotropin-releasing hormone (CRH)-binding protein in the honeybee (Apis mellifera) dates the CRH system to a common ancestor of insects and vertebrates

    NARCIS (Netherlands)

    Huising, M.O.; Flik, G.

    2005-01-01

    CRH-binding protein (CRH-BP) is a key factor in the regulation of CRH signaling; it modulates the bioactivity and bioavailability of CRH and its related peptides. The conservation of CRH-BP throughout vertebrates was only recently demonstrated. Here we report the presence of CRH-BP in the honeybee

  13. Up-regulation of corticotropin releasing hormone is associated with ...

    African Journals Online (AJOL)

    established in literature that stress signals such as psoriasis prompts the release of CRH from the hypothalamus paraventricular nucleus (PVN). CRH in turn triggers ACTH release from anterior pituitary [8] which ultimately controls the glucocorticoid discharge from adrenal cortex. Several of the glucocorticoids, which include ...

  14. 促肾上腺皮质激素释放激素受体1基因多态与抗郁物疗效的关联研究%Association study of corticotropin-releasing hormone receptor1 gene polymorphisms and antidepressant response in major depressive disorder

    Institute of Scientific and Technical Information of China (English)

    王娟; 禹顺英; 沈一峰; 李华芳

    2012-01-01

    Objective To investigate whether the corticotropin-releasing hormone receptorl (CRHR1) gene polymorphisms is associated with the therapeutic response to Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) in majgr depressive disorder patients. Methods Routine dosage of unitary novel antidepressant (SSRIs or SNRIs) was given by at least six weeks to 271 patients with major depressive disorder diagnosed as by Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-Ⅳ). Hamilton Depression Scale 17(HAMD17) was evaluated before and after the treatment. The patients were grouped as responder (decreasing rate of score of HAMD17 ≥50%) and non-responder (decreasing rate of score of HAMD17 0.05). Conclusions The results support that CRHR, gene is involved in the an-tidepressant response of SSRIs and SNRIs in major depressive disorder in the early stage.%目的 探讨促肾上腺皮质激素释放激素受体2(corticotropin-releasing hormone reeeptor1,CRHR1)基因多态性与选择性5-羟色胺再摄取抑制剂(Selective Serotonin Reuptake Inhibitors,SSRIs)、5-羟色胺和去甲肾上腺素再摄取抑制剂(Serotonin and Norepinephrine Reuptake Inhibitors,SNRIs)抗抑郁疗效差异的相关性.方法 对符合美国精神障碍诊断与统计手册第4版(Diagnostic and Statistical Manual of Menial Disorders,Fourth Edition,DSM-Ⅳ)抑郁症诊断标准的271例抑郁症患者予以单一新型抗抑郁药(SSRIs或SNRIs)常规剂量治疗至少6周,以治疗前后17项汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)总分减分率作为评估疗效的指标.采用TaqMan探针法检测CRHR1基因上4个单核苷酸多态性(Single Nucleotide Polymorphism,SNP)的基因型,比较有效组(HAMD-17减分率≥50%)和无效组(HAMD-17减分率<50%)之间4个位点基因型及多位点组成单倍型的不同.结果 治疗4周末:CRHR1基因rs17689966位点A等位基因及AA基因型携带

  15. The affective dimension of pain as a risk factor for drug and alcohol addiction.

    Science.gov (United States)

    LeBlanc, Dana M; McGinn, M Adrienne; Itoga, Christy A; Edwards, Scott

    2015-12-01

    Addiction, or substance use disorder (SUD), is a devastating psychiatric disease composed of multiple elemental features. As a biobehavioral disorder, escalation of drug and/or alcohol intake is both a cause and consequence of molecular neuroadaptations in central brain reinforcement circuitry. Multiple mesolimbic areas mediate a host of negative affective and motivational symptoms that appear to be central to the addiction process. Brain stress- and reinforcement-related regions such as the central amygdala (CeA), prefrontal cortex (PFC), and nucleus accumbens (NAc) also serve as central processors of ascending nociceptive input. We hypothesize that a sensitization of brain mechanisms underlying the processing of persistent and maladaptive pain contributes to a composite negative affective state to drive the enduring, relapsing nature of addiction, particularly in the case of alcohol and opioid use disorder. At the neurochemical level, pain activates central stress-related neuropeptide signaling, including the dynorphin and corticotropin-releasing factor (CRF) systems, and by this process may facilitate negative affect and escalated drug and alcohol use over time. Importantly, the widespread prevalence of unresolved pain and associated affective dysregulation in clinical populations highlights the need for more effective analgesic medications with reduced potential for tolerance and dependence. The burgeoning epidemic of prescription opioid abuse also demands a closer investigation into the neurobiological mechanisms of how pain treatment could potentially represent a significant risk factor for addiction in vulnerable populations. Finally, the continuing convergence of sensory and affective neuroscience fields is expected to generate insight into the critical balance between pain relief and addiction liability, as well as provide more effective therapeutic strategies for chronic pain and addiction. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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

  17. Teacher Governance Factors and Social Cohesion: Insights from Pakistan

    Science.gov (United States)

    Halai, Anjum; Durrani, Naureen

    2016-01-01

    This paper explores teacher governance factors, particularly recruitment and deployment of teachers, in relation to inequalities and social cohesion. Pakistan introduced major reforms in education in the post 9/11 context of escalating conflict. These include a merit and needs-based policy on teacher recruitment to eliminate corruption in…

  18. Insight of patients and their parents into schizophrenia: Exploring agreement and the influence of parental factors.

    Science.gov (United States)

    Macgregor, Alexandra; Norton, Joanna; Bortolon, Catherine; Robichon, Melissa; Rolland, Camille; Boulenger, Jean-Philippe; Raffard, Stéphane; Capdevielle, Delphine

    2015-08-30

    Poor insight is found in up to 80% of schizophrenia patients and has been associated with multiple factors of which cognitive functioning, social and environmental factors. Few studies have explored associations between patient insight and that of their biological parents', and the influence of parental factors. Insight was assessed in 41 patients and their biological parents with Amador's Scale for the assessment of Unawareness of Mental Disorder (SUMD). Parents' knowledge about schizophrenia and critical attitudes were assessed with validated self-report questionnaires. Both groups underwent cognitive assessments for working memory and executive functioning. Insight in patients and their parents was not associated for any of the SUMD dimensions but a significant correlation was found between patient and parent awareness of treatment effect for patient-parent dyads with frequent daily contact. Low parental critical attitude was associated with higher patient awareness of symptoms and a high parental memory task score with high patient insight. Our study is the first to suggest a possible influence of parental factors such as critical attitudes and cognitive performance on patient insight. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Insights into the Functions of a Prophage Recombination Directionality Factor

    Directory of Open Access Journals (Sweden)

    Mireille Ansaldi

    2012-10-01

    Full Text Available Recombination directionality factors (RDFs, or excisionases, are essential players of prophage excisive recombination. Despite the essentially catalytic role of the integrase in both integrative and excisive recombination, RDFs are required to direct the reaction towards excision and to prevent re-integration of the prophage genome when entering a lytic cycle. KplE1, HK620 and numerous (prophages that integrate at the same site in enterobacteria genomes (such as the argW tRNA gene all share a highly conserved recombination module. This module comprises the attL and attR recombination sites and the RDF and integrase genes. The KplE1 RDF was named TorI after its initial identification as a negative regulator of the tor operon. However, it was characterized as an essential factor of excisive recombination. In this study, we designed an extensive random mutagenesis protocol of the torI gene and identified key residues involved in both functions of the TorI protein. We show that, in addition to TorI-TorR protein-protein interaction, TorI interacts in solution with the IntS integrase. Moreover, in vitro, TorR and IntS appear to compete for TorI binding. Finally, our mutagenesis results suggest that the C-terminal part of the TorI protein is dedicated to protein-protein interactions with both proteins TorR and IntS.

  20. MGMT expression: insights into its regulation. 1. Epigenetic factors

    Directory of Open Access Journals (Sweden)

    Iatsyshyna A. P.

    2013-03-01

    Full Text Available O6-methylguanine-DNA methyltransferase (MGMT is the DNA repair enzyme responsible for removing of alkylation adducts from the O6-guanine in DNA. Despite MGMT prevents mutations and cell death, this enzyme can provide resistance of cancer cells to alkylating agents of chemotherapy. The high intra- and inter-individual variations in the human MGMT expression level have been observed indicating to a complicated regulation of this gene. This review is focused on the study of epigenetic factors which could be potentially involved in regulation of the human MGMT gene expression. These include chromatin remodeling via histone modifications and DNA methylation of promoter region and gene body, as well as RNA-based mechanisms, alternative splicing, protein post- translational modifications, and other.

  1. Annuity factors, duration and convexity : insights from a financial engineering perspective

    OpenAIRE

    Ekern, Steinar

    1998-01-01

    This paper applies a unified and integrative financial engineering perspective to key derived concepts in traditional fixed income analysis, with the purpose of enhancing conceptual insights and motivating computational applications. The emphasis on annuity factors and their impact on duration and convexity differs from the focus prevailing in related discussions. By decomposing the cashflow streams of a coupon bond into different, specific, and clearly defined portfolios of component bonds w...

  2. Ethics in Publishing: Complexity Science and Human Factors Offer Insights to Develop a Just Culture.

    Science.gov (United States)

    Saurin, Tarcisio Abreu

    2016-12-01

    While ethics in publishing has been increasingly debated, there seems to be a lack of a theoretical framework for making sense of existing rules of behavior as well as for designing, managing and enforcing such rules. This letter argues that systems-oriented disciplines, such as complexity science and human factors, offer insights into new ways of dealing with ethics in publishing. Some examples of insights are presented. Also, a call is made for empirical studies that unveil the context and details of both retracted papers and the process of writing and publishing academic papers. This is expected to shed light on the complexity of the publication system as well as to support the development of a just culture, in which all participants are accountable.

  3. Wear of resin composites: Current insights into underlying mechanisms, evaluation methods and influential factors

    Directory of Open Access Journals (Sweden)

    Akimasa Tsujimoto

    2018-05-01

    Full Text Available Summary: The application of resin composites in dentistry has become increasingly widespread due to the increased aesthetic demands of patients, improvements in the formulation of resin composites, and the ability of these materials to bond to tooth structures, together with concerns about dental amalgam fillings. As resistance to wear is an important factor in determining the clinical success of resin composite restoratives, this review article defines what constitutes wear and describes the major underlying phenomena involved in this process. Insights are further included on both in vivo and in vitro tests used to determine the wear resistance of resin composite and the relationships between these tests. The discussion focuses on factors that contribute to the wear of resin composite. Finally, future perspectives are included on both clinical and laboratory tests and on the development of resin composite restorations. Keywords: Resin composites, Wear resistance, Wear testing

  4. A deeper view of insight in schizophrenia: Insight dimensions, unawareness and misattribution of particular symptoms and its relation with psychopathological factors.

    Science.gov (United States)

    Pousa, Esther; Ochoa, Susana; Cobo, Jesús; Nieto, Lourdes; Usall, Judith; Gonzalez, Beatriz; Garcia-Ribera, Carles; Pérez Solà, Victor; Ruiz, Ada-I; Baños, Iris; Cobo, Jesús; García-Ribera, Carles; González, Beatriz; Massons, Carmina; Nieto, Lourdes; Monserrat, Clara; Ochoa, Susana; Pousa, Esther; Ruiz, Ada-Inmaculada; Ruiz, Isabel; Sanchez-Cabezudo, Dolores; Usall, Judith

    2017-11-01

    1. To describe insight in a large sample of schizophrenia subjects from a multidimensional point of view, including unawareness of general insight dimensions as well as unawareness and misattribution of particular symptoms. 2. To explore the relationship between unawareness and clinical and socio-demographic variables. 248 schizophrenia patients were assessed with the Positive and Negative Syndrome Scale (PANSS, five factor model of Lindenmayer) and the full Scale of Unawareness of Mental Disorder (SUMD). Bivariate associations and multiple linear regression analyses were used to investigate the relationship between unawareness, symptoms and socio-demographic variables. Around 40% of the sample showed unawareness of mental disorder, of the need for medication and of the social consequences. Levels of unawareness and misattribution of particular symptoms varied considerably. General unawareness dimensions showed small significant correlations with positive, cognitive and excitement factors of psychopathology, whereas these symptom factors showed higher correlations with unawareness of particular symptoms. Similarly, regression models showed a small significant predictive value of positive symptoms in the three general unawareness dimensions while a moderate one in the prediction of particular symptoms. Misattribution showed no significant correlations with any symptom factors. Results confirm that insight in schizophrenia is a multi-phased phenomenon and that unawareness into particular symptoms varies widely. The overlap between unawareness dimensions and psychopathology is small and seems to be restricted to positive and cognitive symptoms, supporting the accounts from cognitive neurosciences that suggest that besides basic cognition poor insight may be in part a failure of self-reflection or strategic metacognition. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. B-GATA transcription factors - insights into their structure, regulation and role in plant development

    Directory of Open Access Journals (Sweden)

    Claus eSchwechheimer

    2015-02-01

    Full Text Available GATA transcription factors are evolutionarily conserved transcriptional regulators that recognize promoter elements with a G-A-T-A core sequence. In comparison to animal genomes, the GATA transcription factor family in plants is comparatively large with approximately 30 members. In spite of a long-standing interest of plant molecular biologists in GATA factors, only research conducted in the last years has led to reliable insights into their functions during plant development. Here, we review the current knowledge on B-GATAs, one of four GATA factor subfamilies from Arabidopsis thaliana. We show that B-GATAs can be subdivided based on structural features and their biological function into family members with a C-terminal LLM- (leucine-leucine-methionine domain or an N-terminal HAN- (HANABA TARANU domain. The paralogous GNC (GATA, NITRATE-INDUCIBLE, CARBON-METABOLISM INVOLVED and CGA1/GNL (CYTOKININ-INDUCED GATA1/GNC-LIKE are introduced as LLM-domain containing B-GATAs from Arabidopsis that control germination, greening, senescence and flowering time downstream from several growth regulatory signals including light and the hormones gibberellin, auxin, and cytokinin. Arabidopsis HAN and its monocot-specific paralogs from rice (NECK LEAF1, maize (TASSEL SHEATH1, and barley (THIRD OUTER GLUME are HAN-domain-containing B-GATAs with a predominant role in embryo development and floral development. We also review GATA23, a regulator of lateral root initiation from Arabidopsis, that is closely related to GNC and GNL but has a degenerate LLM-domain that is seemingly specific for the Brassicaceae family. The Brassicaceae-specific GATA23 together with the above-mentioned monocot-specific HAN-domain GATAs provide evidence that neofunctionalization of the B-GATAs was used during plant evolution to expand the functional repertoire of these transcription factors.

  6. Nerve growth factor, brain-derived neurotrophic factor, and the chronobiology of mood: a new insight into the "neurotrophic hypothesis"

    Directory of Open Access Journals (Sweden)

    Tirassa P

    2015-10-01

    Full Text Available Paola Tirassa,1 Adele Quartini,2 Angela Iannitelli2–4 1National Research Council (CNR, Institute of Cell Biology and Neurobiology (IBCN, 2Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine – "Sapienza" University of Rome, 3Italian Psychoanalytical Society (SPI, Rome, Italy; 4International Psychoanalytical Association (IPA, London, UKAbstract: The light information pathways and their relationship with the body rhythms have generated a new insight into the neurobiology and the neurobehavioral sciences, as well as into the clinical approaches to human diseases associated with disruption of circadian cycles. Light-based strategies and/or drugs acting on the circadian rhythms have widely been used in psychiatric patients characterized by mood-related disorders, but the timing and dosage use of the various treatments, although based on international guidelines, are mainly dependent on the psychiatric experiences. Further, many efforts have been made to identify biomarkers able to disclose the circadian-related aspect of diseases, and therefore serve as diagnostic, prognostic, and therapeutic tools in clinic to assess the different mood-related symptoms, including pain, fatigue, sleep disturbance, loss of interest or pleasure, appetite, psychomotor changes, and cognitive impairments. Among the endogenous factors suggested to be involved in mood regulation, the neurotrophins, nerve growth factor, and brain-derived neurotrophic factor show anatomical and functional link with the circadian system and mediate some of light-induced effects in brain. In addition, in humans, both nerve growth factor and brain-derived neurotrophic factor have showed a daily rhythm, which correlate with the morningness–eveningness dimensions, and are influenced by light, suggesting their potential role as biomarkers for chronotypes and/or chronotherapy. The evidences of the relationship between the diverse mood-related disorders

  7. New Insights into Butyrylcholinesterase Activity Assay: Serum Dilution Factor as a Crucial Parameter.

    Directory of Open Access Journals (Sweden)

    Joanna Jońca

    Full Text Available Butyrylcholinesterase (BChE activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of neuromuscular blocking agents. The assay plays an important role in clinical chemistry as a good diagnostic marker for intoxication with pesticides and nerve agents. Furthermore, the assay is also commonly used for in vitro characterization of cholinesterases, their toxins and drugs. There is still lack of standardized procedure for measurement of BChE activity and many laboratories use different substrates at various concentrations. The purpose of this study was to validate the BChE activity assay to determine the best dilution of human serum and the most optimal concentration of substrates and inhibitors. Serum BChE activity was measured using modified Ellman's method applicable for a microplate reader. We present our experience and new insights into the protocol for high-throughput routine assays of human plasma cholinesterase activities adapted to a microplate reader. During our routine assays used for the determination of BChE activity, we have observed that serum dilution factor influences the results obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine iodide can be successfully used for the accurate measurement of BChE activity in human serum. We also discuss usage of various concentrations of dibucaine and fluoride in BChE phenotyping. This study indicates that some factors of such a multicomponent clinical material like serum can influence kinetic parameters of the BChE. The observed inhibitory effect is dependent on serum dilution factor used in the assay.

  8. The largest human cognitive performance dataset reveals insights into the effects of lifestyle factors and aging

    Directory of Open Access Journals (Sweden)

    Daniel A Sternberg

    2013-06-01

    Full Text Available Making new breakthroughs in understanding the processes underlying human cognition may depend on the availability of very large datasets that have not historically existed in psychology and neuroscience. Lumosity is a web-based cognitive training platform that has grown to include over 600 million cognitive training task results from over 35 million individuals, comprising the largest existing dataset of human cognitive performance. As part of the Human Cognition Project, Lumosity’s collaborative research program to understand the human mind, Lumos Labs researchers and external research collaborators have begun to explore this dataset in order uncover novel insights about the correlates of cognitive performance. This paper presents two preliminary demonstrations of some of the kinds of questions that can be examined with the dataset. The first example focuses on replicating known findings relating lifestyle factors to baseline cognitive performance in a demographically diverse, healthy population at a much larger scale than has previously been available. The second example examines a question that would likely be very difficult to study in laboratory-based and existing online experimental research approaches: specifically, how learning ability for different types of cognitive tasks changes with age. We hope that these examples will provoke the imagination of researchers who are interested in collaborating to answer fundamental questions about human cognitive performance.

  9. New insights in the bacterial spore resistance to extreme terrestrial and extraterrestrial factors

    Science.gov (United States)

    Moeller, Ralf; Horneck, Gerda; Reitz, Guenther

    Based on their unique resistance to various space parameters, Bacillus endospores are one of the model systems used for astrobiological studies. The extremely high resistance of bacterial endospores to environmental stress factors has intrigued researchers since long time and many characteristic spore features, especially those involved in the protection of spore DNA, have already been uncovered. The disclosure of the complete genomic sequence of Bacillus subtilis 168, one of the often used astrobiological model system, and the rapid development of tran-scriptional microarray techniques have opened new opportunities of gaining further insights in the enigma of spore resistance. Spores of B. subtilis were exposed to various extreme ter-restrial and extraterrestrial stressors to reach a better understanding of the DNA protection and repair strategies, which them to cope with the induced DNA damage. Following physical stress factors of environmental importance -either on Earth or in space -were selected for this thesis: (i) mono-and polychromatic UV radiation, (ii) ionizing radiation, (iii) exposure to ultrahigh vacuum; and (iv) high shock pressures simulating meteorite impacts. To reach a most comprehensive understanding of spore resistance to those harsh terrestrial or simulated extraterrestrial conditions, a standardized experimental protocol of the preparation and ana-lyzing methods was established including the determination of the following spore responses: (i) survival, (ii) induced mutations, (iii) DNA damage, (iv) role of different repair pathways by use of a set of repair deficient mutants, and (v) transcriptional responses during spore germi-nation by use of genome-wide transcriptome analyses and confirmation by RT-PCR. From this comprehensive set of data on spore resistance to a variety of environmental stress parameters a model of a "built-in" transcriptional program of bacterial spores in response to DNA damaging treatments to ensure DNA restoration

  10. Genome-wide investigation of transcription factors provides insights into transcriptional regulation in Plutella xylostella.

    Science.gov (United States)

    Zhao, Qian; Ma, Dongna; Huang, Yuping; He, Weiyi; Li, Yiying; Vasseur, Liette; You, Minsheng

    2018-04-01

    Transcription factors (TFs), which play a vital role in regulating gene expression, are prevalent in all organisms and characterization of them may provide important clues for understanding regulation in vivo. The present study reports a genome-wide investigation of TFs in the diamondback moth, Plutella xylostella (L.), a worldwide pest of crucifers. A total of 940 TFs distributed among 133 families were identified. Phylogenetic analysis of insect species showed that some of these families were found to have expanded during the evolution of P. xylostella or Lepidoptera. RNA-seq analysis showed that some of the TF families, such as zinc fingers, homeobox, bZIP, bHLH, and MADF_DNA_bdg genes, were highly expressed in certain tissues including midgut, salivary glands, fat body, and hemocytes, with an obvious sex-biased expression pattern. In addition, a number of TFs showed significant differences in expression between insecticide susceptible and resistant strains, suggesting that these TFs play a role in regulating genes related to insecticide resistance. Finally, we identified an expansion of the HOX cluster in Lepidoptera, which might be related to Lepidoptera-specific evolution. Knockout of this cluster using CRISPR/Cas9 showed that the egg cannot hatch, indicating that this cluster may be related to egg development and maturation. This is the first comprehensive study on identifying and characterizing TFs in P. xylostella. Our results suggest that some TF families are expanded in the P. xylostella genome, and these TFs may have important biological roles in growth, development, sexual dimorphism, and resistance to insecticides. The present work provides a solid foundation for understanding regulation via TFs in P. xylostella and insights into the evolution of the P. xylostella genome.

  11. 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

  12. Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs

    NARCIS (Netherlands)

    Moeniralam, H. S.; Endert, E.; van Lanschot, J. J.; Sauerwein, H. P.; Romijn, J. A.

    1997-01-01

    To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five

  13. Elevated corticotropin releasing hormone (CRH) during pregnancy and risk of postpartum depression (PPD).

    Science.gov (United States)

    Meltzer-Brody, Samantha; Stuebe, Alison; Dole, Nancy; Savitz, David; Rubinow, David; Thorp, John

    2011-01-01

    Perinatal depression has a prevalence of 10% with devastating consequences for mother and baby. The prospective identification of those at risk for postpartum (PPD) or prenatal (PND) depression has led to biomarker searches in pregnancy. There are conflicting reports of associations between midpregnancy placental CRH (pCRH) and PPD or PND. The objective of the study was to quantify the association of maternal pCRH with PPD and PND. This was a prospective cohort study (the Pregnancy, Infection, and Nutrition Study). The study was conducted at a prenatal clinics at the University of North Carolina at Chapel Hill. Patients included 1230 pregnant women. The relationship between pCRH at less than 20 wk and 24-29 wk and maternal depression assessed in pregnancy [Center for Epidemiologic Studies Depression Scale (CES-D)] and postpartum (12 wk and 1 yr) with the Edinburgh Postnatal Depression Scale (EPDS). At 24-29 wk, 24.8% of women had CES-D score of 17 or greater, and 9.7% had a CES-D score of 25 or greater. At 12 wk postpartum, 18.2% of women had an EPDS score of 10 or greater and 7.6% had an EPDS score of 13 or greater. CRH measures at less than 20 wk and 24-29 wk were inversely correlated with a CES-D score at 24-29 wk (n = 1080, P PPD (covariate-adjusted odds ratio per sd 0.99, 95% confidence interval 0.69-1.42). Higher midpregnancy pCRH was not associated with an increased risk of PND or PPD.

  14. Direct measurement of human plasma corticotropin-releasing hormone by two-site immunoradiometric assay

    International Nuclear Information System (INIS)

    Linton, E.A.; McLean, C.; Nieuwenhuyzen Kruseman, A.C.; Tilders, F.J.; Van der Veen, E.A.; Lowry, P.J.

    1987-01-01

    A ''two-site'' immunoradiometric assay (IRMA) which allows the direct estimation of human CRH (hCRH) in plasma is described. Using this IRMA, basal levels of CRH in normal subjects ranged from 2-28 pg/mL [mean, 15 +/- 7 (+/- SD) pg/mL; n = 58]. Values in men and women were similar. Plasma CRH values within this range were also found in patients with Cushing's syndrome, Addison's disease, and Nelson's syndrome, with no correlation between plasma CRH and ACTH levels in these patients. Elevated plasma CRH levels were found in pregnant women near term [1462 +/- 752 (+/- SD) pg/mL; n = 55], and the dilution curve of this CRH-like immunoreactivity paralleled the IRMA standard curve. After its immunoadsorption from maternal plasma, this CRH-like material eluted on reverse phase high performance liquid chromatography with a retention time identical to that of synthetic CRH and had equipotent bioactivity with the synthetic peptide in the perfused anterior pituitary cell bioassay. Circulating CRH was not detected in Wistar rats, even after adrenalectomy and subsequent ether stress. Synthetic hCRH was degraded by fresh human plasma relatively slowly; 65% of added CRH remained after 1 h of incubation at 37 C. Degradation was inhibited by heat treatment (54 C; 1 h), cold treatment (4 C; 4 h), or freezing and thawing. Loss of synthetic rat CRH occurred more rapidly when fresh rat plasma was used; only 20% of added CRH remained under the same conditions. The inability to measure CRH in peripheral rat plasma may be due to the presence of active CRH-degrading enzymes which fragment the CRH molecule into forms not recognized by the CRH IRMA

  15. Corticotropin-releasing activity of gastrin-releasing peptide in normal men

    DEFF Research Database (Denmark)

    Knigge, U; Holst, J J; Knuhtsen, S

    1987-01-01

    than 0.0025). GRP dose-dependently stimulated beta-endorphin immunoreactivity compared with the effect of saline [delta beta-endorphin immunoreactivity before and after treatment: GRP I, 6 +/- 1 vs. -3 +/- 1 pmol/L (P less than 0.01); GRP II, 11 +/- 4 vs. -6 +/- 2 pg/mL (P less than 0.025)]. GRP had...

  16. Elevated Midpregnancy Corticotropin-Releasing Hormone Is Associated with Prenatal, But Not Postpartum, Maternal Depression

    OpenAIRE

    Rich-Edwards, J. W.; Mohllajee, A. P.; Kleinman, K.; Hacker, M. R.; Majzoub, J.; Wright, R. J.; Gillman, M. W.

    2008-01-01

    Context: Elevated hypothalamic CRH has been implicated in melancholic major depression in nonpregnant individuals, but the role of placental CRH in maternal prenatal and postpartum depression is largely unexplored.

  17. Internal and external factors on firms? transfer pricing decisions: Insights from organization studies

    OpenAIRE

    Dan Li; Manuel Portugal Ferreira

    2007-01-01

    Well understood in economics, accounting, finance, and legal research, transfer pricing has rarely been comprehensively explored in organization management literature. This paper explores some theoretical explanations of transfer pricing within multidivisional firms drawing insights from various organizational theories – primarily institutional theory, transaction cost economics, and social networks – to develop a conceptual model of transfer pricing. This model focuses on the nature of multi...

  18. Insight into the Stigma of Suicide Loss Survivors: Factor Analyses of Family Stereotypes, Prejudices, and Discriminations.

    Science.gov (United States)

    Corrigan, Patrick W; Sheehan, Lindsay; Al-Khouja, Maya A; Lewy, Stanley; Major, Deborah R; Mead, Jessica; Redmon, Megghun; Rubey, Charles T; Weber, Stephanie

    2018-01-01

    Families of individuals who die by suicide report public stigma that threatens their well-being. This study used a community-based participatory (CBPR) approach to describe a factor structure for the family stigma of suicide. Candidate items (n = 82) from a previous qualitative study were presented in an online survey format. Members of the public (n = 232) indicated how much they thought items represented public views and behaviors towards family members who lost a loved one to suicide. Factor analyses revealed two factors for stereotypes (dysfunctional, blameworthy), one factor for prejudice (fear and distrust), and three factors for discrimination (exclusion, secrecy, and avoidance).

  19. Exposome in IBD: recent insights in environmental factors that influence the onset and course of IBD.

    Science.gov (United States)

    Rogler, Gerhard; Vavricka, Stephan

    2015-02-01

    It is generally agreed that environmental factors trigger the onset and cause flares of inflammatory bowel disease. Although we have learned much about genetic susceptibility factors of inflammatory bowel disease in recent years, our knowledge on these environmental factors is limited. The sum of all environmental factors a human is exposed to during lifetime has been termed the exposome. The challenge of investigating the exposome is discussed in this overview. The environmental exposure of a subject causes changes in the intestinal microbiota and subsequently changes the epigenetic imprinting of the mucosa and the associated immune system. Some relevant environmental factors have been investigated in recent years in inflammatory bowel disease and other (auto)inflammatory disease. These factors can be categorized in air pollution, diet, drugs, stress, infections, water pollution, food additives, and lifestyle. Examples from those categories and their potential pathophysiological mechanism are discussed.

  20. Organizational and technological insight as important factors for successful implementation of IT.

    Science.gov (United States)

    Nikula, R. E.

    1999-01-01

    Politicians and hospital management in Sweden and Denmark focus on IT and especially Electronic Patient Record, EPR as a tool for changes that will lead to better economy as well as better quality and service to the patients. These changes are not direct effects of the new medium for patient records but indirect effects due to the possibilities embedded in the new technology. To ensure that the implementation is successful, i.e. leads to changes in organization structure and workflow, we need tools to prepare clinicians and management. The focus of this paper is the individual insight in technology and organization and it proposes a model to assess and categorize the possibilities of individuals and groups to participate in and make an implementation process powerful. PMID:10566426

  1. Further insights on the French WISC-IV factor structure through Bayesian structural equation modeling.

    Science.gov (United States)

    Golay, Philippe; Reverte, Isabelle; Rossier, Jérôme; Favez, Nicolas; Lecerf, Thierry

    2013-06-01

    The interpretation of the Wechsler Intelligence Scale for Children--Fourth Edition (WISC-IV) is based on a 4-factor model, which is only partially compatible with the mainstream Cattell-Horn-Carroll (CHC) model of intelligence measurement. The structure of cognitive batteries is frequently analyzed via exploratory factor analysis and/or confirmatory factor analysis. With classical confirmatory factor analysis, almost all cross-loadings between latent variables and measures are fixed to zero in order to allow the model to be identified. However, inappropriate zero cross-loadings can contribute to poor model fit, distorted factors, and biased factor correlations; most important, they do not necessarily faithfully reflect theory. To deal with these methodological and theoretical limitations, we used a new statistical approach, Bayesian structural equation modeling (BSEM), among a sample of 249 French-speaking Swiss children (8-12 years). With BSEM, zero-fixed cross-loadings between latent variables and measures are replaced by approximate zeros, based on informative, small-variance priors. Results indicated that a direct hierarchical CHC-based model with 5 factors plus a general intelligence factor better represented the structure of the WISC-IV than did the 4-factor structure and the higher order models. Because a direct hierarchical CHC model was more adequate, it was concluded that the general factor should be considered as a breadth rather than a superordinate factor. Because it was possible for us to estimate the influence of each of the latent variables on the 15 subtest scores, BSEM allowed improvement of the understanding of the structure of intelligence tests and the clinical interpretation of the subtest scores. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  2. INSIGHT in risk factors and treatment of inhibitors in nonsevere hemophilia A

    NARCIS (Netherlands)

    van Velzen, A.S.

    2016-01-01

    Hemophilia A is an inherited X-linked bleeding disorder that occurs in male offspring of carrier females. In these individuals a mutation in the F8 gene, located on the X-chromosome, causes a deficiency of the factor VIII protein, clotting factor VIII. The worldwide prevalence of hemophilia is 1 in

  3. A close insight to factor VIII inhibitor in the congenital hemophilia A.

    Science.gov (United States)

    Tabriznia-Tabrizi, Shamsoreza; Gholampour, Marzie; Mansouritorghabeh, Hassan

    2016-09-01

    Hemophilia A (HA) has an X-linked pattern of inheritance and is the most common of the hemorrhagic disorders. HA is caused by a decreased or deficiency of the functional clotting factor VIII (FVIII) and effects 1 in 5000-10,000 male births. The common treatment for hemophilia is replacement therapy by plasma-derived or recombinant FVIII. Approximately 20-30% of people with a severe type of HA develop an inhibitor and this phenomenon is the main challenge in the management of these patients. Genetic factors and environmental determinants contribute to inhibitor development. Here, the roles of various genetic and environmental factors such as the type of FVIII concentrate used, the number of exposure days, and peak treatment time will be discussed in detail. It seems this information is helpful for hematologists. A literature review was done in January 2016 on PubMed and Scopus using the following keywords:' h(a)emophilia A & factor VIII inhibitor', 'h(a)emophilia A & factor VIII alloantibody', 'h(a)emophilia A & inhibitor'. There was no time limitation; however, there was an English language limitation placed on the articles selected. Expert commentary: Influential genetic and environmental factors in developing inhibitors have been discussed. Most of the risk factors are related to previously untreated patients with hemophili.

  4. Critical success factors for implementing supply chain information systems : insights from the pork industry

    NARCIS (Netherlands)

    Denolf, J.M.

    2014-01-01

    Critical success factors for implementing supply chain information systems – Janne M. Denolf

    Due to intensified competition, companies realize that they should closely collaborate with their supply-chain partners to further cut costs and stay competitive. To do so,

  5. Franck-Condon Factors for Diatomics: Insights and Analysis Using the Fourier Grid Hamiltonian Method

    Science.gov (United States)

    Ghosh, Supriya; Dixit, Mayank Kumar; Bhattacharyya, S. P.; Tembe, B. L.

    2013-01-01

    Franck-Condon factors (FCFs) play a crucial role in determining the intensities of the vibrational bands in electronic transitions. In this article, a relatively simple method to calculate the FCFs is illustrated. An algorithm for the Fourier Grid Hamiltonian (FGH) method for computing the vibrational wave functions and the corresponding energy…

  6. The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding

    Czech Academy of Sciences Publication Activity Database

    Tarbouriech, N.; Ducournau, C.; Hutin, S.; Mas, P.J.; Man, Petr; Forest, E.; Hart, D.J.; Peyrefitte, Ch.N.; Burmeister, W.P.; Iseni, F.

    2017-01-01

    Roč. 8, NOV 13 (2017), s. 1-12, č. článku 1455. ISSN 2041-1723 R&D Projects: GA MŠk(CZ) LQ1604 Institutional support: RVO:61388971 Keywords : PROTEIN SECONDARY STRUCTURE * CRYSTAL-STRUCTURE * GENETIC-CHARACTERIZATION Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 12.124, year: 2016

  7. Modulation of protein C activation by histones, platelet factor 4, and heparinoids: new insights into activated protein C formation.

    Science.gov (United States)

    Kowalska, M Anna; Zhao, Guohua; Zhai, Li; David, George; Marcus, Stephen; Krishnaswamy, Sriram; Poncz, Mortimer

    2014-01-01

    Histones are detrimental in late sepsis. Both activated protein C (aPC) and heparin can reverse their effect. Here, we investigated whether histones can modulate aPC generation in a manner similar to another positively charged molecule, platelet factor 4, and how heparinoids (unfractionated heparin or oxygen-desulfated unfractionated heparin with marked decrease anticoagulant activity) may modulate this effect. We measured in vitro and in vivo effects of histones, platelet factor 4, and heparinoids on aPC formation, activated partial thromboplastin time, and murine survival. In vitro, histones and platelet factor 4 both affect thrombin/thrombomodulin aPC generation following a bell-shaped curve, with a peak of >5-fold enhancement. Heparinoids shift these curves rightward. Murine aPC generation studies after infusions of histones, platelet factor 4, and heparinoids supported the in vitro data. Importantly, although unfractionated heparin and 2-O, 3-O desulfated heparin both reversed the lethality of high-dose histone infusions, only mice treated with 2-O, 3-O desulfated heparin demonstrated corrected activated partial thromboplastin times and had significant levels of aPC. Our data provide a new contextual model of how histones affect aPC generation, and how heparinoid therapy may be beneficial in sepsis. These studies provide new insights into the complex interactions controlling aPC formation and suggest a novel therapeutic interventional strategy.

  8. Identification of Virulence Factors in Nematode-Trapping Fungi - Insights from Genomics, Transcriptomics and Proteomics

    OpenAIRE

    Andersson, Karl-Magnus

    2013-01-01

    Nematode-trapping fungi are soil-living organisms with the unique ability to capture and infect free-living nematodes. The interest in studying these fungi arises from their potential use as biological control agents for plant- and animal-parasitic nematodes. To enter the parasitic stage, nematode-trapping fungi develop different kinds of trapping structures. In order to understand more about the evolution of parasitism in the nematode-trapping fungi and to identify virulence factors in these...

  9. New Insights into Biology, Prognostic Factors, and Current Therapeutic Strategies in Chronic Lymphocytic Leukemia

    OpenAIRE

    Smolewski, Piotr; Witkowska, Magdalena; Korycka-Wołowiec, Anna

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation and accumulation of mature B lymphocytes. CLL cells show an antiapoptotic profile, suggesting the important role of apoptosis inhibition in the disease development. However, there is some population of proliferating CLL cells, which may also play a role in progression of the disease. There are several newer, biological prognostic factors in CLL. Currently, cytogenetic abnormalities with different prognostic values...

  10. Critical success factors for implementing supply chain information systems : insights from the pork industry

    OpenAIRE

    Denolf, J.M.

    2014-01-01

    Critical success factors for implementing supply chain information systems – Janne M. Denolf Due to intensified competition, companies realize that they should closely collaborate with their supply-chain partners to further cut costs and stay competitive. To do so, supply-chain partners should intensify information sharing, which is often facilitated through supply chain information systems (SCIS). Implementation of such a system is a complex undertaking due to the umpteen technical and organ...

  11. Potentials and Influencing Factors of Dynamic Pricing in Business: Empirical Insights of European Experts

    OpenAIRE

    Christopher Reichstein; Ralf-Christian Härting; Martina Häußler

    2017-01-01

    With a continuously increasing speed of information exchange on the World Wide Web, retailers in the E-Commerce sector are faced with immense possibilities regarding different online purchase processes like dynamic price settings. By use of Dynamic Pricing, retailers are able to set short time price changes in order to optimize producer surplus. The empirical research illustrates the basics of Dynamic Pricing and identifies six influencing factors of Dynamic Pricing. The results of a structur...

  12. DECREASING SCHOOL DROPOUT RATE AS A FACTOR OF ECONOMIC GROWTH AND SOCIAL EMPOWERMENT. THEORETICAL INSIGHTS

    Directory of Open Access Journals (Sweden)

    Alina Badulescu

    2016-07-01

    Full Text Available Economic development and social empowerment in Romania are unconcievable in the absence of a modern education system, which needs both economic and financial investments and social, political, cultural measures to increase the inclusion of young people in school system. In this particular context, given that Romania faces a high degree rate of school dropout, and moreover there are few chances that Romania reach its goals, we try in this paper to look inside the real situation. Indeed, school dropout present serious negative consequences both on individual level and for the whole society. Recognising this fact, next step is to investigate and reveal the determining factors for this situation, and we are particularly interested in the economic and systemic factors. Consequently, we present in this paper first a brief literature review on the fenomenon of school dropping out, including reviewing main studies related to factors, effects, causes etc. In the second part, starting from several statistical data provided by INS, EUROSTAT and UNICEF studies, we propose some theoretical models and policy reccomendations in order to decrease the school dropout rate and especially the early school dropout rate.

  13. Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases.

    Science.gov (United States)

    Scholz, Gerhard H; Hanefeld, Markolf

    2016-10-01

    Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

  14. Factors influencing workplace violence risk among correctional health workers: insights from an Australian survey.

    Science.gov (United States)

    Cashmore, Aaron W; Indig, Devon; Hampton, Stephen E; Hegney, Desley G; Jalaludin, Bin B

    2016-11-01

    Little is known about the environmental and organisational determinants of workplace violence in correctional health settings. This paper describes the views of health professionals working in these settings on the factors influencing workplace violence risk. All employees of a large correctional health service in New South Wales, Australia, were invited to complete an online survey. The survey included an open-ended question seeking the views of participants about the factors influencing workplace violence in correctional health settings. Responses to this question were analysed using qualitative thematic analysis. Participants identified several factors that they felt reduced the risk of violence in their workplace, including: appropriate workplace health and safety policies and procedures; professionalism among health staff; the presence of prison guards and the quality of security provided; and physical barriers within clinics. Conversely, participants perceived workplace violence risk to be increased by: low health staff-to-patient and correctional officer-to-patient ratios; high workloads; insufficient or underperforming security staff; and poor management of violence, especially horizontal violence. The views of these participants should inform efforts to prevent workplace violence among correctional health professionals.

  15. Insights into mRNP biogenesis provided by new genetic interactions among export and transcription factors

    Directory of Open Access Journals (Sweden)

    Estruch Francisco

    2012-09-01

    Full Text Available Abstract Background The various steps of mRNP biogenesis (transcription, processing and export are interconnected. It has been shown that the transcription machinery plays a pivotal role in mRNP assembly, since several mRNA export factors are recruited during transcription and physically interact with components of the transcription machinery. Although the shuttling DEAD-box protein Dbp5p is concentrated on the cytoplasmic fibrils of the NPC, previous studies demonstrated that it interacts physically and genetically with factors involved in transcription initiation. Results We investigated the effect of mutations affecting various components of the transcription initiation apparatus on the phenotypes of mRNA export mutant strains. Our results show that growth and mRNA export defects of dbp5 and mex67 mutant strains can be suppressed by mutation of specific transcription initiation components, but suppression was not observed for mutants acting in the very first steps of the pre-initiation complex (PIC formation. Conclusions Our results indicate that mere reduction in the amount of mRNP produced is not sufficient to suppress the defects caused by a defective mRNA export factor. Suppression occurs only with mutants affecting events within a narrow window of the mRNP biogenesis process. We propose that reducing the speed with which transcription converts from initiation and promoter clearance to elongation may have a positive effect on mRNP formation by permitting more effective recruitment of partially-functional mRNP proteins to the nascent mRNP.

  16. Human Factors Engineering (HFE) insights for advanced reactors based upon operating experience

    International Nuclear Information System (INIS)

    Higgins, J.; Nasta, K.

