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Sample records for human hypothalamus-pituitary-adrenal axis

  1. Effects of high fat diet on the Basal activity of the hypothalamus-pituitary-adrenal axis in mice: a systematic review.

    Science.gov (United States)

    Auvinen, H E; Romijn, J A; Biermasz, N R; Havekes, L M; Smit, J W A; Rensen, P C N; Pereira, A M

    2011-12-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the hypothalamus-pituitary-adrenal-axis activation. The aim of this review was to assess the effects of high fat feeding on the activity of the hypothalamus-pituitary-adrenal-axis in mice. PubMed, EMBASE, Web of Science, the Cochrane database, and Science Direct were electronically searched and reviewed by 2 individual researchers. We included only original mouse studies reporting parameters of the hypothalamus-pituitary-adrenal-axis after high fat feeding, and at least 1 basal corticosterone level with a proper control group. Studies with adrenalectomized mice, transgenic animals only, high fat diet for less than 2 weeks, or other interventions besides high fat diet, were excluded. 20 studies were included. The hypothalamus-pituitary-adrenal-axis evaluation was the primary research question in only 5 studies. Plasma corticosterone levels were unchanged in 40%, elevated in 30%, and decreased in 20% of the studies. The effects in the peripheral tissues and the central nervous system were also inconsistent. However, major differences were found between mouse strains, experimental conditions, and the content and duration of the diets. This systematic review demonstrates that the effects of high fat feeding on the basal activity of the hypothalamus-pituitary-adrenal-axis in mice are limited and inconclusive. Differences in experimental conditions hamper comparisons and accentuate the need for standardized evaluations to discern the effects of diet-induced obesity on the hypothalamus-pituitary-adrenal-axis. © Georg Thieme Verlag KG Stuttgart · New York.

  2. The role of the hypothalamus-pituitary-adrenal/interrenal axis in mediating predator-avoidance trade-offs.

    Science.gov (United States)

    Harris, Breanna N; Carr, James A

    2016-05-01

    Maintaining energy balance and reproducing are important for fitness, yet animals have evolved mechanisms by which the hypothalamus-pituitary-adrenal/interrenal (HPA/HPI) axis can shut these activities off. While HPA/HPI axis inhibition of feeding and reproduction may have evolved as a predator defense, to date there has been no review across taxa of the causal evidence for such a relationship. Here we review the literature on this topic by addressing evidence for three predictions: that exposure to predators decreases reproduction and feeding, that exposure to predators activates the HPA/HPI axis, and that predator-induced activation of the HPA/HPI axis inhibits foraging and reproduction. Weight of evidence indicates that exposure to predator cues inhibits several aspects of foraging and reproduction. While the evidence from fish and mammals supports the hypothesis that predator cues activate the HPA/HPI axis, the existing data in other vertebrate taxa are equivocal. A causal role for the HPA axis in predator-induced suppression of feeding and reproduction has not been demonstrated to date, although many studies report correlative relationships between HPA activity and reproduction and/or feeding. Manipulation of HPA/HPI axis signaling will be required in future studies to demonstrate direct mediation of predator-induced inhibition of feeding and reproduction. Understanding the circuitry linking sensory pathways to their control of the HPA/HPI axis also is needed. Finally, the role that fear and anxiety pathways play in the response of the HPA axis to predator cues is needed to better understand the role that predators have played in shaping anxiety related behaviors in all species, including humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Effects of high fat diet on the basal activity of the hypothalamus- pituitary-adrenal axis in mice: A systematic review

    NARCIS (Netherlands)

    Auvinen, H.E.; Romijn, J.A.; Biermasz, N.R.; Havekes, L.M.; Smit, J.W.A.; Rensen, P.C.N.; Pereira, A.M.

    2011-01-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the

  4. Association analyses of depression and genes in the hypothalamus-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Krogh, Jesper; Nielsen, Marit Nyholm

    2017-01-01

    OBJECTIVE: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme......) was investigated. RESULTS: After quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated...... with depression. One nominally significant interaction, most likely due to chance, was identified. CONCLUSION: The results indicate that ACE could be a potential candidate gene for depression....

  5. Association of IL-6, hypothalamus-pituitary-adrenal axis function, and depression in patients with cancer.

    Science.gov (United States)

    Jehn, Christian Friedrich; Kühnhardt, Dagmar; Bartholomae, Andrea; Pfeiffer, Sebastian; Schmid, Peter; Possinger, Kurt; Flath, Bernd Christian; Lüftner, Diana

    2010-09-01

    Evidence suggests that cytokines (IL-6) and alteration of the hypothalamic-pituitary-adrenal (HPA) axis play a crucial role in the etiology of depression. Patients with cancer show elevated prevalence rates for depression. The objective of this cross-sectional study was to investigate the associations between these abnormalities and depression. Plasma concentrations of IL-6 and cortisol were measured in cancer patients with (N = 31) and without depression (N = 83). The relative diurnal variation of cortisol (cortisol VAR), expressed in percentage, was calculated. There was a significant difference in median plasma concentration of IL-6 between the patients with depression and those without (18.7 vs 2.7 pg/mL; P cancer is associated with increased plasma IL-6 concentrations and dysfunction of the HPA axis.

  6. Adaptation of the hypothalamus-pituitary-adrenal axis to daily repeated stress does not follow the rules of habituation: A new perspective.

    Science.gov (United States)

    Rabasa, Cristina; Gagliano, Humberto; Pastor-Ciurana, Jordi; Fuentes, Silvia; Belda, Xavier; Nadal, Roser; Armario, Antonio

    2015-09-01

    Repeated exposure to a wide range of stressors differing in nature and intensity results in a reduced response of prototypical stress markers (i.e. plasma levels of ACTH and adrenaline) after an acute challenge with the same (homotypic) stressor. This reduction has been considered to be a habituation-like phenomenon. However, direct experimental evidence for this assumption is scarce. In the present work we demonstrate in adult male rats that adaptation of the hypothalamus-pituitary-adrenal (HPA) axis to repeated stress does not follow some of the critical rules of habituation. Briefly, adaptation was stronger and faster with more severe stressors, maximally observed even with a single exposure to severe stressors, extremely long-lasting, negatively related to the interval between the exposures and positively related to the length of daily exposure. We offer a new theoretical view to explain adaptation to daily repeated stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis.

    Science.gov (United States)

    Belda, Xavier; Armario, Antonio

    2009-10-01

    Whereas the role of most biogenic amines in the control of the hypothalamus-pituitary-adrenal (HPA) response to stress has been extensively studied, the role of dopamine has not. We studied the effect of different dopamine receptor antagonists on HPA response to a severe stressor (immobilization, IMO) in adult male Sprague-Dawley rats. Haloperidol administration reduced adrenocorticotropin hormone and corticosterone responses to acute IMO, particularly during the post-IMO period. This effect cannot be explained by a role of dopamine to maintain a sustained activation of the HPA axis as haloperidol did not modify the response to prolonged (up to 6 h) IMO. Administration of more selective D1 and D2 receptor antagonists (SCH23390 and eticlopride, respectively) also resulted in lower and/or shorter lasting HPA response to IMO. Dopamine, acting through both D1 and D2 receptors, exerts a stimulatory role on the activation of the HPA axis in response to a severe stressor. The finding that dopamine is involved in the maintenance of post-stress activation of the HPA axis is potentially important because the actual pathological impact of HPA activation is likely to be related to the area under the curve of plasma glucocorticoid levels, which is critically dependent on how long after stress high levels of glucocorticoid are maintained.

  8. Characterization of central and peripheral components of the hypothalamus-pituitary-adrenal axis in the inbred Roman rat strains.

    Science.gov (United States)

    Carrasco, Javier; Márquez, Cristina; Nadal, Roser; Tobeña, Adolfo; Fernández-Teruel, Albert; Armario, Antonio

    2008-05-01

    Several studies performed in outbred Roman high- and low-avoidance lines (RHA and RLA, respectively) have demonstrated that the more anxious line (RLA) is characterized by a higher hypothalamic-pituitary-adrenal (HPA) response to certain stressors than the less anxious one (RHA). However, inconsistent results have also been reported. Taking advantage of the generation of an inbred colony of RLA and RHA rats (RHA-I and RLA-I, respectively), we have characterized in the two strains not only resting and stress levels of peripheral HPA hormones but also central components of the HPA axis, including CRF gene expression in extra-hypothalamic areas. Whereas resting levels of ACTH and corticosterone did not differ between the strains, a greater response to a novel environment was found in RLA-I as compared to RHA-I rats. RLA-I rats showed enhanced CRF gene expression in the paraventricular nucleus (PVN) of the hypothalamus, with normal arginin-vasopressin gene expression in both parvocellular and magnocellular regions of the PVN. This enhanced CRF gene expression is not apparently related to altered negative corticosteroid feedback as similar levels of expression of brain glucorticoid and mineralocorticoid receptors were found in the two rat strains. CRF gene expression tended to be higher in the central amygdala and it was significantly higher in the dorsal region of the bed nucleus of stria terminalis (BNST) of RLA-I rats, while no differences appeared in the ventral region of BNST. Considering the involvement of CRF and the BNST in anxiety and stress-related behavioral alterations, the present data suggest that the CRF system may be a critical neurobiological substrate underlying differences between the two rat strains.

  9. Beta-endorphin in the plasma: Radioimmunological determination and findings in patients showing disorders at the level of the hypothalamus-pituitary-adrenal axis

    International Nuclear Information System (INIS)

    Hoerl, A.

    1985-01-01

    Beta-endorphin and adrenocorticotropic hormone (ACTH) were determined simultaneously in the plasma using a radioimmunological procedure. It was found that in patients showing imbalances within the hypothalamus-pituitary-adrenal system (Addison's disease, Cushing's Syndrome, Nelson's Syndrome) as well as elevated levels of beta-endorphin the values of ACHT invariably were also increased. The behaviour of the plasma levels of beta-endorphin and ACTH before, during and subsequent to hypophyseal surgery gives evidence to prove the close link between the two hormones. Tests performed to examine the function of the corticotropin releasing factor (CRF) both in healthy volunteers and patients suffering from endocrinological disorders likewise pointed to a parallel behaviour pattern of the two hormones in their responding or failure to respond to stimulation. The fact that a significant correlation was established between all measured values of beta-endorphin and ACTH is further evidence in confirmation of a parallel release of these two hormones in man. (TRV) [de

  10. Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

    Science.gov (United States)

    Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

    2013-01-01

    Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

  11. 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.

  12. The role of hypothalamus-pituitary-adrenal genes and childhood trauma in borderline personality disorder.

    Science.gov (United States)

    Martín-Blanco, Ana; Ferrer, Marc; Soler, Joaquim; Arranz, Maria Jesús; Vega, Daniel; Calvo, Natalia; Elices, Matilde; Sanchez-Mora, Cristina; García-Martinez, Iris; Salazar, Juliana; Carmona, Cristina; Bauzà, Joana; Prat, Mónica; Pérez, Víctor; Pascual, Juan C

    2016-06-01

    Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case-control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.

  13. 注意力缺陷多动障碍儿童下丘脑-垂体-肾上腺轴的功能研究%Function of the hypothalamus-pituitary-adrenal axis in children with attention deficit hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    陈燕惠; 陈辉; 刘艳艳; 林桂秀; 韦立新; 陈丹玲

    2009-01-01

    目的 通过研究注意力缺陷多动障碍(ADHD)儿童下丘脑-垂体-肾上腺轴(HPA)的功能状态,探讨HPA轴在ADHD发生中的作用.方法 128例6~14岁ADHD男童根据DSM-IV ADHD诊断和分型标准,其中注意缺陷为主型(ADHD-I)44例,多动-冲动为主型(ADHD-HI)32例,混合型(ADHD-C)52例,对照组为年龄匹配健康男童30名,于8:00 am空腹采血.分别采用全自动微粒酶免疫分析法及电化学发光法检测血浆皮质醇及促肾上腺皮质激素(ACTH),智力测验采用瑞文标准推理测验.结果 ADHD组IQ(84.5±11.3)低于对照组(94.6±12.4,P<0.01),ADHD 3个亚型组间比较差异有显著性(P<0.01),ADHD-I和ADHD-C两个亚组IQ水低于对照组(P<0.01),ADHD-HI组与对照组比较差异无显著性.ADHD组血浆皮质醇水平(226.5±129.1 mnol/L)较对照组(384.5±141.4 nmol/L)明显降低(P<0.01),ADHD-HI组(154.4±71.6 nmol/L)下降程度较ADHD-I组(219.4±117.7 nmol/L)及ADHD-C组(258.3±136.4 nmol/L)为著(P<0.01),而ADHD各组血浆ACTH水平与对照组比较差异无显著性.结论 在非应激状态下ADHD儿童存在着HPA轴调节功能障碍,这可能系HPA轴低反应性所致.低血浆皮质醇对认知行为影响较小,而与注意缺陷、多动、冲动行为关系更为密切.%Objective To study the function of the hypothalamus-pituitary-adrenal (HPA) axis in children with attention deficit hyperactivity disorder (ADHD). Methods One hundred and twenty-eight boys with ADHD at ages of 6 to 14 years were enrolled. The diagnosis and grouping of ADHD were based on the Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV) : ADHD-predominantly inattention type (ADHD-I, n =44), ADHD-predominantly hyperactive impulsivetype (ADHD-HI, n = 32) and ADHD-combined type (ADHD-C, n =52). Thirty healthy boys served as the control group. Plasma levels of cortisol and adrenocorticotropic hormone ( ACTH) were measured by automatic particle enzyme immunoassay and electrochemiluminescence

  14. [Clinical study on the postburn change in the hypothalamus-pituitary-adrenal hormones in severely burned patients].

    Science.gov (United States)

    Li, Hong-mian; Liang, Zi-qian; Luo, Zuo-jie

    2003-06-01

    To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients. Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically. The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing. Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.