    1997-01-01

    The NRC Human Factors Engineering Program Review Model (HFE PRM, NUREG-0711) was developed to support a design process review for advanced reactor design certification under 10CFR52. The HFE PRM defines ten fundamental elements of a human factors engineering program. An Operating Experience Review (OER) is one of these elements. The main purpose of an OER is to identify potential safety issues from operating plant experience and ensure that they are addressed in a new design. Broad-based experience reviews have typically been performed in the past by reactor designers. For the HFE PRM the intent is to have a more focussed OER that concentrates on HFE issues or experience that would be relevant to the human-system interface (HSI) design process for new advanced reactors. This document provides a detailed list of HFE-relevant operating experience pertinent to the HSI design process for advanced nuclear power plants. This document is intended to be used by NRC reviewers as part of the HFE PRM review process in determining the completeness of an OER performed by an applicant for advanced reactor design certification. 49 refs

  17. Factors affecting embryo viability and uterine receptivity: insights from an analysis of the UK registry data.

    Science.gov (United States)

    Roberts, Stephen A; Hann, Mark; Brison, Daniel R

    2016-02-01

    Many studies have identified prognostic factors for IVF treatment outcome; however, little information is available on the mechanism of their action. Embryo-uterus models have the potential to distinguish between factors acting on the embryo directly and those acting through the uterine environment. Here we apply embryo-uterus models to comprehensive UK registry data from two periods, 2000-2005 and 2007-2011, containing 139,444 and 226,542 embryo transfer cycles, respectively. Given this large dataset, the embryo-uterus model is capable of distinguishing between uterine and embryo effects. Maternal age is the predominant predictor of live birth and acts on both the embryo and uterine components, but with larger effects on the embryo. Prolonged embryo culture is associated with greater embryo viability, reflecting the greater degree of selection, but is also associated with greater uterine receptivity. Cryopreserved embryos are less viable and were associated with poorer uterine receptivity. This work suggests that, in addition to the direct effects of in-vitro culture on the embryonic environment during the first few days of the embryo's life, the delay in transfer after extended culture or cryopreservation can lead to an altered uterine environment for the embryo after transfer. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  18. Living with psoriasis: An insight into factors associated with quality of life

    Directory of Open Access Journals (Sweden)

    Milutinović Jelena D.

    2017-01-01

    Full Text Available Background: Patients with psoriasis show physical discomfort, stigma, loss of productivity, low self-esteem, and are often limited in everyday activities, social contacts and at work. Objective: The aim of this study was to reveal factors which may influence quality of life in patients with psoriasis, using qualitative research methodology. Methods: This study used grounded theory approach, which consist mainly of conducting interviews and collecting observational data. The subjects were patients who suffer from psoriasis. Results: After making interviews which were audio taped, they were transcribed and analysed in detail, revealing semantic units and combining them in seven categories and themes. Advertizing perfect skin through media, promoting it as a social ideal, ignorance and lack of understanding by others and unacceptance of own condition are main factors that significantly affect quality of life in patients suffering from psoriasis. Conclusion: Individual approach to every patient is necessary prerequisite for adequate treatment and building realistic expectation sac cording to severity of the disease. Relatively small changes in lifestyle and attitude towards the disease may significantly improve quality of life.

  19. Evolutionary changes of Hox genes and relevant regulatory factors provide novel insights into mammalian morphological modifications.

    Science.gov (United States)

    Li, Kui; Sun, Xiaohui; Chen, Meixiu; Sun, Yingying; Tian, Ran; Wang, Zhengfei; Xu, Shixia; Yang, Guang

    2018-01-01

    The diversity of body plans of mammals accelerates the innovation of lifestyles and the extensive adaptation to different habitats, including terrestrial, aerial and aquatic habitats. However, the genetic basis of those phenotypic modifications, which have occurred during mammalian evolution, remains poorly explored. In the present study, we synthetically surveyed the evolutionary pattern of Hox clusters that played a powerful role in the morphogenesis along the head-tail axis of animal embryos and the main regulatory factors (Mll, Bmi1 and E2f6) that control the expression of Hox genes. A deflected density of repetitive elements and lineage-specific radical mutations of Mll have been determined in marine mammals with morphological changes, suggesting that evolutionary changes may alter Hox gene expression in these lineages, leading to the morphological modification of these lineages. Although no positive selection was detected at certain ancestor nodes of lineages, the increased ω values of Hox genes implied the relaxation of functional constraints of these genes during the mammalian evolutionary process. More importantly, 49 positively-selected sites were identified in mammalian lineages with phenotypic modifications, indicating adaptive evolution acting on Hox genes and regulatory factors. In addition, 3 parallel amino acid substitutions in some Hox genes were examined in marine mammals, which might be responsible for their streamlined body. © 2017 The Authors. Integrative Zoology published by International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  20. Chesapeake Bay recovery and factors affecting trends: Long-termmonitoring, indicators, and insights

    Science.gov (United States)

    Tango, Peter J.; Batiuk, Richard A.

    2016-01-01

    Monitoring the outcome of restoration efforts is the only way to identify the status of a recovery and the most effective management strategies. In this paper, we discuss Chesapeake Bay and watershed recovery and factors influencing water quality trends. For over 30 years, the Chesapeake Bay Program Partnership’s long-term tidal and watershed water quality monitoring networks have measured physical, chemical and biological parameters throughout the bay and its surrounding watershed underpinning an adaptive management process to drive ecosystem recovery. There are many natural and anthropogenic factors operating and interacting to affect the watershed and bay water quality recovery responses to management actions. Across habitats and indicators, the bay and its watershed continue to express a diverse spatial and temporal fabric of multiscale conditions, stressors and trends that show a range of health conditions and impairments, as well as evidence of progress and degradation. Recurrent independent reviews of the monitoring program have driven a culture of continued adaptation of the monitoring networks to reflect ever evolving management information needs. The adherence to bay and watershed-wide consistent monitoring protocols provides monitoring data supporting analyses and development of scientific syntheses that underpin indicator and model development, regulatory assessments, targeting of management actions, evaluation of management effectiveness, and directing of priorities and policies.

  1. Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: insight into the cytotoxicity and antiangiogenesis.

    Science.gov (United States)

    Yang, Tieshan; Yao, Qian; Cao, Fei; Liu, Qianqian; Liu, Binlei; Wang, Xiu-Hong

    Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that is activated upon exposure to hypoxic stress. It modulates a number of cellular responses including proliferation, apoptosis, angiogenesis, and metabolism by activating a panel of target genes in response to hypoxia. The HIF-1 level is often upregulated in the hypoxic microenvironment of solid tumors, which contributes to cancer treatment failure. Here we report that silver nanoparticles (AgNPs), which are widely used as an antimicrobial agent, are an effective inhibitor of HIF-1. AgNPs inhibited the activation of a HIF-dependent reporter construct after the cells were exposed to hypoxic conditions or treated with cobalt chloride, a hypoxia mimetic agent. The AgNPs also interfered with the accumulation of HIF-1α protein and the induction of the endogenous HIF target genes, VEGF-A and GLUT1. Since both HIF-1 and vascular endothelial growth factor-A play an important role in angiogenesis, AgNPs also inhibited angiogenesis in vitro. Our data reveal a new mechanism of how AgNPs act on cellular function, that is, they disrupt HIF signaling pathway. This finding provides a novel insight into how AgNPs can inhibit cancer cell growth and angiogenesis.

  2. Structural insights into the backbone-circularized granulocyte colony-stimulating factor containing a short connector.

    Science.gov (United States)

    Miyafusa, Takamitsu; Shibuya, Risa; Honda, Shinya

    2018-06-02

    Backbone circularization is a powerful approach for enhancing the structural stability of polypeptides. Herein, we present the crystal structure of the circularized variant of the granulocyte colony-stimulating factor (G-CSF) in which the terminal helical region was circularized using a short, two-amino acid connector. The structure revealed that the N- and C-termini were indeed connected by a peptide bond. The local structure of the C-terminal region transited from an α helix to 3 10 helix with a bend close to the N-terminal region, indicating that the structural change offset the insufficient length of the connector. This is the first-ever report of a crystal structure of the backbone of a circularized protein. It will facilitate the development of backbone circularization methodology. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Use of micro-reactors to obtain new insights into the factors influencing tricalcium silicate dissolution

    International Nuclear Information System (INIS)

    Suraneni, Prannoy; Flatt, Robert J.

    2015-01-01

    A micro-reactor approach, developed previously, is used to study the early dissolution of tricalcium silicate. This approach uses micron-sized gaps mimicking particles in close contact to understand dissolution, nucleation, and growth processes. The main factors influencing the dissolution kinetics of tricalcium silicate are presented. We show that the presence of defects caused by polishing does not affect the extent of dissolution. A strong effect of aluminum in solution reducing the extent of dissolution is however identified. This effect is highly dependent on the pH, and is much lower above pH 13. We show also that superplasticizers reduce the extent of dissolution; however, the exact reason for this effect is not clear.

  4. Evidence for a Pneumocystis carinii Flo8-like transcription factor: insights into organism adhesion.

    Science.gov (United States)

    Kottom, Theodore J; Limper, Andrew H

    2016-02-01

    Pneumocystis carinii (Pc) adhesion to alveolar epithelial cells is well established and is thought to be a prerequisite for the initiation of Pneumocystis pneumonia. Pc binding events occur in part through the major Pc surface glycoprotein Msg, as well as an integrin-like molecule termed PcInt1. Recent data from the Pc sequencing project also demonstrate DNA sequences homologous to other genes important in Candida spp. binding to mammalian host cells, as well as organism binding to polystyrene surfaces and in biofilm formation. One of these genes, flo8, a transcription factor needed for downstream cAMP/PKA-pathway-mediated activation of the major adhesion/flocculin Flo11 in yeast, was cloned from a Pc cDNA library utilizing a partial sequence available in the Pc genome database. A CHEF blot of Pc genomic DNA yielded a single band providing evidence this gene is present in the organism. BLASTP analysis of the predicted protein demonstrated 41 % homology to the Saccharomyces cerevisiae Flo8. Northern blotting demonstrated greatest expression at pH 6.0-8.0, pH comparable to reported fungal biofilm milieu. Western blot and immunoprecipitation assays of PcFlo8 protein in isolated cyst and tropic life forms confirmed the presence of the cognate protein in these Pc life forms. Heterologous expression of Pcflo8 cDNA in flo8Δ-deficient yeast strains demonstrated that the Pcflo8 was able to restore yeast binding to polystyrene and invasive growth of yeast flo8Δ cells. Furthermore, Pcflo8 promoted yeast binding to HEK293 human epithelial cells, strengthening its functional classification as a Flo8 transcription factor. Taken together, these data suggest that PcFlo8 is expressed by Pc and may exert activity in organism adhesion and biofilm formation.

  5. Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: insight into the cytotoxicity and antiangiogenesis

    Directory of Open Access Journals (Sweden)

    Yang T

    2016-12-01

    Full Text Available Tieshan Yang,1 Qian Yao,1 Fei Cao,1 Qianqian Liu,1 Binlei Liu,2 Xiu-Hong Wang1 1Laboratory for Biomedical Photonics, Institute of Laser Engineering, Beijing University of Technology, 2Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Abstract: Hypoxia-inducible factor-1 (HIF-1 is a transcription factor that is activated upon exposure to hypoxic stress. It modulates a number of cellular responses including proliferation, apoptosis, angiogenesis, and metabolism by activating a panel of target genes in response to hypoxia. The HIF-1 level is often upregulated in the hypoxic microenvironment of solid tumors, which contributes to cancer treatment failure. Here we report that silver nanoparticles (AgNPs, which are widely used as an antimicrobial agent, are an effective inhibitor of HIF-1. AgNPs inhibited the activation of a HIF-dependent reporter construct after the cells were exposed to hypoxic conditions or treated with cobalt chloride, a hypoxia mimetic agent. The AgNPs also interfered with the accumulation of HIF-1α protein and the induction of the endogenous HIF target genes, VEGF-A and GLUT1. Since both HIF-1 and vascular endothelial growth factor-A play an important role in angiogenesis, AgNPs also inhibited angiogenesis in vitro. Our data reveal a new mechanism of how AgNPs act on cellular function, that is, they disrupt HIF signaling pathway. This finding provides a novel insight into how AgNPs can inhibit cancer cell growth and angiogenesis. Keywords: silver nanoparticles (AgNPs, hypoxia-inducible factor, transcriptional activity, vascular endothelial growth factor-A, angiogenesis

  6. The linkage between work-related factors, employee satisfaction and organisational commitment: Insights from public health professionals

    Directory of Open Access Journals (Sweden)

    Chengedzai Mafini

    2014-08-01

    public health sector, both at micro and macro levels. The study also provides updated insights into the interplay between these factors in the context of South Africa, thereby addressing a research gap in this subject.

  7. Novel Genomic and Evolutionary Insight of WRKY Transcription Factors in Plant Lineage.

    Science.gov (United States)

    Mohanta, Tapan Kumar; Park, Yong-Hwan; Bae, Hanhong

    2016-11-17

    The evolutionarily conserved WRKY transcription factor (TF) regulates different aspects of gene expression in plants, and modulates growth, development, as well as biotic and abiotic stress responses. Therefore, understanding the details regarding WRKY TFs is very important. In this study, large-scale genomic analyses of the WRKY TF gene family from 43 plant species were conducted. The results of our study revealed that WRKY TFs could be grouped and specifically classified as those belonging to the monocot or dicot plant lineage. In this study, we identified several novel WRKY TFs. To our knowledge, this is the first report on a revised grouping system of the WRKY TF gene family in plants. The different forms of novel chimeric forms of WRKY TFs in the plant genome might play a crucial role in their evolution. Tissue-specific gene expression analyses in Glycine max and Phaseolus vulgaris showed that WRKY11-1, WRKY11-2 and WRKY11-3 were ubiquitously expressed in all tissue types, and WRKY15-2 was highly expressed in the stem, root, nodule and pod tissues in G. max and P. vulgaris.

  8. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes.

    Science.gov (United States)

    Li, Guangyi; Yin, Jimin; Gao, Junjie; Cheng, Tak S; Pavlos, Nathan J; Zhang, Changqing; Zheng, Ming H

    2013-01-01

    Osteoarthritis (OA) is a major cause of disability in the adult population. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone, osteophyte formation, muscle weakness, and inflammation of the synovium tissue and tendon. Although OA has long been viewed as a primary disorder of articular cartilage, subchondral bone is attracting increasing attention. It is commonly reported to play a vital role in the pathogenesis of OA. Subchondral bone sclerosis, together with progressive cartilage degradation, is widely considered as a hallmark of OA. Despite the increase in bone volume fraction, subchondral bone is hypomineralized, due to abnormal bone remodeling. Some histopathological changes in the subchondral bone have also been detected, including microdamage, bone marrow edema-like lesions and bone cysts. This review summarizes basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage. Importantly, we discuss risk factors influencing subchondral bone integrity. We also focus on the microarchitectural and histopathological changes of subchondral bone in OA, and provide an overview of their potential contribution to the progression of OA. A hypothetical model for the pathogenesis of OA is proposed.

  9. Environmental Factors Promoting Neural Plasticity: Insights from Animal and Human Studies

    Directory of Open Access Journals (Sweden)

    Laura Mandolesi

    2017-01-01

    Full Text Available We do not all grow older in the same way. Some individuals have a cognitive decline earlier and faster than others who are older in years but cerebrally younger. This is particularly easy to verify in people who have maintained regular physical activity and healthy and cognitively stimulating lifestyle and even in the clinical field. There are patients with advanced neurodegeneration, such as Alzheimer’s disease (AD, that, despite this, have mild cognitive impairment. What determines this interindividual difference? Certainly, it cannot be the result of only genetic factors. We are made in a certain manner and what we do acts on our brain. In fact, our genetic basis can be modulated, modified, and changed by our experiences such as education and life events; daily, by sleep schedules and habits; or also by dietary elements. And this can be seen as true even if our experiences are indirectly driven by our genetic basis. In this paper, we will review some current scientific research on how our experiences are able to modulate the structural organization of the brain and how a healthy lifestyle (regular physical activity, correct sleep hygiene, and healthy diet appears to positively affect cognitive reserve.

  10. Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance.

    LENUS (Irish Health Repository)

    Finucane, Orla M

    2012-11-01

    High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

  11. On Radiative Factors in Planetary Rings: New Insight Derived from Cassini CIRS Observations at Saturn Equinox

    Science.gov (United States)

    Brooks, S. M.; Spilker, L. J.; Pilorz, S.; Edgington, S. G.; Deau, E.; Morishima, R.

    2012-12-01

    Since arriving at Saturn in 2004, Cassini's Composite Infrared Spectrometer has recorded tens of millions of spectra of Saturn's rings (personal communication, M. Segura). CIRS records far infrared radiation (16.7-1000 microns) at focal plane 1 (FP1). Thermal emission from Saturn's rings peaks at FP1 wavelengths. CIRS spectra are well characterized as blackbody emission at an effective temperature Te, multiplied by a scalar factor related to ring emissivity (Spilker et al. [2005, 2006]). CIRS can therefore characterize the rings' temperature and study the thermal environment to which the ring particles are subject. We focus on CIRS data from the 2009 Saturnian equinox. As the Sun's disk crossed the ring plane, CIRS obtained several radial scans of the rings at a variety of phase angles, local hour angles and distances. With the Sun's rays striking the rings at an incidence angle of zero, solar heating is virtually absent, and thermal radiation from Saturn and sunlight reflected by Saturn dominate the thermal environment. These observations appear to present a paradox. Equinox data show that the flux of thermal energy radiated by the rings can even exceed the energy incident upon them as prescribed by thermal models, particularly in the C ring and Cassini Division (Ferrari and Leyrat [2006], Morishima et al. [2009, 2010]). Conservation principles suggest that such models underestimate heating of the rings in these cases, as it is clearly unphysical for the rings to radiate significantly more energy than is incident upon them. In this presentation, we will describe our efforts to resolve this paradox and determine what doing so can teach us about Saturn's rings. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract with NASA. Copyright 2012 California Institute of Technology. Government sponsorship acknowledged.

  12. Analytical insight into degradation processes of aminopolyphosphonates as potential factors that induce cyanobacterial blooms.

    Science.gov (United States)

    Drzyzga, Damian; Lipok, Jacek

    2017-11-01

    Aminopolyphosphonates (AAPs) are commonly used industrial complexones of metal ions, which upon the action of biotic and abiotic factors undergo a breakdown and release their substructures. Despite the low toxicity of AAPs towards vertebrates, products of their transformations, especially those that contain phosphorus and nitrogen, can affect algal communities. To verify whether such chemical entities are present in water ecosystems, much effort has been made in developing fast, inexpensive, and reliable methods for analyzing phosphonates. However, unfortunately, the methods described thus far require time-consuming sample pretreatment and offer relatively high values of the limit of detection (LOD). The aim of this study was to develop an analytical approach to study the environmental fate of AAPs. Four phosphonic acids, N,N-bis(phosphonomethyl)glycine (GBMP), aminotris(methylenephosphonic) acid (ATMP), hexamethylenediamine-N,N,N',N'-tetrakis(methylphosphonic) acid (HDTMP), and diethylenetriamine penta(methylenephosphonic) acid (DTPMP) were selected and examined in a water matrix. In addition, the susceptibility of these compounds to biotransformations was tested in colonies of five freshwater cyanobacteria-microorganisms responsible for the so-called blooms in the water. Our efforts to track the AAP decomposition were based on derivatization of N-alkyl moieties with p-toluenesulfonyl chloride (tosylation) followed by chromatographic (HPLC-UV) separation of derivatives. This approach allowed us to determine seven products of the breakdown of popular phosphonate chelators, in nanomolar concentrations and in one step. It should be noted that the LOD of four of those products, aminemethylphosphonic acid (AMPA), N-phosphomethyl glycine (NPMG), N-(methyl)aminemethanephosphonic acid (MAMPA), and N-(methyl) glycine (SAR), was set below the concentration of 50 nM. Among those substances, N-(methylamino)methanephosphonic acid (MAMPA) was identified for the first time as

  13. Insights into the gut microbiota of freshwater shrimp and its associations with the surrounding microbiota and environmental factors.

    Science.gov (United States)

    Zhao, Yanting; Duan, Cuilan; Zhang, Xuxiang; Chen, Huangen; Ren, Hongqiang; Yin, Ying; Ye, Lin

    2018-04-23

    The gut microbiota of aquatic animals plays a crucial role in host health through nutrient acquisition and outcompetition of pathogens. In this study, based on the high-throughput sequencing of 16S rRNA gene amplicons, we examined the bacterial communities in the gut of freshwater shrimp ( Macrobrachium nipponense ) and in their living environments (sediment and pond water) and analyzed the effects of abiotic and biotic factors on the shrimp gut bacterial communities. High bacterial heterogeneity was observed in the freshwater shrimp gut samples, and the result indicated that both the surrounding bacterial community and water quality factors (particularly dissolved oxygen and temperature) could affect the shrimp gut bacterial community. Despite the observed heterogeneity, 57 genera, constituting 38~99% of the total genera in each of the 40 shrimp gut samples, were identified as the main bacterial population in the gut of M. nipponense . In addition, a high diversity and abundance of lactic acid bacteria (26 genera), which could play significant roles in the digestion process in shrimp, were observed in the shrimp gut samples. Overall, this study provides insights into the gut bacterial communities of freshwater shrimp and basic information for shrimp farming regarding the application of probiotics and disease prevention.

  14. Aerosol emissions factors from traditional biomass cookstoves in India: insights from field measurements

    Directory of Open Access Journals (Sweden)

    A. Pandey

    2017-11-01

    Full Text Available Residential solid biomass cookstoves are important sources of aerosol emissions in India. Cookstove emissions rates are largely based on laboratory experiments conducted using the standard water-boiling test, but real-world emissions are often higher owing to different stove designs, fuels, and cooking methods. Constraining mass emissions factors (EFs for prevalent cookstoves is important because they serve as inputs to bottom-up emissions inventories used to evaluate health and climate impacts. Real-world EFs were measured during winter 2015 for a traditional cookstove (chulha burning fuel wood, agricultural residue, and dung from different regions of India. Average (±95 % confidence interval EFs for fuel wood, agricultural residue, and dung were (1 PM2.5 mass: 10.5 (7.7–13.4 g kg−1, 11.1 (7.7–15.5 g kg−1, and 22.6 (14.9–32.9 g kg−1, respectively; (2 elemental carbon (EC: 0.9 (0.6–1.4 g kg−1, 1.6 (0.6–3.0 g kg−1, and 1.0 (0.4–2.0 g kg−1, respectively; and (3 organic carbon (OC: 4.9 (3.2–7.1 g kg−1, 7.0 (3.5–12.5 g kg−1, and 12.9 (4.2–15.01 g kg−1, respectively. The mean (±95 % confidence interval OC ∕ EC mass ratios were 6.5 (4.5–9.1, 7.6 (4.4–12.2, and 12.7 (6.5–23.3, respectively, with OC and EC quantified by the IMPROVE_A thermal-optical reflectance protocol. These real-world EFs are higher than those from previous laboratory-based measurements. Combustion conditions have larger effects on EFs than the fuel types. We also report the carbon mass fractions of our aerosol samples determined using the thermal-optical reflectance method. The mass fraction profiles are consistent between the three fuel categories but markedly different from those reported in past literature – including the source profiles for wood stove PM2.5 emissions developed as inputs to receptor modeling studies conducted by the Central Pollution Control Board of India. Thermally

  15. Transcriptomic insight into pathogenicity-associated factors of Conidiobolus obscurus, an obligate aphid-pathogenic fungus belonging to Entomopthoromycota.

    Science.gov (United States)

    Wang, Jianghong; Zhou, Xiang; Guo, Kai; Zhang, Xinqi; Lin, Haiping; Montalva, Cristian

    2018-01-16

    Conidiobolus obscurus is a widespread fungal entomopathogen with aphid biocontrol potential. This study focused on a de novo transcriptomic analysis of C. obscurus. A number of pathogenicity-associated factors were annotated for the first time from the assembled 17 231 fungal unigenes, including those encoding subtilisin-like proteolytic enzymes (Pr1s), trypsin-like proteases, metalloproteases, carboxypeptidases and endochitinases. Many of these genes were transcriptionally up-regulated by at least twofold in mycotized cadavers compared with the in vitro fungal cultures. The resultant transcriptomic database was validated by the transcript levels of three selected pathogenicity-related genes quantified from different in vivo and in vitro material in real-time quantitative polymerase chain reaction (PCR). The involvement of multiple Pr1 proteases in the first stage of fungal infection was also suggested. Interestingly, a unique cytolytic (Cyt)-like δ-endotoxin gene was highly expressed in both mycotized cadavers and fungal cultures, and was more or less distinct from its homologues in bacteria and other fungi. Our findings provide the first global insight into various pathogenicity-related genes in this obligate aphid pathogen and may help to develop novel biocontrol strategy against aphid pests. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  16. Diversification, phylogeny and evolution of auxin response factor (ARF) family: insights gained from analyzing maize ARF genes.

    Science.gov (United States)

    Wang, Yijun; Deng, Dexiang; Shi, Yating; Miao, Nan; Bian, Yunlong; Yin, Zhitong

    2012-03-01

    Auxin response factors (ARFs), member of the plant-specific B3 DNA binding superfamily, target specifically to auxin response elements (AuxREs) in promoters of primary auxin-responsive genes and heterodimerize with Aux/IAA proteins in auxin signaling transduction cascade. In previous research, we have isolated and characterized maize Aux/IAA genes in whole-genome scale. Here, we report the comprehensive analysis of ARF genes in maize. A total of 36 ARF genes were identified and validated from the B73 maize genome through an iterative strategy. Thirty-six maize ARF genes are distributed in all maize chromosomes except chromosome 7. Maize ARF genes expansion is mainly due to recent segmental duplications. Maize ARF proteins share one B3 DNA binding domain which consists of seven-stranded β sheets and two short α helixes. Twelve maize ARFs with glutamine-rich middle regions could be as activators in modulating expression of auxin-responsive genes. Eleven maize ARF proteins are lack of homo- and heterodimerization domains. Putative cis-elements involved in phytohormones and light signaling responses, biotic and abiotic stress adaption locate in promoters of maize ARF genes. Expression patterns vary greatly between clades and sister pairs of maize ARF genes. The B3 DNA binding and auxin response factor domains of maize ARF proteins are primarily subjected to negative selection during selective sweep. The mixed selective forces drive the diversification and evolution of genomic regions outside of B3 and ARF domains. Additionally, the dicot-specific proliferation of ARF genes was detected. Comparative genomics analysis indicated that maize, sorghum and rice duplicate chromosomal blocks containing ARF homologs are highly syntenic. This study provides insights into the distribution, phylogeny and evolution of ARF gene family.

  17. Insight and Lessons Learned on Organizational Factors and Safety Culture from the Review of Human Error-related Events of NPPs in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Tae; Lee, Dhong Hoon; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-08-15

    Event investigation is one of the key means of enhancing nuclear safety deriving effective measures and preventing recurrences. However, it is difficult to analyze organizational factors and safety culture. This paper tries to review human error-related events from perspectives of organizational factors and safety culture, and to derive insights and lessons learned in developing the regulatory infrastructure of plant oversight on safety culture.

  18. Insight and Lessons Learned on Organizational Factors and Safety Culture from the Review of Human Error-related Events of NPPs in Korea

    International Nuclear Information System (INIS)

    Kim, Ji Tae; Lee, Dhong Hoon; Choi, Young Sung

    2014-01-01

    Event investigation is one of the key means of enhancing nuclear safety deriving effective measures and preventing recurrences. However, it is difficult to analyze organizational factors and safety culture. This paper tries to review human error-related events from perspectives of organizational factors and safety culture, and to derive insights and lessons learned in developing the regulatory infrastructure of plant oversight on safety culture

  19. Genetic modifiers of comatose mutations in Drosophila: insights into neuronal NSF (N-ethylmaleimide-sensitive fusion factor) functions.

    Science.gov (United States)

    Sanyal, Subhabrata; Krishnan, K S

    2012-09-01

    By the middle of the 20th century, development of powerful genetic approaches had ensured that the fruit fly would remain a model organism of choice for genetic and developmental studies. But in the 1970s, a few pioneering groups turned their attention to the prospect of using the fly for neurophysiological experiments. They proposed that in a poikilothermic organism such as Drosophila, temperature-sensitive or "ts" mutations in proteins that controlled nerve function would translate to a "ts" paralytic phenotype. This was by no means an obvious or even a likely assumption. However, following directed screens these groups soon reported dramatic demonstrations of reversible ts paralysis in fly mutants. Resultantly, these "simple" experiments led to the isolation of a number of conditional mutations including shibire, paralytic, and comatose. All have since been cloned and have enabled deep mechanistic insights into synaptic transmission and nerve conduction. comatose (comt) mutations, for example, were found to map to missense changes in dNSF1, a neuron-specific fly homolog of mammalian NSF (N-ethylmaleimide-sensitive fusion factor). Studies on comt were also some of the first to discriminate between nuanced models of NSF function during presynaptic transmitter release that have since been borne out by experiments in multiple preparations. Here, the authors present an overview of NSF function as it is understood today, with an emphasis on contributions from Drosophila beginning with experiments carried out by Obaid Siddiqi in the Benzer laboratory. The authors also outline initial results from a genetic screen for phenotypic modifiers of comt that hold the promise of further elucidating NSF function at the synapse. Over the years, the neuromuscular system of Drosophila has served as a uniquely accessible model to unravel mechanisms underlying synaptic transmission. To this day, ts paralysis remains one of the most emphatic demonstrations of nerve function in an

  20. Observational Insights into N2O5 Heterogeneous Chemistry: Influencing Factors and Contribution to Wintertime Air Pollution

    Science.gov (United States)

    McDuffie, E. E.; Fibiger, D. L.; Womack, C.; Dube, W. P.; Lopez-Hilfiker, F.; Goldberger, L.; Thornton, J. A.; Shah, V.; Jaegle, L.; Guo, H.; Weber, R. J.; Schroder, J. C.; Campuzano Jost, P.; Jimenez, J. L.; Franchin, A.; Middlebrook, A. M.; Baasandorj, M.; Brown, S. S.

    2017-12-01

    Chemical mechanisms that underlie wintertime air pollution, including tropospheric ozone and aerosol nitrate, are poorly characterized. Due to colder temperatures and fewer hours of solar radiation, nocturnal heterogeneous uptake of N2O5 plays a relatively larger role during wintertime in controlling the oxidation of NOx (=NO+NO2) and its influence on ozone and soluble nitrate. After uptake to aerosol, N2O5 can act as both a nocturnal NOx reservoir and sink depending on the partitioning between its nitric acid and photo labile, ClNO2 reaction products. In addition, N2O5 itself can act as a NOx reservoir if the aerosol uptake coefficient is small. As a result, the nocturnal fate of N2O5 dictates the amount of NOx in an air parcel and the subsequent formation of aerosol nitrate and following-day ozone. Models of winter air pollution therefore require accurate parameterization of the N2O5 uptake coefficient, as well as factors that control its magnitude and N2O5 product partitioning. There are currently only a small number of ambient N2O5 and ClNO2 observations during the winter season concurrent with measurements of relevant variables such as aerosol size distributions and composition. The Wintertime INvestigation of Transport, Emissions, and Reactivity (WINTER) campaign conducted 10 nighttime research flights with the NCAR C-130 over the eastern U.S. during February and March, 2015. The more recent Utah Wintertime Fine Particulate Study (UWFPS) conducted over 20 research flights with the NOAA twin otter aircraft during January-February 2017 in three mountain basins near and including Salt Lake City, Utah. The two campaigns were similarly instrumented and have provided the first aircraft observations of N2O5, ClNO2, and aerosol composition in the wintertime boundary layer in these urban-influenced regions. Analysis of heterogeneous chemistry under a wide range of real environmental conditions provides insight into the factors controlling the N2O5 uptake coefficient

  1. Hepatic vagotomy alters limbic and hypothalamic neuropeptide responses to insulin-dependent diabetes and voluntary lard ingestion

    NARCIS (Netherlands)

    la Fleur, Susanne E.; Manalo, Sotara L.; Roy, Monica; Houshyar, Hani; Dallman, Mary F.

    2005-01-01

    Hypothalamic anorexigenic [corticotropin-releasing factor (CRF) and proopiomelanocortin] peptides decrease and the orexigen, neuropeptide Y, increases with diabetic hyperphagia. However, when diabetic rats are allowed to eat lard (saturated fat) as well as chow, both caloric intake and hypothalamic

  2. Stress and Female Reproductive System: Disruption of Corticotropin-Releasing Hormone/Opiate Balance by Sympathetic Nerve Traffic

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2009-09-01

    Full Text Available Nowadays stress is an integral part of everyday living and the physiological and behavioral consequences of exposure to stressful situations have been extensively studied for decades. The stress response is a necessary mechanism but disrupts homeostatic process and it is sub served by a complex system located in both the central nervous system (CNS and the periphery. Stressor-induced activation of the hypothalamus–pituitary–adrenal (HPA axis and the sympathetic nervous system (SNS results in a series of neural and endocrine adaptations known as the "stress response" or "stress cascade." The stress cascade is responsible for allowing the body to make the necessary physiological and metabolic changes required to cope with the demands of a homeostatic challenge. Normal activation of the HPA axis is essential for reproduction, growth, metabolic homeostasis, and responses to stress and they are critical for adapting to changes in the external environment. The regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classical feedback mechanisms in the hypothalamus and the pituitary. The present overview focuses on the neuroendocrine infrastructure of the adaptive response to stress and its effects on the female reproductive system. 

  3. Dendritic cell nuclear protein-1, a novel depression-related protein, upregulates corticotropin-releasing hormone expression

    NARCIS (Netherlands)

    Zhou, Tian; Wang, Shanshan; Ren, Haigang; Qi, Xin-Rui; Luchetti, Sabina; Kamphuis, Willem; Zhou, Jiang-Ning; Wang, Guanghui; Swaab, Dick F.

    2010-01-01

    The recently discovered dendritic cell nuclear protein-1 is the product of a novel candidate gene for major depression. The A allele encodes full-length dendritic cell nuclear protein-1, while the T allele encodes a premature termination of translation at codon number 117 on chromosome 5. In the

  4. Gene by Environment Interaction and Resilience: Effects of Child Maltreatment and Serotonin, Corticotropin Releasing Hormone, Dopamine, and Oxytocin Genes

    Science.gov (United States)

    Cicchetti, Dante; Rogosch, Fred A.

    2013-01-01

    In this investigation, gene-environment interaction effects in predicting resilience in adaptive functioning among maltreated and nonmaltreated low-income children (N = 595) were examined. A multi-component index of resilient functioning was derived and levels of resilient functioning were identified. Variants in four genes, 5-HTTLPR, CRHR1, DRD4 -521C/T, and OXTR, were investigated. In a series of ANCOVAs, child maltreatment demonstrated a strong negative main effect on children’s resilient functioning, whereas no main effects for any of the genotypes of the respective genes were found. However, gene-environment interactions involving genotypes of each of the respective genes and maltreatment status were obtained. For each respective gene, among children with a specific genotype, the relative advantage in resilient functioning of nonmaltreated compared to maltreated children was stronger than was the case for nonmaltreated and maltreated children with other genotypes of the respective gene. Across the four genes, a composite of the genotypes that more strongly differentiated resilient functioning between nonmaltreated and maltreated children provided further evidence of genetic variations influencing resilient functioning in nonmaltreated children, whereas genetic variation had a negligible effect on promoting resilience among maltreated children. Additional effects were observed for children based on the number of subtypes of maltreatment children experienced, as well as for abuse and neglect subgroups. Finally, maltreated and nonmaltreated children with high levels of resilience differed in their average number of differentiating genotypes. These results suggest that differential resilient outcomes are based on the interaction between genes and developmental experiences. PMID:22559122

  5. Receptors for corticotropin-releasing hormone in human pituitary: Binding characteristics and autoradiographic localization to immunocytochemically defined proopiomelanocortin cells

    Energy Technology Data Exchange (ETDEWEB)

    Smets, G.; Vauquelin, G.; Moons, L.; Smitz, J.; Kloeppel, G. (Department of Experimental Pathology, Vrije Universiteit Brussel (Belgium))

    1991-08-01

    Using autoradiography combined with immunocytochemistry, the authors demonstrated that the target cells of CRH in the human pituitary were proopiomelanocortin cells. Scatchard analysis of (125I)Tyr0-oCRH saturation binding revealed the presence of one class of saturable, high affinity sites on pituitary tissue homogenate. The equilibrium dissociation constant (Kd) for (125I)Tyr0-oCRH ranged from 1.1-1.6 nM, and the receptor density was between 200-350 fmol/mg protein. Fixation of cryostat sections with 4% paraformaldehyde before tracer incubation improved both tissue preservation and localization of the CRH receptor at the cellular level. Additional postfixation with 1% glutaraldehyde inhibited tracer diffusion during subsequent immunocytochemistry and autoradiography. (125I)Tyr0-oCRH was found in cytoplasmic inclusions or at the cell periphery of ACTH/beta-endorphin cells in the anterior pituitary. Single cells of the posterior pituitary were also CRH receptor positive. Cells staining for PRL or GH were CRH receptor negative. They conclude that CRH binds only to high affinity receptors on ACTH/{beta}-endorphin cells in the human pituitary.

  6. Glucocorticoids and relapse of major depression (dexamethasone/corticotropin-releasing hormone test in relation to relapse of major depression)

    NARCIS (Netherlands)

    Appelhof, Bente C.; Huyser, Jochanan; Verweij, Mijke; Brouwer, Jantien P.; van Dyck, Richard; Fliers, Eric; Hoogendijk, Witte J. G.; Tijssen, Jan G. P.; Wiersinga, Wilmar M.; Schene, Aart H.

    2006-01-01

    BACKGROUND: Knowledge of pathogenic mechanisms and predictors of relapse in major depressive disorder is still limited. Hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation is thought to be related to the development and course of depression. METHODS: We investigated whether

  7. Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression.

    Science.gov (United States)

    Kunugi, Hiroshi; Hori, Hiroaki; Adachi, Naoki; Numakawa, Tadahiro

    2010-10-01

    Although the pathophysiology of depressive disorder remains elusive, two hypothetical frameworks seem to be promising: the involvement of hypothalamic pituitary-adrenal (HPA) axis abnormalities and brain-derived neurotrophic factor (BDNF) in the pathogenesis and in the mechanism of action of antidepressant treatments. In this review, we focused on research based on these two frameworks in relation to depression and related conditions and tried to formulate an integrated theory of the disorder. Hormonal challenge tests, such as the dexamethasone/corticotropin-releasing hormone test, have revealed elevated HPA activity (hypercortisolism) in at least a portion of patients with depression, although growing evidence has suggested that abnormally low HPA axis (hypocortisolism) has also been implicated in a variety of stress-related conditions. Several lines of evidence from postmortem studies, animal studies, blood levels, and genetic studies have suggested that BDNF is involved in the pathogenesis of depression and in the mechanism of action of biological treatments for depression. Considerable evidence has suggested that stress reduces the expression of BDNF and that antidepressant treatments increase it. Moreover, the glucocorticoid receptor interacts with the specific receptor of BDNF, TrkB, and excessive glucocorticoid interferes with BDNF signaling. Altered BDNF function is involved in the structural changes and possibly impaired neurogenesis in the brain of depressed patients. Based on these findings, an integrated schema of the pathological and recovery processes of depression is illustrated. © 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.

  8. A holistic review on the autoimmune disease vitiligo with emphasis on the causal factors.

    Science.gov (United States)

    Patel, Seema; Rauf, Abdur; Khan, Haroon; Meher, Biswa Ranjan; Hassan, Syed Shams Ul

    2017-08-01

    Vitiligo is an idiopathic systemic autoimmune disease affecting skin, hair and oral mucosa. This genetic yet acquired disease characterized by melanin loss is a cause of morbidity across all races. Though thyroid disturbance has been recognized as a key trigger of this pathology, an array of other factors plays critical role in its manifestation. Multiple hormones (corticotropin-releasing hormone, adrenocorticotropic hormone, α-melanocyte-stimulating hormone, melatonin, calcitriol, testosterone, estrogen), genes (Human leukocyte antigen (HLA), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), Forkhead box D3 (FOXD3), Cluster of differentiation 117 (CD117), Estrogen receptor (ESR) 1, Cyclooxygenase-2 (COX2), Vitiligo-associated protein 1 (VIT1)), and lifestyle choices (stress, diet, cosmetic products, and medications) have been suspected as drivers of this disorder. The pathological mechanisms have been understood in recent times, with the aid of genomic studies; however a universally-effective therapy is yet to be achieved. This review discusses these under-investigated facets of vitiligo onset and progression; hence, it is expected to enrich vitiligo research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain.

    Science.gov (United States)

    Schnydrig, Sabine; Korner, Lukas; Landweer, Svenja; Ernst, Beat; Walker, Gaby; Otten, Uwe; Kunz, Dieter

    2007-12-11

    Peripheral inflammation induced by intraperitoneal (i.p.) injection of Lipopolysaccharide (LPS) is known to cause functional impairments in the brain affecting memory and learning. One of mechanisms may be the interference with neurotrophin (NT) expression and function. In the current study we administered a single, high dose of LPS (3mg/kg, i.p.) into mice and investigated changes in brain-derived neurotrophic factor (BDNF) gene expression within 1-6 days after LPS injection. Crude synaptosomes were isolated from brain tissue and subjected to Western-blot analyses. We found transient reductions in synaptosomal proBDNF- and BDNF protein expression, with a maximal decrease at day 3 as compared to saline injected controls. The time course of reduction of BDNF mRNA in whole brain extracts parallels the decrease in protein levels in synaptosomes. LPS effects in the central nervous system (CNS) are known to crucially involve the activation of the hypothalamic-pituitary-adrenal (HPA) axis. We analysed the time course of corticotropin releasing hormone (CRH)- and proopiomelanocortin (POMC) mRNA expression. As observed for BDNF-, CRH- and POMC mRNA levels are also significantly reduced on day 3 indicating a comparable time course. These results suggest that peripheral inflammation causes a reduction of trophic supply in the brain, including BDNF at synaptic sites. The mechanisms involved could be a negative feedback of the activated HPA axis.

  10. Factors contributing to the resilience of middle-adolescents in a South African township: insights from a resilience questionnaire

    Directory of Open Access Journals (Sweden)

    Motlalepule Ruth Mampane

    2014-11-01

    Full Text Available Factors that contribute to resilience are key to the positive development of youths, and knowledge of such factors is essential for promoting resilience in schools through both policy and practice. This study reports on the results of an item and factor analysis of the Resilience Questionnaire for Middle-adolescents in Township Schools (R-MATS that was used to survey 291 Grade 9 middle-adolescent learners from two black-only township secondary schools. The majority of respondents indicated an overall sense of contending with various stressors, especially the exposure to violence, and academic challenges. Respondents attributed their buoyancy to individual and environmental factors, such as self-confidence, an internal locus of control, a tough personality, commitment, being achievement-oriented, as well as positive identification of and access to social support.