  15. Alteration of hypothalamus-pituitary-adrenal gland axis in colorectal cancer patients. Preliminary report.

    Science.gov (United States)

    Crippa, S; Mussi, C; Angelini, C; Caprotti, R; Bonardi, C; Muselli, P; Scotti, M; Piacentini, G; Uggeri, F

    2003-08-01

    In advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period, is often found and is associated with poor prognosis. Cortisol is strictly involved in the response to major surgical stress, is an immunosuppressor and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status. In 21 patients with colorectal cancer undergoing surgery we evaluated the assessment of total lymphocytes, CD4+, cortisolemia, circadian rhythm of cortisol (11 p.m. and 8 a.m.) at baseline and in 3(rd) and 7(th) postoperative days. Increase of cortisolemia, as decrease of total and CD4+ lymphocytes in the postoperative period versus baseline was statistically significant. Patients with an altered circadian rhythm were 47% and 36% at 3rd and 7th postoperative days, respectively. At baseline 19% of patients had an altered cortisol circadian rhythm and it was more frequent in patients with nodal involvement (pcancer patients seems not to be associated with cortisol level and circadian rhythm alteration, either at baseline or after surgical stress. An impairment of circadian rhythm of cortisol was found at baseline in 19% of patients. It was significantly associated with the presence of metastatic disease.

  16. The neuroimmune-endocrine axis: pathophysiological implications for the central nervous system cytokines and hypothalamus-pituitary-adrenal hormone dynamics

    Directory of Open Access Journals (Sweden)

    J. Licinio

    2000-10-01

    Full Text Available Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are expressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The mechanisms by which cytokine signaling affects the function of stress-related neuroendocrine systems are reviewed in this article.

  17. Developmental changes in hypothalamus-pituitary-adrenal activity over the transition to adolescence: normative changes and associations with puberty.

    Science.gov (United States)

    Gunnar, Megan R; Wewerka, Sandi; Frenn, Kristin; Long, Jeffrey D; Griggs, Christopher

    2009-01-01

    Home baseline and laboratory stressor (Trier Social Stress Test for Children) measures of salivary cortisol were obtained from 82 participants (40 girls) aged 9, 11, 13, and 15 years. Measures of pubertal development, self-reported stress, parent reports of child depressive symptoms and fearful temperament, and cardiac measures of sympathetic and parasympathetic activity were also obtained. Significant increases in the home cortisol baselines were found with age and pubertal development. Cortisol stress reactivity differed by age group with 11-year-olds and 13-year-old boys showing blunted reactivity and 9-year-olds, 13-year-old girls, and 15-year-olds showing significant cortisol reactions. Cortisol reactivity correlated marginally with sexual maturation. Measures of sympathetic activity revealed increased sympathetic modulation with age. Higher sympathetic tone was associated with more fearful temperament, whereas greater cortisol reactivity was associated with more anxious and depressed symptoms for girls. The importance of these findings for the hypothesis that puberty-associated increases in hypothalamic-pituitary-adrenal axis activity heightens the risk of psychopathology is discussed.

  18. Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation

    NARCIS (Netherlands)

    Benthem, L; Keizer, Klaas-Jan; Wiegman, CH; De Boer, SF; Strubbe, JH; Steffens, AB; Kuipers, F; Scheurink, AJW

    2000-01-01

    We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistance via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the

  19. Associations between HPA axis functioning and level of anxiety in children and adolescents with an anxiety disorder

    NARCIS (Netherlands)

    Kallen, V. L.; Tulen, J. H. M.; Utens, E. M. W. J.; Treffers, P. D. A.; de Jong, F. H.; Ferdinand, R. F.

    2008-01-01

    The hypothalamus-pituitary-adrenal (HPA) axis becomes active in response to stress. Hence, increased levels of anxiety in children and adolescents may be associated with changes in HPA-axis functioning. The aim of this study was to test if level of anxiety or specific anxiety disorders were

  20. Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

    Science.gov (United States)

    Weik, Ulrike; Kuepper, Yvonne; Hennig, Juergen; Deinzer, Renate

    2013-01-01

    Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective.

  1. Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

    Directory of Open Access Journals (Sweden)

    Ulrike Weik

    Full Text Available BACKGROUND: Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. METHODS: Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22 or inclusion (SI, n = 21, respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. RESULTS: Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. CONCLUSIONS: We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective.

  2. The role of central melanocortin receptors in the activation of the hypothalamus pituitary adrenal axis and the induction of excessive grooming

    NARCIS (Netherlands)

    Gispen, W.H.; Frijtag, J.C. von; Croiset, G.; Adan, R.A.H.; Wiegant, V.M.

    1997-01-01

    In accord with previous studies intracerebroventricular (i.c.v.) injections of ACTH1-24 (1 g) induced a display of excessive grooming, and increased the plasma concentrations of ACTH and corticosterone. Pituitary-adrenal activation was blocked by pretreatment with dexamethasone, indicating that the

  3. Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis

    NARCIS (Netherlands)

    Evers, A.W.M.; Verhoeven, E.W.M.; Middendorp, H. van; Sweep, F.C.; Kraaimaat, F.W.; Donders, A.R.T.; Eijsbouts, A.E.; Laarhoven, A.I.M. van; Brouwer, S.J.M. de; Wirken, L.; Radstake, T.R.D.J.; Riel, P.L.C.M. van

    2014-01-01

    OBJECTIVES: Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present

  4. HPA-axis activity and externalizing behavior problems in early adolescents from the general population : the role of comorbidity and gender The TRAILS study

    NARCIS (Netherlands)

    Marsman, Rianne; Swinkels, Sophie H. N.; Rosmalen, Judith G. M.; Oldehinkel, Albertine J.; Ormel, Johan; Buitelaar, Jan K.

    Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used

  5. Coping with stress: The Impact of the Hypothalamus Pituitary Adrenal (HPA) System and Neurotrophic Circuits in the Learned Helplessness Model of Depression

    OpenAIRE

    Chourbaji, Sabine

    2005-01-01

    Animal models currently represent a viable route for gaining further insights into the mechanisms involved in the pathogenesis of particular diseases. Depression, in this respect, constitutes a major challenge since the characterization of disease-specific traits is complicated due to the multifactorial nature of the disorder. The understanding of diverse factors, e.g. neurotrophic circuits and the role of the HPA axis, which have to be considered in the pathophysiology of the disease represe...