  11. New insights into the interplay between the translation machinery and nonsense-mediated mRNA decay factors.

    Science.gov (United States)

    Raimondeau, Etienne; Bufton, Joshua C; Schaffitzel, Christiane

    2018-06-19

    Faulty mRNAs with a premature stop codon (PTC) are recognized and degraded by nonsense-mediated mRNA decay (NMD). Recognition of a nonsense mRNA depends on translation and on the presence of NMD-enhancing or the absence of NMD-inhibiting factors in the 3'-untranslated region. Our review summarizes our current understanding of the molecular function of the conserved NMD factors UPF3B and UPF1, and of the anti-NMD factor Poly(A)-binding protein, and their interactions with ribosomes translating PTC-containing mRNAs. Our recent discovery that UPF3B interferes with human translation termination and enhances ribosome dissociation in vitro , whereas UPF1 is inactive in these assays, suggests a re-interpretation of previous experiments and modification of prevalent NMD models. Moreover, we discuss recent work suggesting new functions of the key NMD factor UPF1 in ribosome recycling, inhibition of translation re-initiation and nascent chain ubiquitylation. These new findings suggest that the interplay of UPF proteins with the translation machinery is more intricate than previously appreciated, and that this interplay quality-controls the efficiency of termination, ribosome recycling and translation re-initiation. © 2018 The Author(s).

  12. Endothelial cell hypertrophy induced by vascular endothelial growth factor in the retina: new insights into the pathogenesis of capillary nonperfusion

    NARCIS (Netherlands)

    Hofman, P.; van Blijswijk, B. C.; Gaillard, P. J.; Vrensen, G. F.; Schlingemann, R. O.

    2001-01-01

    OBJECTIVE: To investigate the mechanism leading to capillary nonperfusion of the retina in a monkey model of vascular endothelial growth factor A (VEGF)-induced retinopathy in which capillary closure occurs in a late stage after VEGF treatment. METHODS: Two monkeys received 4 intravitreous

  13. The “housing bubble” and financial factors: Insights from a structural model of the French and Spanish residential markets.

    OpenAIRE

    Antipa, P.; Lecat, R.

    2009-01-01

    Over the last decade, France and Spain have experienced property price and residential investment increases which were among the strongest and the lengthiest in the euro area. Although the quality of the underlying data limits the precision of the estimates, the present paper aims at analysing the fundamental factors behind these evolutions. The analysis presented here assesses whether the observed price dynamics may be attributed to a pure expectation bubble phenomenon or to the large change...

  14. Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression.

    Science.gov (United States)

    Ignácio, Z M; Réus, G Z; Abelaira, H M; Quevedo, J

    2014-09-05

    Epidemiological studies have shown significant results in the interaction between the functions of brain-derived neurotrophic factor (BDNF) and 5-HT in mood disorders, such as major depressive disorder (MDD). The latest research has provided convincing evidence that gene transcription of these molecules is a target for epigenetic changes, triggered by stressful stimuli that starts in early childhood and continues throughout life, which are subsequently translated into structural and functional phenotypes culminating in depressive disorders. The short variants of 5-HTTLPR and BDNF-Met are seen as forms which are predisposed to epigenetic aberrations, which leads individuals to a susceptibility to environmental adversities, especially when subjected to stress in early life. Moreover, the polymorphic variants also feature epistatic interactions in directing the functional mechanisms elicited by stress and underlying the onset of depressive disorders. Also emphasized are works which show some mediators between stress and epigenetic changes of the 5-HTT and BDNF genes, such as the hypothalamic-pituitary-adrenal (HPA) axis and the cAMP response element-binding protein (CREB), which is a cellular transcription factor. Both the HPA axis and CREB are also involved in epistatic interactions between polymorphic variants of 5-HTTLPR and Val66Met. This review highlights some research studying changes in the epigenetic patterns intrinsic to genes of 5-HTT and BDNF, which are related to lifelong environmental adversities, which in turn increases the risks of developing MDD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Factors Affecting Leaf Selection by Foregut-fermenting Proboscis Monkeys: New Insight from in vitro Digestibility and Toughness of Leaves

    Science.gov (United States)

    Matsuda, Ikki; Clauss, Marcus; Tuuga, Augustine; Sugau, John; Hanya, Goro; Yumoto, Takakazu; Bernard, Henry; Hummel, Jürgen

    2017-01-01

    Free-living animals must make dietary choices in terms of chemical and physical properties, depending on their digestive physiology and availability of food resources. Here we comprehensively evaluated the dietary choices of proboscis monkeys (Nasalis larvatus) consuming young leaves. We analysed the data for leaf toughness and digestibility measured by an in vitro gas production method, in addition to previously reported data on nutrient composition. Leaf toughness, in general, negatively correlated with the crude protein content, one of the most important nutritional factors affecting food selection by leaf-eating primates. This result suggests that leaf toughness assessed by oral sensation might be a proximate cue for its protein content. We confirmed the importance of the leaf chemical properties in terms of preference shown by N. larvatus; leaves with high protein content and low neutral detergent fibre levels were preferred to those of the common plant species. We also found that these preferred leaves were less tough and more digestible than the alternatives. Our in vitro results also suggested that N. larvatus were little affected by secondary plant compounds. However, the spatial distribution pattern of plant species was the strongest factor explaining the selection of the preferred leaf species. PMID:28211530

  16. Factors influencing deprescribing for residents in Advanced Care Facilities: insights from General Practitioners in Australia and Sweden.

    Science.gov (United States)

    Bolmsjö, Beata Borgström; Palagyi, Anna; Keay, Lisa; Potter, Jan; Lindley, Richard I

    2016-11-05

    General Practitioners (GPs) are responsible for primary prescribing decisions in most settings. Elderly patients living in Advanced Care Facilities (ACFs) often have significant co-morbidities to consider when selecting an appropriate drug therapy. Careful assessment is required when considering appropriate medication use in frail older patients as they have multiple diseases and thus multiple medication. Many physicians seem reluctant to discontinue other physicians' prescriptions, resulting in further polypharmacy. Therefore it is relevant to ascertain and synthesise the GP views from multiple settings to understand the processes that might promote appropriate deprescribing medications in the elderly. The aims of this study were to 1) compare and contrast behavioural factors influencing the deprescribing practices of GPs providing care for ACF residents in two separate countries, 2) review health policy and ACF systems in each setting for their potential impact on the prescribing of medications for an older person in residential care of the elderly, and 3) based on these findings, provide recommendations for future ACF deprescribing initiatives. A review and critical synthesis of qualitative data from two interview studies of knowledge, attitudes, and behavioural practices held by GPs towards medication management and deprescribing for residents of ACFs in Australia and Sweden was conducted. A review of policies and health care infrastructure was also carried out to describe the system of residential aged care in the both countries. Our study has identified that deprescribing by GPs in ACFs is a complex process and that there are numerous barriers to medication reduction for aged care residents in both countries, both with similarities and differences. The factors affecting deprescribing behaviour were identified and divided into: intentions, skills and abilities and environmental factors. In this study we show that the GPs' behaviour of deprescribing in two

  17. Ancient duplications and functional divergence in the interferon regulatory factors of vertebrates provide insights into the evolution of vertebrate immune systems.

    Science.gov (United States)

    Du, Kang; Zhong, Zaixuan; Fang, Chengchi; Dai, Wei; Shen, Yanjun; Gan, Xiaoni; He, Shunping

    2018-04-01

    Interferon regulatory factors (IRFs) were first discovered as transcription factors that regulate the transcription of human interferon (IFN)-β. Increasing evidence shows that they might be important players involved in Adaptive immune system (AIS) evolution. Although numbers of IRFs have been identified in chordates, the evolutionary history and functional diversity of this gene family during the early evolution of vertebrates have remained obscure. Using IRF HMM profile and HMMER searches, we identified 148 IRFs in 11 vertebrates and 4 protochordates. For them, we reconstructed the phylogenetic relationships, determined the synteny conservation, investigated the profile of natural selection, and analyzed the expression patterns in four "living fossil" vertebrates: lamprey, elephant shark, coelacanth and bichir. The results from phylogeny and synteny analysis imply that vertebrate IRFs evolved from three predecessors, instead of four as suggested in a previous study, as results from an ancient duplication followed by special expansions and lost during the vertebrate evolution. The profile of natural selection and expression reveals functional dynamics during the process. Together, they suggest that the 2nd whole-genome duplication (2WGD) provided raw materials for innovation in the IRF family, and that the birth of type-I IFN might be an important factor inducing the establishment of IRF-mediated immune networks. As a member involved in the AIS evolution, IRF provide insights into the process and mechanism involved in the complexity and novelties of vertebrate immune systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Theoretical Insight Into the Empirical Tortuosity-Connectivity Factor in the Burdine-Brooks-Corey Water Relative Permeability Model

    Science.gov (United States)

    Ghanbarian, Behzad; Ioannidis, Marios A.; Hunt, Allen G.

    2017-12-01

    A model commonly applied to the estimation of water relative permeability krw in porous media is the Burdine-Brooks-Corey model, which relies on a simplified picture of pores as a bundle of noninterconnected capillary tubes. In this model, the empirical tortuosity-connectivity factor is assumed to be a power law function of effective saturation with an exponent (μ) commonly set equal to 2 in the literature. Invoking critical path analysis and using percolation theory, we relate the tortuosity-connectivity exponent μ to the critical scaling exponent t of percolation that characterizes the power law behavior of the saturation-dependent electrical conductivity of porous media. We also discuss the cause of the nonuniversality of μ in terms of the nonuniversality of t and compare model estimations with water relative permeability from experiments. The comparison supports determining μ from the electrical conductivity scaling exponent t, but also highlights limitations of the model.

  19. New Insight into the Observation of Spectroscopic Strength Reduction in Atomic Nuclei: Implication for the Physical Meaning of Spectroscopic Factors

    International Nuclear Information System (INIS)

    Timofeyuk, N. K.

    2009-01-01

    Experimental studies of one-nucleon knockout from magic nuclei suggest that their nucleon orbits are not fully occupied. This conflicts a commonly accepted view of the shell closure associated with such nuclei. The conflict can be reconciled if the overlap between initial and final nuclear states in a knockout reaction are calculated by a nonstandard method. The method employs an inhomogeneous equation based on correlation-dependent effective nucleon-nucleon interactions and allows the simplest wave functions, in which all nucleons occupy only the lowest nuclear orbits, to be used. The method also reproduces the recently established relation between reduction of spectroscopic strength, observed in knockout reactions on other nuclei, and nucleon binding energies. The implication of the inhomogeneous equation method for the physical meaning of spectroscopic factors is discussed.

  20. Risk factors associated with brucellosis among slaughtered cattle: Epidemiological insight from two metropolitan abattoirs in Southwestern Nigeria

    Directory of Open Access Journals (Sweden)

    Ogugua Akwoba Joseph

    2015-09-01

    Full Text Available Objective: To investigate risk factors responsible for the epidemiology of brucellosis among cattle slaughtered in Nigeria in a bid to implement control strategies. Methods: This was a cross-sectional and sero-epidemiological survey of bovine brucellosis in two metropolitan abattoirs in Southwestern Nigeria. Between March and August 2013, cattle were screened for antibodies to Brucella spp. by using Rose Bengal test (RBT, and positive samples were subjected to competitive ELISA (cELISA. Parameters of individual animal were also obtained. Data were analyzed by using STATA version 12 and Chi-square; and logistic regression statistics were used to test association. Results: Overall, 2 480 cattle (1 241 in Oyo; 1 239 in Lagos were screened. Analysis using RBT revealed a total sero-prevalence of 4.9% (121/2 480, with 7.8% and 1.9% from Oyo and Lagos States respectively. The cELISA result supported 77.7% (94/121 (90.7% in Oyo; 25.0% in Lagos of the total RBT positive samples. Logistic regression analysis showed that only sex (P ≤ 0.001 and location (P = 0.001 of animal screened had statistically significant effects on seropositivity to Brucella abortus antibodies. Conclusions: Our findings reveal low sero-prevalence of brucellosis among slaughtered cattle in Southwestern Nigeria. Sex and location of abattoirs where animals are slaughtered are major risk factors to be considered in the epidemiology of the disease. Therefore, to promote public health, trade cattle meant for slaughter in Nigeria and African countries where brucellosis is endemic, should be monitored, and positive animals be excluded from the food chain.

  1. Linking the spatial patterns of organisms and abiotic factors to ecosystem function and management: insights from semi-arid environments

    Directory of Open Access Journals (Sweden)

    F. T. Maestre

    2006-12-01

    Full Text Available Numerous theoretical and modeling studies have demonstrated the ecological significance of the spatial patterning of organisms on ecosystem functioning and dynamics. However, there is a paucity of empirical evidence that quantitatively shows how changes in the spatial patterns of the organisms forming biotic communities are directly related to ecosystem structure and functioning. In this article, I review a series of experiments and observational studies conducted in semi-arid environments from Spain (degraded calcareous shrubland, steppes dominated by Stipa tenacissima, and gypsum shrublands to: 1 evaluate whether the spatial patterns of the dominant biotic elements in the community are linked to ecosystem structure and functioning, and 2 test if these patterns, and those of abiotic factors, can be used to improve ecosystem restoration. In the semiarid steppes we found a significant positive relationship between the spatial pattern of the perennial plant community and: i the water status of S. tenacissima and ii perennial species richness and diversity. Experimental plantings conducted in these steppes showed that S. tenacissima facilitated the establishment of shrub seedlings, albeit the magnitude and direction of this effect was dependent on rainfall conditions during the first yr after planting. In the gypsum shrubland, a significant, direct relationship between the spatial pattern of the biological soil crusts and surrogates of ecosystem functioning (soil bulk density and respiration was found. In a degraded shrubland with very low vegetation cover, the survival of an introduced population of the shrub Pistacia lentiscus showed marked spatial patterns, which were related to the spatial patterns of soil properties such as soil compaction and sand content. These results provide empirical evidence on the importance of spatial patterns for maintaining ecosystem structure and functioning in semi-arid ecosystems

  2. Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study.

    Directory of Open Access Journals (Sweden)

    Gabriel Bsteh

    Full Text Available Multiple sclerosis (MS has a highly heterogenic course making prediction of long term outcome very difficult.The objective was to evaluate current and identify additional clinical factors that are linked to long term outcome of relapsing-remitting MS assessed by disability status 10 years after disease onset.This observational study included 793 patients with relapsing-remitting MS. Clinical factors hypothesized to influence long term outcome measured by EDSS scores 10 years after disease onset were analysed by Kaplan-Meier-estimates. Multinomial logistic regression models regarding mild (EDSS ≤2.5, moderate (EDSS 3.0-5.5 or severe (EDSS ≥6.0 disability were calculated to correct for confounders.Secondary progression was the strongest predictor of severe disability (Hazard ratio [HR] 503.8, 95% confidence interval [CI] 160.0-1580.1; p<0.001. Complete remission of neurological symptoms at onset reduced the risk of moderate disability (HR 0.42; CI 0.23-0.77; p = 0.005, while depression (HR 3.59; CI 1.14-11.24; p = 0.028 and cognitive dysfunction (HR 4.64; CI 1.11-19.50; p = 0.036 10 years after disease onset were associated with severe disability. Oligoclonal bands and pregnancy were not correlated with disability.We were able to identify clinically apparent chronic depression and cognitive dysfunction to be associated with adverse long term outcome in MS and to confirm that pregnancy has no negative impact. Additionally, we emphasize the positive predictive value of complete remission of initial symptoms.

  3. THE IDENTIFICATION OF KEY SUCCESS FACTORS IN SUSTAINABLE COLD CHAIN MANAGEMENT: INSIGHTS FROM THE INDIAN FOOD INDUSTRY

    Directory of Open Access Journals (Sweden)

    Shashi

    2016-12-01

    Full Text Available Supply chain sustainability has emerged as an indispensable research agenda for the government, industry as well as non-profit orientation bodies. As a developing country, cold supply chain management in India is still in infancy. The demand pattern of food products has been dramatically changing since last few years. Nowadays, the customers are more conscious to use products for better health and highly expecting for food safety, toxic free and eco-friendly delivery of food products. However, sustainable cold supply chain has not yet received good heed throughout the world. Hence, in this paper an attempt has been made to address these important issues. A conceptual model was proposed in the consultation of practitioners and literature support to address the important issues in cold supply chain management for food companies. Therefore, in order to identify the key success factors for sustainable cold chain management, in this study a conceptual model developed. The proposed framework is then validated by an empirical research in the Indian food industry. This research has several alarming findings. Explicitly, in India i environmental issues and social responsibility are not as important as other ‎economical supplier selection criteria, ii among 19 food supplier selection criteria, the rank of social responsibility is 18‎, iii low carbon emission is less important value addition trait as compare to ‎other sustainable cold chain value addition (which means in India the buyers focus more on their individual and prompt received ‎benefits rather than long ‎lasting advantages, iv the use of life cycle analysis, renewable energy sources and passive cold chain are the least important ‎implemented sustainable cold chain practices (although this might be because of utilization complexities, v the joint development of product is implemented at the lowest extent judging against other dynamic capacity ‎factors, vii government usually backed

  4. Mechanistic Insights into Elastin Degradation by Pseudolysin, the Major Virulence Factor of the Opportunistic Pathogen Pseudomonas aeruginosa

    Science.gov (United States)

    Yang, Jie; Zhao, Hui-Lin; Ran, Li-Yuan; Li, Chun-Yang; Zhang, Xi-Ying; Su, Hai-Nan; Shi, Mei; Zhou, Bai-Cheng; Chen, Xiu-Lan; Zhang, Yu-Zhong

    2015-01-01

    Pseudolysin is the most abundant protease secreted by Pseudomonas aeruginosa and is the major extracellular virulence factor of this opportunistic human pathogen. Pseudolysin destroys human tissues by solubilizing elastin. However, the mechanisms by which pseudolysin binds to and degrades elastin remain elusive. In this study, we investigated the mechanism of action of pseudolysin on elastin binding and degradation by biochemical assay, microscopy and site-directed mutagenesis. Pseudolysin bound to bovine elastin fibers and preferred to attack peptide bonds with hydrophobic residues at the P1 and P1’ positions in the hydrophobic domains of elastin. The time-course degradation processes of both bovine elastin fibers and cross-linked human tropoelastin by pseudolysin were further investigated by microscopy. Altogether, the results indicate that elastin degradation by pseudolysin began with the hydrophobic domains on the fiber surface, followed by the progressive disassembly of macroscopic elastin fibers into primary structural elements. Moreover, our site-directed mutational results indicate that five hydrophobic residues in the S1-S1’ sub-sites played key roles in the binding of pseudolysin to elastin. This study sheds lights on the pathogenesis of P. aeruginosa infection. PMID:25905792

  5. Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: Novel insights into angiogenesis

    International Nuclear Information System (INIS)

    Sun, Hui-Yan; Wei, Shu-Ping; Xu, Rui-Cheng; Xu, Peng-Xiao; Zhang, Wen-Cheng

    2010-01-01

    Sphingosine-1-phosphate (S1P)-induced migration and proliferation of endothelial cells are critical for angiogenesis. C2H2-zinc finger (ZNF) proteins usually play an essential role in altering gene expression and regulating the angiogenesis. The aim of this study is to investigate whether a novel human C2H2-zinc finger gene ZNF580 (Gene ID: 51157) is involved in the migration and proliferation of endothelial cells stimulated by S1P. Our study shows that EAhy926 endothelial cells express S1P1, S1P3 and S1P5 receptors. Furthermore, S1P upregulates both ZNF580 mRNA and protein levels in a concentration- and time-dependent manner. SB203580, the specific inhibitor of the p38 mitogen-activated protein kinase (p38 MAPK) pathway, blocks the S1P-induced upregulation of ZNF580. Moreover, overexpression/downexpression of ZNF580 in EAhy926 cells leads to the enhancement/decrease of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) expression as well as the migration and proliferation of EAhy926 endothelial cells. These results elucidate the important role that ZNF580 plays in the process of migration and proliferation of endothelial cells, which provides a foundation for a novel approach to regulate angiogenesis.

  6. Sex, ageing and resting blood pressure: gaining insights from the integrated balance of neural and haemodynamic factors.

    Science.gov (United States)

    Hart, Emma C; Joyner, Michael J; Wallin, B Gunnar; Charkoudian, Nisha

    2012-05-01

    Young women tend to have lower blood pressure, and less risk of hypertension, compared to young men. As people age, both blood pressure and the risk of hypertension increase in both sexes; this occurs most strikingly in women after menopause. However, the mechanisms for these influences of sex and age remain incompletely understood. In this review we are specifically interested in the interaction between neural (sympathetic nerve activity; SNA) and haemodynamic factors (cardiac output, blood pressure and vascular resistance) and how these change with sex and age. While peripheral vascular SNA can vary 7- to 10-fold among normotensive young men and women, it is reproducible in a given individual. Surprisingly, higher levels of SNA are not associated with higher blood pressures in these groups. In young men, high SNA is associated with higher total peripheral vascular resistance (TPR), and appears to be balanced by lower cardiac output and less peripheral vascular responsiveness to adrenergic stimulation. Young women do not exhibit the SNA-TPR relationship. Recent evidence suggests that β-adrenergic vasodilatation offsets the vasoconstrictor effects of α-adrenergic vasoconstriction in young women, which may contribute to the generally lower blood pressures in this group. Sympathetic nerve activity increases with age, and in groups over 40, levels of SNA are more tightly linked to levels of blood pressure. The potentially protective β-adrenergic effect seen in young women appears to be lost after menopause and probably contributes to the increased blood pressure and increased risk of hypertension seen in older women.

  7. Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: Novel insights into angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Hui-Yan, E-mail: shy35309@sohu.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Wei, Shu-Ping, E-mail: weishuping_83@163.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Xu, Rui-Cheng, E-mail: xu_rc@sohu.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Xu, Peng-Xiao, E-mail: xupengxiao1228@sina.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Zhang, Wen-Cheng, E-mail: wenchengzhang@yahoo.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China)

    2010-05-07

    Sphingosine-1-phosphate (S1P)-induced migration and proliferation of endothelial cells are critical for angiogenesis. C2H2-zinc finger (ZNF) proteins usually play an essential role in altering gene expression and regulating the angiogenesis. The aim of this study is to investigate whether a novel human C2H2-zinc finger gene ZNF580 (Gene ID: 51157) is involved in the migration and proliferation of endothelial cells stimulated by S1P. Our study shows that EAhy926 endothelial cells express S1P1, S1P3 and S1P5 receptors. Furthermore, S1P upregulates both ZNF580 mRNA and protein levels in a concentration- and time-dependent manner. SB203580, the specific inhibitor of the p38 mitogen-activated protein kinase (p38 MAPK) pathway, blocks the S1P-induced upregulation of ZNF580. Moreover, overexpression/downexpression of ZNF580 in EAhy926 cells leads to the enhancement/decrease of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) expression as well as the migration and proliferation of EAhy926 endothelial cells. These results elucidate the important role that ZNF580 plays in the process of migration and proliferation of endothelial cells, which provides a foundation for a novel approach to regulate angiogenesis.

  8. Sources and atmospheric processing of organic aerosol in the Mediterranean: insights from aerosol mass spectrometer factor analysis

    Directory of Open Access Journals (Sweden)

    L. Hildebrandt

    2011-12-01

    Full Text Available Atmospheric particles were measured in the late winter (25 February–26 March 2009 at a remote coastal site on the island of Crete, Greece during the Finokalia Aerosol Measurement Experiment-2009. A quadrupole aerosol mass spectrometer (Q-AMS was employed to quantify the size-resolved chemical composition of non-refractory submicron aerosol, and a thermodenuder was used to analyze the organic aerosol (OA volatility. Complementary measurements included particle size distributions from a scanning mobility particle sizer, inorganic and organic particle composition from filter analysis, air ion concentrations, O3, NOx and NOy concentrations, and meteorological measurements. Factor analysis was performed on the OA mass spectra, and the variability in OA composition could best be explained with three OA components. The oxygenated organic aerosol (OOA was similar in composition and volatility to the summertime OA previously measured at this site and may represent an effective endpoint in particle-phase oxidation of organics. The two other OA components, one associated with amines (Amine-OA and the other probably associated with the burning of olive branches (OB-OA, had very low volatility but were less oxygenated. Hydrocarbon-like organic aerosol (HOA was not detected. The absence of OB-OA and Amine-OA in the summer data may be due to lower emissions and/or photochemical conversion of these components to OOA.

  9. Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor.

    Science.gov (United States)

    Stone, Matthew D; Harvey, Stephen B; Martinez, Michael B; Bach, Ronald R; Nelsestuen, Gary L

    2005-04-26

    Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.

  10. Dash Cam videos on YouTube™ offer insights into factors related to moose-vehicle collisions.

    Science.gov (United States)

    Rea, Roy V; Johnson, Chris J; Aitken, Daniel A; Child, Kenneth N; Hesse, Gayle

    2018-03-26

    To gain a better understanding of the dynamics of moose-vehicle collisions, we analyzed 96 videos of moose-vehicle interactions recorded by vehicle dash-mounted cameras (Dash Cams) that had been posted to the video-sharing website YouTube™. Our objective was to determine the effects of road conditions, season and weather, moose behavior, and driver response to actual collisions compared to near misses when the collision was avoided. We identified 11 variables that were consistently observable in each video and that we hypothesized would help to explain a collision or near miss. The most parsimonious logistic regression model contained variables for number of moose, sight time, vehicle slows, and vehicle swerves (AIC c w = 0.529). This model had good predictive accuracy (AUC = 0.860, SE = 0.041). The only statistically significant variable from this model that explained the difference between moose-vehicle collisions and near misses was 'Vehicle slows'. Our results provide no evidence that road surface conditions (dry, wet, ice or snow), roadside habitat type (forested or cleared), the extent to which roadside vegetation was cleared, natural light conditions (overcast, clear, twilight, dark), season (winter, spring and summer, fall), the presence of oncoming traffic, or the direction from which the moose entered the roadway had any influence on whether a motorist collided with a moose. Dash Cam videos posted to YouTube™ provide a unique source of data for road safety planners trying to understand what happens in the moments just before a moose-vehicle collision and how those factors may differ from moose-vehicle encounters that do not result in a collision. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: a novel mechanistic insight into progressive obesity.

    Science.gov (United States)

    Dai, Zhiyu; Qi, Weiwei; Li, Cen; Lu, Juling; Mao, Yuling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Zhou, Ti; Yang, Zhonghan; Yang, Xia; Gao, Guoquan; Cai, Weibin

    2013-09-05

    Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Evolution of pigment-dispersing factor neuropeptides in Panarthropoda: Insights from Onychophora (velvet worms) and Tardigrada (water bears).

    Science.gov (United States)

    Mayer, Georg; Hering, Lars; Stosch, Juliane M; Stevenson, Paul A; Dircksen, Heinrich

    2015-09-01

    Pigment-dispersing factor (PDF) denotes a conserved family of homologous neuropeptides present in several invertebrate groups, including mollusks, nematodes, insects, and crustaceans (referred to here as pigment-dispersing hormone [PDH]). With regard to their encoding genes (pdf, pdh), insects possess only one, nematodes two, and decapod crustaceans up to three, but their phylogenetic relationship is unknown. To shed light on the origin and diversification of pdf/pdh homologs in Panarthropoda (Onychophora + Tardigrada + Arthropoda) and other molting animals (Ecdysozoa), we analyzed the transcriptomes of five distantly related onychophorans and a representative tardigrade and searched for putative pdf homologs in publically available genomes of other protostomes. This revealed only one pdf homolog in several mollusk and annelid species; two in Onychophora, Priapulida, and Nematoda; and three in Tardigrada. Phylogenetic analyses suggest that the last common ancestor of Panarthropoda possessed two pdf homologs, one of which was lost in the arthropod or arthropod/tardigrade lineage, followed by subsequent duplications of the remaining homolog in some taxa. Immunolocalization of PDF-like peptides in six onychophoran species, by using a broadly reactive antibody that recognizes PDF/PDH peptides in numerous species, revealed an elaborate system of neurons and fibers in their central and peripheral nervous systems. Large varicose projections in the heart suggest that the PDF neuropeptides functioned as both circulating hormones and locally released transmitters in the last common ancestor of Onychophora and Arthropoda. The lack of PDF-like-immunoreactive somata associated with the onychophoran optic ganglion conforms to the hypothesis that onychophoran eyes are homologous to the arthropod median ocelli. © 2015 Wiley Periodicals, Inc.

  13. Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

    Science.gov (United States)

    Pettipher, E R; Labasi, J M; Salter, E D; Stam, E J; Cheng, J B; Griffiths, R J

    1996-04-01

    1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice

  14. Risk Factor Burden, Heart Failure, and Survival in Women of Different Ethnic Groups: Insights From the Women's Health Initiative.

    Science.gov (United States)

    Breathett, Khadijah; Leng, Iris; Foraker, Randi E; Abraham, William T; Coker, Laura; Whitfield, Keith E; Shumaker, Sally; Manson, JoAnn E; Eaton, Charles B; Howard, Barbara V; Ijioma, Nkechinyere; Cené, Crystal W; Martin, Lisa W; Johnson, Karen C; Klein, Liviu

    2018-05-01

    The higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups. In the WHI (Women's Health Initiative; 1993-2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased ( P ethnicity and RF number P =0.18)-African-Americans 1 RF: 1.80 (1.01-3.20), 2 RFs: 3.19 (1.84-5.54), 3+ RFs: 7.31 (4.26-12.56); Whites 1 RF: 1.27 (1.04-1.54), 2 RFs: 1.95 (1.60-2.36), 3+ RFs: 4.07 (3.36-4.93); Hispanics 1 RF: 1.72 (0.68-4.34), 2 RFs: 3.87 (1.60-9.37), 3+ RFs: 8.80 (3.62-21.42). Risk of death before developing HF increased with subsequent RFs ( P ethnic group (interaction P =0.001). The number of RFs was not associated with the risk of death after developing HF in any group ( P =0.25; interaction P =0.48). Among diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups. © 2018 American Heart Association, Inc.

  15. Interacting mechanism of ID3 HLH domain towards E2A/E12 transcription factor – An Insight through molecular dynamics and docking approach

    Directory of Open Access Journals (Sweden)

    Nishith Saurav Topno

    2016-03-01

    Full Text Available Inhibitor of DNA binding protein 3 (ID3 has long been characterized as an oncogene that implicates its functional role through its Helix–Loop–Helix (HLH domain upon protein–protein interaction. An insight into the dimerization brought by this domain helps in identifying the key residues that favor the mechanism behind it. Molecular dynamics (MD simulations were performed for the HLH proteins ID3 and Transcription factor E2-alpha (E2A/E12 and their ensemble complex (ID3-E2A/E12 to gather information about the HLH domain region and its role in the interaction process. Further evaluation of the results by Principal Component Analysis (PCA and Free Energy Landscape (FEL helped in revealing residues of E2A/E12: Lys570, Ala595, Val598, and Ile599 and ID3: Glu53, Gln63, and Gln66 buried in their HLH motifs imparting key roles in dimerization process. Furthermore the T-pad analysis results helped in identifying the key fluctuations and conformational transitions using the intrinsic properties of the residues present in the domain region of the proteins thus specifying their crucial role towards molecular recognition. The study provides an insight into the interacting mechanism of the ID3-E2A/E12 complex and maps the structural transitions arising in the essential conformational space indicating the key structural changes within the helical regions of the motif. It thereby describes how the internal dynamics of the proteins might regulate their intrinsic structural features and its subsequent functionality.

  16. Low level tumor necrosis factor-alpha protects cardiomyocytes against high level tumor necrosis factor-alpha: brief insight into a beneficial paradox.

    Science.gov (United States)

    Cacciapaglia, Fabio; Salvatorelli, Emanuela; Minotti, Giorgio; Afeltra, Antonella; Menna, Pierantonio

    2014-12-01

    Whether tumor necrosis factor-alpha (TNFα) caused beneficial or detrimental cardiovascular effects remains poorly defined. Anti-TNFα agents improved cardiac end points in chronic rheumatic diseases characterized by progressive deterioration of cardiac function. In contrast, anti-TNFα agents did not always improve but actually worsened cardiac function in non-rheumatic patients with heart failure (HF), in spite of that HF usually accompanies with high circulating levels of TNFα. To shed light on these mixed findings, we characterized the effects of TNFα in H9c2 cardiomyocytes. Cells were incubated for 24 h with increasing concentrations of TNFα, hydrogen peroxide, aminotriazole, or etoposide. Posttreatment cell viability was assessed by antimycin A-inhibitable reduction of 3-(4,dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and the IC50 value of each test compound was defined. H9c2 cells were also preconditioned with a low non-toxic concentration of TNFα and then re-challenged with increasing concentrations of TNFα and other stressor agents. In re-challenge experiments, all of the IC50 values increased significantly, with the IC50 value of TNFα increasing approximately 16-fold. TNFα preconditioning increased cardiomyocytes shedding of the external portion of transmembrane type 1 and type 2 TNFα receptors [(soluble TNFα receptors (sTNFR)]. Levels of survival-oriented soluble TNFR2 (sTNFR2) always exceeded those of death-oriented sTNFR1. When exposed to TNFα at its IC50 value, preconditioned cardiomyocytes showed an increased release of sTNFR2 but not sTNFR1. These results denoted that preconditioning by "low TNFα" helped cardiomyocyte to withstand toxicity from "high TNFα" or other agents. These results also suggested that beneficial or detrimental effects of anti-TNFα agents might well depend on whether these agents spared or intercepted discrete amounts of TNFα that preconditioned cardiomyocytes and made them more resistant to high

  17. The obesity-associated transcription factor ETV5 modulates circulating glucocorticoids

    Science.gov (United States)

    Gutierrez-Aguilar, Ruth; Thompson, Abigail; Marchand, Nathalie; Dumont, Patrick; Woods, Stephen C.; de Launoit, Yvan; Seeley, Randy J.; Ulrich-Lai, Yvonne M.

    2015-01-01

    The transcription factor E-twenty-six version 5 (ETV5) has been linked with obesity in genome-wide association studies. Moreover, ETV5-deficient mice (knockout; KO) have reduced body weight, lower fat mass, and are resistant to diet-induced obesity, directly linking ETV5 to the regulation of energy balance and metabolism. ETV5 is expressed in hypothalamic brain regions that regulate both metabolism and HPA axis activity, suggesting that ETV5 may also modulate HPA axis function. In order to test this possibility, plasma corticosterone levels were measured in ETV5 KO and wildtype (WT) mice before (pre-stress) and after (post-stress) a mild stressor (intraperitoneal injection). ETV5 deficiency increased both pre- and post-stress plasma corticosterone, suggesting that loss of ETV5 elevated glucocorticoid tone. Consistent with this idea, ETV5 KO mice have reduced thymus weight, suggestive of increased glucocorticoid-induced thymic involution. ETV5 deficiency also decreased the mRNA expression of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and vasopressin receptor 1A in the hypothalamus, without altering vasopressin, corticotropin-releasing hormone, or oxytocin mRNA expression. In order to test whether reduced MR and GR expression affected glucocorticoid negative feedback, a dexamethasone suppression test was performed. Dexamethasone reduced plasma corticosterone in both ETV5 KO and WT mice, suggesting that glucocorticoid negative feedback was unaltered by ETV5 deficiency. In summary, these data suggest that the obesity-associated transcription factor ETV5 normally acts to diminish circulating glucocorticoids. This might occur directly via ETV5 actions on HPA-regulatory brain circuitry, and/or indirectly via ETV5-induced alterations in metabolic factors that then influence the HPA axis. PMID:25813907

  18. Africa Insight

    African Journals Online (AJOL)

    Africa Insight is a quarterly, peer-reviewed journal of the Africa Institute of South Africa. It is accredited by the South African National Department of Higher Education and Training (DHET) and is indexed in the International Bibliography of Social Science (IBSS). It is a multi-disciplinary journal primarily focusing on African ...

  19. Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: results of the INSIGHT case-control study.

    Science.gov (United States)

    van Velzen, A S; Eckhardt, C L; Peters, M; Leebeek, F W G; Escuriola-Ettingshausen, C; Hermans, C; Keenan, R; Astermark, J; Male, C; Peerlinck, K; le Cessie, S; van der Bom, J G; Fijnvandraat, K

    2017-07-01

    Essentials Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. Background Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg -1 /ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians

  20. Quantifying the Qualitative: Measuring the Insight Experience

    Science.gov (United States)

    Jarman, Matthew S.

    2014-01-01

    No scales currently exist that measure variability in the insight experience. Two scales were created to measure two factors hypothesized to be key drivers of the insight experience: insight radicality (i.e., perceived deviation between previous and new problem representations) and restructuring experience (i.e., the subjective experience of the…

  1. Effects of technological learning and uranium price on nuclear cost: Preliminary insights from a multiple factors learning curve and uranium market modeling

    International Nuclear Information System (INIS)

    Kahouli, Sondes

    2011-01-01

    This paper studies the effects of returns to scale, technological learning, i.e. learning-by-doing and learning-by-searching, and uranium price on the prospects of nuclear cost decrease. We use an extended learning curve specification, named multiple factors learning curve (MFLC). In a first stage, we estimate a single MFLC. In a second stage, we estimate the MFLC under the framework of simultaneous system of equations which takes into account the uranium supply and demand. This permits not only to enhance the reliability of the estimation by incorporating the uranium price formation mechanisms in the MFLC via the price variable, but also to give preliminary insights about uranium supply and demand behaviors and the associated effects on the nuclear expansion. Results point out that the nuclear cost has important prospects for decrease via capacity expansion, i.e. learning-by-doing effects. In contrast, they show that the learning-by-searching as well as the scale effects have a limited effect on the cost decrease prospects. Conversely, results also show that uranium price exerts a positive and significant effect on nuclear cost, implying that when the uranium price increases, the nuclear power generation cost decreases. Since uranium is characterized by important physical availability, and since it represents only a minor part in the total nuclear cost, we consider that in a context of increasing demand for nuclear energy the latter result can be explained by the fact that the positive learning effects on the cost of nuclear act in a way to dissipate the negative ones that an increase in uranium price may exert. Further, results give evidence of important inertia in the supply and demand sides as well as evidence of slow correlation between the uranium market and oil market which may limit the inter-fuels substituability effects, that is, nuclear capacity expansion and associated learning-by-doing benefits. - Highlights: → We study the prospects of nuclear cost

  2. Insights into the phylogeny of Northern Hemisphere Armillaria: Neighbor-net and Bayesian analyses of translation elongation factor 1-α gene sequences.

    Science.gov (United States)

    Klopfenstein, Ned B; Stewart, Jane E; Ota, Yuko; Hanna, John W; Richardson, Bryce A; Ross-Davis, Amy L; Elías-Román, Rubén D; Korhonen, Kari; Keča, Nenad; Iturritxa, Eugenia; Alvarado-Rosales, Dionicio; Solheim, Halvor; Brazee, Nicholas J; Łakomy, Piotr; Cleary, Michelle R; Hasegawa, Eri; Kikuchi, Taisei; Garza-Ocañas, Fortunato; Tsopelas, Panaghiotis; Rigling, Daniel; Prospero, Simone; Tsykun, Tetyana; Bérubé, Jean A; Stefani, Franck O P; Jafarpour, Saeideh; Antonín, Vladimír; Tomšovský, Michal; McDonald, Geral I; Woodward, Stephen; Kim, Mee-Sook

    2017-01-01

    Armillaria possesses several intriguing characteristics that have inspired wide interest in understanding phylogenetic relationships within and among species of this genus. Nuclear ribosomal DNA sequence-based analyses of Armillaria provide only limited information for phylogenetic studies among widely divergent taxa. More recent studies have shown that translation elongation factor 1-α (tef1) sequences are highly informative for phylogenetic analysis of Armillaria species within diverse global regions. This study used Neighbor-net and coalescence-based Bayesian analyses to examine phylogenetic relationships of newly determined and existing tef1 sequences derived from diverse Armillaria species from across the Northern Hemisphere, with Southern Hemisphere Armillaria species included for reference. Based on the Bayesian analysis of tef1 sequences, Armillaria species from the Northern Hemisphere are generally contained within the following four superclades, which are named according to the specific epithet of the most frequently cited species within the superclade: (i) Socialis/Tabescens (exannulate) superclade including Eurasian A. ectypa, North American A. socialis (A. tabescens), and Eurasian A. socialis (A. tabescens) clades; (ii) Mellea superclade including undescribed annulate North American Armillaria sp. (Mexico) and four separate clades of A. mellea (Europe and Iran, eastern Asia, and two groups from North America); (iii) Gallica superclade including Armillaria Nag E (Japan), multiple clades of A. gallica (Asia and Europe), A. calvescens (eastern North America), A. cepistipes (North America), A. altimontana (western USA), A. nabsnona (North America and Japan), and at least two A. gallica clades (North America); and (iv) Solidipes/Ostoyae superclade including two A. solidipes/ostoyae clades (North America), A. gemina (eastern USA), A. solidipes/ostoyae (Eurasia), A. cepistipes (Europe and Japan), A. sinapina (North America and Japan), and A. borealis

  3. [Poor insight and psychosis].

    Science.gov (United States)

    Giotakos, O

    2017-01-01

    this direction, research have implicated the role of self-monitoring in disorders of awareness and many of the core symptoms of schizophrenia, and has been suggested that these symptoms are the result of a disturbance of a medial frontal system involving anterior hippocampus, cingulated gyrus, supplementary motor area, and dorsolateral prefrontal cortex. Poor insight seems to be something more than a symptom or an epi-phenomenon and its mechanism may constitute a core factor into the psychosis process. Also, poor insight would be involves a common mechanism for many other mental disorders or even it would be an independent and trans-diagnostic factor into the human personality, probably like the dimension of psychotism.

  4. Insights into factors contributing to the observability of a submarine at periscope depth by modern radar, Part 2: EM simulation of mast RCS in a realistic sea surface environment

    CSIR Research Space (South Africa)

    Smit, JC

    2012-09-01

    Full Text Available IEEE-APS Topical Conference on Antennas and Propagation in Wireless Communications (APWC), Cape Town 2-7 September 2012 Insights into factors contributing to the observability of a submarine at periscope depth by modern radar, Part 2: EM... simulation of mast RCS in a realistic sea surface environment Smit JC; Cilliers JE CSIR, Defence, Peace, Safety and Security. PO Box 395, Pretoria, 0001 Abstract Recently, a set of high resolution radar measurements were undertaken in South...

  5. Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats.

    Science.gov (United States)

    Naert, Gaëlle; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

    2007-01-01

    Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and have some antidepressant effects. BDNF is highly involved in regulation of the HPA axis, whereas neurosteroids effects have never been clearly established. In this systematic in vivo study, we showed that the principal neuroactive steroids, namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA axis activity, while also modulating central BDNF contents. In detail, DHEA, DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred concomitantly with BDNF modifications at the hippocampus, amygdala and hypothalamus levels. We showed that these neurosteroids induced rapid effects, probably via neurotransmitter receptors and delayed effects perhaps after metabolization in other neuroactive steroids. We highlighted that they had peripheral effects directly at the adrenal level by inducing CORT release, certainly after estrogenic metabolization. In addition, we showed that, at the dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In conclusion, these results highly suggest that part of the HPA axis and antidepressant effects of neuroactive steroids could be mediated by BDNF, particularly at the amygdala level. They also suggest that neurosteroids effects on central BDNF could partially explain the trophic properties of these molecules.

  6. Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone.

    NARCIS (Netherlands)

    Wu, Y.-H.; Zhou, J.-N.; Balesar, R.; Unmehopa, U.; Bao, A.; Jockers, R.; Heerikhuize, J.; Swaab, D.F.

    2006-01-01

    Melatonin is implicated in numerous physiological processes, including circadian rhythms, stress, and reproduction, many of which are mediated by the hypothalamus and pituitary. The physiological actions of melatonin are mainly mediated by melatonin receptors. We here describe the distribution of

  7. The metabolic, stress axis, and hematology response of zilpaterol hydrochloride supplemented beef heifers when exposed to a dual corticotropin-releasing hormone and vasopressin challenge

    Science.gov (United States)

    The objective of this study was to determine the metabolic, stress, and hematology cell response of beef heifers supplemented with zilpaterol hydrochloride (ZH) when exposed to an endocrine stress challenge. Heifers (n = 20; 556 ± 7 kg BW) were randomized into two treatment groups: 1) Control (CON):...

  8. Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse

    NARCIS (Netherlands)

    Rinne, Thomas; de Kloet, E. Ronald; Wouters, Luuk; Goekoop, Jaap G.; DeRijk, Roel H.; van den Brink, Wim

    2002-01-01

    Background: High coincidence of childhood abuse, major depressive disorder (MDD), and posttraumatic stress disorder (PTSD) has been reported in patients with borderline personality disorder (BPD). Animals exposed to early trauma show increased stress-induced hypothalamic-pituitary-adrenal (HPA) axis

  9. Theory of mind correlates with clinical insight but not cognitive insight in patients with schizophrenia.

    Science.gov (United States)

    Zhang, Qi; Li, Xu; Parker, Giverny J; Hong, Xiao-Hong; Wang, Yi; Lui, Simon S Y; Neumann, David L; Cheung, Eric F C; Shum, David H K; Chan, Raymond C K

    2016-03-30

    Research on the relationship between insight and social cognition, in particular Theory of Mind (ToM), in schizophrenia has yielded mixed findings to date. Very few studies, however, have assessed both clinical insight and cognitive insight when examining their relationships with ToM in schizophrenia. The current study thus investigated the relationship between clinical insight, cognitive insight, and ToM in a sample of 56 patients with schizophrenia and 30 healthy controls. Twenty-seven patients were classified as low in clinical insight according to their scores on the 'insight' item (G12) of the Positive and Negative Syndrome Scale (PANSS). Moreover, cognitive insight and ToM were assessed with the Beck Cognitive Insight Scale (BCIS) and the Yoni task, respectively. The results indicated that patients with poor clinical insight performed worse on tasks of second-order cognitive and affective ToM, while the ToM performance of patients with high clinical insight was equivalent to that of healthy controls. Furthermore, while clinical insight was correlated with ToM and clinical symptoms, cognitive insight did not correlate with clinical insight, ToM, or clinical symptoms. Clinical insight thus appears to be an important factor related to ToM in schizophrenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Alarin-induced antidepressant-like effects and their relationship with hypothalamus-pituitary-adrenal axis activity and brain derived neurotrophic factor levels in mice.

    Science.gov (United States)

    Wang, Ming; Chen, Qian; Li, Mei; Zhou, Wei; Ma, Tengfei; Wang, Yun; Gu, Shuling

    2014-06-01

    Alarin is a newly identified member of the galanin family of peptides. Galanin has been shown to exert regulatory effects on depression. Similar to galanin in distribution, alarin is also expressed in the medial amygdala and hypothalamus, i.e., regions interrelated with depression. However, it remains a puzzle whether alarin is involved in depression. Accordingly, we established the depression-like mouse model using behavioral tests to ascertain the possible involvement of alarin, with fluoxetine as a positive control. With the positive antidepressant-like effects of alarin, we further examined its relationship to HPA axis activity and brain-derived neurotrophic factor (BDNF) levels in different brain areas in a chronic unpredictable mild stress (CUMS) paradigm. In the acute studies, alarin produced a dose-related reduction in the immobility duration in tail suspension test (TST) in mice. In the open-field test, intracerebroventricular (i.c.v.) injection of alarin (1.0 nmol) did not impair locomotion or motor coordination in the treated mice. In the CUMS paradigm, alarin administration (1.0 nmol, i.c.v.) significantly improved murine behaviors (FST and locomotor activity), which was associated with a decrease in corticotropin-releasing hormone (CRH) mRNA levels in the hypothalamus, as well as a decline in serum levels of CRH, adrenocorticotropic hormone (ACTH) and corticosterone (CORT), all of which are key hormones of the HPA axis. Furthermore, alarin upregulated BDNF mRNA levels in the prefrontal cortex and hippocampus. These findings suggest that alarin may potentiate the development of new antidepressants, which would be further secured with the identification of its receptor(s). Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Enhanced motivation for food reward induced by stress and attenuation by corticotrophin-releasing factor receptor antagonism in rats: implications for overeating and obesity.

    Science.gov (United States)

    Liu, Xiu

    2015-06-01

    Overeating beyond individuals' homeostatic needs critically contributes to obesity. The neurobehavioral mechanisms underlying the motivation to consume excessive foods with high calories are not fully understood. The present study examined whether a pharmacological stressor, yohimbine, enhances the motivation to procure food reward with an emphasis on comparisons between standard lab chow and high-fat foods. The effects of corticotropin-releasing factor (CRF) receptor blockade by a CRF1-selective antagonist NBI on the stress-enhanced motivation for food reward were also assessed. Male Sprague-Dawley rats with chow available ad libitum in their home cages were trained to press a lever under a progressive ratio schedule for deliveries of either standard or high-fat food pellets. For testing yohimbine stress effects, rats received an intraperitoneal administration of yohimbine 10 min before start of the test sessions. For testing effects of CRF1 receptor blockade on stress responses, NBI was administered 20 min prior to yohimbine challenge. The rats emitted higher levels of lever responses to procure the high-fat food pellets compared with their counterparts on standard food pellets. Yohimbine challenge facilitated lever responses for the reward in all of the rats, whereas the effect was more robust in the rats on high-fat food pellets compared with their counterparts on standard food pellets. An inhibitory effect of pretreatment with NBI was observed on the enhancing effect of yohimbine challenge but not on the responses under baseline condition without yohimbine administration. Stress challenge significantly enhanced the motivation of satiated rats to procure extra food reward, especially the high-fat food pellets. Activation of CRF1 receptors is required for the stress-enhanced motivation for food reward. These results may have implications for our better understanding of the biobehavioral mechanisms of overeating and obesity.

  12. Factors affecting domestic water consumption in rural households upon access to improved water supply: insights from the Wei River Basin, China

    NARCIS (Netherlands)

    Fan, L.; Liu, G.; Wang, F.; Geissen, V.; Ritsema, C.J.

    2013-01-01

    Comprehensively understanding water consumption behavior is necessary to design efficient and effective water use strategies. Despite global efforts to identify the factors that affect domestic water consumption, those related to domestic water use in rural regions have not been sufficiently

  13. Further structural insights into the binding of complement factor H by complement regulator-acquiring surface protein 1 (CspA) of Borrelia burgdorferi

    International Nuclear Information System (INIS)

    Caesar, Joseph J. E.; Wallich, Reinhard; Kraiczy, Peter; Zipfel, Peter F.; Lea, Susan M.

    2013-01-01

    B. burgdorferi binds complement factor H using a dimeric surface protein, CspA (BbCRASP-1). Presented here is a new structure of CspA that suggests that there is a degree of flexibility between subunits which may have implications for complement regulator binding. Borrelia burgdorferi has evolved many mechanisms of evading the different immune systems across its range of reservoir hosts, including the capture and presentation of host complement regulators factor H and factor H-like protein-1 (FHL-1). Acquisition is mediated by a family of complement regulator-acquiring surface proteins (CRASPs), of which the atomic structure of CspA (BbCRASP-1) is known and shows the formation of a homodimeric species which is required for binding. Mutagenesis studies have mapped a putative factor H binding site to a cleft between the two subunits. Presented here is a new atomic structure of CspA which shows a degree of flexibility between the subunits which may be critical for factor H scavenging by increasing access to the binding interface and allows the possibility that the assembly can clamp around the bound complement regulators

  14. The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

    Science.gov (United States)

    de Chassey, Benoît; Aublin-Gex, Anne; Ruggieri, Alessia; Meyniel-Schicklin, Laurène; Pradezynski, Fabrine; Davoust, Nathalie; Chantier, Thibault; Tafforeau, Lionel; Mangeot, Philippe-Emmanuel; Ciancia, Claire; Perrin-Cocon, Laure; Bartenschlager, Ralf; André, Patrice; Lotteau, Vincent

    2013-01-01

    Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

  15. The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

    Directory of Open Access Journals (Sweden)

    Benoît de Chassey

    Full Text Available Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1 appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

  16. Analysis of DNA binding by human factor xeroderma pigmentosum complementation group A (XPA) provides insight into its interactions with nucleotide excision repair substrates.

    Science.gov (United States)

    Sugitani, Norie; Voehler, Markus W; Roh, Michelle S; Topolska-Woś, Agnieszka M; Chazin, Walter J

    2017-10-13

    Xeroderma pigmentosum (XP) complementation group A (XPA) is an essential scaffolding protein in the multiprotein nucleotide excision repair (NER) machinery. The interaction of XPA with DNA is a core function of this protein; a number of mutations in the DNA-binding domain (DBD) are associated with XP disease. Although structures of the central globular domain of human XPA and data on binding of DNA substrates have been reported, the structural basis for XPA's DNA-binding activity remains unknown. X-ray crystal structures of the central globular domain of yeast XPA (Rad14) with lesion-containing DNA duplexes have provided valuable insights, but the DNA substrates used for this study do not correspond to the substrates of XPA as it functions within the NER machinery. To better understand the DNA-binding activity of human XPA in NER, we used NMR to investigate the interaction of its DBD with a range of DNA substrates. We found that XPA binds different single-stranded/double-stranded junction DNA substrates with a common surface. Comparisons of our NMR-based mapping of binding residues with the previously reported Rad14-DNA crystal structures revealed similarities and differences in substrate binding between XPA and Rad14. This includes direct evidence for DNA contacts to the residues extending C-terminally from the globular core, which are lacking in the Rad14 construct. Moreover, mutation of the XPA residue corresponding to Phe-262 in Rad14, previously reported as being critical for DNA binding, had only a moderate effect on the DNA-binding activity of XPA. The DNA-binding properties of several disease-associated mutations in the DBD were investigated. These results suggest that for XPA mutants exhibiting altered DNA-binding properties, a correlation exists between the extent of reduction in DNA-binding affinity and the severity of symptoms in XP patients. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. 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. Copyright © 2014 the authors 0270-6474/14/3411316-09$15.00/0.

  18. Biological insights into the expression of translation initiation factors from recombinant CHOK1SV cell lines and their relationship to enhanced productivity.

    Science.gov (United States)

    Mead, Emma J; Masterton, Rosalyn J; Feary, Marc; Obrezanova, Olga; Zhang, Lin; Young, Robert; Smales, C Mark

    2015-12-15

    Translation initiation is on the critical pathway for the production of monoclonal antibodies (mAbs) by mammalian cells. Formation of a closed loop structure comprised of mRNA, a number of eukaryotic initiation factors (eIFs) and ribosomal proteins has been proposed to aid re-initiation of translation and therefore increase global translational efficiency. We have determined mRNA and protein levels of the key components of the closed loop, eIFs (eIF3a, eIF3b, eIF3c, eIF3h, eIF3i and eIF4G1), poly(A)-binding protein (PABP) 1 and PABP-interacting protein 1 (PAIP1), across a panel of 30 recombinant mAb-producing GS-CHOK1SV cell lines with a broad range of growth characteristics and production levels of a model recombinant mAb. We have used a multi-level statistical approach to investigate the relationship between key performance indicators (cell growth and recombinant antibody productivity) and the intracellular amounts of target translation initiation factor proteins and the mRNAs encoding them. We show that high-producing cell lines maintain amounts of the translation initiation factors involved in the formation of the closed loop mRNA, maintaining these proteins at appropriate levels to deliver enhanced recombinant protein production. We then utilize knowledge of the amounts of these factors to build predictive models for and use cluster analysis to identify, high-producing cell lines. The present study therefore defines the translation initiation factor amounts that are associated with highly productive recombinant GS-CHOK1SV cell lines that may be targets for screening highly productive cell lines or to engineer new host cell lines with the potential for enhanced recombinant antibody productivity. © 2015 Authors; published by Portland Press Limited.

  19. How do individuals cope with stress? Behavioural, physiological and neuronal differences between proactive and reactive coping styles in fish

    DEFF Research Database (Denmark)

    Vindas, Marco A; Gorissen, Marnix; Höglund, Erik

    2017-01-01

    of the 5-HT1A receptor abundance) in the proposed amygdala homologue (Dm), increased expression of the neuroplasticity marker brain derived neurotropic factor (bdnf) in both Dl and Vv (lateral septum homologue), as well as increased expression of the corticotropin releasing factor 1 (crf1) receptor...

  20. Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances.

    NARCIS (Netherlands)

    Wang, S.S.; Kamphuis, W.; Huitinga, I.; Zhou, J.N.; Swaab, D.F.

    2008-01-01

    Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors

  1. Origin of red pelagic carbonates as an interplay of global climate and local basin factors: Insight from the Lower Devonian of the Prague Basin, Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Bábek, O.; Faměra, Martin; Hladil, Jindřich; Kapusta, J.; Weinerová, Hedvika; Šimíček, D.; Slavík, Ladislav; Ďurišová, Jana

    2018-01-01

    Roč. 364, FEB (2018), s. 71-88 ISSN 0037-0738 R&D Projects: GA ČR(CZ) GA14-18183S Institutional support: RVO:61388980 ; RVO:67985831 Keywords : Bottom redox conditions * Geochemistry * Palaeoceanography * Spectral reflectance * Pragian stage * Red pelagic carbonates * Trophic levels Subject RIV: DD - Geochemistry; DB - Geology ; Mineralogy (GLU-S) OBOR OECD: Geology; Mineralogy (GLU-S) Impact factor: 2.373, year: 2016

  2. Proofs that Develop Insight

    Science.gov (United States)

    Weber, Keith

    2010-01-01

    Many mathematics educators have noted that mathematicians do not only read proofs to gain conviction but also to obtain insight. The goal of this article is to discuss what this insight is from mathematicians' perspective. Based on interviews with nine research-active mathematicians, two sources of insight are discussed. The first is reading a…

  3. New insight in the derivation of amplification factor by taking into account soil parameters. In : Proceedings of the 16th World Conference on Earthquake Engineering

    OpenAIRE

    ZENDAGUI, Djawad; STAMBOULI BOUDGHENE, Ahmed; BARD, Pierre Yves; DERRAS, Boumédiène

    2017-01-01

    It is currently admitted that the amplification factor (AF) is one of the best tools to describe site effects. AF depends on soil parameters that are derived from the geometrical and mechanical soil properties of the soil profile. Thus, it is important to identify which soil parameters shape the form of the AF. The aim of this paper is to measure the effects of various site parameters on the variation of AF. As the problem is highly complex, a tool using the GRNN (Generalized Regression Neura...

  4. In Psycho-Spiritual Integrative Therapy for Women with Primary Breast Cancer, What Factors Account for the Benefits? Insights from a Multiple Case Analysis

    Directory of Open Access Journals (Sweden)

    John Rettger

    2015-05-01

    Full Text Available This study sought to understand the context in which Psycho-Spiritual Integrative Therapy (PSIT, a group intervention, promotes varying degrees of spiritual growth and quality of life change in breast cancer survivors. A secondary aim was to explore the relationship between spiritual well-being (SWB and Quality of Life (QL in PSIT participants. A qualitative, multiple case analysis was undertaken to examine the experiences of two participants with the highest change scores on the Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale-Expanded Version (FACIT-Sp-Ex and two participants with among the lowest change scores on this measure. The participant factors thought to contribute to SWB and QL changes included utilization of metacognitive psychological skills and spiritual/religious frameworks, while PSIT factors included application of PSIT core intervention components, cognitive restructuring, group dynamics, and the role of the facilitator. The nature and extent of participant use of spiritual practices appeared to shape the relationship between SWB and OL. The findings suggest directions for future research to investigate potential moderators and mediators of treatment efficacy of PSIT specifically, as well as other psycho-spiritual interventions for cancer survivors more generally.

  5. In Psycho-Spiritual Integrative Therapy for Women with Primary Breast Cancer, What Factors Account for the Benefits? Insights from a Multiple Case Analysis.

    Science.gov (United States)

    Rettger, John; Wall, Kathleen; Corwin, Diana; Davidson, Alexandra N; Lukoff, David; Koopman, Cheryl

    2015-05-12

    This study sought to understand the context in which Psycho-Spiritual Integrative Therapy (PSIT), a group intervention, promotes varying degrees of spiritual growth and quality of life change in breast cancer survivors. A secondary aim was to explore the relationship between spiritual well-being (SWB) and Quality of Life (QL) in PSIT participants. A qualitative, multiple case analysis was undertaken to examine the experiences of two participants with the highest change scores on the Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale-Expanded Version (FACIT-Sp-Ex) and two participants with among the lowest change scores on this measure. The participant factors thought to contribute to SWB and QL changes included utilization of metacognitive psychological skills and spiritual/religious frameworks, while PSIT factors included application of PSIT core intervention components, cognitive restructuring, group dynamics, and the role of the facilitator. The nature and extent of participant use of spiritual practices appeared to shape the relationship between SWB and OL. The findings suggest directions for future research to investigate potential moderators and mediators of treatment efficacy of PSIT specifically, as well as other psycho-spiritual interventions for cancer survivors more generally.

  6. Insights from the design and implementation of a single-entry model of referral for total joint replacement surgery: Critical success factors and unanticipated consequences.

    Science.gov (United States)

    Damani, Zaheed; MacKean, Gail; Bohm, Eric; Noseworthy, Tom; Wang, Jenney Meng Han; DeMone, Brie; Wright, Brock; Marshall, Deborah A

    2018-02-01

    Single-entry models (SEMs) in healthcare allow patients to see the next-available provider and have been shown to improve waiting times, access and patient flow for preference-sensitive, scheduled services. The Winnipeg Central Intake Service (WCIS) for hip and knee replacement surgery was implemented to improve access in the Winnipeg Regional Health Authority. This paper describes the system's design/implementation; successes, challenges, and unanticipated consequences. On two occasions, during and following implementation, we interviewed all members of the WCIS project team, including processing engineers, waiting list coordinators, administrators and policy-makers regarding their experiences. We used semi-structured telephone interviews to collect data and qualitative thematic analysis to analyze and interpret the findings. Respondents indicated that the overarching objectives of the WCIS were being met. Benefits included streamlined processes, greater patient access, improved measurement and monitoring of outcomes. Challenges included low awareness, change readiness, and initial participation among stakeholders. Unanticipated consequences included workload increases, confusion around stakeholder expectations and under-reporting of data by surgeons' offices. Critical success factors for implementation included a requirement for clear communication, robust data collection, physician leadership and patience by all, especially implementation teams. Although successfully implemented, key lessons and critical success factors were learned related to change management, which if considered and applied, can reduce unanticipated consequences, improve uptake and benefit new models of care. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Health-related quality of life in current smokers with COPD: factors associated with current smoking and new insights into sex differences

    Directory of Open Access Journals (Sweden)

    Cheruvu VK

    2016-09-01

    Full Text Available Vinay K Cheruvu,1 Lorriane A Odhiambo,1 Dana S Mowls,2 Melissa D Zullo,1 Abdi T Gudina1 1Department of Biostatistics, Environmental Health Sciences, and Epidemiology, College of Public Health, Kent State University, Kent, OH, 2Department of Biostatistics & Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Abstract: Findings from studies that examined the association between health-related ­quality of life (HRQOL and smoking status among COPD patients have been mixed. Moreover, factors associated with current smoking in COPD patients and differences by sex have not been fully elucidated. Data from the 2011 and 2012 Behavioral Risk Factor Surveillance System was used in this study. Four HRQOL indicators were examined in this study: general health, physical health, mental health, and activity limitations. General health was dichotomized into two groups: “excellent/very good/good” and “fair/poor”, and the other three HRQOL indicators were dichotomized into <14 (infrequent and ≥14 (frequent unhealthy days in the past 30 days. To examine HRQOL indicators in association with current versus former smoking and identify factors associated with current smoking, logistic regression models were used. Sex differences were explored. In COPD patients, current smokers compared to former smokers had significantly poor HRQOL on all subdomains: “fair/poor” general health (adjusted odds ratio [AOR]: 1.2 [95% confidence interval {CI}: 1.1–1.5]; poor physical health (AOR: 1.3 [CI: 1.1–1.5]; poor mental health (AOR: 1.8 [CI: 1.4–2.2]; and poor activity limitations (AOR: 1.5 [CI: 1.3–1.9]. HRQOL subdomains affected by current smoking differed by sex except activity limitations. General health (AOR: 1.5 [CI: 1.1–2.0] and activity limitations (AOR: 1.6 [95% CI: 1.2–2.2] in males and physical health (AOR: 1.3 [CI: 1.0–1.6], mental health (AOR: 2.1 [CI: 1.7–2.6], and activity

  8. Building a Formal Model of a Human-Interactive System: Insights into the Integration of Formal Methods and Human Factors Engineering

    Science.gov (United States)

    Bolton, Matthew L.; Bass, Ellen J.

    2009-01-01

    Both the human factors engineering (HFE) and formal methods communities are concerned with finding and eliminating problems with safety-critical systems. This work discusses a modeling effort that leveraged methods from both fields to use model checking with HFE practices to perform formal verification of a human-interactive system. Despite the use of a seemingly simple target system, a patient controlled analgesia pump, the initial model proved to be difficult for the model checker to verify in a reasonable amount of time. This resulted in a number of model revisions that affected the HFE architectural, representativeness, and understandability goals of the effort. If formal methods are to meet the needs of the HFE community, additional modeling tools and technological developments are necessary.

  9. Factors affecting domestic water consumption in rural households upon access to improved water supply: insights from the Wei River Basin, China.

    Science.gov (United States)

    Fan, Liangxin; Liu, Guobin; Wang, Fei; Geissen, Violette; Ritsema, Coen J

    2013-01-01

    Comprehensively understanding water consumption behavior is necessary to design efficient and effective water use strategies. Despite global efforts to identify the factors that affect domestic water consumption, those related to domestic water use in rural regions have not been sufficiently studied, particularly in villages that have gained access to improved water supply. To address this gap, we investigated 247 households in eight villages in the Wei River Basin where three types of improved water supply systems are implemented. Results show that domestic water consumption in liters per capita per day was significantly correlated with water supply pattern and vegetable garden area, and significantly negatively correlated with family size and age of household head. Traditional hygiene habits, use of water appliances, and preference for vegetable gardening remain dominant behaviors in the villages with access to improved water supply. Future studies on rural domestic water consumption should pay more attention to user lifestyles (water appliance usage habits, outdoor water use) and cultural backgrounds (age, education).

  10. First insights into the mode of action of a "lachrymatory factor synthase"--implications for the mechanism of lachrymator formation in Petiveria alliacea, Allium cepa and Nectaroscordum species.

    Science.gov (United States)

    He, Quan; Kubec, Roman; Jadhav, Abhijit P; Musah, Rabi A

    2011-11-01

    A study of an enzyme that reacts with the sulfenic acid produced by the alliinase in Petiveria alliacea L. (Phytolaccaceae) to yield the P. alliacea lachrymator (phenylmethanethial S-oxide) showed the protein to be a dehydrogenase. It functions by abstracting hydride from sulfenic acids of appropriate structure to form their corresponding sulfines. Successful hydride abstraction is dependent upon the presence of a benzyl group on the sulfur to stabilize the intermediate formed on abstraction of hydride. This dehydrogenase activity contrasts with that of the lachrymatory factor synthase (LFS) found in onion, which catalyzes the rearrangement of 1-propenesulfenic acid to (Z)-propanethial S-oxide, the onion lachrymator. Based on the type of reaction it catalyzes, the onion LFS should be classified as an isomerase and would be called a "sulfenic acid isomerase", whereas the P. alliacea LFS would be termed a "sulfenic acid dehydrogenase". Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Age-related changes of healthy bone marrow cell signaling in response to growth factors provide insight into low risk MDS.

    Science.gov (United States)

    Kornblau, Steven M; Cohen, Aileen C; Soper, David; Huang, Ying-Wen; Cesano, Alessandra

    2014-11-01

    Single Cell Network Profiling (SCNP) is a multiparametric flow cytometry-based assay that quantifiably and simultaneously measures changes in intracellular signaling proteins in response to in vitro extracellular modulators at the single cell level. Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder of hematopoietic stem cells that occurs in elderly subjects and is characterized by dysplasia and ineffective hematopoiesis. The functional responsiveness of MDS bone marrow (BM) hematopoietic cells, including functionally distinct myeloid and erythroid precursor subsets, to hematopoietic growth factors (HGF) and the relationship of modulated signaling to disease characteristics is poorly understood. SCNP was used first to examine the effects of age on erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF)-induced signaling in myeloid, nucleated red blood cells (nRBC), and CD34 expressing cell subsets in healthy BM (n = 15). SCNP was then used to map functional signaling profiles in low risk (LR) MDS (n = 7) for comparison to signaling in samples from healthy donors and to probe signaling associations within clinically defined subgroups. In healthy BM samples, signaling responses to HGF were quite homogeneous (i.e., tightly regulated) with age-dependent effects observed in response to EPO but not to GCSF. Despite the relatively small number of samples assayed in the study, LR MDS could be classified into distinct subgroups based on both cell subset frequency and signaling profiles. As a correlate of underlying genetic abnormalities, signal transduction analyses may provide a functional and potentially clinically relevant classification of MDS. Further evaluation in a larger cohort is warranted. © 2013 Clinical Cytometry Society.

  12. First genome-wide association study in an Australian aboriginal population provides insights into genetic risk factors for body mass index and type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Denise Anderson

    Full Text Available A body mass index (BMI >22kg/m2 is a risk factor for type 2 diabetes (T2D in Aboriginal Australians. To identify loci associated with BMI and T2D we undertook a genome-wide association study using 1,075,436 quality-controlled single nucleotide polymorphisms (SNPs genotyped (Illumina 2.5M Duo Beadchip in 402 individuals in extended pedigrees from a Western Australian Aboriginal community. Imputation using the thousand genomes (1000G reference panel extended the analysis to 6,724,284 post quality-control autosomal SNPs. No associations achieved genome-wide significance, commonly accepted as P45,000 years ago. The top hit (rs10868204 Pgenotyped = 1.50x10-6; rs11140653 Pimputed_1000G = 2.90x10-7 for BMI lies 5' of NTRK2, the type 2 neurotrophic tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF that regulates energy balance downstream of melanocortin-4 receptor (MC4R. PIK3C2G (rs12816270 Pgenotyped = 8.06x10-6; rs10841048 Pimputed_1000G = 6.28x10-7 was associated with BMI, but not with T2D as reported elsewhere. BMI also associated with CNTNAP2 (rs6960319 Pgenotyped = 4.65x10-5; rs13225016 Pimputed_1000G = 6.57x10-5, previously identified as the strongest gene-by-environment interaction for BMI in African-Americans. The top hit (rs11240074 Pgenotyped = 5.59x10-6, Pimputed_1000G = 5.73x10-6 for T2D lies 5' of BCL9 that, along with TCF7L2, promotes beta-catenin's transcriptional activity in the WNT signaling pathway. Additional hits occurred in genes affecting pancreatic (KCNJ6, KCNA1 and/or GABA (GABRR1, KCNA1 functions. Notable associations observed for genes previously identified at genome-wide significance in other populations included MC4R (Pgenotyped = 4.49x10-4 for BMI and IGF2BP2 Pimputed_1000G = 2.55x10-6 for T2D. Our results may provide novel functional leads in understanding disease pathogenesis in this Australian Aboriginal population.

  13. Insights into iron and nuclear factor-kappa B (NF-kappaB) involvement in chronic inflammatory processes in peritoneal endometriosis.

    Science.gov (United States)

    Defrère, Sylvie; González-Ramos, Reinaldo; Lousse, Jean-Christophe; Colette, Sébastien; Donnez, Olivier; Donnez, Jacques; Van Langendonckt, Anne

    2011-08-01

    Endometriosis is a chronic pelvic inflammatory process. Local inflammation is known to play a role in pain and infertility associated with the disease, and may be extensively involved in molecular and cellular processes leading to endometriosis development. In this review, we focus on two inflammatory mediators clearly implicated in the pathogenesis of endometriosis, iron and NF-kappaB, and their potential association. Iron is essential for all living organisms, but excess iron results in toxicity and is linked to pathological disorders. In endometriosis patients, iron overload has been demonstrated in the different compartments of the peritoneal cavity (peritoneal fluid, endometriotic lesions, peritoneum and macrophages). This iron overload affects numerous mechanisms involved in endometriosis development. Moreover, iron can generate free radical species able to react with a wide range of cellular constituents, inducing cellular damage. Overproduction of reactive oxygen species also impairs cellular function by altering gene expression via regulation of redox-sensitive transcription factors such as NF-kappaB, which is clearly implicated in endometriosis. Indeed, NF-kappaB is activated in endometriotic lesions and peritoneal macrophages of endometriosis patients, which stimulates synthesis of proinflammatory cytokines, generating a positive feedback loop in the NF-kappaB pathway. NF-kappaB-mediated gene transcription promotes a variety of processes, including endometriotic lesion establishment, maintenance and development. In conclusion, iron and NF-kappaB appear to be linked and both are clearly involved in endometriosis development, making these pathways an attractive target for future treatment and prevention of this disease.

  14. A new analysis approach of epidermal growth factor receptor pathway activation patterns provides insights into cetuximab resistance mechanisms in head and neck cancer

    Directory of Open Access Journals (Sweden)

    von der Heyde Silvia

    2012-05-01

    Full Text Available Abstract The pathways downstream of the epidermal growth factor receptor (EGFR have often been implicated to play crucial roles in the development and progression of various cancer types. Different authors have proposed models in cell lines in which they study the modes of pathway activities after perturbation experiments. It is prudent to believe that a better understanding of these pathway activation patterns might lead to novel treatment concepts for cancer patients or at least allow a better stratification of patient collectives into different risk groups or into groups that might respond to different treatments. Traditionally, such analyses focused on the individual players of the pathways. More recently in the field of systems biology, a plethora of approaches that take a more holistic view on the signaling pathways and their downstream transcriptional targets has been developed. Fertig et al. have recently developed a new method to identify patterns and biological process activity from transcriptomics data, and they demonstrate the utility of this methodology to analyze gene expression activity downstream of the EGFR in head and neck squamous cell carcinoma to study cetuximab resistance. Please see related article: http://www.biomedcentral.com/1471-2164/13/160

  15. Factors affecting domestic water consumption in rural households upon access to improved water supply: insights from the Wei River Basin, China.

    Directory of Open Access Journals (Sweden)

    Liangxin Fan

    Full Text Available Comprehensively understanding water consumption behavior is necessary to design efficient and effective water use strategies. Despite global efforts to identify the factors that affect domestic water consumption, those related to domestic water use in rural regions have not been sufficiently studied, particularly in villages that have gained access to improved water supply. To address this gap, we investigated 247 households in eight villages in the Wei River Basin where three types of improved water supply systems are implemented. Results show that domestic water consumption in liters per capita per day was significantly correlated with water supply pattern and vegetable garden area, and significantly negatively correlated with family size and age of household head. Traditional hygiene habits, use of water appliances, and preference for vegetable gardening remain dominant behaviors in the villages with access to improved water supply. Future studies on rural domestic water consumption should pay more attention to user lifestyles (water appliance usage habits, outdoor water use and cultural backgrounds (age, education.

  16. Modeling the diversity of spontaneous and agonist-induced electrical activity in anterior pituitary corticotrophs

    Czech Academy of Sciences Publication Activity Database

    Fletcher, P. A.; Zemková, Hana; Stojilkovic, S. S.; Sherman, A.

    2017-01-01

    Roč. 117, č. 6 (2017), s. 2298-2311 ISSN 0022-3077 R&D Projects: GA ČR(CZ) GA16-12695S Institutional support: RVO:67985823 Keywords : corticotrophs * corticotropin-releasing hormone * vasopressin * action potentials * ion channels Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 2.396, year: 2016

  17. Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation

    NARCIS (Netherlands)

    Atsak, P.; Hauer, D.; Campolongo, P.; Schelling, G.; Fornari, R.V.; Roozendaal, B.

    2015-01-01

    Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory

  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 uncharacterized...

  19. CRFR1 is expressed on pancreatic beta cells, promotes beta cell proliferation, and potentiates insulin secretion in a glucose-dependent manner

    DEFF Research Database (Denmark)

    Huising, Mark O; van der Meulen, Talitha; Vaughan, Joan M

    2009-01-01

    Corticotropin-releasing factor (CRF), originally characterized as the principal neuroregulator of the hypothalamus-pituitary-adrenal axis, has broad central and peripheral distribution and actions. We demonstrate the presence of CRF receptor type 1 (CRFR1) on primary beta cells and show that acti...

  20. Chronic stress and comfort foods: self-medication and abdominal obesity

    NARCIS (Netherlands)

    Dallman, Mary F.; Pecoraro, Norman C.; la Fleur, Susanne E.

    2005-01-01

    Central corticotropin-releasing factor (CRF) networks are recruited by chronic stressors and elevated glucocorticoids (GCs) that initiate recruitment of central CRF activity in the amygdala. Increased central activity of the CRF network stimulates all monoaminergic cell groups, as well as premotor

  1. Peripheral a-helical CRF (9-41) does not reverse stress-induced mast cell dependent visceral hypersensitivity in maternally separated rats

    NARCIS (Netherlands)

    van den Wijngaard, R. M.; Stanisor, O. I.; van Diest, S. A.; Welting, O.; Wouters, M. M.; de Jonge, W. J.; Boeckxstaens, G. E.

    2012-01-01

    Background Acute stress-induced hypersensitivity to colorectal distention was shown to depend on corticotropin releasing factor (CRF)-induced mast cell degranulation. At present it remains unclear whether CRF also induces chronic poststress activation of these cells. Accordingly, the objective of

  2. Structural Insight Into the Role of Mutual Polymorphism and Conservatism in the Contact Zone of the NFR5-K1 Heterodimer With the Nod Factor.

    Science.gov (United States)

    Igolkina, A A; Porozov, Yu B; Chizhevskaya, E P; Andronov, E E

    2018-01-01

    Sandwich-like docking configurations of the heterodimeric complex of NFR5 and K1 Vicia sativa receptor-like kinases together with the putative ligand, Nod factor (NF) of Rhizobium leguminosarum bv. viciae , were modeled and two of the most probable configurations were assessed through the analysis of the mutual polymorphisms and conservatism. We carried out this analysis based on the hypothesis that in a contact zone of two docked components (proteins or ligands) the population polymorphism or conservatism is mutual, i.e., the variation in one component has a reflected variation in the other component. The population material of 30 wild-growing V. sativa (leaf pieces) was collected from a large field (uncultivated for the past 25-years) and pooled; form this pool, 100 randomly selected cloned fragments of NFR5 gene and 100 of K1 gene were sequenced by the Sanger method. Congruence between population trees of NFR5 and K1 haplotypes allowed us to select two respective haplotypes, build their 3D structures, and perform protein-protein docking. In a separate simulation, the protein-ligand docking between NFR5 and NF was carried out. We merged the results of the two docking experiments and extracted NFR5-NF-K1 complexes, in which NF was located within the cavity between two receptors. Molecular dynamics simulations indicated two out of six complexes as stable. Regions of mutual polymorphism in the contact zone of one complex overlapped with known NF structural variations produced by R. leguminosarum bv. viciae . A total of 74% of the contact zone of another complex contained mutually polymorphic and conservative areas. Common traits of the obtained two stable structures allowed us to hypothesize the functional role of three-domain structure of plant LysM-RLKs in their heteromers.

  3. Structural Insight Into the Role of Mutual Polymorphism and Conservatism in the Contact Zone of the NFR5–K1 Heterodimer With the Nod Factor

    Directory of Open Access Journals (Sweden)

    A. A. Igolkina

    2018-04-01

    Full Text Available Sandwich-like docking configurations of the heterodimeric complex of NFR5 and K1 Vicia sativa receptor-like kinases together with the putative ligand, Nod factor (NF of Rhizobium leguminosarum bv. viciae, were modeled and two of the most probable configurations were assessed through the analysis of the mutual polymorphisms and conservatism. We carried out this analysis based on the hypothesis that in a contact zone of two docked components (proteins or ligands the population polymorphism or conservatism is mutual, i.e., the variation in one component has a reflected variation in the other component. The population material of 30 wild-growing V. sativa (leaf pieces was collected from a large field (uncultivated for the past 25-years and pooled; form this pool, 100 randomly selected cloned fragments of NFR5 gene and 100 of K1 gene were sequenced by the Sanger method. Congruence between population trees of NFR5 and K1 haplotypes allowed us to select two respective haplotypes, build their 3D structures, and perform protein–protein docking. In a separate simulation, the protein-ligand docking between NFR5 and NF was carried out. We merged the results of the two docking experiments and extracted NFR5–NF–K1 complexes, in which NF was located within the cavity between two receptors. Molecular dynamics simulations indicated two out of six complexes as stable. Regions of mutual polymorphism in the contact zone of one complex overlapped with known NF structural variations produced by R. leguminosarum bv. viciae. A total of 74% of the contact zone of another complex contained mutually polymorphic and conservative areas. Common traits of the obtained two stable structures allowed us to hypothesize the functional role of three-domain structure of plant LysM-RLKs in their heteromers.

  4. Insight into the heterogeneous adsorption of humic acid fluorescent components on multi-walled carbon nanotubes by excitation-emission matrix and parallel factor analysis.

    Science.gov (United States)

    Yang, Chenghu; Liu, Yangzhi; Cen, Qiulin; Zhu, Yaxian; Zhang, Yong

    2018-02-01

    The heterogeneous adsorption behavior of commercial humic acid (HA) on pristine and functionalized multi-walled carbon nanotubes (MWCNTs) was investigated by fluorescence excitation-emission matrix and parallel factor (EEM- PARAFAC) analysis. The kinetics, isotherms, thermodynamics and mechanisms of adsorption of HA fluorescent components onto MWCNTs were the focus of the present study. Three humic-like fluorescent components were distinguished, including one carboxylic-like fluorophore C1 (λ ex /λ em = (250, 310) nm/428nm), and two phenolic-like fluorophores, C2 (λ ex /λ em = (300, 460) nm/552nm) and C3 (λ ex /λ em = (270, 375) nm/520nm). The Lagergren pseudo-second-order model can be used to describe the adsorption kinetics of the HA fluorescent components. In addition, both the Freundlich and Langmuir models can be suitably employed to describe the adsorption of the HA fluorescent components onto MWCNTs with significantly high correlation coefficients (R 2 > 0.94, Padsorption affinity (K d ) and nonlinear adsorption degree from the HA fluorescent components to MWCNTs was clearly observed. The adsorption mechanism suggested that the π-π electron donor-acceptor (EDA) interaction played an important role in the interaction between HA fluorescent components and the three MWCNTs. Furthermore, the values of the thermodynamic parameters, including the Gibbs free energy change (ΔG°), enthalpy change (ΔH°) and entropy change (ΔS°), showed that the adsorption of the HA fluorescent components on MWCNTs was spontaneous and exothermic. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Insights into the therapeutic potential of hypoxia-inducible factor-1α small interfering RNA in malignant melanoma delivered via folate-decorated cationic liposomes

    Directory of Open Access Journals (Sweden)

    Chen Z

    2016-03-01

    Full Text Available Zhongjian Chen,1,* Tianpeng Zhang,2,* Baojian Wu,2 Xingwang Zhang2 1Department of Pharmaceutics, Shanghai Dermatology Hospital, 2Division of Pharmaceutics, College of Pharmacy, Jinan University, Gangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Malignant melanoma (MM represents the most dangerous form of skin cancer, and its incidence is expected to rise in the coming time. However, therapy for MM is limited by low topical drug concentration and multidrug resistance. This article aimed to develop folate-decorated cationic liposomes (fc-LPs for hypoxia-inducible factor-1α (HIF-1α small interfering (siRNA delivery, and to evaluate the potential of such siRNA/liposome complexes in MM therapy. HIF-1α siRNA-loaded fc-LPs (siRNA-fc-LPs were prepared by a film hydration method followed by siRNA incubation. Folate decoration of liposomes was achieved by incorporation of folate/oleic acid-diacylated oligochitosans. The resulting siRNA-fc-LPs were 95.3 nm in size with a ζ potential of 2.41 mV. The liposomal vectors exhibited excellent loading capacity and protective effect toward siRNA. The in vitro cell transfection efficiency was almost parallel to the commercially available Lipofectamine™ 2000. Moreover, the anti-melanoma activity of HIF-1α siRNA was significantly enhanced through fc-LPs. Western blot analysis and apoptosis test demonstrated that siRNA-fc-LPs substantially reduced the production of HIF-1α-associated protein and induced the apoptosis of hypoxia-tolerant melanoma cells. Our designed liposomal vectors might be applicable as siRNA delivery vehicle to systemically or topically treat MM. Keywords: malignant melanoma, HIF-1α siRNA, chitosan, cationic liposomes, gene therapy

  6. Factors influencing uptake of pre-exposure prophylaxis: some qualitative insights from an intervention study of men who have sex with men in China.

    Science.gov (United States)

    Liu, Chunxing; Ding, Yingying; Ning, Zhen; Gao, Meiyang; Liu, Xing; Wong, Frank Y; He, Na

    2018-02-01

    Pre-exposure prophylaxis (PrEP) is a biomedical approach for preventing the acquisition of HIV in populations at substantial risk for HIV. However, its uptake among men who have sex with men (MSM) is low in China. The study aimed to identify factors that might influence MSM's uptake and use of PrEP. In-depth interviews were conducted with 32 self-identified MSM from a PrEP intervention study evaluating daily oral tenofovir disoproxil fumarate (TDF) to prevent HIV infection. Of these men, 11 were presently using the 'TDF' group; 8 from the 'change-over' group (i.e. initially used PrEP but subsequently quitted); and 13 from the non-user group. Data were analysed using thematic approach. Perception of low HIV risk, mistrust of the national PrEP program, and concerns of side effects were the main reasons for not wanting to use PrEP. Also, lack of main sexual partner's support, difficulties in adhering to the daily TDF regimen, and the inconvenient schedules in securing the medicine were the major reasons for not wanting to use or quitting the use of PrEP. On the other hand, perceived high HIV risk, beliefs in efficacy of PrEP, and worries of transmitting HIV to families were the major motives for PrEP uptake. Findings suggest that PrEP implementation strategies should first address issues including but not limited to accurate self-assessment of HIV risk, mistrust and limited knowledge about medical trials and PrEP, and ease of accessing PrEP.