  6. Stress and memory in humans: twelve years of progress?

    Science.gov (United States)

    Wolf, Oliver T

    2009-10-13

    Stress leads to an enhanced activity of the hypothalamus-pituitary adrenal (HPA) axis resulting in an increased release of glucocorticoids from the adrenal cortex. These hormones influence target systems in the periphery as well as in the brain. The present review paper describes the impact of the human stress hormone cortisol on episodic long-term memory. Starting out with our early observation that stress as well as cortisol treatment impaired declarative memory, experiments by the author are described, which result in an enhanced understanding of how cortisol influences memory. The main conclusions are that stress or cortisol treatment temporarily blocks memory retrieval. The effect is stronger for emotional arousing material independent of its valence. In addition cortisol only influences memory when a certain amount of testing induced arousal occurs. A functional magnetic resonance imaging (fMRI) study suggests that the neuronal correlate of the cortisol induced retrieval blockade is a reduced activity of the hippocampus. In contrast to the effects on retrieval cortisol enhances memory consolidation. Again this effect is often stronger for emotionally arousing material and sometimes occurs at the cost of memory for neutral material. A fMRI study revealed that higher cortisol levels were associated with a stronger amygdala response to emotional stimuli. Thus stimulatory effects of cortisol on this structure might underlie the cortisol induced enhancement of emotional memory consolidation. The findings presented are in line with models derived from experiments in rodents and are of relevance for our understanding of stress associated psychiatric disorders.

  7. Agricultural land use and human presence around breeding sites increase stress-hormone levels and decrease body mass in barn owl nestlings.

    Science.gov (United States)

    Almasi, Bettina; Béziers, Paul; Roulin, Alexandre; Jenni, Lukas

    2015-09-01

    Human activities can have a suite of positive and negative effects on animals and thus can affect various life history parameters. Human presence and agricultural practice can be perceived as stressors to which animals react with the secretion of glucocorticoids. The acute short-term secretion of glucocorticoids is considered beneficial and helps an animal to redirect energy and behaviour to cope with a critical situation. However, a long-term increase of glucocorticoids can impair e.g. growth and immune functions. We investigated how nestling barn owls (Tyto alba) are affected by the surrounding landscape and by human activities around their nest sites. We studied these effects on two response levels: (a) the physiological level of the hypothalamus-pituitary-adrenal axis, represented by baseline concentrations of corticosterone and the concentration attained by a standardized stressor; (b) fitness parameters: growth of the nestlings and breeding performance. Nestlings growing up in intensively cultivated areas showed increased baseline corticosterone levels late in the season and had an increased corticosterone release after a stressful event, while their body mass was decreased. Nestlings experiencing frequent anthropogenic disturbance had elevated baseline corticosterone levels, an increased corticosterone stress response and a lower body mass. Finally, breeding performance was better in structurally more diverse landscapes. In conclusion, anthropogenic disturbance affects offspring quality rather than quantity, whereas agricultural practices affect both life history traits.

  8. Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes.

    Science.gov (United States)

    Clark, Allison; Mach, Núria

    2016-01-01

    Fatigue, mood disturbances, under performance and gastrointestinal distress are common among athletes during training and competition. The psychosocial and physical demands during intense exercise can initiate a stress response activating the sympathetic-adrenomedullary and hypothalamus-pituitary-adrenal (HPA) axes, resulting in the release of stress and catabolic hormones, inflammatory cytokines and microbial molecules. The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including metabolism, endocrine, neuronal and immune function. The gut microbiome and its influence on host behavior, intestinal barrier and immune function are believed to be a critical aspect of the brain-gut axis. Recent evidence in murine models shows that there is a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition. For instance, induced exercise-stress decreased cecal levels of Turicibacter spp and increased Ruminococcus gnavus, which have well defined roles in intestinal mucus degradation and immune function. Diet is known to dramatically modulate the composition of the gut microbiota. Due to the considerable complexity of stress responses in elite athletes (from leaky gut to increased catabolism and depression), defining standard diet regimes is difficult. However, some preliminary experimental data obtained from studies using probiotics and prebiotics studies show some interesting results, indicating that the microbiota acts like an endocrine organ (e.g. secreting serotonin, dopamine or other neurotransmitters) and may control the HPA axis in athletes. What is troubling is that dietary recommendations for elite athletes are primarily based on a low consumption of plant polysaccharides, which is associated with reduced microbiota diversity and functionality (e.g. less synthesis of byproducts such as short chain fatty acids and neurotransmitters). As more

  9. Cognition and HPA axis reactivity in mildly to moderately depressed outpatients

    DEFF Research Database (Denmark)

    Krogh, Jesper; Videbech, Poul; Renvillard, Signe Groth

    2012-01-01

    Background: Patients with depression display neurobiological changes of the hypothalamic-pituitary axis as well as cognitive disturbances. Aims: To assess any association between hypothalamus-pituitary-adrenal (HPA) axis reactivity and memory-related cognitive functions. Methods: Depressed...... the following day at the same times. Results: Patients and controls did not differ on any memory-related cognitive skills. After dexamethasone the cortisol level was 1.7 nmol/l higher (95% CI 0.0-2.8, P =¿0.05) in depressed patients compared with controls. In the control group, but not in the patients...... after dexamethasone and visuo-spatial memory primarily driven by the healthy controls. Otherwise, no association were found between HPA axis reactivity and memory-related cognitive function....

  10. Contact with attractive women affects the release of cortisol in men

    NARCIS (Netherlands)

    van der Meij, Leander; Buunk, Abraham P.; Salvador, Alicia

    Previous studies have shown that situations relevant for human mating can affect the levels of many hormones. This study focused on the hypothalamus-pituitary-adrenal axis by measuring salivary cortisol levels in 84 young men prior to and after a period of short social contact with a woman or man.

  11. Individual variations in maternal care early in life correlate with later life decision-making and c-fos expression in prefrontal subregions of rats.

    NARCIS (Netherlands)

    van Hasselt, F.N.; Visser, L.; Tieskens, J.M.; Cornelisse, S.; Baars, A.M.; Lavrijsen, M.; Krugers, H.J.; van den Bos, R.; Joëls, M.

    2012-01-01

    Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology-e.g. depression, anxiety and schizophrenia- later in life. Here we investigated whether subtle natural variations among

  12. Individual variations in maternal care early in life correlate with later life decision-making and c-fos expression in prefrontal subregions of rats

    NARCIS (Netherlands)

    van Hasselt, F.N.; de Visser, L.; Tieskens, J.M.; Cornelisse, S.; Baars, A.M.; Lavrijsen, M.; Krugers, H.J.; van den Bos, R.; Joëls, M.

    2012-01-01

    Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology--e.g. depression, anxiety and schizophrenia--later in life. Here we investigated whether subtle natural variations among

  13. Companion animal welfare and possible implications on the human-pet relationship

    Directory of Open Access Journals (Sweden)

    Marina Verga

    2010-01-01

    Full Text Available The role of pets (dogs and cats in particular in human society has changed in recent years. Nowadays pets are an integral part of the human family and this aspect has many social and emotional implications. For their positive effects on human health, pets are also employed in some special and therapeutic activities known by the generic term of “Pet Therapy”. In these programmes the animal becomes an integral part of the therapeutic plan in order to induce some physical, social, emotional, and cognitive improvements in human patients. However, the close bond between companion animals and man is not always the herald of beneficial effects. Sometimes the welfare of pets may be compromised by distress due to many factors, mostly related to the environment and to management by humans. Both behavioural and physiological variables may be analysed in order to evaluate welfare level in pets. Reduced welfare may be indicated by the onset of some behavioural problems, which have usually a multifactorial aetiology, related both to the genetic individual basis and environmental factors. Physiological variables which may be analysed in order to evaluate pet welfare include hormone levels, mainly related to the HPA (hypothalamus-pituitary-adrenal- axis and to the immune systems activations. Behavioural problems may also lead to the relinquishment of pets to shelters. Animals housed in rescue shelters cannot display their ethogram and show behavioural and physiological signs of distress. Thus it is very important to improve the human-pet relationship both by educating owners and reducing the number of stray animals, in accordance with the indications of the European Convention for the Protection of Pet Animals stated at Strasbourg in 1987, mainly as regards pet breeding and welfare. Humans have to realise that adopting pets implies the responsibility to care for their health and welfare, avoiding undue stress in the living environment and improving the

  14. Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

    Science.gov (United States)

    Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

    2015-09-01

    Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary

  15. Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive-Like Behavior When Combined with Postweaning Social Isolation in Rats.