  7. The structural insights of stem cell factor receptor (c-Kit interaction with tyrosine phosphatase-2 (Shp-2: An in silico analysis

    Directory of Open Access Journals (Sweden)

    Gurudutta Gangenahalli U

    2010-01-01

    Full Text Available Abstract Background Stem cell factor (SCF receptor c-Kit is recognized as a key signaling molecule, which transduces signals for the proliferation, differentiation and survival of stem cells. Binding of SCF to its receptor triggers transactivation, leading to the recruitment of kinases and phosphatases to the docking platforms of c-Kit catalytic domain. Tyrosine phosphatase-1 (Shp-1 deactivates/attenuates 'Kit' kinase activity. Whereas, Asp816Val mutation in the Kit activation loop transforms kinase domain to a constitutively activated state (switch off-to-on state, in a ligand-independent manner. This phenomenon completely abrogates negative regulation of Shp-1. To predict the possible molecular basis of interaction between c-Kit and Shp-1, we have performed an in silico protein-protein docking study between crystal structure of activated c-Kit (phosphorylated c-Kit and full length crystal structure of Shp-2, a close structural counterpart of Shp-1. Findings Study revealed a stretch of conserved amino acids (Lys818 to Ser821 in the Kit activation domain, which makes decisive H-bonds with N-sh2 and phosphotyrosine binding pocket residues of the phosphatase. These H-bonds may impose an inhibitory steric hindrance to the catalytic domain of c-Kit, there by blocking further interaction of the activation loop molecules with incoming kinases. We have also predicted a phosphotyrosine binding pocket in SH2 domains of Shp-1, which is found to be predominantly closer to a catalytic groove like structure in c-Kit kinase domain. Conclusions This study predicts that crucial hydrogen bonding between N-sh2 domain of Shp-1 and Kit activation loop can modulate the negative regulation of c-Kit kinase by Shp-1. Thus, this finding is expected to play a significant role in designing suitable gain-of-function c-Kit mutants for inducing conditional proliferation of hematopoietic stem cells.

  8. Glycaemic control and cardiovascular risk factor management in patients with diabetes with and without coronary artery disease: insights from the diabetes mellitus status in Canada survey.

    Science.gov (United States)

    Grenier, Jasmine; Leiter, Lawrence A; Langer, Anatoly; Goldin, Lianne; Teoh, Hwee; Connelly, Kim A; Cheng, Alice Y Y; Tan, Mary K; Fitchett, David; McGuire, Darren K; Goodman, Shaun G; Yan, Andrew T

    2016-10-01

    Current diabetes guidelines recommend an individualized approach to glycaemic control. There are limited data on the contemporary and comprehensive management of patients with diabetes in relation to coronary artery disease (CAD). The Diabetes Mellitus Status in Canada (DM-SCAN) survey included 5123 patients with type 2 diabetes seen in primary care in November 2012. Primary care physicians (PCPs) collected clinical data and specified the A1C target for each patient on standardized forms. We compared management strategies and achievement of treatment targets in patients with and without CAD. Among the 4994 patients with data on CAD history, 22.5% had CAD. Primary care physicians were more likely to select a higher A1C target for patients with CAD (≤7.5 or ≤8.0%) versus without (≤7.0%). There was no difference in median A1C or in the proportion of patients with A1C ≤7.0% between the two groups. Compared with the group without known CAD, patients with CAD had a higher reported prevalence of hypoglycaemia in the preceding 6 months; more frequently received aspirin, statins, ACE inhibitors, or angiotensin receptor blockers, and were more likely to achieve blood pressure and low-density lipoprotein-cholesterol targets. Only 15.4 and 12.0% of patients with and without CAD (P = 0.002), respectively, achieved all three guideline-recommended targets. Compared with patients with diabetes without CAD, those with CAD more frequently had a less stringent A1C target selected by their PCPs but achieved similar glycaemic control. Overall, risk factor management remained suboptimal in both groups. There remains an important opportunity to improve the care and outcome of patients with diabetes.

  9. Sex Differences in Demographics, Risk Factors, Presentation, and Noninvasive Testing in Stable Outpatients with Suspected Coronary Artery Disease: Insights from the PROMISE Trial

    Science.gov (United States)

    Hemal, Kshipra; Pagidipati, Neha J.; Coles, Adrian; Dolor, Rowena J.; Mark, Daniel B.; Pellikka, Patricia A.; Hoffmann, Udo; Litwin, Sheldon E.; Daubert, Melissa A.; Shah, Svati H.; Ariani, Kevin; Bullock-Palmer, Renee; Martinez, Beth; Lee, Kerry L.; Douglas, Pamela S.

    2016-01-01

    STRUCTURED ABSTRACT Objectives To determine whether presentation, risk assessment, testing choices, and results differ by sex in stable symptomatic outpatients with suspected coronary artery disease (CAD). Background Although established CAD presentations differ by sex, little is known about stable, suspected CAD. Methods Characteristics of 10,003 men and women in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial were compared using chi-square and Wilcoxon rank sum tests. Sex differences in test selection and predictors of test positivity were examined using logistic regression. Results Women were older (62.4 years vs. 59.0) and more likely to be hypertensive (66.6% vs. 63.2%), dyslipidemic (68.9% vs. 66.3%), and to have a family history of premature CAD (34.6% vs. 29.3) (all p-values<0.005). Women were less likely to smoke (45.6% vs. 57.0%; p<0.001), while diabetes prevalence was similar (21.8% vs. 21.0%; p=0.30). Chest pain was the primary symptom in 73.2% of women vs. 72.3% of men (p=0.30) and was characterized as “crushing/pressure/squeezing/tightness” in 52.5% of women vs. 46.2% of men (p<0.001). Compared to men, all risk scores characterized women as lower risk, and providers were more likely to characterize women as having low (<30%) pre-test probability for CAD (40.7% vs. 34.1%; p<0.001). Compared with men, women were more often referred to imaging tests (adjusted OR 1.21; 95% CI 1.01–1.44) than non-imaging tests. Women were less likely to have a positive test (9.7% vs. 15.1%; p<0.001). Although univariate predictors of test positivity were similar, in multivariable models, age, BMI, and Framingham risk score were predictive of a positive test in women, while Framingham and Diamond and Forrester risk scores were predictive in men. Conclusion Patient sex influences the entire diagnostic pathway for possible CAD, from baseline risk factors and presentation to noninvasive test outcomes. These differences highlight the

  10. The relationship between insight and psychosis in state patients with ...

    African Journals Online (AJOL)

    Objective. State patients committed under the Mental Health Act must have insight into their illness and the crime they committed before they can be discharged. Patients with schizophrenia are described as having poor insight into the nature and severity of their disorder. Various factors influence insight, and in some studies ...

  11. In Search of Insight.

    Science.gov (United States)

    Kaplan, Craig A.; Simon, Herbert A.

    1990-01-01

    Attaining the insight needed to solve the Mutilated Checkerboard problem, which requires discovery of an effective problem representation (EPR), is described. Performance on insight problems can be predicted from the availability of generators and constraints in the search for an EPR. Data for 23 undergraduates were analyzed. (TJH)

  12. Course of insight in manic episode

    Directory of Open Access Journals (Sweden)

    A Kumar

    2013-01-01

    Full Text Available Background: Insight is an important factor associated with non compliance and poor outcome. Poor level of insight has been described as a characteristic in patients with acute bipolar disorder with more unawareness in social consequences with increasing severity in manic episode. Aim: Main aim of study was to see the baseline and longitudinal relationship between dimensions of insight with improvement in psychopathology. Setting and Design: Forty four patients diagnosed with mania, were selected from an inpatient setting at Institute of Mental Health and Hospital, Agra with mean age of 31.07(±9.00 years. They were assessed at base line and were followed up weekly or psychopathology and insight. Materials and Methods: The Young′s mania rating scale for psychopathology and insight was assessed on three dimensions of SUMD. Results: Twenty five patients eventually completed the study. There was a positive correlation with global insight and with psychopathology consistent in longitudinal follow-up (P<0.05, but not correlating for awareness for achieved effect of medication and social consequences. Linear regression showed a positive relationship at the first and second week of assessment of SUMD and YMRS scores (P=0.001; 0.019. Conclusion: Improvement in insight is graded in a manic episode as compared to psychopathology. There is slower improvement in awareness of social consequences of mental disorder. It means that improvement in psychopathology may not necessarily indicate remission and need further supervision to improve insight and hence monitoring.

  13. Clinical correlates of loss of insight in bipolar depression

    Directory of Open Access Journals (Sweden)

    Rafael de Assis da Silva

    Full Text Available Abstract Introduction Affective state may influence insight, especially regarding mania. Nevertheless, studies have so far suggested that depression seems not to significantly impair insight. To the best of our knowledge, this study pioneers the evaluation of how insight variations in bipolar depression correlate with clinical variables. Method A group of 165 bipolar patients, 52 of whom had depressive episodes according to DSM-5 criteria, were followed during a year. All patients underwent clinical assessment, and insight was evaluated through the Insight Scale for Affective Disorders (ISAD. Repeated-measures ANOVA was calculated comparing scores on the four ISAD factors (insight into symptoms, the condition itself, self-esteem and social relationships in order to investigate differences in insight according to different objects. Correlational analysis explored which clinical symptoms were linked to reduced insight. Results Worse total insight correlated with suicide attempt/ideation and fewer subsyndromal manic symptoms such as mood elevation, increased energy and sexual interest. Worse self-esteem insight was associated with not only suicide ideation/attempt but also with activity reduction and psychomotor retardation. Worse symptom insight also correlated with psychomotor retardation. Better insight into having an affective disorder was associated with more intense hypochondria symptoms. Finally, worse insight into having an illness was associated with psychotic episodes. Conclusion Our study found that symptoms other than psychosis – suicide ideation, psychomotor retardation and reduction of activity and work – correlate with insight impairment in bipolar depression.

  14. Human reliability guidance - How to increase the synergies between human reliability, human factors, and system design and engineering. Phase 2: The American Point of View - Insights of how the US nuclear industry works with human reliability analysis

    Energy Technology Data Exchange (ETDEWEB)

    Oxstrand, J. (Vattenfall Ringhals AB, Stockholm (Sweden))

    2010-12-15

    The main goal of this Nordic Nuclear Safety Research Council (NKS) project is to produce guidance for how to use human reliability analysis (HRA) to strengthen overall safety. The project consists of two substudies: The Nordic Point of View - A User Needs Analysis, and The American Point of View - Insights of How the US Nuclear Industry Works with HRA. The purpose of the Nordic Point of View study was a user needs analysis that aimed to survey current HRA practices in the Nordic nuclear industry, with the main focus being to connect HRA to system design. In this study, 26 Nordic (Swedish and Finnish) nuclear power plant specialists with research, practitioner, and regulatory expertise in HRA, PRA, HSI, and human performance were interviewed. This study was completed in 2009. This study concludes that HRA is an important tool when dealing with human factors in control room design or modernizations. The Nordic Point of View study showed areas where the use of HRA in the Nordic nuclear industry could be improved. To gain more knowledge about how these improvements could be made, and what improvements to focus on, the second study was conducted. The second study is focused on the American nuclear industry, which has many more years of experience with risk assessment and human reliability than the Nordic nuclear industry. Interviews were conducted to collect information to help the author understand the similarities and differences between the American and the Nordic nuclear industries, and to find data regarding the findings from the first study. The main focus of this report is to identify potential HRA improvements based on the data collected in the American Point of View survey. (Author)

  15. Insights into the multifunctional role of natural killer enhancing factor-A (NKEF-A/Prx1) in big-belly seahorse (Hippocampus abdominalis): DNA protection, insulin reduction, H2O2 scavenging, and immune modulation activity.

    Science.gov (United States)

    Godahewa, G I; Perera, N C N; Lee, Jehee

    2018-02-05

    Natural killer enhancing factor A (NKEF-A), also known as peroxiredoxin 1 (Prx1), is a well-known antioxidant involved in innate immunity. Although NKEF-A/Prx1 has been studied in different fish species, the present study broadens the knowledge of NKEF-A gene in terms of molecular structure, function, and immune responses in fish species. Hippocampus abdominalis NKEF-A (HaNKEF-A) cDNA encoded a putative protein of 198 amino acids containing a thioredoxin_2 domain, VCP motifs, and three conserved cysteine residues including peroxidatic and resolving cysteines. Amino acid sequence comparison and phylogenetic breakdown showed the higher sequence identity and closer evolutionary position of HaNKEF-A to those of other fish counterparts. A recombinant protein of HaNKEF-A was shown to i) protect supercoiled DNA against mixed catalyzed oxidation, ii) reduce insulin disulfide bonds, and iii) scavenge extracellular H 2 O 2 . Results of in vitro assays demonstrated the concentration dependent antioxidant function of recombinant HaNKEF-A. In addition, qPCR assessments revealed that the HaNKEF-A transcripts were constitutively expressed in fourteen tissues with the highest expression in liver. As an innate immune response, HaNKEF-A transcripts were up-regulated in liver post injection of LPS, Edwardsiella tarda, Streptococcus iniae, and polyinosinic-polycytidylic acid. Thus, HaNKEF-A can safeguards big-belly seahorse from oxidative damage and pathogenic infections. This study provides insight into the functions of NKEF-A/Prx1 in fish species. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Mapping the resistance-associated mobilome of a carbapenem-resistant Klebsiella pneumoniae strain reveals insights into factors shaping these regions and facilitates generation of a 'resistance-disarmed' model organism.

    Science.gov (United States)

    Bi, Dexi; Jiang, Xiaofei; Sheng, Zi-Ke; Ngmenterebo, David; Tai, Cui; Wang, Minggui; Deng, Zixin; Rajakumar, Kumar; Ou, Hong-Yu

    2015-10-01

    This study aims to investigate the landscape of the mobile genome, with a focus on antibiotic resistance-associated factors in carbapenem-resistant Klebsiella pneumoniae. The mobile genome of the completely sequenced K. pneumoniae HS11286 strain (an ST11, carbapenem-resistant, near-pan-resistant, clinical isolate) was annotated in fine detail. The identified mobile genetic elements were mapped to the genetic contexts of resistance genes. The blaKPC-2 gene and a 26 kb region containing 12 clustered antibiotic resistance genes and one biocide resistance gene were deleted, and the MICs were determined again to ensure that antibiotic resistance had been lost. HS11286 contains six plasmids, 49 ISs, nine transposons, two separate In2-related integron remnants, two integrative and conjugative elements (ICEs) and seven prophages. Sixteen plasmid-borne resistance genes were identified, 14 of which were found to be directly associated with Tn1721-, Tn3-, Tn5393-, In2-, ISCR2- and ISCR3-derived elements. IS26 appears to have actively moulded several of these genetic regions. The deletion of blaKPC-2, followed by the deletion of a 26 kb region containing 12 clustered antibiotic resistance genes, progressively decreased the spectrum and level of resistance exhibited by the resultant mutant strains. This study has reiterated the role of plasmids as bearers of the vast majority of resistance genes in this species and has provided valuable insights into the vital role played by ISs, transposons and integrons in shaping the resistance-coding regions in this important strain. The 'resistance-disarmed' K. pneumoniae ST11 strain generated in this study will offer a more benign and readily genetically modifiable model organism for future extensive functional studies. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Human reliability guidance - How to increase the synergies between human reliability, human factors, and system design and engineering. Phase 2: The American Point of View - Insights of how the US nuclear industry works with human reliability analysis

    International Nuclear Information System (INIS)

    Oxstrand, J.

    2010-12-01

    The main goal of this Nordic Nuclear Safety Research Council (NKS) project is to produce guidance for how to use human reliability analysis (HRA) to strengthen overall safety. The project consists of two substudies: The Nordic Point of View - A User Needs Analysis, and The American Point of View - Insights of How the US Nuclear Industry Works with HRA. The purpose of the Nordic Point of View study was a user needs analysis that aimed to survey current HRA practices in the Nordic nuclear industry, with the main focus being to connect HRA to system design. In this study, 26 Nordic (Swedish and Finnish) nuclear power plant specialists with research, practitioner, and regulatory expertise in HRA, PRA, HSI, and human performance were interviewed. This study was completed in 2009. This study concludes that HRA is an important tool when dealing with human factors in control room design or modernizations. The Nordic Point of View study showed areas where the use of HRA in the Nordic nuclear industry could be improved. To gain more knowledge about how these improvements could be made, and what improvements to focus on, the second study was conducted. The second study is focused on the American nuclear industry, which has many more years of experience with risk assessment and human reliability than the Nordic nuclear industry. Interviews were conducted to collect information to help the author understand the similarities and differences between the American and the Nordic nuclear industries, and to find data regarding the findings from the first study. The main focus of this report is to identify potential HRA improvements based on the data collected in the American Point of View survey. (Author)

  18. Dreaming and insight

    Science.gov (United States)

    Edwards, Christopher L.; Ruby, Perrine M.; Malinowski, Josie E.; Bennett, Paul D.; Blagrove, Mark T.

    2013-01-01

    This paper addresses claims that dreams can be a source of personal insight. Whereas there has been anecdotal backing for such claims, there is now tangential support from findings of the facilitative effect of sleep on cognitive insight, and of REM sleep in particular on emotional memory consolidation. Furthermore, the presence in dreams of metaphorical representations of waking life indicates the possibility of novel insight as an emergent feature of such metaphorical mappings. In order to assess whether personal insight can occur as a result of the consideration of dream content, 11 dream group discussion sessions were conducted which followed the Ullman Dream Appreciation technique, one session for each of 11 participants (10 females, 1 male; mean age = 19.2 years). Self-ratings of deepened self-perception and personal gains from participation in the group sessions showed that the Ullman technique is an effective procedure for establishing connections between dream content and recent waking life experiences, although wake life sources were found for only 14% of dream report text. The mean Exploration-Insight score on the Gains from Dream Interpretation questionnaire was very high and comparable to outcomes from the well-established Hill (1996) therapist-led dream interpretation method. This score was associated between-subjects with pre-group positive Attitude Toward Dreams (ATD). The need to distinguish “aha” experiences as a result of discovering a waking life source for part of a dream, from “aha” experiences of personal insight as a result of considering dream content, is discussed. Difficulties are described in designing a control condition to which the dream report condition can be compared. PMID:24550849

  19. OpenGL Insights

    CERN Document Server

    Cozzi, Patrick

    2012-01-01

    Get Real-World Insight from Experienced Professionals in the OpenGL Community With OpenGL, OpenGL ES, and WebGL, real-time rendering is becoming available everywhere, from AAA games to mobile phones to web pages. Assembling contributions from experienced developers, vendors, researchers, and educators, OpenGL Insights presents real-world techniques for intermediate and advanced OpenGL, OpenGL ES, and WebGL developers. Go Beyond the Basics The book thoroughly covers a range of topics, including OpenGL 4.2 and recent extensions. It explains how to optimize for mobile devices, explores the design

  20. World energy insight 2011

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-11-15

    The World Energy Insight 2011 is the official publication of the World Energy Council. It includes interviews, articles and case studies from a distinguished panel of World Energy Council Officers, CEOs, government ministers, academics and opinion formers from all areas of the energy sector and provides perspectives from around the globe. Government, industry and NGO's offer both policy and technology perspectives. The insights within this publication add to the work that WEC is doing to provide the forum for energy leaders, along with the on-going WEC studies and programmes on Energy Policies, 2050 Energy Scenarios, Energy Resources & Technologies, Energy for Urban Innovation, Rules Of Energy Trade and Global Energy Access.

  1. Global China Insights

    NARCIS (Netherlands)

    Segers, Rien; Fischer, Ingrid

    Journal in which the Groningen Confucius Institute (GCI) shares different perspectives on China and provides insights into China from as many different aspects as possible. GCI aims to provide a full view of real China to the readers as well as featuring international and comprehensive perspectives,

  2. Global China Insights

    NARCIS (Netherlands)

    Segers, Rien; Havinga, Marieke; Fischer, Ingrid

    2013-01-01

    Journal in which the Groningen Confucius Institute (GCI) shares different perspectives on China and provides insights into China from as many different aspects as possible. GCI aims to provide a full view of real China to the readers as well as featuring international and comprehensive perspectives,

  3. Africa Insight: Submissions

    African Journals Online (AJOL)

    Author Guidelines. Africa Insight is a quarterly, peer-reviewed journal of the Africa Institute of South Africa (AISA). It is accredited by the Department of Higher ... Abstract: All articles should be accompanied by an abstract of between 100 and 125 words stating the main research problem, major findings and conclusion(s).

  4. Developmental Social Cognitive Neuroscience: Insights from Deafness

    Science.gov (United States)

    Corina, David; Singleton, Jenny

    2009-01-01

    The condition of deafness presents a developmental context that provides insight into the biological, cultural, and linguistic factors underlying the development of neural systems that impact social cognition. Studies of visual attention, behavioral regulation, language development, and face and human action perception are discussed. Visually…

  5. The "Insight Paradox" in Schizophrenia: Magnitude, Moderators and Mediators of the Association Between Insight and Depression.

    Science.gov (United States)

    Belvederi Murri, Martino; Amore, Mario; Calcagno, Pietro; Respino, Matteo; Marozzi, Valentina; Masotti, Mattia; Bugliani, Michele; Innamorati, Marco; Pompili, Maurizio; Galderisi, Silvana; Maj, Mario

    2016-09-01

    The so-called "insight paradox" posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved

  6. World energy insight 2011

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-11-15

    The World Energy Insight 2011 is the official publication of the World Energy Council. It includes interviews, articles and case studies from a distinguished panel of World Energy Council Officers, CEOs, government ministers, academics and opinion formers from all areas of the energy sector and provides perspectives from around the globe. Government, industry and NGO's offer both policy and technology perspectives. The insights within this publication add to the work that WEC is doing to provide the forum for energy leaders, along with the on-going WEC studies and programmes on Energy Policies, 2050 Energy Scenarios, Energy Resources & Technologies, Energy for Urban Innovation, Rules Of Energy Trade and Global Energy Access.

  7. The politics of insight

    OpenAIRE

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insig...

  8. HPC Insights, Fall 2011

    Science.gov (United States)

    2011-01-01

    Power 6 ( Davinci ) systems. We have also made use of the Air Force Research Laboratory DSRC Altix (Hawk) and the Engineer Research and Development...the design and development of high performance gas turbine combustion systems both as a pretest analysis tool to predict static and dynamic...application while gaining insight into MATLAB’s value as an engineering tool . I would like to thank the MHPCC and the Akamai Workforce Initiative

  9. The politics of insight.

    Science.gov (United States)

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs.

  10. The politics of insight

    Science.gov (United States)

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs. PMID:26810954

  11. Dispositional Insight Scale: Development and Validation of a Tool That Measures Propensity toward Insight in Problem Solving

    Science.gov (United States)

    Ovington, Linda A.; Saliba, Anthony J.; Goldring, Jeremy

    2016-01-01

    This article reports the development of a brief self-report measure of dispositional insight problem solving, the Dispositional Insight Scale (DIS). From a representative Australian database, 1,069 adults (536 women and 533 men) completed an online questionnaire. An exploratory and confirmatory factor analysis revealed a 5-item scale, with all…

  12. What are System Dynamics Insights?

    OpenAIRE

    Stave, K.; Zimmermann, N. S.; Kim, H.

    2016-01-01

    This paper explores the concept of system dynamics insights. In our field, the term “insight” is generally understood to mean dynamic insight, that is, a deep understanding about the relationship between structure and behavior. We argue this is only one aspect of the range of insights possible from system dynamics activities, and describe a broader range of potential system dynamics insights. We also propose an initial framework for discussion that relates different types of system dynamics a...

  13. Oligodendrocyte differentiation and implantation : new insights for remyelinating cell therapy

    NARCIS (Netherlands)

    Sher, Falak; Balasubramaniyan, Veerakumar; Boddeke, Erik; Copray, Sjef

    2008-01-01

    Purpose of review Recent research on oligodendrocyte development has yielded new insights on the involvement of morphogens and differentiation factors in oligodendrogenesis. This knowledge has improved strategies to control neural stem cell-derived oligodendrocyte differentiation and functional

  14. Insight into nucleon structure from generalized parton distributions

    International Nuclear Information System (INIS)

    J.W. Negele; R.C. Brower; P. Dreher; R. Edwards; G. Fleming; Ph. Hagler; Th. Lippert; A.V.Pochinsky; D.B. Renner; D. Richards; K. Schilling; W. Schroers

    2004-01-01

    The lowest three moments of generalized parton distributions are calculated in full QCD and provide new insight into the behavior of nucleon electromagnetic form factors, the origin of the nucleon spin, and the transverse structure of the nucleon

  15. Insight and illness perception in Mexican patients with psychosis.

    Science.gov (United States)

    Gómez-de-Regil, Lizzette

    2015-03-01

    Insight and illness perception are two concepts of interest in the study of factors related to clinical outcome in patients with psychosis. Insight implies a risk of emotional distress for the patient. Illness perceptions, regardless of their accuracy, might be favorable or not to illness. Literature provides evidence of significant correlates of these factors with clinical outcome, but they are rarely included in a single study. 1) assessing insight and illness perception in a sample of Mexican patients who have experienced psychosis and, 2) analyzing how insight and illness perception relate to each other and how they relate to clinical status (i.e., positive, negative, and general psychopathology, depression, and anxiety). Sixty-one participants (55.7% females) were recruited from a public psychiatric hospital; insight and illness perceptions were assessed with the SUMD and the Brief-IPQ, respectively. Clinical status was assessed with the PANSS, CDS and BAI scales. Participants showed good insight, favorable illness perceptions for the cognitive and comprehension dimensions, but unfavorable for the emotional dimension. Clinical status of sample was characterized by mild symptoms. Poor insight related to positive symptoms and general psychopathology. Cognitive and emotional perceptions of illness were significantly associated to most clinical status parameters, whereas comprehension showed no significant results. The study not only replicates the significant association on insight and illness perception with clinical outcome, but shows how their patterns of interactions are different, reinforcing the idea that they are two distinct factors worthy of being habitually acknowledged in research and clinical practice.

  16. Insight in seasonal affective disorder.

    Science.gov (United States)

    Ghaemi, S N; Sachs, G S; Baldassano, C F; Truman, C J

    1997-01-01

    Lack of insight complicates the evaluation and treatment of patients with psychotic and affective disorders. No studies of insight in seasonal affective disorder (SAD) have been reported. Thirty patients with SAD diagnosed by the Structured Clinical Interview for DSM-III-R but no other axis I conditions were treated short-term with light-therapy. Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) as modified by the authors to assess the self-report of insight into depressive symptoms. Increasing scores (1 to 5) indicated increasing unawareness of illness (i.e., less insight). SAD patients displayed a moderate amount of insight when depressed (mean SUMD score, 2.5). When recovered, they showed no significant change in insight into past depressive symptoms (mean SUMD score, 2.8). Greater insight into current depressive symptoms correlated with more depressive symptoms on the Hamilton Rating Scale for Depression score ([HRSD] r = .35, P depressive symptoms that does not change after recovery, a result in agreement with studies of insight in psychosis and mania. Further, in SAD, increased severity of illness may be associated with increased insight into depressive symptoms, consistent with the hypothesis of depressive realism.

  17. The Association of Insight and Change in Insight with Clinical Symptoms in Depressed Inpatients.

    Science.gov (United States)

    He, Hongbo; Chang, Qing; Ma, Yarong

    2018-04-25

    Lack of insight has been extensively studied and was found to be adversely correlated with impaired treatment compliance and worse long term clinical outcomes among patients with schizophrenia, while not much is known about this phenonmenon in patients with severe depression. To explore the correlates of insight and its relation to symptom changes among the most seriously ill patients with affective disorders, those who require hospitalization. Patients hospitalized in a large psychiatric hospital in south China with either major depressive disorder (MDD)(N=55) or bipolar depression (BD) (N=85) based on ICD-10 diagnostic criteria were assessed with the Insight and Treatment Attitudes Questionnaire (ITAQ) one week after admission and at the time of discharge. Clinical symptoms were measured at the same time with the Hamilton Rating Scale for Depression (HAMD-17) and the Depression subscale of the Symptom Check list-90 (SCL-90). Length of stay (LOS), duration of illness, duration of untreated mood disorder, number of previous episodes of depression and previous admissions for depression were documented during interviews with patients and their families and from a review of medical records. Bivariate correlations and multiple regression analysis were used to examine the relationship of sociodemographic characteristics, clinical symptomatology and clinical history, to insight at the time of admission. The relationships between change in clinical symptoms and change in insight from admission to discharge were also examined. Stepwise multiple regression models suggested that any previous admissions for depression and higher anxiety factor scores on the HAMD-17 are significant independent predictors of insight accounting for 22.9% of the variance. Multiple regression analysis residual change scores (change scores adjusted for baseline values) on the ITAQ showed that improved insight over average stays of 51 days were inversely related to the residual psychomotor

  18. Insights on STEM Careers

    Energy Technology Data Exchange (ETDEWEB)

    Wendelberger, Joanne Roth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-11-05

    This presentation will provide career advice for individuals seeking to go beyond just having a job to building a successful career in the areas of Science, Technology, Engineering, and Mathematics. Careful planning can be used to turn a job into a springboard for professional advancement and personal satisfaction. Topics to be addressed include setting priorities, understanding career ladders, making tough choices, overcoming stereotypes and assumptions by others, networking, developing a professional identify, and balancing a career with family and other personal responsibilities. Insights on the transition from individual technical work to leadership will also be provided. The author will draw upon experiences gained in academic, industrial, and government laboratory settings, as well as extensive professional service and community involvement.

  19. Osho - Insights on sex.

    Science.gov (United States)

    Nagaraj, Anil Kumar Mysore

    2013-01-01

    Sex is a mysterious phenomenon, which has puzzled even great sages. Human beings have researched and mastered the biology of sex. But that is not all. Sex needs to be understood from the spiritual perspective too. The vision of Osho is an enlightening experience in this regard. Out of the thousands of lectures, five lectures on sex made Osho most notorious. Born into a Jain family of Madhya Pradesh, Rajneesh, who later wanted himself to be called Osho, is a great master. He has spoken volumes on a wide range of topics ranging from sex to super-consciousness. His contributions in the area of sex are based on the principles of "Tantra" which has its origin from Buddhism. This article focuses on his life and insights on sex, which if understood properly, can be a stepping stone for enlightenment.

  20. Outsourcing/Offshoring Insights

    DEFF Research Database (Denmark)

    Tate, Wendy; Bals, Lydia

    2017-01-01

    Findings: Both the geographical and governance dimensions are part of the rightshoring decision which is an important conceptual foundation for this special issue, as it invited insightful pieces on all of these phenomena (e.g. outsourcing, insourcing, offshoring, reshoring), acknowledging...... for future research out of the six papers are summarized in Table III. There is ample opportunity to further shed light on these suggestions as well as to cover parts of the “rightshoring” framework presented, that remain less covered here (e.g. insourcing and/or reshoring). Practical implications: The array...... of potential “rightshoring” options fosters clarity about the phenomena studied and their implications. The main practical implications of the six papers are summarized in Table II. Originality/value: The overall conceptual framework highlights the positioning of the final papers included into the special...

  1. Gonadal Steroid Hormones and the Hypothalamo-Pituitary-Adrenal Axis

    OpenAIRE

    Handa, Robert J.; Weiser, Michael J.

    2013-01-01

    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, pr...

  2. Self-Reflection, Insight, and Individual Differences in Various Language Tasks

    Science.gov (United States)

    Xu, Xu

    2011-01-01

    This study explored the relationships of self-reflection and insight with individuals' performances on various language tasks. The Self-Reflection and Insight Scale (SRIS; Grant, Franklin, & Langford, 2002) assessed individual differences in three factors: engagement in reflection, need for reflection, and insight. A high need for reflection was…

  3. Insights into business student's book

    CERN Document Server

    Lannon, Michael; Trappe, Tonya

    1993-01-01

    With Challenging reading and listening texts from a range of authentic business sources, New Insights into Business will really engage your students. The thorough language and vocabulary syllabus together with the strong focus on business skills development gives students everything they need to function effectively in the workplace. New Insights into Business is a self-contained course and is also an ideal follow-on to First Insights into Business.

  4. Insight in schizophrenia: a review.

    Science.gov (United States)

    Dam, Jesper

    2006-01-01

    The issue of insight in schizophrenia must be assumed to be one of the most important aspects of the clinical examination. Comprehensive studies have shown that between 50% and 80% of all patients suffering from schizophrenia do not believe that they have a disorder. In recent years, poor insight in schizophrenia has been the subject of increasing interest, as manifested in a number of studies discussed in the present review. Some of these studies focus on insight correlated to various parameters such as psychopathology, neuropsychology, clinical relevance and compliance. Other studies refer to more theoretical implications, among these the issue of defining the concept of insight: whether insight can be seen as a "primary" phenomenon in schizophrenia, and whether insight may be graduated, dimensioned or increased. Several authors have developed rating scales in an attempt to obtain a measure for the degree or dimension of insight. Here, the range of parameters employed gives an excellent impression of the complexity of the concept of insight. In the concluding discussion, a phenomenological aspect is brought in, in an attempt to place the concept of insight in relation to disturbances of the self in schizophrenia and to primary symptoms in schizophrenia, amongst these autism.

  5. Insights into PRA methodologies

    International Nuclear Information System (INIS)

    Gallagher, D.; Lofgren, E.; Atefi, B.; Liner, R.; Blond, R.; Amico, P.

    1984-08-01

    Probabilistic Risk Assessments (PRAs) for six nuclear power plants were examined to gain insight into how the choice of analytical methods can affect the results of PRAs. The PRA sreflectope considered was limited to internally initiated accidents sequences through core melt. For twenty methodological topic areas, a baseline or minimal methodology was specified. The choice of methods for each topic in the six PRAs was characterized in terms of the incremental level of effort above the baseline. A higher level of effort generally reflects a higher level of detail or a higher degree of sophistication in the analytical approach to a particular topic area. The impact on results was measured in terms of how additional effort beyond the baseline level changed the relative importance and ordering of dominant accident sequences compared to what would have been observed had methods corresponding to the baseline level of effort been employed. This measure of impact is a more useful indicator of how methods affect perceptions of plant vulnerabilities than changes in core melt frequency would be. However, the change in core melt frequency was used as a secondary measure of impact for nine topics where availability of information permitted. Results are presented primarily in the form of effort-impact matrices for each of the twenty topic areas. A suggested effort-impact profile for future PRAs is presented

  6. Grigor Narekatsi's astronomical insights

    Science.gov (United States)

    Poghosyan, Samvel

    2015-07-01

    What stand out in the solid system of Gr. Narekatsi's naturalistic views are his astronomical insights on the material nature of light, its high speed and the Sun being composed of "material air". Especially surprising and fascinating are his views on stars and their clusters. What astronomers, including great Armenian academician V. Ambartsumian (scattering of stellar associations), would understand and prove with much difficulty thousand years later, Narekatsi predicted in the 10th century: "Stars appear and disappear untimely", "You who gather and scatter the speechless constellations, like a flock of sheep". Gr. Narekatsti's reformative views were manifested in all the spheres of the 10th century social life; he is a reformer of church life, great language constructor, innovator in literature and music, freethinker in philosophy and science. His ideology is the reflection of the 10th century Armenian Renaissance. During the 9th-10th centuries, great masses of Armenians, forced to migrate to the Balkans, took with them and spread reformative ideas. The forefather of the western science, which originated in the period of Reformation, is considered to be the great philosopher Nicholas of Cusa. The study of Gr. Narekatsti's logic and naturalistic views enables us to claim that Gr. Narekatsti is the great grandfather of European science.

  7. O insight em psiquiatria

    Directory of Open Access Journals (Sweden)

    Ana Margarida P. Cardoso

    2008-12-01

    Full Text Available O sinal de que algo está a acontecer contribui para que o paciente reconheça que alguma coisa de estranho se está a passar consigo. Este reconhecimento faz com que o sujeito possa desempenhar uma função activa e seja um elemento colaborante do seu processo de recuperação. Cada doença apresenta, contudo, diferentes sintomas, uma vez que cada doença psiquiátrica consiste em diferentes perturbações com diversos efeitos sobre o funcionamento mental. Desta maneira, o fenómeno do insight que é registado em cada doença é diferente e expressa-se sob diferentes formas, não somente devido às manifestações clínicas da doença mas também devido às características individuais do sujeito.

  8. Cognitive insight: A systematic review.

    Science.gov (United States)

    Van Camp, L S C; Sabbe, B G C; Oldenburg, J F E

    2017-07-01

    Cognitive insight is the ability to re-evaluate thoughts and beliefs in order to make thoughtful conclusions. It differs from clinical insight, as it focuses on more general metacognitive processes. Therefore, it could be relevant to diverse disorders and non-clinical subjects. There is a growing body of research on cognitive insight in individuals with and without psychosis. This review has summarised the current state of the art regarding this topic. We conclude that while cognitive insight in its current form seems valid for use in individuals with psychosis, it is less so for individuals without psychosis. Additionally, higher cognitive insight not always leads to better psychological functioning. For instance, higher levels of self-reflection are often associated with depressive mood. We therefore recommend the sub-components of cognitive insight to be studied separately. Also, it is unclear what position cognitive insight takes within the spectrum of metacognitive processes and how it relates to other self-related concepts that have been defined previously in literature. Combining future and past research on cognitive insight and its analogue concepts will help in the formation of a uniform definition that fits all subjects discussed here. Copyright © 2017. Published by Elsevier Ltd.

  9. Hyperons: Insights into baryon structures

    International Nuclear Information System (INIS)

    Lach, J.

    1991-08-01

    The baryon octet is composed mainly of hyperons. Modern high energy hyperon beams provide a tool for the study of hyperon static properties and interactions. Experiments with these beams have provided new insights into hyperon rare decays, magnetic moments, and interactions. These experiments provide us with insights into the strong, weak, and electromagnetic structure of the baryons. 65 refs., 45 figs., 5 tabs

  10. Fear extinction learning can be impaired or enhanced by modulation of the CRF system in the basolateral nucleus of the amygdala

    OpenAIRE

    Abiri, Dina; Douglas, Christina E.; Calakos, Katina C.; Barbayannis, Georgia; Roberts, Andrea; Bauer, Elizabeth P.

    2014-01-01

    The neuropeptide corticotropin-releasing factor (CRF) is released during periods of anxiety and modulates learning and memory formation. One region with particularly dense concentrations of CRF receptors is the basolateral nucleus of the amygdala (BLA), a critical structure for both Pavlovian fear conditioning and fear extinction. While CRF has the potential to modify amygdala-dependent learning, its effect on fear extinction has not yet been assessed. In the present study, we examined the mo...

  11. Pituitary tumor evaluation

    International Nuclear Information System (INIS)

    Albertson, B.; Binney, S.

    1995-01-01

    This paper describes research on the following: the structure of 10 B 10 -ovine corticotropin releasing hormone and 10 B 10 -growth hormone releasing hormone; the BNCT effect on AtT-20 cell 10 B 10 -CRH incubations in vitro; BNCT effects on GH 4 C 1 cell 10 B 10 growth hormone releasing factor incubation in vitro; and competitive inhibition of AtT-20 cell BNCT effect

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

    OpenAIRE

    Andreas Stengel; Yvette F. Taché; Yvette F. Taché

    2017-01-01

    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 br...

  13. Acute Social Stress Engages Synergistic Activity of Stress Mediators in the VTA to Promote Pavlovian Reward Learning

    OpenAIRE

    Kan, Russell; Pomrenze, Matthew; Tovar-Diaz, Jorge; Morikawa, Hitoshi; Drew, Michael; Pahlavan, Bahram

    2017-01-01

    Stressful events rapidly trigger activity-dependent synaptic plasticity in certain brain areas, driving the formation of aversive memories. However, it remains unclear how stressful experience affects plasticity mechanisms to regulate learning of appetitive events, such as intake of addictive drugs or palatable foods. Using rats, we show that two acute stress mediators, corticotropin-releasing factor (CRF) and norepinephrine (NE), enhance plasticity of NMDA receptor-mediated glutamatergic tra...

  14. Clinical Perspectives of Urocortin and Related Agents for the Treatment of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2012-01-01

    Full Text Available The effects of corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF, on the cardiovascular system have been intensively researched since its discovery. Moreover, the actions of urocortin (Ucn I on the cardiovascular system have also been intensively scrutinized following the cloning and identification of its receptor, CRF receptor type 2 (CRFR2, in peripheral tissues including the heart. Given the cardioprotective actions of CRFR2 ligands, the clinical potential of not only Ucn I but also Ucn II and III, which were later identified as more specific ligands for CRFR2, has received considerable attention from researchers. In addition, recent work has indicated that CRF type 1 receptor may be also involved in cardioprotection against ischemic/reperfusion injury. Here we provide a historical overview of research on Ucn I and related agents, their effects on the cardiovascular system, and the clinical potential of the use of such agents to treat cardiovascular diseases.

  15. Insights into the efficacy of golimumab plus methotrexate in patients with active rheumatoid arthritis who discontinued prior anti-tumour necrosis factor therapy: post-hoc analyses from the GO-AFTER study

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Matteson, Eric L.; Landewé, Robert; Hsia, Elizabeth C.; Xu, Stephen; Zhou, Yiying; Doyle, Mittie K.

    2014-01-01

    Evaluate golimumab in patients with active rheumatoid arthritis (RA) and previous tumour necrosis factor-α (TNF) inhibitor use. Patients (n=461) previously receiving ≥1 TNF inhibitor were randomised to subcutaneous injections of placebo, golimumab 50 mg or golimumab 100 mg q4 weeks. Primary endpoint

  16. Stability of 2 ',3 ' and 3 ',5 ' cyclic nucleotides in formamide and in water: a theoretical insight into the factors controlling the accumulation of nucleic acid building blocks in a prebiotic pool

    Czech Academy of Sciences Publication Activity Database

    Cassone, Giuseppe; Šponer, Jiří; Saija, F.; Di Mauro, E.; Saitta, A. M.; Šponer, Judit E.

    2017-01-01

    Roč. 19, č. 3 (2017), s. 1817-1825 ISSN 1463-9076 R&D Projects: GA ČR(CZ) GA14-12010S Institutional support: RVO:68081707 Keywords : density- functional theory * liquid formamide * 2,3-cyclic nucleotides * molecular-dynamics Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 4.123, year: 2016

  17. Newer insights in teledermatology practice

    Directory of Open Access Journals (Sweden)

    Garehatty Rudrappa Kanthraj

    2011-01-01

    Full Text Available The study and practice of dermatology care using interactive audio, visual, and data communications from a distance is called teledermatology. A teledermatology practice (TP provides teleconsultation as well tele-education. Initially, dermatologists used videoconference. Convenience, cost-effectiveness and easy application of the practice made "store and forward" to emerge as a basic teledermatology tool. The advent of newer technologies like third generation (3G and fourth generation (4G mobile teledermatology (MT and dermatologists′ interest to adopt tertiary TP to pool expert (second opinion to address difficult-to-manage cases (DMCs has resulted in a rapid change in TP. Online discussion groups (ODGs, author-based second opinion teledermatology (AST, or a combination of both are the types of tertiary TP. This article analyzes the feasibility studies and provides latest insight into TP with a revised classification to plan and allocate budget and apply appropriate technology. Using the acronym CAP-HAT, which represents five important factors like case, approach, purpose, health care professionals, and technology, one can frame a TP. Store-and-forward teledermatology (SAFT is used to address routine cases (spotters. Chronic cases need frequent follow-up care. Leg ulcer and localized vitiligo need MT while psoriasis and leprosy require SAFT. Pigmented skin lesions require MT for triage and combination of teledermoscopy, telepathology, and teledermatology for diagnosis. A self-practising dermatologist and national health care system dermatologist use SAFT for routine cases and a combination of ASTwith an ODG to address a DMC. A TP alone or in combination with face-to-face consultation delivers quality care.

  18. Parental insightfulness: retrospect and prospect.

    Science.gov (United States)

    Koren-Karie, Nina; Oppenheim, David

    2018-06-01

    We open this introductory paper to the special issue with the theoretical and clinical roots of the insightfulness concept. Next, the Insightfulness Assessment (IA) is presented, followed by a review of key empirical findings supporting the IA. The central points in the papers in this special issue are reviewed next. These include the use of the IA with parents of children ranging in age from infancy to adolescence, its applicability outside the parent-child relationship (e.g. insightfulness toward a close friend), its use with high-risk mothers, and the usefulness of insightfulness both as a continuous and a categorical measure. The clinical applications of the IA are discussed, and we close with future directions for IA research.

  19. Franchise Business Model: Theoretical Insights

    OpenAIRE

    Levickaitė, Rasa; Reimeris, Ramojus

    2010-01-01

    The article is based on literature review, theoretical insights, and deals with the topic of franchise business model. The objective of the paper is to analyse peculiarities of franchise business model and its developing conditions in Lithuania. The aim of the paper is to make an overview on franchise business model and its environment in Lithuanian business context. The overview is based on international and local theoretical insights. In terms of practical meaning, this article should be re...

  20. The “Insight Paradox” in Schizophrenia: Magnitude, Moderators and Mediators of the Association Between Insight and Depression

    Science.gov (United States)

    Belvederi Murri, Martino; Amore, Mario; Calcagno, Pietro; Respino, Matteo; Marozzi, Valentina; Masotti, Mattia; Bugliani, Michele; Innamorati, Marco; Pompili, Maurizio; Galderisi, Silvana; Maj, Mario

    2016-01-01

    The so-called “insight paradox” posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia. PMID:27069064

  1. Sex, social status, and CRF receptor densities in naked mole-rats.

    Science.gov (United States)

    Beery, Annaliese K; Bicks, Lucy; Mooney, Skyler J; Goodwin, Nastacia L; Holmes, Melissa M

    2016-02-01

    Naked mole-rats (Heterocephalus glaber) live in groups that are notable for their large size and caste structure, with breeding monopolized by a single female and a small number of males. Recent studies have demonstrated substantial differences between the brains of breeders and subordinates induced by changes in social standing. Corticotropin-releasing factor (CRF) receptors-which bind the hormone CRF as well as related peptides-are important regulators of stress and anxiety, and are emerging as factors affecting social behavior. We conducted autoradiographic analyses of CRF1 and CRF2 receptor binding densities in female and male naked mole-rats varying in breeding status. Both globally and in specific brain regions, CRF1 receptor densities varied with breeding status. CRF1 receptor densities were higher in subordinates across brain regions, and particularly in the piriform cortex and cortical amygdala. Sex differences were present in CRF2 receptor binding densities, as is the case in multiple vole species. CRF2 receptor densities were higher in females, both globally and in the cortical amygdala and lateral amygdalar nucleus. These results provide novel insights into the neurobiology of social hierarchy in naked mole-rats, and add to a growing body of work that links changes in the CRF system with social behavior. © 2015 Wiley Periodicals, Inc.

  2. Deletion of Core-binding factor β (Cbfβ) in mesenchymal progenitor cells provides new insights into Cbfβ/Runxs complex function in cartilage and bone development

    Science.gov (United States)

    Wu, Mengrui; Li, Chenguan; Zhu, Guochun; Wang, Yiping; Jules, Joel; Lu, Yun; McConnell, Matthew; Wang, Yong-Jun; Shao, Jian-Zhong; Li, Yi-Ping; Chen, Wei

    2015-01-01

    Core-binding factor β (Cbfβ) is a subunit of the Cbf family of heterodimeric transcription factors which plays a critical role in skeletal development through its interaction with the Cbfα subunits, also known as Runt-related transcription factors (Runxs). However, the mechanism by which Cbfβ regulates cartilage and bone development remains unclear. Existing Cbfβ-deficient mouse models cannot specify the role of Cbfβ in skeletal cell lineage. Herein, we sought to specifically address the role of Cbfβ in cartilage and bone development by using a conditional knockout (CKO) approach. A mesenchymal-specific Cbfβ CKO mouse model was generated by using the Dermo1-Cre mouse line to specifically delete Cbfβ in mesenchymal stem cells, which give rise to osteoblasts and chondrocytes. Surprisingly, the mutant mice had under-developed larynx and tracheal cartilage causing alveolus defects which led to death shortly after birth from suffocation. Also, the mutant mice exhibited severe skeletal deformities from defective intramembranous and endochondral ossification, owing to delayed chondrocyte maturation and impaired osteoblast differentiation. Almost all bones of the mutant mice, including the calvariae, vertebrae, tibiae, femurs, ribs, limbs and sternums were defective. Importantly, we showed that Cbfβ was expressed throughout the skeleton during both embryonic and postnatal development, which explains the multiple-skeletal defects observed in the mutant mice. Consistently, Cbfβ deficiency impaired both chondrocyte proliferation and hypertrophy zone hypertrophy during growth-plate development in the long bones of mutant mice. Notably, Cbfβ, Runx1 and Runx2 displayed different expression patterns in the growth plates of the wildtype mice indicating that Cbfβ/Runx1 complex and Cbfβ/Runx2 complex may regulate chondrocyte proliferation and hypertrophy, respectively, in a spatial and temporal manner. Cbfβ deletion in the mesenchymal progenitors impacted bone

  3. In situ rainwater harvesting using dead level contours in semi-arid southern Zimbabwe: Insights on the role of socio-economic factors on performance and effectiveness in Gwanda District

    Science.gov (United States)

    Munamati, Muchaneta; Nyagumbo, Isaiah

    Droughts and dry spells which have characterised the past decade in Zimbabwe have seen a marked increase in the promotion and use of in situ rainwater harvesting technologies (RWHTs) as a drought mitigating strategy. A number of these technologies have been tried in recent years which include dead level contours with infiltration pits and deepened contours. Although in situ RWHTs are known to increase food security in drought prone areas, the role of socio-economic factors on their performance in terms of crop yield and scaling out is still not well understood. This study sought to investigate the socio-economic factors which influence the effectiveness of dead level contours for in situ rainwater harvesting and consequently on crop yield. The study involved 14 key informants interviews and questionnaire administration to a total of 55 respondent farmers practising in situ rainwater harvesting with dead level contours. A statistical package (Statistical Package for Social Scientists, SPSS) was used to analyse relationships between performance of RWHTs and attributes such as labour, resources, gender, experience and education. The results show a strong correlation between performance and resource status ( p = 0.004). For example, within the wealthy category, 42.1% were successful, while 14.3% and 13.8% were average and poor performers respectively. Thus within the successful category, 42.1% were wealthy, while 42.1% and 15.8% were medium-rich and resource-constrained respectively. Performance rating was also significantly correlated ( p = 0.007) to gender of household head e.g., within the most successful group 94.7% were men compared to 5.3% women. There was also a significant correlation between resource status and gender ( p = 0.039) such that within the wealthy category, 69.2% of the respondents were men compared to 30.8% women. Labour was found to have no significance on performance ( p > 0.05) even though the majority of key informants (93%) alluded that the

  4. Spermatogenesis in mammals: proteomic insights.

    Science.gov (United States)

    Chocu, Sophie; Calvel, Pierre; Rolland, Antoine D; Pineau, Charles

    2012-08-01

    Spermatogenesis is a highly sophisticated process involved in the transmission of genetic heritage. It includes halving ploidy, repackaging of the chromatin for transport, and the equipment of developing spermatids and eventually spermatozoa with the advanced apparatus (e.g., tightly packed mitochondrial sheat in the mid piece, elongating of the tail, reduction of cytoplasmic volume) to elicit motility once they reach the epididymis. Mammalian spermatogenesis is divided into three phases. In the first the primitive germ cells or spermatogonia undergo a series of mitotic divisions. In the second the spermatocytes undergo two consecutive divisions in meiosis to produce haploid spermatids. In the third the spermatids differentiate into spermatozoa in a process called spermiogenesis. Paracrine, autocrine, juxtacrine, and endocrine pathways all contribute to the regulation of the process. The array of structural elements and chemical factors modulating somatic and germ cell activity is such that the network linking the various cellular activities during spermatogenesis is unimaginably complex. Over the past two decades, advances in genomics have greatly improved our knowledge of spermatogenesis, by identifying numerous genes essential for the development of functional male gametes. Large-scale analyses of testicular function have deepened our insight into normal and pathological spermatogenesis. Progress in genome sequencing and microarray technology have been exploited for genome-wide expression studies, leading to the identification of hundreds of genes differentially expressed within the testis. However, although proteomics has now come of age, the proteomics-based investigation of spermatogenesis remains in its infancy. Here, we review the state-of-the-art of large-scale proteomic analyses of spermatogenesis, from germ cell development during sex determination to spermatogenesis in the adult. Indeed, a few laboratories have undertaken differential protein profiling

  5. Structural and Functional Insights into WRKY3 and WRKY4 Transcription Factors to Unravel the WRKY–DNA (W-Box Complex Interaction in Tomato (Solanum lycopersicum L.. A Computational Approach

    Directory of Open Access Journals (Sweden)

    Mohd Aamir

    2017-05-01

    Full Text Available The WRKY transcription factors (TFs, play crucial role in plant defense response against various abiotic and biotic stresses. The role of WRKY3 and WRKY4 genes in plant defense response against necrotrophic pathogens is well-reported. However, their functional annotation in tomato is largely unknown. In the present work, we have characterized the structural and functional attributes of the two identified tomato WRKY transcription factors, WRKY3 (SlWRKY3, and WRKY4 (SlWRKY4 using computational approaches. Arabidopsis WRKY3 (AtWRKY3: NP_178433 and WRKY4 (AtWRKY4: NP_172849 protein sequences were retrieved from TAIR database and protein BLAST was done for finding their sequential homologs in tomato. Sequence alignment, phylogenetic classification, and motif composition analysis revealed the remarkable sequential variation between, these two WRKYs. The tomato WRKY3 and WRKY4 clusters with Solanum pennellii showing the monophyletic origin and evolution from their wild homolog. The functional domain region responsible for sequence specific DNA-binding occupied in both proteins were modeled [using AtWRKY4 (PDB ID:1WJ2 and AtWRKY1 (PDBID:2AYD as template protein structures] through homology modeling using Discovery Studio 3.0. The generated models were further evaluated for their accuracy and reliability based on qualitative and quantitative parameters. The modeled proteins were found to satisfy all the crucial energy parameters and showed acceptable Ramachandran statistics when compared to the experimentally resolved NMR solution structures and/or X-Ray diffracted crystal structures (templates. The superimposition of the functional WRKY domains from SlWRKY3 and SlWRKY4 revealed remarkable structural similarity. The sequence specific DNA binding for two WRKYs was explored through DNA-protein interaction using Hex Docking server. The interaction studies found that SlWRKY4 binds with the W-box DNA through WRKYGQK with Tyr408, Arg409, and Lys419 with the

  6. Structural and Functional Insights into WRKY3 and WRKY4 Transcription Factors to Unravel the WRKY–DNA (W-Box) Complex Interaction in Tomato (Solanum lycopersicum L.). A Computational Approach

    Science.gov (United States)

    Aamir, Mohd; Singh, Vinay K.; Meena, Mukesh; Upadhyay, Ram S.; Gupta, Vijai K.; Singh, Surendra

    2017-01-01

    The WRKY transcription factors (TFs), play crucial role in plant defense response against various abiotic and biotic stresses. The role of WRKY3 and WRKY4 genes in plant defense response against necrotrophic pathogens is well-reported. However, their functional annotation in tomato is largely unknown. In the present work, we have characterized the structural and functional attributes of the two identified tomato WRKY transcription factors, WRKY3 (SlWRKY3), and WRKY4 (SlWRKY4) using computational approaches. Arabidopsis WRKY3 (AtWRKY3: NP_178433) and WRKY4 (AtWRKY4: NP_172849) protein sequences were retrieved from TAIR database and protein BLAST was done for finding their sequential homologs in tomato. Sequence alignment, phylogenetic classification, and motif composition analysis revealed the remarkable sequential variation between, these two WRKYs. The tomato WRKY3 and WRKY4 clusters with Solanum pennellii showing the monophyletic origin and evolution from their wild homolog. The functional domain region responsible for sequence specific DNA-binding occupied in both proteins were modeled [using AtWRKY4 (PDB ID:1WJ2) and AtWRKY1 (PDBID:2AYD) as template protein structures] through homology modeling using Discovery Studio 3.0. The generated models were further evaluated for their accuracy and reliability based on qualitative and quantitative parameters. The modeled proteins were found to satisfy all the crucial energy parameters and showed acceptable Ramachandran statistics when compared to the experimentally resolved NMR solution structures and/or X-Ray diffracted crystal structures (templates). The superimposition of the functional WRKY domains from SlWRKY3 and SlWRKY4 revealed remarkable structural similarity. The sequence specific DNA binding for two WRKYs was explored through DNA-protein interaction using Hex Docking server. The interaction studies found that SlWRKY4 binds with the W-box DNA through WRKYGQK with Tyr408, Arg409, and Lys419 with the initial

  7. Understanding Insight in the Context of Q

    Science.gov (United States)

    Coghlan, David

    2012-01-01

    In Revans' learning formula, L = P + Q, Q represents "questioning insight", by which Revans means that insight comes out of the process of questioning programmed knowledge (P) in the light of experience. We typically focus on the content of an insight rather than on the act of insight. Drawing primarily on the work of Bernard Lonergan this paper…

  8. Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2016-01-01

    Full Text Available Currently, equine metabolic syndrome (EMS, an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC. Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN and horses suffering from EMS (ASCEMS. ASCEMS displayed senescent phenotype associated with β-galactosidase accumulation, enlarged cell bodies and nuclei, increased apoptosis, and reduced heterochromatin architecture. Moreover, we observed increased amounts of nitric oxide (NO and reactive oxygen species (ROS in these cells, accompanied by reduced superoxide dismutase (SOD activity. We also found in ASCEMS an elevated number of impaired mitochondria, characterized by membrane raptures, disarrayed cristae, and vacuole formation. Our results suggest that the toxic compounds, accumulating in the mitochondria under oxidative stress, lead to alternations in their morphology and may be partially responsible for the senescent phenotype and decreased proliferation potential of ASCEMS.

  9. Approaching the Distinction between Intuition and Insight.

    Science.gov (United States)

    Zhang, Zhonglu; Lei, Yi; Li, Hong

    2016-01-01

    Intuition and insight share similar cognitive and neural basis. Though, there are still some essential differences between the two. Here in this short review, we discriminated between intuition, and insight in two aspects. First, intuition, and insight are toward different aspects of information processing. Whereas intuition involves judgment about "yes or no," insight is related to "what" is the solution. Second, tacit knowledge play different roles in between intuition and insight. On the one hand, tacit knowledge is conducive to intuitive judgment. On the other hand, tacit knowledge may first impede but later facilitate insight occurrence. Furthermore, we share theoretical, and methodological views on how to access the distinction between intuition and insight.

  10. Assessing cognitive insight in nonpsychiatric individuals and outpatients with schizophrenia in Taiwan: an investigation using the Beck Cognitive Insight Scale

    Directory of Open Access Journals (Sweden)

    Lu Chien-Wen

    2011-10-01

    Full Text Available Abstract Background The Beck Cognitive Insight Scale (BCIS was designed for the assessment of the cognitive processes involved in self-reflection and the ability to modify erroneous beliefs and misinterpretations. Studies investigating the factor structure of the BCIS have indicated a two-factor model in the psychotic population. The factor structure of the BCIS, however, has not received much consideration in the nonpsychiatric population. The present study examined the factor structure and validity of the BCIS and compared its scores between nonpsychiatric individuals and outpatients with psychosis. Method The Taiwanese version of the BCIS was administered to 507 nonpsychiatric individuals and 118 outpatients with schizophrenia. The psychometric properties of the BCIS were examined through the following analyses: exploratory and confirmatory factor analyses, reliability, correlation analyses, and discriminative validity. Results The BCIS showed adequate internal consistency and stability over time. Exploratory and confirmatory factor analyses on the 15-item measure indicated a two-factor solution that supported the two dimensions of the Taiwanese BCIS, which was also observed with the original BCIS. Following the construct validation, we obtained a composite index (self-reflectiveness minus self-certainty of the Taiwanese BCIS that reflected cognitive insight. Consistent with previous studies, our results indicated that psychosis is associated with low self-reflectiveness and high self-certainty, which possibly reflect lower cognitive insight. Our results also showed that better cognitive insight is related to worse depression in patients with schizophrenia spectrum disorders, but not in nonpsychiatric individuals. The receiver operating characteristic (ROC analyses revealed that the area under the curve (AUC was 0.731. A composite index of 3 was a good limit, with a sensitivity of 87% and a specificity of 51%. Conclusion The BCIS proved to be

  11. Natural factors and mining activity bearings on the water quality of the Choapa basin, North Central Chile: insights on the role of mafic volcanic rocks in the buffering of the acid drainage process.

    Science.gov (United States)

    Parra, Amparo; Oyarzún, Jorge; Maturana, Hugo; Kretschmer, Nicole; Meza, Francisco; Oyarzún, Ricardo

    2011-10-01

    This contribution analyzes water chemical data for the Choapa basin, North Central Chile, for the period 1980-2004. The parameters considered are As, Cu Fe, pH, EC, SO₄⁻², Cl⁻¹, and HCO[Formula: see text], from samples taken in nine monitoring stations throughout the basin. Results show rather moderate contents of As, Cu, and Fe, with the exception of the Cuncumén River and the Aucó creek, explained by the influence of the huge porphyry copper deposit of Los Pelambres and by the presence of mining operations, respectively. When compared against results obtained in previous researches at the neighboring Elqui river basin, which host the El Indio Au-Cu-As district, a much reduced grade of pollution is recognized for the Choapa basin. Considering the effect of acid rock drainage (ARD)-related Cu contents on the fine fraction of the sediments of both river basins, the differences recorded are even more striking. Although the Los Pelambres porphyry copper deposit, on the headwaters of the Choapa river basin, is between one and two orders of magnitude bigger than El Indio, stream water and sediments of the former exhibit significantly lower copper contents than those of the latter. A main factor which may explain these results is the smaller degree of H( + )-metasomatism on the host rocks of the Los Pelambres deposit, where mafic andesitic volcanic rocks presenting propylitic hydrothermal alteration are dominant. This fact contrast with the highly altered host rocks of El Indio district, where most of them have lost their potential to neutralize ARD.

  12. Insight in psychosis: Metacognitive processes and treatment

    OpenAIRE

    de Vos, Annerieke

    2016-01-01

    Insight is impaired in 50- 80% of the patients with schizophrenia. Annerieke de Vos working at GGZ Drenthe and the University Medical Hospital Groningen, aimed to elucidate which processes underlie impaired insight and tried to improve insight in patients by targeting these processes. On September 21st she will defend her thesis entitled: "Insight in psychosis. Metacognitive processes and treatment.". Patients with impaired insight may fail to recognize that things in life are not going well ...

  13. New Insights into Behavioral Finance

    NARCIS (Netherlands)

    G. Baltussen (Guido)

    2008-01-01

    textabstractThis thesis applies insights from psychology and other behavioral sciences to overcome the shortcomings of the traditional finance approach (which assumes that agents and markets are rational) and improves our understanding of financial markets and its participants. More specific, this

  14. Investigating Insight as Sudden Learning

    Science.gov (United States)

    Ash, Ivan K.; Jee, Benjamin D.; Wiley, Jennifer

    2012-01-01

    Gestalt psychologists proposed two distinct learning mechanisms. Associative learning occurs gradually through the repeated co-occurrence of external stimuli or memories. Insight learning occurs suddenly when people discover new relationships within their prior knowledge as a result of reasoning or problem solving processes that re-organize or…

  15. Gaining insight into the effects : the supplier perspective

    NARCIS (Netherlands)

    Michiel Steeman; Christiaan de Goeij; Paulien de Graaf-Muller

    2016-01-01

    In this paper we discuss what suppliers can do to get insight into the effects of Reverse Factoring (RF), currently the most used form of Supply Chain Finance (SCF). Even though the usage of RF is increasing, empirical evidence is scarce, especially from the point of view of suppliers.

  16. Insight and illness perception in Mexican patients with psychosis

    Directory of Open Access Journals (Sweden)

    Lizzette Gómez-de-Regil

    2015-03-01

    Conclusions: The study not only replicates the significant association on insight and illness perception with clinical outcome, but shows how their patterns of interactions are different, reinforcing the idea that they are two distinct factors worthy of being habitually acknowledged in research and clinical practice.

  17. Making Sustainable Energy Choices: Insights on the Energy/Water/Land Nexus

    Energy Technology Data Exchange (ETDEWEB)

    2014-10-01

    This periodic publication summarizes insights from the body of NREL analysis work. In this issue of Analysis Insights, we examine the implications of our energy choices on water, land use, climate, developmental goals, and other factors. Collectively, NREL's work helps policymakers and investors understand and evaluate energy choices within the complex web of connections, or nexus, between energy, water, and land.

  18. Phylogeographic insights into cryptic glacial refugia.

    Science.gov (United States)

    Provan, Jim; Bennett, K D

    2008-10-01

    The glacial episodes of the Quaternary (2.6 million years ago-present) were a major factor in shaping the present-day distributions of extant flora and fauna, with expansions and contractions of the ice sheets rendering large areas uninhabitable for most species. Fossil records suggest that many species survived glacial maxima by retreating to refugia, usually at lower latitudes. Recently, phylogeographic studies have given support to the existence of previously unknown, or cryptic, refugia. Here we summarise many of these insights into the glacial histories of species in cryptic refugia gained through phylogeographic approaches. Understanding such refugia might be important as the Earth heads into another period of climate change, in terms of predicting the effects on species distribution and survival.

  19. [Parkinson's disease(s): recent insight into genetic factors

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de; Scheffer, H.; Heutink, P.; Bloem, B.R.

    2007-01-01

    In recent years, 5 genes have been identified that are unambiguously associated with genetic forms of Parkinson's disease. These genes probably explain less than 10% of all cases of Parkinson's disease. Clinically, these genetic forms can closely resemble idiopathic Parkinson's disease. Mutation

  20. Factors affecting Purchase behavior of Women grocery consumer- An Insight

    OpenAIRE

    Chopra, Dr. Anu Nagpal

    2014-01-01

    Women are most powerful consumers in the world as they control almost 80 percent of the household spending. And no longer can the womens spending powers and influence be neglected. The role of women in the society and their effects has changed. Most of the marketers know that women are different, but we actually need a deep rooted understanding of how and why they are different. Studying women could be interesting as Family grocery shopping is the accepted domain of women; however, modern so...

  1. Leptospira Immunoglobulin-Like Protein B (LigB Binds to Both the C-Terminal 23 Amino Acids of Fibrinogen αC Domain and Factor XIII: Insight into the Mechanism of LigB-Mediated Blockage of Fibrinogen α Chain Cross-Linking.

    Directory of Open Access Journals (Sweden)

    Ching-Lin Hsieh

    2016-09-01

    Full Text Available The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII. The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12, a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC. In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8. The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12 and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12. Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis.

  2. Leptospira Immunoglobulin-Like Protein B (LigB) Binds to Both the C-Terminal 23 Amino Acids of Fibrinogen αC Domain and Factor XIII: Insight into the Mechanism of LigB-Mediated Blockage of Fibrinogen α Chain Cross-Linking.

    Science.gov (United States)

    Hsieh, Ching-Lin; Chang, Eric; Tseng, Andrew; Ptak, Christopher; Wu, Li-Chen; Su, Chun-Li; McDonough, Sean P; Lin, Yi-Pin; Chang, Yung-Fu

    2016-09-01

    The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg) monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII). The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12), a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC). In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8). The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM) was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12) and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12). Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis.

  3. Insight in psychosis : Metacognitive processes and treatment

    NARCIS (Netherlands)

    de Vos, Annerieke

    2016-01-01

    Insight is impaired in 50- 80% of the patients with schizophrenia. Annerieke de Vos working at GGZ Drenthe and the University Medical Hospital Groningen, aimed to elucidate which processes underlie impaired insight and tried to improve insight in patients by targeting these processes. On September

  4. Use of Human Reliability Insights to Improve Decision-Making

    International Nuclear Information System (INIS)

    Julius, J. A.; Moieni, P.; Grobbelaar, J.; Kohlhepp, K.

    2016-01-01

    This paper describes the use of insights obtained during the development and application of human reliability analysis (HRA) as part of a probabilistic risk assessment (PRA) to support decision-making, including improvements to operations, training, and safety culture. Insights have been gained from the development and application of HRA as part of a PRA for nuclear power plants in the USA, Europe and Asia over the last two decades. These models consist of Level 1 and Level 2 PRA models of internal and external events, during full power and shutdown modes of plant operation. These insights include the use of human factors information to improve the qualitative portion of the HRA. The subsequent quantification in the HRA effectively prioritises the contributors to the unreliability of operator actions, and the process facilitates the identification of the factors that are important to the success of the operator actions. Additionally, the tools and techniques also allow for the evaluation of key assumptions and sources of uncertainty. The end results have been used to effectively support decision-making for day-to-day plant operations as well as licensing issues. HRA results have been used to provide feedback and improvements to plant procedures, operator training and other areas contributing the plant safety culture. Examples of the types of insights are presented in this paper. (author)

  5. Researching organizational factors

    International Nuclear Information System (INIS)

    Coffman, F.

    1991-01-01

    This paper discusses feedback and insights from experience (both successful and unsuccessful) with the past and the ongoing organizational factors research. That experience suggests a leading set of ingredients that appear proper for performing regulatory research on organizational processes. By keeping focused upon these proper ingredients, the research will contribute to the regulatory assessments of utility management through the use of improved methods and measures in investigations, inspections, diagnostics, performance indicators, and PRA insights. This paper is organized into (1) an introductory description of what the agency is doing to assess organizational effectiveness, (2) some insights from past and ongoing research, (3) an opinion on a leading set of ingredients to properly research organizational factors, and (4) a summary

  6. GOES-R: Satellite Insight

    Science.gov (United States)

    Fitzpatrick, Austin J.; Leon, Nancy J.; Novati, Alexander; Lincoln, Laura K.; Fisher, Diane K.

    2012-01-01

    GOES-R: Satellite Insight seeks to bring awareness of the GOES-R (Geostationary Operational Environmental Satellite -- R Series) satellite currently in development to an audience of all ages on the emerging medium of mobile games. The iPhone app (Satellite Insight) was created for the GOES-R Program. The app describes in simple terms the types of data products that can be produced from GOES-R measurements. The game is easy to learn, yet challenging for all audiences. It includes educational content and a path to further information about GOESR, its technology, and the benefits of the data it collects. The game features action-puzzle game play in which the player must prevent an overflow of data by matching falling blocks that represent different types of GOES-R data. The game adds more different types of data blocks over time, as long as the player can prevent a data overflow condition. Points are awarded for matches, and players can compete with themselves to beat their highest score.

  7. Insight in psychotic disorder: relation with psychopathology and frontal lobe function.

    Science.gov (United States)

    Kumar, Atmesh; Sharma, Pranjal; Das, Shyamanta; Nath, Kamal; Talukdar, Uddip; Bhagabati, Dipesh

    2014-01-01

    Through conceptualising poor insight in psychotic disorders as a form of anosognosia, frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. The objective of this study was to compare the relation of insight in patients with psychotic illness to that of psychopathology and frontal lobe function. Forty patients with psychotic disorder were selected from those attending the Department of Psychiatry in a tertiary care teaching hospital. The evaluation of insight was carried out using the Schedule for Assessment of Insight (SAI), that of frontal lobe function by the Frontal Assessment Battery (FAB) and psychopathology by the Brief Psychiatric Rating Scale (BPRS). The correlation coefficients were determined. A negative correlation between SAI and BPRS scores means that the BPRS score is opposite to SAI scores. When the SAI total score was compared with the FAB total score, the correlation coefficient demonstrated a positive correlation. Better insight predicted lesser psychopathology and also that poor insight would exist with greater psychopathology. Better insight predicted a higher functional status of frontal lobes and prefrontal cortex in particular. Insight deficits in schizophrenia and other psychotic illnesses are multidimensional. Integration of different aetiological factors like biological, psychopathological, environmental ones and others are necessary for a better understanding of insight in psychosis. Copyright © 2013 S. Karger AG, Basel.

  8. Managing complexity insights, concepts, applications

    CERN Document Server

    Helbing, Dirk

    2007-01-01

    Each chapter in Managing Complexity focuses on analyzing real-world complex systems and transferring knowledge from the complex-systems sciences to applications in business, industry and society. The interdisciplinary contributions range from markets and production through logistics, traffic control, and critical infrastructures, up to network design, information systems, social conflicts and building consensus. They serve to raise readers' awareness concerning the often counter-intuitive behavior of complex systems and to help them integrate insights gained in complexity research into everyday planning, decision making, strategic optimization, and policy. Intended for a broad readership, the contributions have been kept largely non-technical and address a general, scientifically literate audience involved in corporate, academic, and public institutions.

  9. Is good insight associated with depression among patients with schizophrenia? Systematic review and meta-analysis.

    Science.gov (United States)

    Belvederi Murri, Martino; Respino, Matteo; Innamorati, Marco; Cervetti, Alice; Calcagno, Pietro; Pompili, Maurizio; Lamis, Dorian A; Ghio, Lucio; Amore, Mario

    2015-03-01

    Among patients with schizophrenia, better insight may be associated with depression, but the findings on this issue are mixed. We examined the association between insight and depression in schizophrenia by conducting a systematic review and meta-analysis. The meta-analysis was based on 59 correlational studies and showed that global clinical insight was associated weakly, but significantly with depression (effect size r=0.14), as were the insight into the mental disorder (r=0.14), insight into symptoms (r=0.14), and symptoms' attributions (r=0.17). Conversely, neither insight into the social consequences of the disorder nor into the need for treatment was associated with symptoms of depression. Better cognitive insight was significantly associated with higher levels of depression. The exploratory meta-regression showed that methodological factors (e.g. the instrument used to assess depression and the phase of the illness) can significantly influence the magnitude of the association between insight and depression. Moreover, results from longitudinal studies suggest that the relation between insight and depression might be stronger than what is observed at the cross-sectional level. Finally, internalized stigma, illness perception, recovery attitudes, ruminative style, and premorbid adjustment seem to be relevant moderators and/or mediators of the association between insight and depression. In conclusion, literature indicates that among patients with schizophrenia, better insight is associated with higher levels of depressive symptoms. Thus, interventions aimed at promoting patients' insight should take into account the clinical implications of these findings. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Do behavioural insights matter for competition policy?

    OpenAIRE

    CIRIOLO Emanuele

    2016-01-01

    Behavioural insights make use of behavioural economics and psychology to analyse how humans behave when adopting economic decisions. The use of behavioural insights to improve policy-making is becoming increasing popular all over the world. Pensions, taxes, unemployment, energy efficiency, adult education, charitable giving and, of course, competition policy have benefitted from the application of behavioural insights. Emanuele Ciriolo, from the European Commission Joint Research Centre, expl...

  11. Genetic correlates of insight in schizophrenia.

    Science.gov (United States)

    Xavier, Rose Mary; Vorderstrasse, Allison; Keefe, Richard S E; Dungan, Jennifer R

    2018-05-01

    Insight in schizophrenia is clinically important as it is associated with several adverse outcomes. Genetic contributions to insight are unknown. We examined genetic contributions to insight by investigating if polygenic risk scores (PRS) and candidate regions were associated with insight. Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of Intervention Effectiveness trial. Schizophrenia PRS was constructed using Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set. For candidate regions, we selected 105 schizophrenia-associated autosomal loci and 11 schizophrenia-related oligodendrocyte genes. We used regressions to examine PRS associations and set-based testing for candidate analysis. We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was associated with total insight (R 2 =0.005, P=0.05, empirical P=0.054) and treatment insight (R 2 =0.005, P=0.048, empirical P=0.048). For models that controlled for neurocognition, PRS significantly predicted treatment insight but at higher p-thresholds (0.1 to 0.5) but did not survive correction. Patients with highest polygenic burden had 5.9 times increased risk for poor insight compared to patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of variance in poor insight. Set-based analyses identified two variants associated with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). To the best of our knowledge, this is the first study examining genetic basis of insight. We provide evidence for genetic contributions to impaired insight. Relevance of findings and necessity for replication are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Probabilistic safety assessment applications and insights

    International Nuclear Information System (INIS)

    Hitchler, M.J.; Burns, N.L.; Liparulo, N.J.; Mink, F.J.

    1987-01-01

    The insights gained through a comparison of seven PRA studies (Italian PUN, Sizewell B, Ringhals 2, Millstone 3, Zion 1 and 2, Oconee 3, and Seabrook) included insights regarding the adequacy of the PRA technology utilized in the studies and the potential areas for improvement and insights regarding the adequacy of plant designs and how PRA has been utilized to enhance the design and operation of nuclear power plants. (orig.)

  13. Insights gained through probabilistic risk assessments

    International Nuclear Information System (INIS)

    Hitchler, M.J.; Burns, N.L.; Liparulo, N.J.; Mink, F.J.

    1987-01-01

    The insights gained through a comparison of seven probabilistic risk assessments (PRA) studies (Italian PUN, Sizewell B, Ringhals 2, Millstone 3, Zion 1 and 2, Oconee 3, and Seabrook) included insights regarding the adequacy of the PRA technology utilized in the studies and the potential areas for improvement and insights regarding the adequacy of plant designs and how PRA has been utilized to enhance the design and operation of nuclear power plants

  14. The relationship between insight and the level of expressed emotion in patients with obsessive-compulsive disorder.

    Science.gov (United States)

    Ozkiris, Ayse; Essizoglu, Altan; Gulec, Gulcan; Aksaray, Gokay

    2015-04-01

    The aim of this study is firstly to compare the obsessive-compulsive disorder (OCD) patients with good insight and OCD patients with poor insight in terms of socio-demographic and clinical features; to investigate the relation between insight and the level of the expressed emotion (EE) in the patients; and lastly to specify the factors that predict level of insight. OCD patients with good insight and patients with poor insight were compared in terms of clinical features and the perceived EE level of the patients and the individuals that they live with in order to specify the factors that predict the insight level, and to investigate the relationship between insight level and EE. It was found that the total Expressed Emotion Scale, total Level of Expressed Emotion (LEE), LEE-Emotional Response and LEE-Tolerance/Expectation subscale scores of the group comprised of patients with poor insight are higher than the other group. The results also show that the duration of illness and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score predict insight level. This study shows that the level of EE perceived by the patients with poor insight and the person that he/she lives with, is higher than the group with good insight. The studies that investigate the relationship between the factors of insight level and EE level, which are indicated to determine the level of the illness severity and its chronicity, will enable the researchers to understand the importance of the role of the family on the treatment processes of OCD.

  15. Depot-medication compliance for patients with psychotic disorders: the importance of illness insight and treatment motivation.

    Science.gov (United States)

    Noordraven, Ernst L; Wierdsma, André I; Blanken, Peter; Bloemendaal, Anthony Ft; Mulder, Cornelis L

    2016-01-01

    Noncompliance is a major problem for patients with a psychotic disorder. Two important risk factors for noncompliance that have a severe negative impact on treatment outcomes are impaired illness insight and lack of motivation. Our cross-sectional study explored how they are related to each other and their compliance with depot medication. Interviews were conducted in 169 outpatients with a psychotic disorder taking depot medication. Four patient groups were defined based on low or high illness insight and on low or high motivation. The associations between depot-medication compliance, motivation, and insight were illustrated using generalized linear models. Generalized linear model showed a significant interaction effect between motivation and insight. Patients with poor insight and high motivation for treatment were more compliant (94%) (95% confidence interval [CI]: 1.821, 3.489) with their depot medication than patients with poor insight and low motivation (61%) (95% CI: 0.288, 0.615). Patients with both insight and high motivation for treatment were less compliant (73%) (95% CI: 0.719, 1.315) than those with poor insight and high motivation. Motivation for treatment was more strongly associated with depot-medication compliance than with illness insight. Being motivated to take medication, whether to get better or for other reasons, may be a more important factor than having illness insight in terms of improving depot-medication compliance. Possible implications for clinical practice are discussed.

  16. Research Insights About Risk Governance

    Directory of Open Access Journals (Sweden)

    Therese R. Viscelli

    2016-11-01

    Full Text Available In recent years, expectations for increased risk governance have been placed explicitly on boards of directors. In response, boards are being held responsible for not only understanding and approving management’s risk management processes, but they are also being held responsible for assessing the risks identified by those processes as part of overseeing management’s pursuit of value. These increasing responsibilities have led a number of organizations to adopt enterprise risk management (ERM as a holistic approach to risk management that extends beyond traditional silo-based risk management techniques. As boards, often through their audit committee, consider management’s implementation of ERM as part of the board’s risk oversight, a number of questions emerge that can be informed by academic research related to ERM. This article summarizes findings from ERM research to provide insights related to the board’s risk governance responsibilities. We also identify a number of research questions that warrant further analysis by governance scholars. It is our hope that this article will spawn varying types of research about ERM and corporate governance.

  17. Chronic alcoholism: insights from neurophysiology.

    Science.gov (United States)

    Campanella, S; Petit, G; Maurage, P; Kornreich, C; Verbanck, P; Noël, X

    2009-01-01

    Increasing knowledge of the anatomical structures and cellular processes underlying psychiatric disorders may help bridge the gap between clinical signs and basic physiological processes. Accordingly, considerable insight has been gained in recent years into a common psychiatric condition, i.e., chronic alcoholism. We reviewed various physiological parameters that are altered in chronic alcoholic patients compared to healthy individuals--continuous electroencephalogram, oculomotor measures, cognitive event-related potentials and event-related oscillations--to identify links between these physiological parameters, altered cognitive processes and specific clinical symptoms. Alcoholic patients display: (1) high beta and theta power in the resting electroencephalogram, suggesting hyperarousal of their central nervous system; (2) abnormalities in smooth pursuit eye movements, in saccadic inhibition during antisaccade tasks, and in prepulse inhibition, suggesting disturbed attention modulation and abnormal patterns of prefrontal activation that may stem from the same prefrontal "inhibitory" cortical dysfunction; (3) decreased amplitude for cognitive event-related potentials situated along the continuum of information-processing, suggesting that alcoholism is associated with neurophysiological deficits at the level of the sensory cortex and not only disturbances involving associative cortices and limbic structures; and (4) decreased theta, gamma and delta oscillations, suggesting cognitive disinhibition at a functional level. The heterogeneity of alcoholic disorders in terms of symptomatology, course and outcome is the result of various pathophysiological processes that physiological parameters may help to define. These alterations may be related to precise cognitive processes that could be easily monitored neurophysiologically in order to create more homogeneous subgroups of alcoholic individuals.

  18. Functional Insights from Structural Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Forouhar,F.; Kuzin, A.; Seetharaman, J.; Lee, I.; Zhou, W.; Abashidze, M.; Chen, Y.; Montelione, G.; Tong, L.; et al

    2007-01-01

    Structural genomics efforts have produced structural information, either directly or by modeling, for thousands of proteins over the past few years. While many of these proteins have known functions, a large percentage of them have not been characterized at the functional level. The structural information has provided valuable functional insights on some of these proteins, through careful structural analyses, serendipity, and structure-guided functional screening. Some of the success stories based on structures solved at the Northeast Structural Genomics Consortium (NESG) are reported here. These include a novel methyl salicylate esterase with important role in plant innate immunity, a novel RNA methyltransferase (H. influenzae yggJ (HI0303)), a novel spermidine/spermine N-acetyltransferase (B. subtilis PaiA), a novel methyltransferase or AdoMet binding protein (A. fulgidus AF{_}0241), an ATP:cob(I)alamin adenosyltransferase (B. subtilis YvqK), a novel carboxysome pore (E. coli EutN), a proline racemase homolog with a disrupted active site (B. melitensis BME11586), an FMN-dependent enzyme (S. pneumoniae SP{_}1951), and a 12-stranded {beta}-barrel with a novel fold (V. parahaemolyticus VPA1032).

  19. A Microgenetic Study of Insightful Problem Solving

    Science.gov (United States)

    Luwel, Koen; Siegler, Robert S.; Verschaffel, Lieven

    2008-01-01

    An eight-session microgenetic study of acquisition of an insightful problem-solving strategy was conducted. A total of 35 second graders who did not use this insightful strategy initially were assigned to two groups that differed in the frequency of problems likely to facilitate discovery and generalization of the strategy. Children in the…

  20. Mining Login Data for Actionable Student Insight

    Science.gov (United States)

    Agnihotri, Lalitha; Aghababyan, Ani; Mojarad, Shirin; Riedesel, Mark; Essa, Alfred

    2015-01-01

    Student login data is a key resource for gaining insight into their learning experience. However, the scale and the complexity of this data necessitate a thorough exploration to identify potential actionable insights, thus rendering it less valuable compared to student achievement data. To compensate for the underestimation of login data…

  1. Relationship between insight and theory of mind in schizophrenia: A meta-analysis.

    Science.gov (United States)

    Bora, Emre

    2017-12-01

    Poor insight in schizophrenia has been associated with executive dysfunction and deficits in general cognitive ability. The overall outcome of available neurocognitive studies suggests that there is a significant but modest relationship between cognitive deficits and poor insight in schizophrenia. However, social cognitive abilities, particularly, theory of mind (ToM), might also play a role in poor insight in schizophrenia. A novel meta-analysis of the relationship between ToM and insight in schizophrenia was conducted. Current meta-analysis included 16 studies including 1085 patients with schizophrenia-spectrum disorders. There was a significant association between ToM and clinical insight (r=0.28, CI=0.20-0.36). By contrast, there was no significant relationship between ToM and cognitive insight. Current findings suggest that there is a small but significant relationship between ToM and clinical insight in schizophrenia. ToM impairment is one of the factors contributing to poor insight in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Perioperative leadership: managing change with insights, priorities, and tools.