    Science.gov (United States)

    Vargas, Javier; Junco, Mariana; Gomez, Carlos; Lajud, Naima

    2016-01-01

    Early-life stress is associated with depression and metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. Such associations could be due to increased glucocorticoid levels. Periodic maternal separation in the neonate and rearing in social isolation are potent stressors that increase hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes feed intake and body weight gain in rats subjected to periodic maternal separation; however, its effects on metabolic risks have not been described. In the present study, we evaluated whether periodic maternal separation, social isolation rearing, and a combination of these two stressors (periodic maternal separation + social isolation rearing) impair glucose homeostasis and its relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior. Periodic maternal separation increased basal corticosterone levels, induced a passive coping strategy in the forced swimming test, and was associated with a mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia. Rearing in social isolation increased stress reactivity in comparison to both controls and in combination with periodic maternal separation, without affecting the coping strategy associated with the forced swimming test. However, social isolation also increased body weight gain, fasting glucose (120%), and insulin levels in rats subjected to periodic maternal separation. Correlation analyses showed that stress-induced effects on coping strategy on the forced swimming test (but not on metabolic risk markers) are associated with basal corticosterone levels. These findings suggest that maternal separation and postweaning social isolation affect stress and metabolic vulnerability differentially and that early-life stress-related effects on metabolism are not directly dependent on glucocorticoid levels. In conclusion, our study supports the cumulative stress hypothesis, which suggests that

  16. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  17. Hypothalamic-pituitary-adrenal axis, childhood adversity and adolescent nonsuicidal self-injury.

    Science.gov (United States)

    Reichl, Corinna; Heyer, Anne; Brunner, Romuald; Parzer, Peter; Völker, Julia Madeleine; Resch, Franz; Kaess, Michael

    2016-12-01

    Whereas childhood adversity (CA) and the hypothalamus-pituitary-adrenal (HPA) axis have been suggested to play a major role in the etiology of non-suicidal self-injury (NSSI), no study has thus far investigated both its associations and interactions with adolescent NSSI. We investigated CA (antipathy, neglect, physical, psychological, and sexual abuse) and indices of HPA axis activity (salivary and hair cortisol) in a clinical sample of 26 adolescents engaging in NSSI and 26 age- and gender-matched healthy controls (HC). We used standardized interviews for the assessment of CA (CECA), NSSI (SITBI-G), and axis I diagnoses (MINI-KID). Salivary cortisol sampling was surveyed using a monitoring system and instructed via telephone calls. Adolescents engaging in NSSI exhibited significantly higher cortisol awakening responses compared to HC. No differences were found with respect to the diurnal slope or hair cortisol. In the presence of CA, healthy adolescents showed flatted diurnal cortisol slopes while those engaging in NSSI exhibited significantly steeper ones. Our findings indicate that adolescents engaging in NSSI may exhibit a stronger cortisol awakening response, potentially in expectation of strain. However, elevated cortisol levels may not be maintained throughout the day, especially among adolescents with a history of CA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.

    Science.gov (United States)

    Merlo, Eduardo; Podratz, Priscila L; Sena, Gabriela C; de Araújo, Julia F P; Lima, Leandro C F; Alves, Izabela S S; Gama-de-Souza, Letícia N; Pelição, Renan; Rodrigues, Lívia C M; Brandão, Poliane A A; Carneiro, Maria T W D; Pires, Rita G W; Martins-Silva, Cristina; Alarcon, Tamara A; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

    2016-08-01

    Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.

  19. Stress-induced sensitization: the hypothalamic-pituitary-adrenal axis and beyond.

    Science.gov (United States)

    Belda, Xavier; Fuentes, Silvia; Daviu, Nuria; Nadal, Roser; Armario, Antonio

    2015-01-01

    Exposure to certain acute and chronic stressors results in an immediate behavioral and physiological response to the situation followed by a period of days when cross-sensitization to further novel stressors is observed. Cross-sensitization affects to different behavioral and physiological systems, more particularly to the hypothalamus-pituitary-adrenal (HPA) axis. It appears that the nature of the initial (triggering) stressor plays a major role, HPA cross-sensitization being more widely observed with systemic or high-intensity emotional stressors. Less important appears to be the nature of the novel (challenging) stressor, although HPA cross-sensitization is better observed with short duration (5-15 min) challenging stressors. In some studies with acute immune stressors, HPA sensitization appears to develop over time (incubation), but most results indicate a strong initial sensitization that progressively declines over the days. Sensitization can affect other physiological system (i.e. plasma catecholamines, brain monoamines), but it is not a general phenomenon. When studied concurrently, behavioral sensitization appears to persist longer than that of the HPA axis, a finding of interest regarding long-term consequences of traumatic stress. In many cases, behavioral and physiological consequences of prior stress can only be observed following imposition of a new stressor, suggesting long-term latent effects of the initial exposure.

  20. Psychological distress, cortisol stress response and subclinical coronary calcification

    NARCIS (Netherlands)

    Seldenrijk, A.; Hamer, M.; Lahiri, A.; Penninx, B.W.J.H.; Steptoe, A.

    2012-01-01

    Objectives: Poor mental health has been associated with coronary heart disease (CHD). One hypothesized underlying mechanism is hypothalamus pituitary adrenal axis dysfunction. We examined the associations between psychological distress, cortisol response to laboratory-induced mental stress and

  1. Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats.

    Science.gov (United States)

    Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically impaired models. We...

  2. Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats

    Science.gov (United States)

    Previous studies have demonstrated that exposure to ozone, a pulmonary irritant, causes myriad systemic metabolic and pulmonary effects that are attributed to neuronal and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically-impaired models...

  3. Stressed lungs: unveiling the role of circulating stress hormones in ozone-induced lung injury and inflammation

    Science.gov (United States)

    Our recent work demonstrated that circulating stress hormones, epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects through the activation of hypothalamus-pituitary-adrenal (HPA) axis. Adrenalectomy in Wistar Kyoto (WKY) rats diminished circu...

  4. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

    Science.gov (United States)

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

    2011-01-01

    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  5. Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress.

    Science.gov (United States)

    Li-Tempel, Ting; Larra, Mauro F; Winnikes, Ulrike; Tempel, Tobias; DeRijk, Roel H; Schulz, André; Schächinger, Hartmut; Meyer, Jobst; Schote, Andrea B

    2016-09-01

    The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

    Directory of Open Access Journals (Sweden)

    Jessica M. F. Hall

    2012-01-01

    Full Text Available Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity and alters antigen presentation by epidermal Langerhans cells (adaptive immunity. Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.

  7. Processing of pro-opiomelanocortin-derived amidated joining peptide and glycine-extended precursor in monkey pituitary

    DEFF Research Database (Denmark)

    Fenger, M

    1991-01-01

    The molecular forms of proopiomelanocortin (POMC) derived amidated and C-terminal glycine-extended joining peptide from monkey (Macaca mulatta) pituitary were determined. The predominant forms of joining peptide found were the low molecular peptides POMC(76-105) and POMC(76-106), respectively...... sequence of monkey and human POMC extremely conserved, but also the processing patterns are similar. The monkey therefore serves as a suitable model for studying regulation of the processing of POMC and the hypothalamus-pituitary-adrenal axis in man....

  8. A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear.

    Science.gov (United States)

    Meyer, R M; Burgos-Robles, A; Liu, E; Correia, S S; Goosens, K A

    2014-12-01

    Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is no clear relationship between the levels of these hormones and stress-associated mental illnesses such as posttraumatic stress disorder (PTSD). Therefore, other hormones are likely to be involved in this effect of stress. Here we used a rodent model of PTSD in which rats repeatedly exposed to a stressor display heightened fear learning following auditory Pavlovian fear conditioning. Our results show that stress-related increases in circulating ghrelin, a peptide hormone, are necessary and sufficient for stress-associated vulnerability to exacerbated fear learning and these actions of ghrelin occur in the amygdala. Importantly, these actions are also independent of the classic HPA stress axis. Repeated systemic administration of a ghrelin receptor agonist enhanced fear memory but did not increase either corticotropin-releasing factor (CRF) or corticosterone. Repeated intraamygdala infusion of a ghrelin receptor agonist produced a similar enhancement of fear memory. Ghrelin receptor antagonism during repeated stress abolished stress-related enhancement of fear memory without blunting stress-induced corticosterone release. We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear-enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin and

  9. Association of HPA axis hormones with copeptin after psychological stress differs by sex.

    Science.gov (United States)

    Spanakis, Elias K; Wand, Gary S; Ji, Nan; Golden, Sherita Hill

    2016-01-01

    Copeptin levels are elevated in severe medical conditions, an effect that is attributed to elevated arginine vasopressin (AVP) levels in response to physiological stress, resulting in activation of hypothalamus-pituitary-adrenal (HPA) axis. In the current study, we wanted to determine if copeptin is responsive to psychological stress, correlates with cortisol and adrenocorticotropin hormone (ACTH), and if associations differed by sex. In a cross-sectional study that included 100 healthy men (41%) and women (59%) (aged 18-30 years; mean 24.6 ± 3 years), who underwent the Trier Social Stress Test (TSST), we examined the association between percent change (peak-baseline/baseline) in copeptin levels and percent change in log ACTH and cortisol. Three baselines samples were drawn followed by blood sampling at 20, 35, 50, 65 and 85 min after TSST. There was a significant positive association between the percent change in copeptin and the percent change in log-transformed salivary cortisol (β-coefficient=0.95; p=0.02). The association between percent change in copeptin and log-transformed serum cortisol was not statistically significant in the overall population. There was a trend for a non-significant association between percent change in copeptin and percent change in log-transformed ACTH (β-coefficient=1.14; p=0.06). In males, there was a significant positive association between the percent change in copeptin levels and log-transformed salivary (β-coefficient=1.33, p=0.016) and serum cortisol (β-coefficient=0.69, p=0.01), whereas in women there was no statistically significant association. We found a significant positive association between percent change in copeptin and percent change in salivary and serum cortisol among males only. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback.

    Science.gov (United States)

    Zschucke, Elisabeth; Renneberg, Babette; Dimeo, Fernando; Wüstenberg, Torsten; Ströhle, Andreas

    2015-01-01

    According to the cross-stressor adaptation hypothesis, physically trained individuals show lower physiological and psychological responses to stressors other than exercise, e.g. psychosocial stress. Reduced stress reactivity may constitute a mechanism of action for the beneficial effects of exercise in maintaining mental health. With regard to neural and psychoneuroendocrine stress responses, the acute stress-buffering effects of exercise have not been investigated yet. A sample of highly trained (HT) and sedentary (SED) young men was randomized to either exercise on a treadmill at moderate intensity (60-70% VO2max; AER) for 30 min, or to perform 30 min of "placebo" exercise (PLAC). 90 min later, an fMRI experiment was conducted using an adapted version of the Montreal Imaging Stress Task (MIST). The subjective and psychoneuroendocrine (cortisol and α-amylase) changes induced by the exercise intervention and the MIST were assessed, as well as neural activations during the MIST. Finally, associations between the different stress responses were analysed. Participants of the AER group showed a significantly reduced cortisol response to the MIST, which was inversely related to the previous exercise-induced α-amylase and cortisol fluctuations. With regard to the sustained BOLD signal, we found higher bilateral hippocampus (Hipp) activity and lower prefrontal cortex (PFC) activity in the AER group. Participants with a higher aerobic fitness showed lower cortisol responses to the MIST. As the Hipp and PFC are brain structures prominently involved in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, these findings indicate that the acute stress-buffering effect of exercise relies on negative feedback mechanisms. Positive affective changes after exercise appear as important moderators largely accounting for the effects related to physical fitness. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis.

    Science.gov (United States)

    Evers, Andrea W M; Verhoeven, Elisabeth W M; van Middendorp, Henriët; Sweep, Fred C G J; Kraaimaat, Floris W; Donders, A Rogier T; Eijsbouts, Agnes E; van Laarhoven, Antoinette I M; de Brouwer, Sabine J M; Wirken, Lieke; Radstake, Timothy R D J; van Riel, Piet L C M

    2014-09-01

    Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present study was to investigate whether daily stressors and worrying as stress vulnerability factor as well as immune and HPA axis activity markers predict short-term disease activity and symptom fluctuations in patients with RA. In a prospective design, daily stressors, worrying, HPA axis (cortisol) and immune system (interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, tumour necrosis factor α) markers, clinical and self-reported disease activity (disease activity score in 28 joints, RA disease activity index), and physical symptoms of pain and fatigue were monitored monthly during 6 months in 80 RA patients. Multilevel modelling indicated that daily stressors predicted increased fatigue in the next month and that worrying predicted increased self-reported disease activity, swollen joint count and pain in the next month. In addition, specific cytokines of IL-1β and IFN-γ predicted increased fatigue 1 month later. Overall, relationships remained relatively unchanged after controlling for medication use, disease duration and demographic variables. No evidence was found for immune and HPA axis activity markers as mediators of the stress-disease relationship. Daily stressors and the stress-vulnerability factor worrying predict indicators of the short-term course of RA disease activity and fatigue and pain, while specific cytokines predict short-term fluctuations of fatigue. These stress-related variables and immune markers seem to affect different aspects of disease activity or symptom fluctuations independently in RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. 24 h urinary free cortisol in large-scale epidemiological studies : Short-term and long-term stability and sources of variability

    NARCIS (Netherlands)

    Rosmalen, Judith G M; Kema, Ido P; Wüst, Stefan; van der Ley, Claude; Visser, Sipke T; Snieder, Harold; Bakker, Stephan J L

    Background: Function of the hypothalamus-pituitary-adrenal (HPA) axis has been associated with several somatic and psychiatric health problems. The amount of free cortisol excreted in the urine during 24 h (24-h UFC) has often been used as a proxy for HPA-axis function. Reference values for 24-h UFC

  13. A low cortisol response to acute stress is related to worse basal memory performance in older people

    NARCIS (Netherlands)

    Almela, M.; Hidalgo, V.; van der Meij, L.; Villada, C.; Pulopulos, M. M.; Salvador, A.