    Science.gov (United States)

    Taylor, David L

    2014-07-01

    The personal leadership of the perioperative director is a critical factor in the success of any change management initiative. This article presents an approach to perioperative nursing leadership that addresses obstacles that prevent surgical departments from achieving high performance in clinical and financial outcomes. This leadership approach consists of specific insights, priorities, and tools: key insights include self-understanding of personal barriers to leadership and accuracy at understanding economic and strategic considerations related to the OR environment; key priorities include creating a customer-centered organization, focusing on process improvement, and concentrating on culture change; and key tools include using techniques (e.g., direct engagement, collaborative leadership) to align surgical organizations with leadership priorities and mitigate specific perioperative management risks. Included in this article is a leadership development plan for perioperative directors. Copyright © 2014 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  3. Exploring the reducing role of boron: added insights from theory.

    Science.gov (United States)

    Dangat, Yuvraj; Vanka, Kumar

    2016-04-14

    Carbon-carbon coupling in CO molecules is a challenging proposition, and very few main group complexes have been shown to effect this process. A recently reported triply bonded diboryne system (1) is notable for coupling four CO molecules to produce a (bis)boralactone species. The current full quantum chemical computational investigation with density functional theory (DFT) provides important insights into the nature of the CO coupling process by triply bonded diboryne systems. The complete reaction pathway leading to the formation of the (bis)boralactone has been determined. Factors that make this system so successful in coupling CO groups have been elucidated, and pertinent issues, such as why the coupling process stops after four CO additions, have been explored. Also, importantly, insights have been gained through the natural bond orbital (NBO) analysis into how the back-donation from diboryne activates CO.

  4. Two-factor authentication

    CERN Document Server

    Stanislav, Mark

    2015-01-01

    During the book, readers will learn about the various technical methods by which two-factor authentication is implemented, security concerns with each type of implementation, and contextual details to frame why and when these technologies should be used. Readers will also be provided with insight about the reasons that two-factor authentication is a critical security control, events in history that have been important to prove why organization and individual would want to use two factor, and core milestones in the progress of growing the market.

  5. Breast Cancer Vaccines: New Insights

    OpenAIRE

    Benedetti, Rosaria; Dell’Aversana, Carmela; Giorgio, Cristina; Astorri, Roberta; Altucci, Lucia

    2017-01-01

    Breast cancer (BC) is a persistent global challenge for its high frequency in women (although it seldom occurs in men), due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and rec...

  6. Blindness and Insight in King Lear

    Institute of Scientific and Technical Information of China (English)

    岳元玉

    2008-01-01

    This paper intends to explore how William Shakespeare illustrates the theme of blindness and insight in his great tragedy "King Lear".Four characters’ deeds and their fate are used as a case study to examine what blindness is,what insight is,and the relationship between the two.The writer finds that by depicting the characters’ deeds and their fate in a double plot,Shakespeare renders the folly of blindness,the transition from blindness to insight,and the use of reason and thought to understand the truth.

  7. A cross-sectional study of insight and family accommodation in pediatric obsessive-compulsive disorder

    Science.gov (United States)

    2013-01-01

    Background Factors predicting treatment outcome in pediatric patients with obsessive-compulsive disorder (OCD) include disease severity, functional impairment, comorbid disorders, insight, and family accommodation (FA). Treatment of pediatric OCD is often only partly successful as some of these predictors are not targeted with conventional therapy. Among these, insight and FA were identified to be modifiable predictors of special relevance to pediatric OCD. Despite their clinical relevance, insight and FA remain understudied in youth with OCD. This study examined the clinical correlates of insight and FA and determined whether FA mediates the relationship between symptom severity and functional impairment in pediatric OCD. Methods This was a cross-sectional, outpatient study. Thirty-five treatment-naive children and adolescentswith DSM-IV diagnosis of OCD (mean age: 13.11 ± 3.16; 54.3% males) were included. Standard questionnaires were administered for assessing the study variables. Insight and comorbidities were assessed based on clinician’s interview. Subjects were categorized as belonging to a high insight or a low insight group, and the differences between these two groups were analyzed using ANOVA. Pearson’s correlation coefficients were calculated for the remaining variables of interest. Mediation analysis was carried out using structural equation modeling. Results Relative to those in the high insight group, subjects in the low insight group were younger, had more severe disease and symptoms, and were accommodated to a greater extent by their families. In addition, comorbid depression was more frequent in subjects belonging to the low insight group. Family accommodation was positively related to disease severity, symptom severity, and functional impairment. Family accommodation totally mediated the relationship between symptom severity and functional impairment. Conclusions Results support the differences in the diagnostic criteria between adult and

  8. Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

    2001-09-01

    To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

  9. Insight Is Not in the Problem: Investigating Insight in Problem Solving across Task Types.

    Science.gov (United States)

    Webb, Margaret E; Little, Daniel R; Cropper, Simon J

    2016-01-01

    The feeling of insight in problem solving is typically associated with the sudden realization of a solution that appears obviously correct (Kounios et al., 2006). Salvi et al. (2016) found that a solution accompanied with sudden insight is more likely to be correct than a problem solved through conscious and incremental steps. However, Metcalfe (1986) indicated that participants would often present an inelegant but plausible (wrong) answer as correct with a high feeling of warmth (a subjective measure of closeness to solution). This discrepancy may be due to the use of different tasks or due to different methods in the measurement of insight (i.e., using a binary vs. continuous scale). In three experiments, we investigated both findings, using many different problem tasks (e.g., Compound Remote Associates, so-called classic insight problems, and non-insight problems). Participants rated insight-related affect (feelings of Aha-experience, confidence, surprise, impasse, and pleasure) on continuous scales. As expected we found that, for problems designed to elicit insight, correct solutions elicited higher proportions of reported insight in the solution compared to non-insight solutions; further, correct solutions elicited stronger feelings of insight compared to incorrect solutions.

  10. Impaired insight into illness and cognitive insight in schizophrenia spectrum disorders: Resting state functional connectivity

    Science.gov (United States)

    Gerretsen, Philip; Menon, Mahesh; Mamo, David C.; Fervaha, Gagan; Remington, Gary; Pollock, Bruce G.; Graff-Guerrero, Ariel

    2015-01-01

    Background Impaired insight into illness (clinical insight) in schizophrenia has negative effects on treatment adherence and clinical outcomes. Schizophrenia is described as a disorder of disrupted brain connectivity. In line with this concept, resting state networks (RSNs) appear differentially affected in persons with schizophrenia. Therefore, impaired clinical, or the related construct of cognitive insight (which posits that impaired clinical insight is a function of metacognitive deficits), may reflect alterations in RSN functional connectivity (fc). Based on our previous research, which showed that impaired insight into illness was associated with increased left hemisphere volume relative to right, we hypothesized that impaired clinical insight would be associated with increased connectivity in the DMN with specific left hemisphere brain regions. Methods Resting state MRI scans were acquired for participants with schizophrenia or schizoaffective disorder (n = 20). Seed-to-voxel and ROI-to-ROI fc analyses were performed using the CONN-fMRI fc toolbox v13 for established RSNs. Clinical and cognitive insight were measured with the Schedule for the Assessment of Insight—Expanded Version and Beck Cognitive Insight Scale, respectively, and included as the regressors in fc analyses. Results As hypothesized, impaired clinical insight was associated with increased connectivity in the default mode network (DMN) with the left angular gyrus, and also in the self-referential network (SRN) with the left insula. Cognitive insight was associated with increased connectivity in the dorsal attention network (DAN) with the right inferior frontal cortex (IFC) and left anterior cingulate cortex (ACC). Conclusion Increased connectivity in DMN and SRN with the left angular gyrus and insula, respectively, may represent neural correlates of impaired clinical insight in schizophrenia spectrum disorders, and is consistent with the literature attributing impaired insight to left

  11. Physiological and molecular insights into drought tolerance ...

    African Journals Online (AJOL)

    Physiological and molecular insights into drought tolerance. Sagadevan G Mundree, Bienyameen Baker, Shaheen Mowla, Shaun Peters, Saberi Marais, Clare Vander Willigen, Kershini Govender, Alice Maredza, Samson Muyanga, Jill M Farrant, Jennifer A Thomson ...

  12. Marketing biofortified crops: insights from consumer research ...

    African Journals Online (AJOL)

    Marketing biofortified crops: insights from consumer research. ... To develop a global strategy for consumer marketing of biofortified crops, research is needed to understand consumer ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  13. Proteus, New Insights for a New Age

    National Research Council Canada - National Science Library

    Waddell, William; Kim, Joanne; Smith, Jack

    2004-01-01

    .... The Proteus concept offers a range of new insights that, when used in the planning process, will assist military, intelligence, and industry leaders in their efforts to prepare for future success...

  14. New Insights into the Operating Voltage of Aqueous Supercapacitors.

    Science.gov (United States)

    Yu, Minghao; Lu, Yongzhuang; Zheng, Haibing; Lu, Xihong

    2018-03-12

    The main limitation of aqueous supercapacitors (SCs) lies in their narrow operating voltages, especially when compared with organic SCs. Fundamental understanding of factors relevant to the operating voltage helps providing guidance for the assembly of high-voltage aqueous SCs. In this regard, this concept analyzes the deciding factors for the operating voltage of aqueous SCs. Strategies applied to expand the operating voltage are summarized and discussed from the aspects of electrolyte, electrode, and asymmetric structure. Dynamic factors associated with water electrolysis and maximally using the available potential ranges of electrodes are particularly emphasized. Finally, other promising approaches that have not been explored and their challenges are also elaborated, hoping to provide more insights for the design of high-voltage aqueous SCs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Rare primary headaches: clinical insights.

    Science.gov (United States)

    Casucci, G; d'Onofrio, F; Torelli, P

    2004-10-01

    So-called "rare" headaches, whose prevalence rate is lower than 1% or is not known at all and have been reported in only a few dozen cases to date, constitute a very heterogeneous group. Those that are best characterised from the clinical point of view can be classified into forms with prominent autonomic features and forms with sparse or no autonomic features. Among the former are trigeminal autonomic cephalalgias (TACs) and hemicrania continua, while the latter comprise classical trigeminal neuralgia, hypnic headache, primary thunderclap headache, and exploding head syndrome. The major clinical discriminating factor for the differential diagnosis of TACs is the relationship between duration and frequency of attacks: the forms in which pain is shorter lived are those with the higher frequency of daily attacks. Other aspects to be considered are the time pattern of symptoms, intensity and timing of attacks, the patient's behaviour during the attacks, the presence of any triggering factors and of the refractory period after an induced attack, and response to therapy, especially with indomethacin. Often these are little known clinical entities, which are not easily detected in clinical practice. For some of them, e. g., thunderclap headache, it is always necessary to perform instrumental tests to exclude the presence of underlying organic diseases.

  16. Overlap and distinction between measures of insight and self-stigma.

    Science.gov (United States)

    Hasson-Ohayon, Ilanit

    2018-05-24

    Multiple studies on insight into one's illness and self-stigma among patients with serious mental illness and their relatives have shown that these constructs are related to one another and that they affect outcome. However, a critical exploration of the items used to assess both constructs raises questions with regard to the possible overlapping and centrality of items. The current study used five different samples to explore the possible overlap and distinction between insight and self-stigma, and to identify central items, via network analyses and principal component factor analysis. Findings from the network analyses showed overlap between insight and self-stigma exist with a relatively clearer observational distinction between the constructs among the two parent samples in comparison to the patient samples. Principal component factor analysis constrained to two factors showed that a relatively high percentage of items were not loaded on either factor, and in a few datasets, several insight items were loaded on the self-stigma scale and vice versa. The author discusses implications for research and calls for rethinking the way insight is assessed. Clinical implications are also discussed in reference to central items of social isolation, future worries and stereotype endorsement among the different study groups. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Ruminant Nutrition Symposium: Acidosis: new insights into the persistent problem.

    Science.gov (United States)

    Oba, M; Wertz-Lutz, A E

    2011-04-01

    The Ruminant Nutrition Symposium titled "Acidosis: New insights into the persistent problem" was held at the Joint Annual Meeting of the American Dairy Science Association, American Society of Animal Science, Poultry Science Association, Asociación Mexicana de Producción Animal, Western Section-ASAS, and the Canadian Society of Animal Science in Denver, Colorado, July 11 to 15, 2010. The objective of the symposium was to provide the ruminant nutrition community with new insights and perspectives from recent research findings on acidosis. Under modern production systems, ruminants are fed high-grain diets to maximize their energy intake and productivity. However, feeding highly fermentable diets often causes excess fermentation and results in accumulation of fermentation acids in the rumen, leading to a decrease in feed intake, poor feed efficiency, liver abscesses, and lameness in feedlot cattle or lactating dairy cows. Although our understanding of nutritional factors (i.e., effects of type and processing method of grains and importance of physically effective fiber) affecting rumen pH have increased substantially over the past few decades, rumen acidosis has continued to be a common problem in the ruminant livestock industry. The symposium program was organized to review recent research findings in acidosis with more emphasis on physiological aspects, and provide novel insights into the persistent problem.

  18. Insight into mental illness and child maltreatment risk among mothers with major psychiatric disorders.

    Science.gov (United States)

    Mullick, M; Miller, L J; Jacobsen, T

    2001-04-01

    This study examined the relationship between insight into mental illness and current child maltreatment risk among mothers who had a major psychiatric disorder and who had lost custody of a child because of abuse, neglect, or having placed the child at risk of harm. Specifically, a measure of insight was examined in relation to systematically observed parenting behaviors known to be correlated with past child maltreatment and in relation to a comprehensive clinical determination of risk. Forty-four mothers who had a major psychiatric disorder were independently rated for their insight into their illness, the quality of mother-child interaction, and the overall clinical risk of maltreatment. Better insight into mental illness was associated with more sensitive mothering behavior and with lower assessed clinical risk of maltreatment. The association remained when mothers with current psychotic symptoms were excluded from the analyses. Better insight did not appear to be associated with past psychotic symptoms, maternal psychiatric diagnosis, or the mother's level of education. Insight into mental illness may function as a protective factor that influences the risk of child maltreatment in mothers with mental illness. Measures of insight could be usefully incorporated into comprehensive parenting assessments for mothers with psychiatric disorders.

  19. Insight and subjective measures of quality of life in chronic schizophrenia.

    Science.gov (United States)

    Siu, Cynthia O; Harvey, Philip D; Agid, Ofer; Waye, Mary; Brambilla, Carla; Choi, Wing-Kit; Remington, Gary

    2015-09-01

    Lack of insight is a well-established phenomenon in schizophrenia, and has been associated with reduced rater-assessed functional performance but increased self-reported well-being in previous studies. The objective of this study was to examine factors that might influence insight (as assessed by the Insight and Treatment Attitudes Questionnaire [ITAQ] or PANSS item G12) and subjective quality-of-life (as assessed by Lehman QoL Interview [LQOLI]), using the large National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset. Uncooperativeness was assessed by PANSS item G8 ("Uncooperativeness"). In the analysis, we found significant moderating effects for insight on the relationships of subjective life satisfaction assessment to symptom severity (as assessed by CGI-S score), objective everyday functioning (as assessed by rater-administered Heinrichs-Carpenter Quality of Life scale), clinically rated uncooperativeness (as assessed by PANSS G8), and discontinuation of treatment for all causes (all P > 0.05 for statistical interaction between insight and subject QoL). Patients with chronic schizophrenia who reported being "pleased" or "delighted" on LQOLI were found to have significantly lower neurocognitive reasoning performance and poorer insight (ITAQ total score). Our findings underscore the importance of reducing cognitive and insight impairments for both treatment compliance and improved functional outcomes.

  20. Insight into magnetorheological shock absorbers

    CERN Document Server

    Gołdasz, Janusz

    2015-01-01

    This book deals with magnetorheological fluid theory, modeling and applications of automotive magnetorheological dampers. On the theoretical side a review of MR fluid compositions and key factors affecting the characteristics of these fluids is followed by a description of existing applications in the area of vibration isolation and flow-mode shock absorbers in particular. As a majority of existing magnetorheological devices operates in a so-called flow mode a critical review is carried out in that regard. Specifically, the authors highlight common configurations of flow-mode magnetorheological shock absorbers, or so-called MR dampers that have been considered by the automotive industry for controlled chassis applications. The authors focus on single-tube dampers utilizing a piston assembly with one coil or multiple coils and at least one annular flow channel in the piston.

  1. Pulsatile luteinizing hormone secretion in patients with Addison's disease. Impact of glucocorticoid substitution

    DEFF Research Database (Denmark)

    Hangaard, J; Andersen, M; Grodum, E

    1998-01-01

    The physiological and pathophysiological role of cortisol in pulsatile LH release was investigated in 14 patients (5 men, 6 premenopausal women, and 3 postmenopausal women) with Addison's disease. The explicit effect of cortisol in relation to the effect of corticotropin-releasing factor (CRF......), ACTH, and opioids was ensured by hypo-, normo-, and hypercortisolism. Hypocortisolism was obtained by 24-h discontinuation of hydrocortisone (HC) followed by 23-h saline infusion. Eucortisolism was secured by infusion of HC (0.5 mg/kg) over 23 h. Stress-appropriate hypercortisolism was obtained...

  2. 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.

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

    Science.gov (United States)

    Stengel, Andreas; Taché, Yvette F

    2017-01-01

    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.

  4. Synthesis and evaluation of radioiodinated NPC 22009, a putative CRF receptor antagonist

    International Nuclear Information System (INIS)

    Balasubramanian, V.; Hiner, R.N.; Mavunkel, B.J.; Elliott, R.L.; Abreu, M.E.

    1992-01-01

    Several studies have suggested that corticotropin-releasing factor (CRF) plays a role in stress-related disorders such as anxiety, depression, anorexia nervosa and stress-induced immune suppression. Hence CRF antagonists have potential therapeutic utility. Recently the authors discovered that pyrazolones such as NPC 22009 and the corresponding disulfide behave as CRF antagonists in vitro with micromolar potency. To probe the nature of this CRF antagonism they developed a convenient synthesis of radioiodinated NPC 22009. Details of the synthesis and preliminary pharmacological studies are presented

  5. Depression

    DEFF Research Database (Denmark)

    Cizza, G; Ravn, Pernille; Chrousos, G P

    2001-01-01

    Existing studies of the relationship between depression and osteoporosis have been heterogeneous in their design and use of diagnostic instruments for depression, which might have contributed to the different results on the comorbidity of these two conditions. Nevertheless, these studies reveal...... a strong association between depression and osteoporosis. Endocrine factors such as depression-induced hypersecretion of corticotropin-releasing hormone and hypercortisolism, hypogonadism, growth hormone deficiency and increased concentration of circulating interleukin 6, might play a crucial role...... in the bone loss observed in subjects suffering from major depression....

  6. Breast Cancer Vaccines: New Insights

    Directory of Open Access Journals (Sweden)

    Rosaria Benedetti

    2017-10-01

    Full Text Available Breast cancer (BC is a persistent global challenge for its high frequency in women (although it seldom occurs in men, due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and recurrence with different modalities. Despite these relatively wide chances, also used in combinatory protocols, relevant mortality and relapse rates, often associated with resistant phenotypes, stress the need for a personalized-medicine based on prompting the patient’s immune system (IS against cancer cells. BC immunogenicity was latterly proven, so the whole immunotherapy field for BC is still at a very early stage. This immunotherapeutic approach exploits both the high specificity of adaptive immune response and the immunological memory. This review is focused on some of the majorly relevant BC vaccines available (NeuVax, AVX901, and INO-1400, providing a description of the more promising clinical trials. The efficacy of cancer vaccines highly depends on the patient’s IS, and a wide optimization is needed in terms of targets’ selection, drug design and combinations, dose finding, protocol structuring, and patients’ recruitment; moreover, new standards are being discussed for the outcome evaluation. However, early-phases excellent results suggest that the manipulation of the IS via specific vaccines is a highly attractive approach for BC.

  7. Avoidant personality disorder: current insights.

    Science.gov (United States)

    Lampe, Lisa; Malhi, Gin S

    2018-01-01

    Avoidant personality disorder (AVPD) is a relatively common disorder that is associated with significant distress, impairment, and disability. It is a chronic disorder with an early age at onset and a lifelong impact. Yet it is underrecognized and poorly studied. Little is known regarding the most effective treatment. The impetus for research into this condition has waxed and waned, possibly due to concerns regarding its distinctiveness from other disorders, especially social anxiety disorder (SAD), schizoid personality disorder, and dependent personality disorder. The prevailing paradigm subscribes to the "severity continuum hypothesis", in which AVPD is viewed essentially as a severe variant of SAD. However, areas of discontinuity have been described, and there is support for retaining AVPD as a distinct diagnostic category. Recent research has focused on the phenomenology of AVPD, factors of possible etiological significance such as early parenting experiences, attachment style, temperament, and cognitive processing. Self-concept, avoidant behavior, early attachments, and attachment style may represent points of difference from SAD that also have relevance to treatment. Additional areas of research not focused specifically on AVPD, including the literature on social cognition as it relates to attachment and personality style, report findings that are promising for future research aimed at better delineating AVPD and informing treatment.

  8. Avoidant personality disorder: current insights

    Directory of Open Access Journals (Sweden)

    Lampe L

    2018-03-01

    Full Text Available Lisa Lampe,1 Gin S Malhi2 1Discipline of Psychiatry, University of Newcastle, Newcastle, NSW, Australia; 2Discipline of Psychiatry, University of Sydney, Sydney, NSW, Australia Abstract: Avoidant personality disorder (AVPD is a relatively common disorder that is associated with significant distress, impairment, and disability. It is a chronic disorder with an early age at onset and a lifelong impact. Yet it is underrecognized and poorly studied. Little is known regarding the most effective treatment. The impetus for research into this condition has waxed and waned, possibly due to concerns regarding its distinctiveness from other disorders, especially social anxiety disorder (SAD, schizoid personality disorder, and dependent personality disorder. The prevailing paradigm subscribes to the “severity continuum hypothesis”, in which AVPD is viewed essentially as a severe variant of SAD. However, areas of discontinuity have been described, and there is support for retaining AVPD as a distinct diagnostic category. Recent research has focused on the phenomenology of AVPD, factors of possible etiological significance such as early parenting experiences, attachment style, temperament, and cognitive processing. Self-concept, avoidant behavior, early attachments, and attachment style may represent points of difference from SAD that also have relevance to treatment. Additional areas of research not focused specifically on AVPD, including the literature on social cognition as it relates to attachment and personality style, report findings that are promising for future research aimed at better delineating AVPD and informing treatment. Keywords: avoidant personality disorder, social anxiety disorder, social cognition, psychotherapy, attachment

  9. Avoidant personality disorder: current insights

    Science.gov (United States)

    Lampe, Lisa; Malhi, Gin S

    2018-01-01

    Avoidant personality disorder (AVPD) is a relatively common disorder that is associated with significant distress, impairment, and disability. It is a chronic disorder with an early age at onset and a lifelong impact. Yet it is underrecognized and poorly studied. Little is known regarding the most effective treatment. The impetus for research into this condition has waxed and waned, possibly due to concerns regarding its distinctiveness from other disorders, especially social anxiety disorder (SAD), schizoid personality disorder, and dependent personality disorder. The prevailing paradigm subscribes to the “severity continuum hypothesis”, in which AVPD is viewed essentially as a severe variant of SAD. However, areas of discontinuity have been described, and there is support for retaining AVPD as a distinct diagnostic category. Recent research has focused on the phenomenology of AVPD, factors of possible etiological significance such as early parenting experiences, attachment style, temperament, and cognitive processing. Self-concept, avoidant behavior, early attachments, and attachment style may represent points of difference from SAD that also have relevance to treatment. Additional areas of research not focused specifically on AVPD, including the literature on social cognition as it relates to attachment and personality style, report findings that are promising for future research aimed at better delineating AVPD and informing treatment. PMID:29563846

  10. [Insight and psychiatric dangerousness: A review of the literature].

    Science.gov (United States)

    Bonnet, S; Lacambre, M; Schandrin, A; Capdevielle, D; Courtet, P

    2017-04-01

    Violence committed by individuals with severe mental illness has become an increasing focus of concern among clinicians, policy makers, and the general public, often as the result of tragic events. Research has shown in the past two decades an increased risk of violence among patients with mental disorder. Nevertheless, of those suffering from mental illness, perpetrators of other directed violence form a minority subgroup. The means by which there is this association between mental illness and violence has remained controversial. Factors such as positive psychotic symptoms, medication non-adherence, alcohol or psychoactive substance abuse and antisocial personality were found to be predictive of violence. Overall, literature provides support to the assertion that violent behavior of mentally ill patients is a heterogeneous phenomenon that is driven by multiple inter-related and independent factors. Furthermore, psychiatrists are often asked to predict an individual's future dangerousness, in a medical or a legal context. In the process of risk assessment of dangerousness, more focus has been placed on dynamic risk factor. In this context, lack of insight has established itself both as a part of violence risk models and as a clinical item in structured approaches to measure dangerousness. However, few studies have tested these associations. The main purpose of this paper is to review the literature concerning the relationship between insight and dangerousness and discuss the contributions of the insight in the assessment of dangerousness in patients with mental illness. We included twenty studies that evaluated the association between insight and variable such as physical or verbal violence, aggressiveness, hostility or sexual aggression. According to the findings of this review, the strength and specific nature of this relationship remain unclear due to considerable methodological and conceptual shortcomings, including heterogeneity in the definition and

  11. New insights into human nondisjunction of chromosome 21 in oocytes.

    Directory of Open Access Journals (Sweden)

    Tiffany Renee Oliver

    2008-03-01

    Full Text Available Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the association between these two well established risk factors for chromosome 21 nondisjunction. In our approach, short tandem repeat markers along chromosome 21 were genotyped in DNA collected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunction error and the maternal recombination profile. We analyzed 615 maternal meiosis I and 253 maternal meiosis II cases stratified by maternal age. The examination of meiosis II errors, the first of its type, suggests that the presence of a single exchange within the pericentromeric region of 21q interacts with maternal age-related risk factors. This observation could be explained in two general ways: 1 a pericentromeric exchange initiates or exacerbates the susceptibility to maternal age risk factors or 2 a pericentromeric exchange protects the bivalent against age-related risk factors allowing proper segregation of homologues at meiosis I, but not segregation of sisters at meiosis II. In contrast, analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte. Our results emphasize the fact that human nondisjunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors.

  12. New Insights in Celiac Disease

    Directory of Open Access Journals (Sweden)

    David Branski

    2012-01-01

    Full Text Available Celiac disease (CD is an autoimmune disorder occurring in genetically susceptible subjects. The incidence of CD is around 1%, and it is much more common in first-degree relatives of CD patients, 10%–18%. However, the pattern of the genetic inheritance is still obscure. Environmental factors are undoubtedly affecting the disease’s clinical presentation, time at presentation, and may have an effect on the characteristics of the disease. The clinical presentation of CD has shifted during the previous decades from the classical presentation in which the toddler suffers from diarrhea, constipation, vomiting, failure to thrive, abdominal distension, etc., to the child with a monosymptomatic presentation, such as anemia, as well as an enlarged list of extra-intestinal disorders. The diagnosis of CD is being established by symptoms consistent with CD and positive serology. The ultimate diagnosis should be made upon histological evaluation of the small bowel mucosa. The treatment of CD is a lifelong, strict gluten-free diet (GFD. Compliance with a GFD is quite difficult. Therefore, new strategies for prevention and treatment modalities other than GFD are greatly needed. Recently several promising therapeutic modalities have been developed; these include resuming traditional baking techniques. Another methodology is using probiotic-driven prolylendopeptidase. Another pathway to tackle the therapeutic option in CD is by down-regulation of the activity of zonulin—the active pump enabling gluten to enter the enterocytes. We are facing an era where other modalities beyond a GFD might allow CD patients to be able to tolerate occasionally a small amount of gluten in their diet.

  13. Oppositional defiant disorder: current insight

    Directory of Open Access Journals (Sweden)

    Ghosh A

    2017-11-01

    Full Text Available Abhishek Ghosh,1 Anirban Ray,2 Aniruddha Basu1 1Drug De-addiction and Treatment Centre, Department of Psychiatry, Postgraduate Institute of Medical Education and Research (PGIMER, Chandigarh, 2Department of Psychiatry, Institute of Psychiatry, Institute of Post Graduate Medical Education and Research, Kolkata, India Abstract: Oppositional defiant disorder (ODD is diagnosed broadly on the basis of frequent and persistent angry or irritable mood, argumentativeness/defiance, and vindictiveness. Since its inception in the third Diagnostic and Statistical Manual of Mental Disorders, epidemiological and longitudinal studies have strongly suggested a distinct existence of ODD that is different from other closely related externalizing disorders, with different course and outcome and possibly discrete subtypes. However, several issues, such as symptom threshold, dimensional versus categorical conceptualization, and sex-specific symptoms, are yet to be addressed. Although ODD was found to be highly heritable, no genetic polymorphism has been identified with confidence. There has been a definite genetic overlap with other externalizing disorders. Studies have begun to explore its epigenetics and gene–environment interaction. Neuroimaging findings converge to implicate various parts of the prefrontal cortex, amygdala, and insula. Alteration in cortisol levels has also been demonstrated consistently. Although a range of environmental factors, both familial and extrafamilial, have been studied in the past, current research has combined these with other biological parameters. Psychosocial treatment continues to be time-tested and effective. These include parental management training, school-based training, functional family therapy/brief strategic family therapy, and cognitive behavior therapy. Management of severe aggression and treatment of co-morbid disorders are indications for pharmacotherapy. In line with previous conceptualization of chronic

  14. Is Insight Always the Same? A Protocol Analysis of Insight in Compound Remote Associate Problems

    Science.gov (United States)

    Cranford, Edward A.; Moss, Jarrod

    2012-01-01

    Compound Remote Associate (CRA) problems have been used to investigate insight problem solving using both behavioral and neuroimaging techniques. However, it is unclear to what extent CRA problems exhibit characteristics of insight such as impasses and restructuring. CRA problem-solving characteristics were examined in a study in which…

  15. IPE data base structure and insights

    International Nuclear Information System (INIS)

    Lehner, J.; Youngblood, R.

    1993-01-01

    A data base (the ''IPE Insights Data Base''), has been developed that stores data obtained from the Individual Plant Examinations (IPEs) which licensees of nuclear power plants are conducting in response to the Nuclear Regulatory Commission's (NRC) Generic Letter GL88-20. The data base, which is a collection of linked dbase files, stores information about individual plant designs, core damage frequency, and containment performance in a uniform, structured way. This data base can be queried and used as a computational tool to derive insights regarding the plants for which data is stored. This paper sets out the objectives of the IPE Insights Data Base, describes its structure and contents, illustrates sample queries, and discusses possible future uses

  16. IPE data base structure and insights

    International Nuclear Information System (INIS)

    Lehner, J.; Youngblood, R.

    1994-01-01

    A data base (the open-quotes IPE Insights Data Baseclose quotes), has been developed that stores data obtained from the Individual Plant Examinations (IPEs) which licensees of nuclear power plants are conducting in response to the Nuclear Regulatory Commission's (NRC) Generic Letter GL88-20. The data base, which is a collection of linked dBase files, stores information about individual plant designs, core damage frequency, and containment performance in a uniform, structured way. This data base can be queried and used as a computational tool to derive insights regarding the plants for which data is stored. This paper sets out the objectives of the IPE Insights Data Base, describes its structure and contents, illustrates sample queries, and discusses possible future uses

  17. Illness Insight and Recovery: How Important is Illness Insight in Peoples’ Recovery Process?

    DEFF Research Database (Denmark)

    Korsbek, Lisa

    2013-01-01

    . Sources Used:The writing is based on research literature related to illness insight and on personal recovery experiences.Conclusions and Implications for Practice: It is helpful to consider the integration of the issue of illness insight when addressing the questions and consequences of diagnosis......Topic: This account reflects on the topic of illness insight and recovery. Purpose: The purpose of the account is to clarify our understanding about the importance of illness insight in peoples’ recovery process, especially when relating the question of illness insight to the question of identity......, and to assist individuals to work through the false analogy between illness and identity while supporting the transformation from patient to person. It is also necessary for clinicians to develop a clear understanding of peoples’ actual needs and gain more knowledge about peoples’ own views and experiences...

  18. Decision insight into stakeholder conflict for ERN.

    Energy Technology Data Exchange (ETDEWEB)

    Siirola, John; Tidwell, Vincent Carroll; Benz, Zachary O.; Stansbury, Melanie; Richards, Elizabeth H.; Turnley, Jessica Glicken (Galisteo Consulting); Warrender, Christina E.; Morrow, James Dan

    2012-02-01

    Participatory modeling has become an important tool in facilitating resource decision making and dispute resolution. Approaches to modeling that are commonly used in this context often do not adequately account for important human factors. Current techniques provide insights into how certain human activities and variables affect resource outcomes; however, they do not directly simulate the complex variables that shape how, why, and under what conditions different human agents behave in ways that affect resources and human interactions related to them. Current approaches also do not adequately reveal how the effects of individual decisions scale up to have systemic level effects in complex resource systems. This lack of integration prevents the development of more robust models to support decision making and dispute resolution processes. Development of integrated tools is further hampered by the fact that collection of primary data for decision-making modeling is costly and time consuming. This project seeks to develop a new approach to resource modeling that incorporates both technical and behavioral modeling techniques into a single decision-making architecture. The modeling platform is enhanced by use of traditional and advanced processes and tools for expedited data capture. Specific objectives of the project are: (1) Develop a proof of concept for a new technical approach to resource modeling that combines the computational techniques of system dynamics and agent based modeling, (2) Develop an iterative, participatory modeling process supported with traditional and advance data capture techniques that may be utilized to facilitate decision making, dispute resolution, and collaborative learning processes, and (3) Examine potential applications of this technology and process. The development of this decision support architecture included both the engineering of the technology and the development of a participatory method to build and apply the technology

  19. Human Performance on Insight Problem Solving: A Review

    Science.gov (United States)

    Chu, Yun; MacGregor, James N.

    2011-01-01

    The article provides a review of recent research on insight problem-solving performance. We discuss what insight problems are, the different types of classic and newer insight problems, and how we can classify them. We also explain some of the other aspects that affect insight performance, such as hints, analogs, training, thinking aloud, and…

  20. Insight, Cognitive Insight and Sociodemographic Features in Obsessive Compulsive Disorder Presenting with Reactive and Autogeneus Features

    Directory of Open Access Journals (Sweden)

    Katre ÇAMLI

    2012-03-01

    Full Text Available Objective: The aim of the present study was to test hypothesis that obsessive compulsive disorder (OCD patients who have autogenous obsessions and reactive obsessions show different sociodemographic and clinical characteristics with different insight and cognitive insight levels. Method: Sixty-one patients diagnosed as OCD according to the Structured Clinical Interview for DSM-III-R (SCID-I are recruited. 31 patients had reactive obsessions and 30 had autogenous obsessions. The sociodemographic characteristics of patients and the symptomatology were evaluated using psychiatric scales including SCID-I, Yale Brown Obsessive- Compulsive Scale (YBOCS, Yale Brown Obsessive-Compulsive Scale-Symptom Checklist (YBOCS-SC and Beck Insight Scale. Results: The percentage of women in reactive obsessive group was higher and also this group had significantly less antipsychotic medication prescribed than the autogenous obsessive group. No significant difference was found for the other demographic variables. No significant difference was identified for the Beck Insight Self-Reflectiveness subscale but for the Self-Certainty subscale, reactive obsessives had higher scores. Although there was no significant difference for the composit index points, which is the subtraction of the two subscales, the p value was close to the limit. On the other hand YBOCS item- 11 scores which evaluates insight were higher in autogenous obsessives meaning low levels of insight. Conclusion: For the sociodemographic and clinical characteristics; there was no significant difference between the groups except gender distribution and antipsychotic medication. Our data about insight seems inconsistent but insight and cognitive insight can be different entities which show different levels of insight. Further investigation with different obsession types is needed.

  1. Development of mechanical hypersensitivity in rats during heroin and ethanol dependence: alleviation by CRF₁ receptor antagonism.

    Science.gov (United States)

    Edwards, Scott; Vendruscolo, Leandro F; Schlosburg, Joel E; Misra, Kaushik K; Wee, Sunmee; Park, Paula E; Schulteis, Gery; Koob, George F

    2012-02-01

    Animal models of drug dependence have described both reductions in brain reward processes and potentiation of stress-like (or anti-reward) mechanisms, including a recruitment of corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to opiates often leads to the development of mechanical hypersensitivity. We measured paw withdrawal thresholds (PWTs) in male Wistar rats allowed limited (short access group: ShA) or extended (long access group: LgA) access to heroin or cocaine self-administration, or in rats made dependent on ethanol via ethanol vapor exposure (ethanol-dependent group). In heroin self-administering animals, after transition to LgA conditions, thresholds were reduced to around 50% of levels observed at baseline, and were also significantly lower than thresholds measured in animals remaining on the ShA schedule. In contrast, thresholds in animals self-administering cocaine under either ShA (1 h) or LgA (6 h) conditions were unaltered. Similar to heroin LgA rats, ethanol-dependent rats also developed mechanical hypersensitivity after eight weeks of ethanol vapor exposure compared to non-dependent animals. Systemic administration of the CRF1R antagonist MPZP significantly alleviated the hypersensitivity observed in rats dependent on heroin or ethanol. The emergence of mechanical hypersensitivity with heroin and ethanol dependence may thus represent one critical drug-associated negative emotional state driving dependence on these substances. These results also suggest a recruitment of CRF-regulated nociceptive pathways associated with escalation of intake and dependence. A greater understanding of relationships between chronic drug exposure and pain-related states may provide insight into mechanisms underlying the transition to drug addiction, as well as reveal new treatment opportunities. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Behavioral, biological, and chemical perspectives on targeting CRF1 receptor antagonists to treat alcoholism

    Science.gov (United States)

    Zorrilla, Eric P.; Heilig, Markus; de Wit, Harriet; Shaham, Yavin

    2013-01-01

    Background Alcohol use disorders are chronic disabling conditions for which existing pharmacotherapies have only modest efficacy. In the present review, derived from the 2012 Behavior, Biology and Chemistry “Translational Research in Addiction” symposium, we summarize the anti-relapse potential of corticotropin-releasing factor type 1 (CRF1) receptor antagonists to reduce negative emotional symptoms of acute and protracted alcohol withdrawal and stress-induced relapse to alcohol seeking. Methods We review the biology of CRF1 systems, the activity of CRF1 receptor antagonists in animal models of anxiolytic and antidepressant activity, and experimental findings in alcohol addiction models. We also update the clinical trial status of CRF1 receptor antagonists, including pexacerfont (BMS-562086), emicerfont (GW876008), verucerfont (GSK561679), CP316311, SSR125543A, R121919/NBI30775, R317573/19567470/CRA5626, and ONO-2333Ms. Finally, we discuss the potential heterogeneity and pharmacogenomics of CRF1 receptor pharmacotherapy for alcohol dependence. Results The evidence suggests that brain penetrant-CRF1 receptor antagonists have therapeutic potential for alcohol dependence. Lead compounds with clinically desirable pharmacokinetic properties now exist, and longer receptor residence rates (i.e., slow dissociation) may predict greater CRF1 receptor antagonist efficacy. Functional variants in genes that encode CRF system molecules, including polymorphisms in Crhr1 (rs110402, rs1876831, rs242938) and Crhbp genes (rs10055255, rs3811939) may promote alcohol seeking and consumption by altering basal or stress-induced CRF system activation. Conclusions Ongoing clinical trials with pexacerfont and verucerfont in moderately to highly severe dependent anxious alcoholics may yield insight as to the role of CRF1 receptor antagonists in a personalized medicine approach to treat drug or alcohol dependence. PMID:23294766

  3. The CRF system mediates increased passive stress-coping behavior following the loss of a bonded partner in a monogamous rodent.

    Science.gov (United States)

    Bosch, Oliver J; Nair, Hemanth P; Ahern, Todd H; Neumann, Inga D; Young, Larry J

    2009-05-01

    Social relationships significantly influence physiology and behavior, including the hypothalamo-pituitary-adrenal axis, anxiety, and mental health. Disruption of social bonds through separation or death often results in profound grieving, depression, and physical illness. As the monogamous prairie vole forms enduring, selective pair bonds with the mating partner, they provide an animal model to study the physiological consequences of pair bonding and, thus, the loss of the bonded partner. Male prairie voles were paired with a novel female or male sibling. After 5 days, half of the males of each group were separated from the partner. Elevated plus-maze, forced swim, and tail suspension tests were used to assess anxiety-like and passive stress-coping behaviors indicative of depressive-like behavior. Following 4 days of separation from the female but not the male partner, experimental males displayed increased passive stress-coping. This effect was abolished by long-term intracerebroventricular infusion of a nonselective corticotropin-releasing factor (CRF) receptor antagonist without disrupting the bond itself. Both CRF type 1 and 2 receptors were involved in the emergence of passive stress-coping behavior. Furthermore, pairing with a female was associated with elevated CRF mRNA in the bed nucleus of the stria terminalis, and partner loss elicited a pronounced increase in circulating corticosteroid and adrenal weight. We speculate that the CRF system may mediate an aversive affect following separation from the female partner, which may facilitate proximity seeking between the pair-bonded individuals. Hence, the prairie vole model may provide insights into brain mechanisms involved in the psychopathological consequences of partner loss.

  4. Chronic and acute effects of stress on energy balance: are there appropriate animal models?

    Science.gov (United States)

    Harris, Ruth B S

    2015-02-15

    Stress activates multiple neural and endocrine systems to allow an animal to respond to and survive in a threatening environment. The corticotropin-releasing factor system is a primary initiator of this integrated response, which includes activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The energetic response to acute stress is determined by the nature and severity of the stressor, but a typical response to an acute stressor is inhibition of food intake, increased heat production, and increased activity with sustained changes in body weight, behavior, and HPA reactivity. The effect of chronic psychological stress is more variable. In humans, chronic stress may cause weight gain in restrained eaters who show increased HPA reactivity to acute stress. This phenotype is difficult to replicate in rodent models where chronic psychological stress is more likely to cause weight loss than weight gain. An exception may be hamsters subjected to repeated bouts of social defeat or foot shock, but the data are limited. Recent reports on the food intake and body composition of subordinate members of group-housed female monkeys indicate that these animals have a similar phenotype to human stress-induced eaters, but there are a limited number of investigators with access to the model. Few stress experiments focus on energy balance, but more information on the phenotype of both humans and animal models during and after exposure to acute or chronic stress may provide novel insight into mechanisms that normally control body weight. Copyright © 2015 the American Physiological Society.