    2014-01-01

    Age-related memory decline has been associated with a faulty regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis). The aim of this study was to investigate whether the magnitude of the stress-induced cortisol increase is related to memory performance when memory is measured in

  14. The Psychophysiology of the burnout syndrome: cortisol sampling in burned out subjects.

    NARCIS (Netherlands)

    Mommersteeg, P.M.C.; Doornen, L.J.P. van; Heijnen, C.J.

    2003-01-01

    Burnout symptoms of emotional exhaustion, depersonalisation and reduced personal accomplishment are the result of chronic stress. Specifically the hypothalamus pituitary adrenal (HPA)-axis is involved in long-term stress adaptation. Upon stimulation the HPA-axis releases cortisol from the adrenal

  15. A psychology of the human brain-gut-microbiome axis.

    Science.gov (United States)

    Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

    2017-04-01

    In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

  16. A psychology of the human brain–gut–microbiome axis

    Science.gov (United States)

    Allen, Andrew P.; Dinan, Timothy G.; Clarke, Gerard

    2017-01-01

    Abstract In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain–gut–microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress‐related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain–gut–microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain–gut–microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain–gut–microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain–gut–microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology. PMID:28804508

  17. Psychological traits and the cortisol awakening response: results from the Netherlands Study of Depression and Anxiety

    NARCIS (Netherlands)

    van Santen, A.; Vreeburg, S.A.; van der Does, A.; Spinhoven, P.; Zitman, F.G.; Penninx, B.W.J.H.

    2011-01-01

    Background: Hypothalamus-Pituitary-Adrenal (HPA) axis dysregulation is often seen in major depression, and is thought to represent a trait vulnerability - rather than merely an illness marker - for depressive disorder and possibly anxiety disorder. Vulnerability traits associated with stress-related

  18. Psychological traits and the cortisol awakening response : Results from the Netherlands Study of Depression and Anxiety

    NARCIS (Netherlands)

    van Santen, Aafke; Vreeburg, Sophie A.; van der Does, A. J. Willem; Spinhoven, Philip; Zitman, Frans G.; Penninx, Brenda W. J. H.

    Background: Hypothalamus-Pituitary-Adrenal (HPA) axis dysregulation is often seen in major depression, and is thought to represent a trait vulnerability - rather than merely an illness marker - for depressive disorder and possibly anxiety disorder. Vulnerability traits associated with stress-related

  19. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress

    NARCIS (Netherlands)

    Henckens, Marloes J. A. G.; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C.; van Wingen, Guido A.; Fernández, Guillén

    2016-01-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both

  20. Basal hypercortisolism and trauma in patients with psychogenic nonepileptic seizures

    NARCIS (Netherlands)

    Bakvis, P.; Spinhoven, P.; Giltay, E.J.; Kuyk, J.; Edelbroek, P.M.; Zitman, F.G.; Roelofs, K.

    2010-01-01

    Purpose: Several studies have indicated that psychogenic nonepileptic seizures (PNES) are associated with psychological trauma, but only a few studies have examined the associations with neurobiologic stress systems, such as the hypothalamus-pituitary-adrenal (HPA) axis and its end-product cortisol.

  1. Corticosteroids and interleukin-1, messengers for communication between the endocrine and immune system in carp

    NARCIS (Netherlands)

    Weyts, F.A.A.

    1998-01-01

    Summary

    Stress-induced inummosuppression is a well known phenomenon and mostly attributed to actions of steroid hormones released upon activation of the hypothalamus-pituitary-adrenal (HPA)-axis. In mammals, this endocrine-immune interaction is part of a

  2. 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...

  3. Systemic Metabolic Impairment and Lung Injury Following Acrolein Inhalation

    Science.gov (United States)

    A single ozone exposure causes pulmonary injury and systemic metabolic alterations through neuronal and hypothalamus pituitary adrenal axis activation. Metabolically impaired Goto Kakizaki (GK) rats with non-obese type-2 diabetes are more sensitive to ozone induced changes than h...

  4. A Laboratory Exercise to Illustrate Increased Salivary Cortisol in Response to Three Stressful Conditions Using Competitive ELISA

    Science.gov (United States)

    Haussmann, Mark F.; Vleck, Carol M; Farrar, Eugenia S.

    2007-01-01

    Perceived stress activates the hypothalamus-pituitary-adrenal axis, resulting in the release of glucocorticoids into the systemic circulation. Glucocorticoids cause the elevation of blood glucose, providing the necessary energy for the organism to cope with stress. Here, we outline a laboratory exercise that uses a competitive ELISA kit to…

  5. In the aftermath of trauma : Marks of stress-related psychopathology

    NARCIS (Netherlands)

    Schür, RR

    2017-01-01

    In this thesis we investigated (traumatic) stress and psychopathology with a focus on the potential roles of the hypothalamus-pituitary-adrenal (HPA) axis, the GABA system, their association, and the general genetic background of major depressive disorder (MDD) and posttraumatic stress disorder

  6. Ozone-Induced Pulmonary Injury and Vascular Contractility are Differentially Impacted by Coconut, Fish, and Olive Oil-Rich Diets

    Science.gov (United States)

    Pulmonary and systemic effects of ozone (O3) are mediated by hypothalamus pituitary adrenal (HPA)-axis activation. Fish oil (FO) and olive oil (OO) dietary supplementation have several cardioprotective benefits, but it is not established if these supplements can protect against t...

  7. Development of cortisol circadian rhythm in infancy.

    NARCIS (Netherlands)

    Weerth, C. de; Zijl, R.H.

    2003-01-01

    BACKGROUND AND AIMS: Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not

  8. Hair Cortisol in Twins

    DEFF Research Database (Denmark)

    Rietschel, Liz; Streit, Fabian; Zhu, Gu

    2017-01-01

    Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors...

  9. Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats.