  5. The CRF system and social behavior: a review.

    Science.gov (United States)

    Hostetler, Caroline M; Ryabinin, Andrey E

    2013-01-01

    The corticotropin-releasing factor (CRF) system plays a key role in a diversity of behaviors accompanying stress, anxiety and depression. There is also substantial research on relationships between social behaviors and the CRF system in a variety of taxa including fish, birds, rodents, and primates. Some of these relationships are due to the broad role of CRF and urocortins in stress and anxiety, but these peptides also modulate social behavior specifically. For example, the social interaction (SI) test is often used to measure anxiety-like behavior. Many components of the CRF system including CRF, urocortin1, and the R1 receptor have been implicated in SI, via general effects on anxiety as well as specific effects depending on the brain region. The CRF system is also highly responsive to chronic social stressors such as social defeat and isolation. Animals exposed to these stressors display a number of anxiety- and stress-related behaviors, accompanied by changes in specific components the CRF system. Although the primary focus of CRF research on social behavior has been on the deleterious effects of social stress, there are also insights on a role for CRF and urocortins in prosocial and affiliative behaviors. The CRF system has been implicated in parental care, maternal defense, sexual behavior, and pair bonding. Species differences in the ligands and CRF receptors have been observed in vole and bird species differing in social behavior. Exogenous administration of CRF facilitates partner preference formation in monogamous male prairie voles, and these effects are dependent on both the CRF R1 and R2 receptors. These findings are particularly interesting as studies have also implicated the CRF and urocortins in social memory. With the rapid progress of social neuroscience and in understanding the complex structure of the CRF system, the next challenge is in parsing the exact contribution of individual components of this system to specific social behaviors.

  6. The CRF System and Social Behavior: A Review

    Directory of Open Access Journals (Sweden)

    Caroline M Hostetler

    2013-05-01

    Full Text Available The corticotropin-releasing factor (CRF system plays a key role in a diversity of behaviors accompanying stress, anxiety and depression. There is also substantial research on relationships between social behaviors and the CRF system in a variety of taxa including fish, birds, rodents, and primates. Some of these relationships are due to the broad role of CRF and urocortins in stress and anxiety, but these peptides also modulate social behavior specifically. For example, the social interaction (SI test is often used to measure anxiety-like behavior. Many components of the CRF system including CRF, urocortin1, and the R1 receptor have been implicated in SI, via general effects on anxiety as well as specific effects depending on the brain region. The CRF system is also highly responsive to chronic social stressors such as social defeat and isolation. Animals exposed to these stressors display a number of anxiety- and stress-related behaviors, accompanied by changes in specific components the CRF system. Although the primary focus of CRF research on social behavior has been on the deleterious effects of social stress, there are also insights on a role for CRF and urocortins in prosocial and affiliative behaviors. The CRF system has been implicated in parental care, maternal defense, sexual behavior, and pair bonding. Species differences in the ligands and CRF receptors have been observed in vole and bird species differing in social behavior. Exogenous administration of CRF facilitates partner preference formation in monogamous male prairie voles, and these effects are dependent on both the CRF R1 and R2 receptors. These findings are particularly interesting as studies have also implicated the CRF and urocortins in social memory. With the rapid progress of social neuroscience and in understanding the complex structure of the CRF system, the next challenge is in parsing the exact contribution of individual components of this system to specific social

  7. Georgetown University Research Psychologist Shares Terrorism Insight

    OpenAIRE

    Center for Homeland Defense and Security

    2013-01-01

    Georgetown University research psychologist Dr. Anne Speckhard has spent the last decade interviewing more than four hundred terrorists, terrorist supporters, family members, close associates and even terrorist's hostages in Western Europe and the Middle East. Speckhard shared her insights with students at the Naval Postgraduate School Center for Homeland Defense and Security in July.

  8. Creativity and Insight in Problem Solving

    Science.gov (United States)

    Golnabi, Laura

    2016-01-01

    This paper analyzes the thought process involved in problem solving and its categorization as creative thinking as defined by psychologist R. Weisberg (2006). Additionally, the notion of insight, sometimes present in unconscious creative thinking and often leading to creative ideas, is discussed in the context of geometry problem solving. In…

  9. Some new insights into collimator design

    International Nuclear Information System (INIS)

    Metz, C.E.; Atkins, F.B.; Tsui, B.M.W.; Beck, R.N.

    1978-01-01

    Relationships among collimator design parameters, physical properties of the resulting images, and human observer performance are discussed. The insight provided by these relationships hopefully will prove useful to the individual who must design or select a collimator for a particular imaging task

  10. Gestures and Insight in Advanced Mathematical Thinking

    Science.gov (United States)

    Yoon, Caroline; Thomas, Michael O. J.; Dreyfus, Tommy

    2011-01-01

    What role do gestures play in advanced mathematical thinking? We argue that the role of gestures goes beyond merely communicating thought and supporting understanding--in some cases, gestures can help generate new mathematical insights. Gestures feature prominently in a case study of two participants working on a sequence of calculus activities.…

  11. Scientific Visualization: From Data to Insight

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 7. Scientific Visualization: From Data to Insight. Vijay Natarajan. General Article Volume 18 Issue 7 July 2013 pp 615-629. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/018/07/0615-0629 ...

  12. Innovative Leadership: Insights from a Learning Technologist

    Science.gov (United States)

    Campbell, Bruce

    2012-01-01

    Professor Ricardo Torres Kompen is a leading proponent for, and researcher in, personal learning environments (PLEs). During his interview, Torres Kompen clarified his research on PLEs, particularly the digital toolbox within PLEs. He elaborated on experiences with implementing PLE initiatives, personal insights on using social media and Web 2.0…

  13. Vitamin B12: advances and insights

    DEFF Research Database (Denmark)

    individuals in critical life phases. This book has been written by experts who documented latest developments in the field. It is written for individuals looking for in depth knowledge of the nutritional, chemistry, biochemistry, health and medical relevance of the vitamin. The book provides insights...

  14. Innovate or perish: The RSM Insight debate

    OpenAIRE

    Gilbert, Russell

    2014-01-01

    markdownabstract__Abstract__ Although innovation is one the hottest management topics of the 21st century, very few firms excel at it. Here, in the first RSM Insight debate, three of the school’s leading management scholars discuss how firms should approach the subject of innovation and what it takes to be successful at it.

  15. Innovate or perish : The RSM Insight debate

    NARCIS (Netherlands)

    R. Gilbert (Russell)

    2014-01-01

    markdownabstract__Abstract__ Although innovation is one the hottest management topics of the 21st century, very few firms excel at it. Here, in the first RSM Insight debate, three of the school’s leading management scholars discuss how firms should approach the subject of innovation and what

  16. Insight in schizophrenia : Associations with empathy

    NARCIS (Netherlands)

    Pijnenborg, G. H. M.; Spikman, J. M.; Jeronimus, B. F.; Aleman, A.

    Many people with schizophrenia (50-80 %) demonstrate impaired insight, something which has been associated with a poorer outcome. Two types of empathy can be distinguished: affective empathy via shared emotions and cognitive empathy, also referred to as Theory of Mind (ToM). ToM can be subdivided

  17. Tour Guiding Research Insights, Issues and Implications

    DEFF Research Database (Denmark)

    Meged, Jane Widtfeldt

    2017-01-01

    The book Tour guiding research – insights, issues and implications by Betty Weiler and Rosemary Black is a most welcome contribution to the specific research field of guided tours within tourism studies. It sets forth to “give an authoritative state-of-art review of the scholarly literature on tour...

  18. Insights and their emergence in everyday practices

    DEFF Research Database (Denmark)

    Trasmundi, Sarah Bro; Linell, Per

    2017-01-01

    of sense-making, problem-solving and task performance in naturalistic contexts. Second, it presents a promising method for the analysis of cognitive activities, Cognitive Event Analysis (CEA), with which we investigate real-life medical interactions, especially the emergence of insights in procedural task......-cultural patterns of behaviour....

  19. Safeguarding our environment: insight from an African ...

    African Journals Online (AJOL)

    The care and management of the natural environment constitutes an important aspect of environmental philosophy; an area of study that critically scrutinizes and evaluates human activities in his environment. African environmental ethics approaches problematic fundamental issues in deep ecology with a unique insight, ...

  20. Swahili residential architecture reconsidered | Steyn | Africa Insight

    African Journals Online (AJOL)

    Africa Insight. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 32, No 2 (2002) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT ...

  1. Insights on some chiral smectic phases

    Indian Academy of Sciences (India)

    journal of. August 2003 physics pp. 285–295. Insights on some chiral ... Liquid crystals; smectics; chirality; frustrated phases; twist grain boundary phases. ... molecules are more or less packed in layers and smectic phases can be seen ..... (imaging plate or CCD camera) which was located at about 300 mm from the sample.

  2. Cognitive Psychology--An Educational Insight

    Science.gov (United States)

    Muirhead, Brent

    2007-01-01

    Cognitive psychology offers relevant insights into improving the teaching and learning process. The author has selected ten questions from a graduate class in cognition and learning taken at The Teachers College, Columbia University. The questions will be used to examine the most effective ways to learn and recall information.

  3. Insights into Participants' Behaviours in Educational Games, Simulations and Workshops: A Catastrophe Theory Application to Motivation.

    Science.gov (United States)

    Cryer, Patricia

    1988-01-01

    Develops models for participants' behaviors in games, simulations, and workshops based on Catastrophe Theory and Herzberg's two-factor theory of motivation. Examples are given of how these models can be used, both for describing and understanding the behaviors of individuals, and for eliciting insights into why participants behave as they do. (11…

  4. Matching Student Expectations with Instructors' Dispositions: Insight into Quality of Online Teaching

    Science.gov (United States)

    Welch, Anita G.; Orso, Don; Doolittle, Joan; Areepattamannil, Shaljan

    2015-01-01

    This paper explores the similarities and differences between student expectations of online instructors and the teaching dispositions of online instructors. Our research goal is to develop insight into factors related to online student success. Although researchers have identified key characteristics of effective teaching in the face-to-face…

  5. Biodiversity Business fron India to Peru; Insights into successes and chellenges

    NARCIS (Netherlands)

    Vollaard, B.; Verweij, P.A.

    2013-01-01

    The Copernicus Institute of Sustainable Development recently released the report 'Biodiversity Business from India to Peru'. The study, commissioned by Hivos, provides new insights in the impacts and success factors of the upcoming concept of biodiversity-friendly enterprise across the globe. By

  6. Detailed insights into the influence of flood-coping appraisals on mitigation behaviour

    NARCIS (Netherlands)

    Bubeck, P.; Botzen, W.J.W.; Kreibich, H.; Aerts, J.C.J.H.

    2013-01-01

    Insights into flood mitigation behaviour are important because of the ongoing shift to risk-based flood management approaches in Europe and worldwide, which envisage a contribution from flood-prone households to risk reduction. The recent literature on factors that influence flood mitigation

  7. The Satisfaction of Pretended Insight: The Iranian Crisis in Selected U.S. Editorial Cartoons.

    Science.gov (United States)

    DeSousa, Michael A.

    An examination of a year's worth of editorial cartoons portraying the U.S. hostage crisis in Iran indicates a surprising lack of coverage or treatment of the deposed Shah and his subsequent admission into the United States as factors precipitating the crisis. Throughout the crisis, cartoonists focused on providing readers with some insight into…

  8. New insights into the evolutionary history of biological nitrogen fixation

    Directory of Open Access Journals (Sweden)

    Eric eBoyd

    2013-08-01

    Full Text Available Nitrogenase, which catalyzes the ATP-dependent reduction of dinitrogen (N2 to ammonia (NH3, accounts for roughly half of the bioavailable nitrogen supporting extant life. The fundamental requirement for fixed forms of nitrogen for life on Earth, both at present and in the past, has led to broad and significant interest in the origin and evolution of this fundamental biological process. One key question is whether the limited availability of fixed nitrogen was a factor in life’s origin or whether there were ample sources of fixed nitrogen produced by abiotic processes or delivered through the weathering of bolide impact materials to support this early life. If the latter, the key questions become what were the characteristics of the environment that precipitated the evolution of this oxygen sensitive process, when did this occur, and how was its subsequent evolutionary history impacted by the advent of oxygenic photosynthesis and the rise of oxygen in the Earth’s biosphere. Since the availability of fixed sources of nitrogen capable of supporting early life is difficult to glean from the geologic record, there are limited means to get direct insights into these questions. Indirect insights, however, can be gained by deep phylogenetic studies of nitrogenase structural gene products and additional gene products involved in the biosynthesis of the complex metal-containing prosthetic groups associated with this enzyme complex. Insights gained from such studies, as reviewed herein, challenge traditional models for the evolution of biological nitrogen fixation and provide the basis for the development of new conceptual models that explain the stepwise evolution of this highly complex and life sustaining process.

  9. Readiness for self-directed change in professional behaviours: factorial validation of the Self-Reflection and Insight Scale.

    Science.gov (United States)

    Roberts, Chris; Stark, Patsy

    2008-11-01

    Self-reflection, the practice of inspecting and evaluating one's own thoughts, feelings and behaviour, and insight, the ability to understand one's own thoughts, feelings and behaviour, are central to the self-regulation of behaviours. The Self-Reflection and Insight Scale (SRIS) measures three factors in the self-regulation cycle: need for reflection; engagement in reflection, and insight. We used structural equation modelling to undertake a confirmatory factor analysis of the SRIS. We re-specified our model to analyse all of the data to explain relationships between the SRIS, medical student characteristics, and responses to issues of teaching and learning in professionalism. The factorial validity of a modified SRIS showed all items loading significantly on their expected factors, with a good fit to the data. Each subscale had good internal reliability (> 0.8). There was a strong relationship between the need for reflection and engagement in reflection (r = 0.77). Insight was related to need for reflection (0.22) and age (0.21), but not to the process of engaging in reflection (0.06). Validation of the SRIS provides researchers with a new instrument with which to measure and investigate the processes of self-reflection and insight in the context of students' self-regulation of their professionalism. Insight is related to the motive or need for reflection, but the process of reflection does not lead to insight. Attending to feelings is an important and integral aspect of self-reflection and insight. Effective strategies are needed to develop students' insight as they reflect on their professionalism.

  10. The association of lifetime insight and cognition in psychosis.

    Science.gov (United States)

    Sánchez-Torres, Ana M; Zarzuela, Amalia; Peralta, Victor; Cuesta, Manuel J

    2015-03-01

    Poor insight has been related to poor course in psychosis. However, the role of cognition in insight remains unclear. The aim of this study was to examine the influence of cognition and lifetime psychopathological dimensions on insight in psychosis. We followed up 42 patients with psychotic disorders over 10years. Lifetime psychopathological dimensions and cognitive performance were assessed. Patients were divided into two groups by lifetime patterns of insight and compared with 42 healthy volunteers. Lower IQ and poorer social cognition were associated with higher risks of poorer lifetime insight of feeling ill and global insight respectively. Lifetime negative symptoms were associated with a higher risk of poorer lifetime insight into symptoms. Lifetime lack of insight is independent of cognitive impairment in specific domains, except for social cognition. Higher IQ may contribute to better lifetime awareness of illness, while better ability to manage emotions is involved in lifetime global insight. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Insight in schizophrenia spectrum disorders: relationship with behavior, mood and perceived quality of life, underlying causes and emerging treatments.

    Science.gov (United States)

    Lysaker, Paul H; Pattison, Michelle L; Leonhardt, Bethany L; Phelps, Scott; Vohs, Jenifer L

    2018-02-01

    Poor insight in schizophrenia is prevalent across cultures and phases of illness. In this review, we examine the recent research on the relationship of insight with behavior, mood and perceived quality of life, on its complex roots, and on the effects of existing and emerging treatments. This research indicates that poor insight predicts poorer treatment adherence and therapeutic alliance, higher symptom severity and more impaired community function, while good insight predicts a higher frequency of depression and demoralization, especially when coupled with stigma and social disadvantage. This research also suggests that poor insight may arise in response to biological, experiential, neuropsychological, social-cognitive, metacognitive and socio-political factors. Studies of the effects of existing and developing treatments indicate that they may influence insight. In the context of earlier research and historical models, these findings support an integrative model of poor insight. This model suggests that insight requires the integration of information about changes in internal states, external circumstances, others' perspectives and life trajectory as well as the multifaceted consequences and causes of each of those changes. One implication is that treatments should, beyond providing education, seek to assist persons with schizophrenia to integrate the broad range of complex and potentially deeply painful experiences which are associated with mental illness into their own personally meaningful, coherent and adaptive picture. © 2018 World Psychiatric Association.

  12. Hybrid discrete choice models: Gained insights versus increasing effort

    International Nuclear Information System (INIS)

    Mariel, Petr; Meyerhoff, Jürgen

    2016-01-01

    Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

  13. Hybrid discrete choice models: Gained insights versus increasing effort

    Energy Technology Data Exchange (ETDEWEB)

    Mariel, Petr, E-mail: petr.mariel@ehu.es [UPV/EHU, Economía Aplicada III, Avda. Lehendakari Aguire, 83, 48015 Bilbao (Spain); Meyerhoff, Jürgen [Institute for Landscape Architecture and Environmental Planning, Technical University of Berlin, D-10623 Berlin, Germany and The Kiel Institute for the World Economy, Duesternbrooker Weg 120, 24105 Kiel (Germany)

    2016-10-15

    Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

  14. Insights from Human/Mouse genome comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.

    2003-03-30

    Large-scale public genomic sequencing efforts have provided a wealth of vertebrate sequence data poised to provide insights into mammalian biology. These include deep genomic sequence coverage of human, mouse, rat, zebrafish, and two pufferfish (Fugu rubripes and Tetraodon nigroviridis) (Aparicio et al. 2002; Lander et al. 2001; Venter et al. 2001; Waterston et al. 2002). In addition, a high-priority has been placed on determining the genomic sequence of chimpanzee, dog, cow, frog, and chicken (Boguski 2002). While only recently available, whole genome sequence data have provided the unique opportunity to globally compare complete genome contents. Furthermore, the shared evolutionary ancestry of vertebrate species has allowed the development of comparative genomic approaches to identify ancient conserved sequences with functionality. Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis.

  15. Safety insights from forensics evaluations at Daiichi

    Directory of Open Access Journals (Sweden)

    J. Rempe

    2017-01-01

    Information obtained from Daiichi is required to inform Decontamination and Decommissioning activities, improving the ability of the Tokyo Electric Power Company (TEPCO to characterize potential hazards and to ensure the safety of workers involved with cleanup activities. This paper reports initial results from the US Forensics Effort to utilize examination information obtained by TEPCO to enhance the safety of existing and future nuclear power plant designs. In this paper, three examples are presented in which examination information, such as visual images, dose surveys, sample evaluations, and muon tomography examinations, along with data from plant instrumentation, are used to obtain significant safety insights in the areas of component performance, fission product release and transport, debris end-state location, and combustible gas generation and transport. In addition to reducing uncertainties related to severe accident modeling progression, these insights confirm actions, such as the importance of water addition and containment venting, that are emphasized in updated guidance for severe accident prevention, mitigation, and emergency planning.

  16. Determining criminal responsibility: How relevant are insight and personal attitudes to mock jurors?

    Science.gov (United States)

    Jung, Sandy

    2015-01-01

    High levels of insight are interpreted as indications of a treatment compliance and good outcome by clinical professionals. However, it is unclear whether a defendant's insight plays a role in the decision-making of jurors when determining criminal responsibility. It may be the case that personal biases and attitudes toward the mentally ill and the insanity defense are more relevant in such decisions. This study examines the influence of two core dimensions of insight and personal attitudes on juror decision-making. Participants read trial scenarios describing a defendant who is accused of a violent crime and is diagnosed with schizophrenia. Assigning a verdict of not criminally responsible to the defendant was not influenced by insight, but instead, by supportive attitudes of the insanity defense and higher attributions of blame to external factors and to psychological factors. These findings highlight the need for continued investigation in the area of extra-legal factors that guide legal decision-making when defendants have a mental disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Forming a Perceived Franchise Value: Theoretical Insights

    OpenAIRE

    Levickaitė, Rasa; Reimeris, Ramojus

    2011-01-01

    The article is based on literature review, theoretical insights and deals with the topic of perceived franchise value. The objective of the paper is – what elements form the franchisee's perceived value in service business (comparing with alternative of own business model). The aim of the paper is to propose systematic value elements in the process of forming a value of a franchise business model perceived by the franchisee. In terms of practical meaning, this article should be relevant to en...

  18. Biblical Leadership: Insights for Today's Managers

    OpenAIRE

    Friedman, Hershey H.; Friedman, Linda

    2004-01-01

    The scholarly literature in management has paid little attention to the study of Biblical figures as leaders. This paper aims to advance the effort to fill this gap by demonstrating that many insights about successful and unsuccessful leadership may be derived from the Bible. Successful leaders demonstrated a willingness to be different, a passion for justice, humility, and a concern for others. Unsuccessful leaders were sidetracked from their mission by the hunger for power or by lust and envy.

  19. Paris after Trump: An Inconvenient Insight

    OpenAIRE

    Böhringer, Christoph; Rutherford, Thomas F.

    2017-01-01

    With his announcement to pull the US out of the Paris Agreement US President Donald Trump has snubbed the international climate policy community. Key remaining parties to the Agreement such as Europe and China might call for carbon tariffs on US imports as a sanctioning instrument to coerce US compliance. Our analysis, however, reveals an inconvenient insight for advocates of carbon tariffs: given the possibility of retaliatory tariffs across all imported goods, carbon tariffs do not constitu...

  20. Exploring Insight: Focus on Shifts of Attention

    Science.gov (United States)

    Palatnik, Alik; Koichu, Boris

    2015-01-01

    The paper presents and analyses a sequence of events that preceded an insight solution to a challenging problem in the context of numerical sequences. A three­week long solution process by a pair of ninth­-grade students is analysed by means of the theory of shifts of attention. The goal for this article is to reveal the potential of this theory…

  1. Egypt: Pharoahs and Fundamentalists? | Swart | Africa Insight

    African Journals Online (AJOL)

    Gerrie Swart, Hussein Solomon, Anneli Botha. Abstract. Africa Insight Vol.33(4) 2003: 78-81. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/ai.v33i4.22345 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

  2. Insightful problem solving in an Asian elephant.

    Directory of Open Access Journals (Sweden)

    Preston Foerder

    Full Text Available The "aha" moment or the sudden arrival of the solution to a problem is a common human experience. Spontaneous problem solving without evident trial and error behavior in humans and other animals has been referred to as insight. Surprisingly, elephants, thought to be highly intelligent, have failed to exhibit insightful problem solving in previous cognitive studies. We tested whether three Asian elephants (Elephas maximus would use sticks or other objects to obtain food items placed out-of-reach and overhead. Without prior trial and error behavior, a 7-year-old male Asian elephant showed spontaneous problem solving by moving a large plastic cube, on which he then stood, to acquire the food. In further testing he showed behavioral flexibility, using this technique to reach other items and retrieving the cube from various locations to use as a tool to acquire food. In the cube's absence, he generalized this tool utilization technique to other objects and, when given smaller objects, stacked them in an attempt to reach the food. The elephant's overall behavior was consistent with the definition of insightful problem solving. Previous failures to demonstrate this ability in elephants may have resulted not from a lack of cognitive ability but from the presentation of tasks requiring trunk-held sticks as potential tools, thereby interfering with the trunk's use as a sensory organ to locate the targeted food.

  3. Risk insights from seismic margin reviews

    International Nuclear Information System (INIS)

    Budnitz, R.J.

    1990-01-01

    This paper discusses the information that has been derived from the three seismic-margin reviews conducted so far, and the information that is potentially available from using the seismic-margin method more generally. There are two different methodologies for conducting seismic margin reviews of nuclear power plants, one developed under NRC sponsorship and one developed under sponsorship of the Electric Power Research Institute. Both methodologies will be covered in this paper. The paper begins with a summary of the steps necessary to complete a margin review, and will then outline the key technical difficulties that need to be addressed. After this introduction, the paper covers the safety and operational insights derived from the three seismic-margin reviews already completed: the NRC-sponsored review at Maine Yankee; the EPRI-sponsored review at Catawba; and the joint EPRI/NRC/utility effort at Hatch. The emphasis is on engineering insights, with attention to the aspects of the reviews that are easiest to perform and that provide the most readily available insights

  4. 2016 Mars Insight Mission Design and Navigation

    Science.gov (United States)

    Abilleira, Fernando; Frauenholz, Ray; Fujii, Ken; Wallace, Mark; You, Tung-Han

    2014-01-01

    Scheduled for a launch in the 2016 Earth to Mars opportunity, the Interior Exploration using Seismic Investigations, Geodesy, and Heat Transport (InSight) Mission will arrive to Mars in late September 2016 with the primary objective of placing a science lander on the surface of the Red Planet followed by the deployment of two science instruments to investigate the fundamental processes of terrestrial planet formation and evolution. In order to achieve a successful landing, the InSight Project has selected a launch/arrival strategy that satisfies the following key and driving requirements: (1) Deliver a total launch mass of 727 kg, (2) target a nominal landing site with a cumulative Delta V99 less than 30 m/s, and (3) approach EDL with a V-infinity upper limit of 3.941 km/s and (4) an entry flight-path angle (EFPA) of -12.5 +/- 0.26 deg, 3-sigma; the InSight trajectories have been designed such that they (5) provide UHF-band communications via Direct-To-Earth and MRO from Entry through landing plus 60 s, (6) with injection aimpoints biased away from Mars such that the probability of the launch vehicle upper stage impacting Mars is less than 1.0 X 10(exp 4) for fifty years after launch, and (7) non-nominal impact probabilities due to failure during the Cruise phase less than 1.0 X 10(exp 2).

  5. Insights from an overview of four PRAs

    International Nuclear Information System (INIS)

    Fitzpatrick, R.; Arrieta, L.; Teichmann, T.; Davis, P.

    1987-01-01

    This paper summarizes the findings of an investigation of four probabilistic risk assessments (PRAs), those for Millstone 3 Seabrook, Shoreham, and Oconee 3, performed by Brookhaven National Laboratory (BNL) for the Reliability and Risk Assessment branch of the U.S. Nuclear Regulatory Commission (NRC). This group of four PRAs was subjected to an overview process with the basic goal of ascertaining what insights might be gained (beyond those already documented within the individual PRAs) by an independent evaluation of the group with respect to nuclear plant safety and vulnerability. Specifically, the objectives of the study were 1) to identify and rank initiators, systems, components, and failure modes from dominant accident sequences according to their contribution to core melt probability and public risk; and 2) to derive from this process plant-specific and generic insights. The effort was not intended to verify the specific details and results of each PRA but rather - having accepted the results - to see what they might mean in a more global context. This paper also presents some comments and insights into the amenability of certain features of these PRAs to this type of overview process

  6. Insightful problem solving in an Asian elephant.

    Science.gov (United States)

    Foerder, Preston; Galloway, Marie; Barthel, Tony; Moore, Donald E; Reiss, Diana

    2011-01-01

    The "aha" moment or the sudden arrival of the solution to a problem is a common human experience. Spontaneous problem solving without evident trial and error behavior in humans and other animals has been referred to as insight. Surprisingly, elephants, thought to be highly intelligent, have failed to exhibit insightful problem solving in previous cognitive studies. We tested whether three Asian elephants (Elephas maximus) would use sticks or other objects to obtain food items placed out-of-reach and overhead. Without prior trial and error behavior, a 7-year-old male Asian elephant showed spontaneous problem solving by moving a large plastic cube, on which he then stood, to acquire the food. In further testing he showed behavioral flexibility, using this technique to reach other items and retrieving the cube from various locations to use as a tool to acquire food. In the cube's absence, he generalized this tool utilization technique to other objects and, when given smaller objects, stacked them in an attempt to reach the food. The elephant's overall behavior was consistent with the definition of insightful problem solving. Previous failures to demonstrate this ability in elephants may have resulted not from a lack of cognitive ability but from the presentation of tasks requiring trunk-held sticks as potential tools, thereby interfering with the trunk's use as a sensory organ to locate the targeted food.

  7. Electrochemical Insights into Platinum Catalysts for Fuel Cells

    DEFF Research Database (Denmark)

    Jensen, Kim Degn

    . A preliminary electrochemical study of in-house synthesized Pt-Y nanoparticles have also been presented revealing specific mass actives of 0.3 ± 0.1A/mgPt in HClO4. The study revealed that extensive optimizations of the Pt-Y nanoparticles are required and their performance is severely impeded by poor......Development of sustainable energy production, conversion and storage technologies must be considered one of the major challenges of the 21st century. Insight and understanding of the oxygen reduction reaction is imperative in these pursuits. In this work electrochemical investigations and physical...... characterization of various model systems ranging from extended surfaces, to thin films and nanoparticle electrocatalysts have been presented and discussed. This have been done with a special focus on governing factors controlling the electroreduction of oxygen. Preparation of Cu/Pt(111) near-surface alloys...

  8. Insights from human genetic studies of lung and organ fibrosis.

    Science.gov (United States)

    Garcia, Christine Kim

    2018-01-02

    Genetic investigations of fibrotic diseases, including those of late onset, often yield unanticipated insights into disease pathogenesis. This Review focuses on pathways underlying lung fibrosis that are generalizable to other organs. Herein, we discuss genetic variants subdivided into those that shorten telomeres, activate the DNA damage response, change resident protein expression or function, or affect organelle activity. Genetic studies provide a window into the downstream cascade of maladaptive responses and pathways that lead to tissue fibrosis. In addition, these studies reveal interactions between genetic variants, environmental factors, and age that influence the phenotypic spectrum of disease. The discovery of forces counterbalancing inherited risk alleles identifies potential therapeutic targets, thus providing hope for future prevention or reversal of fibrosis.

  9. New insights into innate immune control of systemic candidiasis

    Science.gov (United States)

    Lionakis, Michail S.

    2014-01-01

    Systemic infection caused by Candida species is the fourth leading cause of nosocomial bloodstream infection in modern hospitals and carries high morbidity and mortality despite antifungal therapy. A recent surge of immunological studies in the mouse models of systemic candidiasis and the parallel discovery and phenotypic characterization of inherited genetic disorders in antifungal immune factors that are associated with enhanced susceptibility or resistance to the infection have provided new insights into the cellular and molecular basis of protective innate immune responses against Candida. In this review, the new developments in our understanding of how the mammalian immune system responds to systemic Candida challenge are synthesized and important future research directions are highlighted. PMID:25023483

  10. Current insights into hormonal regulation of microspore embryogenesis

    Directory of Open Access Journals (Sweden)

    Iwona eŻur

    2015-06-01

    Full Text Available Plant growth regulator (PGR crosstalk and interaction with the plant’s genotype and environmental factors play a crucial role in microspore embryogenesis (ME, controlling microspore-derived embryo differentiation and development as well as haploid/doubled haploid plant regeneration. The complexity of the PGR network which could exist at the level of biosynthesis, distribution, gene expression or signaling pathways, renders the creation of an integrated model of ME-control crosstalk impossible at present. However, the analysis of the published data together with the results received recently with the use of modern analytical techniques brings new insights into hormonal regulation of this process. This review presents a short historical overview of the most important milestones in the recognition of hormonal requirements for effective ME in the most important crop plant species and complements it with new concepts that evolved over the last decade of ME studies.

  11. Molecular-level insights into aging processes of skin elastin

    DEFF Research Database (Denmark)

    Mora Huertas, Angela C; Schmelzer, Christian E H; Hoehenwarter, Wolfgang

    2016-01-01

    Skin aging is characterized by different features including wrinkling, atrophy of the dermis and loss of elasticity associated with damage to the extracellular matrix protein elastin. The aim of this study was to investigate the aging process of skin elastin at the molecular level by evaluating...... the influence of intrinsic (chronological aging) and extrinsic factors (sun exposure) on the morphology and susceptibility of elastin towards enzymatic degradation. Elastin was isolated from biopsies derived from sun-protected or sun-exposed skin of differently aged individuals. The morphology of the elastin...... pronounced in sun-exposed tissue. Marker peptides were identified, which showed an age-related increase or decrease in their abundances and provide insights into the progression of the aging process of elastin fibers. Strong age-related cleavage occurs in hydrophobic tropoelastin domains 18, 20, 24 and 26...

  12. Insight, working through, and practice: the role of procedural knowledge.

    Science.gov (United States)

    Rosenblatt, Allan

    2004-01-01

    A conception of insight is proposed, based on a systems and information-processing framework and using current neuroscience concepts, as an integration of information that results in a new symbolization of experience with a significant change in self-image and a transformation of non-declarative procedural knowledge into declarative knowledge. Since procedural memory and knowledge, seen to include emotional and relationship issues, is slow to change, durable emotional and behavioral change often requires repeated practice, a need not explicitly addressed in standard psychoanalytic technique. Working through is thus seen as also encompassing nondynamic factors. The application of these ideas to therapeutic technique suggests possible therapeutic interventions beyond interpretation. An illustrative clinical vignette is presented.

  13. New insight in magnetic saturation behavior of nickel hierarchical structures

    Science.gov (United States)

    Ma, Ji; Zhang, Jianxing; Liu, Chunting; Chen, Kezheng

    2017-09-01

    It is unanimously accepted that non-ferromagnetic inclusions in a ferromagnetic system will lower down total saturation magnetization in unit of emu/g. In this study, ;lattice strain; was found to be another key factor to have critical impact on magnetic saturation behavior of the system. The lattice strain determined assembling patterns of primary nanoparticles in hierarchical structures and was intimately related with the formation process of these architectures. Therefore, flower-necklace-like and cauliflower-like nickel hierarchical structures were used as prototype systems to evidence the relationship between assembling patterns of primary nanoparticles and magnetic saturation behaviors of these architectures. It was found that the influence of lattice strain on saturation magnetization outperformed that of non-ferromagnetic inclusions in these hierarchical structures. This will enable new insights into fundamental understanding of related magnetic effects.

  14. Psychosis: clinical insight and beliefs in immigrants in their first episode.

    Science.gov (United States)

    Berg, Akiah Ottesen; Barrett, Elizabeth Ann; Nerhus, Mari; Büchman, Camilla; Simonsen, Carmen; Faerden, Ann; Andreassen, Ole A; Melle, Ingrid

    2018-04-01

    Lack of insight into illness is frequent in psychotic disorders and seen as part of their primary pathology. The recognition of symptoms as psychotic, and beliefs about treatment alternatives, is also influenced by socio-cultural factors. Here we examined clinical insight into illness and beliefs about psychosis in immigrants in their first episode of psychosis compared with a reference group. A total of 277 first-episode psychosis participants were recruited to this cross-sectional study; 40 first- and 40 second-generation immigrants from Europe, Americas and Oceania (n = 37), Asia including Turkey (n = 28) or Africa (n = 15). The Birchwood Insight Scale was used to measure clinical insight and 'The Attitudes and Beliefs about Mental Health Problems' schizophrenia version to assess socio-cultural beliefs. Immigrants did not differ from the reference sample in clinical insight. After controlling for education level, first-generation immigrants were less likely to recognize psychotic symptoms (odds ratio (OR) 2.9; Wald = 8.977, degrees of freedom (d.f.) 1, P = 0.003) and viewed hospitalization (OR 5.2; Wald = 20.388, d.f. 1, P = 0.001) and treatment by a psychiatrist (OR 4.9; Wald = 6.609, d.f. 1, P = 0.01)) as less beneficial than the reference group. Immigrants from Asia held more alternative explanations (OR 0.3; Wald = 6.567, d.f. 1, P = 0.010). There were significantly stronger associations between clinical insight and socio-cultural beliefs in the reference group. Socio-cultural beliefs about psychosis in immigrants in first-episode psychosis call for more tailored information to this group, and emphasize the importance of treatment interventions involving both a cultural and personal perspective of insight. © 2015 Wiley Publishing Asia Pty Ltd.

  15. Relationship between cognitive insight and subjective quality of life in outpatients with schizophrenia.

    Science.gov (United States)

    Kim, Jong-Hoon; Lee, Seul; Han, Ah-Young; Kim, Kyungwook; Lee, Jinyoung

    2015-01-01

    The concept of cognitive insight refers to the cognitive processes involved in patients' re-evaluation of their anomalous experiences and of their misinterpretations. The purpose of the present study was to examine the relationship between cognitive insight and subjective quality of life in patients with schizophrenia to further shed light on the nature of cognitive insight and its functional correlates in schizophrenia. Seventy-one stable outpatients with schizophrenia were evaluated for cognitive insight and subjective quality of life using the Beck Cognitive Insight Scale (BCIS) and the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4). The symptoms of schizophrenia were also assessed. Pearson's correlation analysis and partial correlation analysis that controlled for the severity of symptoms were performed to adjust for the possible effects of symptoms. The self-reflectiveness subscale score of the BCIS had significant positive correlations with the SQLS-R4 psychosocial domain and total SQLS-R4 scores, indicating that the higher the level of cognitive insight, the lower the subjective quality of life. In partial correlation analysis controlling for symptoms, the BCIS self-reflectiveness subscale score still had a significant correlation with the SQLS-R4 psychosocial domain score. The correlation coefficient between the BCIS self-reflectiveness and total SQLS-R4 scores was reduced to a nonsignificant statistical tendency. The results of our study suggest that cognitive insight, particularly the level of self-reflectiveness, is negatively associated with the level of subjective quality of life in outpatients with schizophrenia and that this relationship is not wholly due to the confounding effect of symptoms. Future studies are necessary to explore possible mediating and moderating factors and to evaluate the effects of therapeutic interventions on the relationship.

  16. Cross-cultural psychometric assessment of the VAGUS insight into psychosis scale - Spanish version.

    Science.gov (United States)

    de León, Patricia Ponce; Gerretsen, Philip; Shah, Parita; Saracco-Alvarez, Ricardo; Graff-Guerrero, Ariel; Fresán, Ana

    2018-01-01

    Impaired insight into illness, a core feature of schizophrenia with negative clinical implications, is a multidimensional phenomenon existing on a continuum. However, the degree to which illness perception in distinct cultures influences the appraisal of insight into illness in schizophrenia remains unclear. As such, we aimed to determine if the psychometric properties of the VAGUS insight into psychosis scale (www.vagusonline.com), which was originally assessed in English speaking Canadians, were similar in a sample of Latino Mexican Spanish speaking patients with schizophrenia. To accomplish this, the VAGUS - Self-Report (SR) version was translated from English to Spanish and psychometrically evaluated in 95 participants. The Spanish version of the VAGUS-SR was internally consistent (ᾳ = 0.713), and demonstrated good convergent and discriminant validity with the subscales of the Positive and Negative Syndrome Scale. Factor analysis identified two components of insight, congruent with two of the components of the English version of the VAGUS-SR. In conclusion, the VAGUS-SR is a brief, novel, and valid measure of insight into illness in schizophrenia, which demonstrated similar psychometric properties in two culturally and linguistically distinct samples with schizophrenia. Future studies should assess whether the VAGUS demonstrates similar psychometric properties in non-Western cultures. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Policy entrepreneurship in UK central government: The behavioural insights team and the use of randomized controlled trials.

    Science.gov (United States)

    John, Peter

    2014-07-01

    What factors explain the success of the UK Cabinet Office's Behavioural Insights Team? To answer this question, this article applies insights from organizational theory, particularly accounts of change agents. Change agents are able-with senior sponsorship-to foster innovation by determination and skill: they win allies and circumvent more traditional bureaucratic procedures. Although Behavioural Insights Team is a change agent-maybe even a skunkworks unit-not all the facilitating factors identified in the literature apply in this central government context. Key factors are its willingness to work in a non-hierarchical way, skills at forming alliances, and the ability to form good relationships with expert audiences. It has been able to promote a more entrepreneurial approach to government by using randomized controlled trials as a robust method of policy evaluation.

  18. Hydrogeology of Montserrat review and new insights

    Directory of Open Access Journals (Sweden)

    Brioch Hemmings

    2015-03-01

    Full Text Available Study region: The tropical, active volcanic arc island of Montserrat, Lesser Antilles, Caribbean. Study focus: New insights into hydrological recharge distribution, measurements of aquifer permeability, and geological and hydrological field observations from Montserrat are combined with a review of the current understanding of volcanic island hydrology. The aim is to begin to develop a conceptual model for the hydrology of Montserrat, and to inform and stimulate further investigation into the hydrology of volcanic arc islands, by combining a review of the current understanding of essential components of the hydrological system with fresh analysis of existing data, and new observations, data collection and analysis. This study provides new insights into hydrological recharge distribution, measurements of aquifer permeability, and geological and hydrological field observations from Montserrat. New hydrological insights for the region: A new groundwater recharge model predicts whole island recharge of 266 mm/year, between 10% and 20% of annual rainfall. Core scale permeability tests reveal ranges from 10−14 to 10−12 m2 for volcaniclastic rocks with coarse matrix, to a minimum of 10−18 m2 for andesitic lavas and volcaniclastics with fine or altered matrix. Analysis of historical pumping tests on aquifers in reworked, channel and alluvial sediment indicate permeabilities ∼10−10 m2. Springs at elevations between 200 and 400 m above mean sea level on Centre Hills currently discharge over 45 L/s. High discharge require a reasonably laterally continuous low permeability body. Contrasting conceptual models are presented to illustrate two potential hydrogeological scenarios. New field observations also reveal systematic spatial variations in spring water temperature and specific electrical conductivity indicating that meteoric waters supplying the springs are mixed with a deeper groundwater source at some sites. Keywords: Volcanic island

  19. Risk Factors

    Science.gov (United States)

    ... cells do not invade nearby tissues or spread. Risk Factors Key Points Factors That are Known to ... chemicals . Factors That are Known to Increase the Risk of Cancer Cigarette Smoking and Tobacco Use Tobacco ...

  20. Third-person Diagnostic Interview on the Cognitive Insight Level of Psychotic Patients with an Insight at the Denial Level.

    Science.gov (United States)

    Mehdizadeh, Mahsa; Rezaei, Omid

    2016-01-01

    According to the previous findings, the third-person technique improved the clinical insight of psychotic patients, therefore the present study aims to examine the effect of a third-person interview compared to a first-person interview on the level of cognitive insight of psychotic patients with an insight at the denial level. In this study, using interviews and questionnaires, a total number of 44 patients of Razi Psychiatric Educational and Treatment Center with an insight at the denial level being assessed using diagnostic interviews were divided randomly into two groups. Then, the two groups of patients' cognitive insights were evaluated using Beck Cognitive Insight Scale. The findings indicated that in psychotic patients with an insight at the denial level, the third-person technique of interview compared to the first-person had little effect on the improvement of overall cognitive insight and its components, including self-reflection and self-assurance; however, this effect was not strong enough to make a significant difference between the two groups of patients. According to the study findings, we can conclude that the third-person interview compared to the first-person interview has no effect on the improvement of the cognitive insight of psychotic patients with an insight at the denial level. This finding is consistent with the previous studies indicating that although the theory of mind has some correlations with the clinical insight of patients, it has no effect on their cognitive insight.