    Science.gov (United States)

    Surapaneni, Dinesh Kumar; Adapa, Sree Rama Shiva Shanker; Preeti, Kumari; Teja, Gangineni Ravi; Veeraragavan, Muruganandam; Krishnamurthy, Sairam

    2012-08-30

    Shilajit has been used as a rejuvenator for ages in Indian ancient traditional medicine and has been validated for a number of pharmacological activities. The effect of processed shilajit which was standardized to dibenzo-α-pyrones (DBPs;0.43% w/w), DBP-chromoproteins (DCPs; 20.45% w/w) and fulvic acids (56.75% w/w) was evaluated in a rat model of chronic fatigue syndrome (CFS). The mitochondrial bioenergetics and the activity of hypothalamus-pituitary-adrenal (HPA) axis were evaluated for the plausible mechanism of action of shilajit. CFS was induced by forcing the rats to swim for 15mins for 21 consecutive days. The rats were treated with shilajit (25, 50 and 100mg/kg) for 21 days before exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility and the climbing period. The post-CFS anxiety level was assessed by elevated plus maze (EPM) test. Plasma corticosterone and adrenal gland weight were estimated as indices of HPA axis activity. Analysis of mitochondrial complex chain enzymes (Complex I, II, IV and V) and mitochondrial membrane potential (MMP) in prefrontal cortex (PFC) were performed to evaluate the mitochondrial bioenergetics and integrity respectively. Shilajit reversed the CFS-induced increase in immobility period and decrease in climbing behavior as well as attenuated anxiety in the EPM test. Shilajit reversed CFS-induced decrease in plasma corticosterone level and loss of adrenal gland weight indicating modulation of HPA axis. Shilajit prevented CFS-induced mitochondrial dysfunction by stabilizing the complex enzyme activities and the loss of MMP. Shilajit reversed CFS-induced mitochondrial oxidative stress in terms of NO concentration and, LPO, SOD and catalase activities. The results indicate that shilajit mitigates the effects of CFS in this model possibly through the modulation of HPA axis and preservation of mitochondrial function and integrity. The reversal of CFS-induced behavioral symptoms and

  10. Interaction between circadian rhythms and stress

    Directory of Open Access Journals (Sweden)

    C.E. Koch

    2017-02-01

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

  11. Palatable food avoidance and acceptance learning with different stressors in female rats

    OpenAIRE

    Liang, Nu-Chu; Smith, Megan E.; Moran, Timothy H.

    2013-01-01

    Stress activates the hypothalamus- pituitary-adrenal (HPA) axis leading to the release of glucocorticoids (GC). Increased activity of the HPA axis and GC exposure has been suggested to facilitate the development of obesity and metabolic syndrome. Nonetheless, different stressors can produce distinct effects on food intake and may support different directions of food learning e.g. avoidance or acceptance. This study examined whether interoceptive (LiCl and exendin-4) and restraint stress suppo...

  12. Mechanical impedance of the sitting human body in single-axis compared to multi-axis whole-body vibration exposure.

    Science.gov (United States)

    Holmlund, P; Lundström, R

    2001-01-01

    The study was aimed to investigate the mechanical impedance of the sitting human body and to compare data obtained in laboratory single-axis investigations with multi-axis data from in vehicle measurements. The experiments were performed in a laboratory for single-axis measurements. The multi-axis exposure was generated with an eight-seat minibus where the rear seats had been replaced with a rigid one. The subjects in the multi-axis experiment all participated in the single-axis experiments. There are quite a few investigations in the literature describing the human response to single-axis exposure. The response from the human body can be expected to be affected by multi-axis input in a different way than from a single-axis exposure. The present knowledge of the effect of multiple axis exposure is very limited. The measurements were performed using a specially designed force and accelerometer plate. This plate was placed between the subject and the hard seat. Outcome shows a clear difference between mechanical impedance for multi-axis exposure compared to single-axis. This is especially clear in the x-direction where the difference is very large. The conclusion is that it seems unlikely that single-axis mechanical impedance data can be directly transferred to a multi-axis environment. This is due to the force cross-talk between different directions.

  13. Salivary alpha-amylase: More than an enzyme Investigating confounders of stress-induced and basal amylase activity

    OpenAIRE

    Strahler, Jana

    2010-01-01

    Summary: Salivary alpha-amylase: More than an enzyme - Investigating confounders of stress-induced and basal amylase activity (Dipl.-Psych. Jana Strahler) The hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are two of the major systems playing a role in the adaptation of organisms to developmental changes that threaten homeostasis. The HPA system involves the secretion of glucocorticoids, including cortisol, into the circulatory system. Numerous studies hav...

  14. In the aftermath of trauma : Marks of stress-related psychopathology

    OpenAIRE

    Schür, RR

    2017-01-01

    In this thesis we investigated (traumatic) stress and psychopathology with a focus on the potential roles of the hypothalamus-pituitary-adrenal (HPA) axis, the GABA system, their association, and the general genetic background of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). We first reviewed the evidence on the cortisol response to psychosocial stress across psychiatric disorders and found that sex and symptomatic state are crucial factors to consider when compari...

  15. Human cancers converge at the HIF-2alpha oncogenic axis.

    Science.gov (United States)

    Franovic, Aleksandra; Holterman, Chet E; Payette, Josianne; Lee, Stephen

    2009-12-15

    Cancer development is a multistep process, driven by a series of genetic and environmental alterations, that endows cells with a set of hallmark traits required for tumorigenesis. It is broadly accepted that growth signal autonomy, the first hallmark of malignancies, can be acquired through multiple genetic mutations that activate an array of complex, cancer-specific growth circuits [Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70; Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789-799]. The superfluous nature of these pathways is thought to severely limit therapeutic approaches targeting tumor proliferation, and it has been suggested that this strategy be abandoned in favor of inhibiting more systemic hallmarks, including angiogenesis (Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: Mechanisms of anti-tumor activity. Nat Rev Cancer 8:579-591; Stommel JM, et al. (2007) Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318:287-290; Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727-739; Kaiser J (2008) Cancer genetics: A detailed genetic portrait of the deadliest human cancers. Science 321:1280-1281]. Here, we report the unexpected observation that genetically diverse cancers converge at a common and obligatory growth axis instigated by HIF-2alpha, an element of the oxygen-sensing machinery. Inhibition of HIF-2alpha prevents the in vivo growth and tumorigenesis of highly aggressive glioblastoma, colorectal, and non-small-cell lung carcinomas and the in vitro autonomous proliferation of several others, regardless of their mutational status and tissue of origin. The concomitant deactivation of select receptor tyrosine kinases, including the EGFR and IGF1R, as well as downstream ERK/Akt signaling, suggests that HIF-2alpha exerts its proliferative effects by endorsing these major pathways. Consistently

  16. Pituitary gonodal axis in fertile and infertile human males

    International Nuclear Information System (INIS)

    Hafiez, A.A.; Mahmoud, K.Z.; Abbas, E.Z.; Halawa, F.

    1984-01-01

    Radioimmunoassays of serum PRL, LH, FSH, testosterone and estradiol were performed in normal fertile subjects and infertile patients. The findings in the fertile group suggest that prolactin in human males has a role in steroidogenesis. Oligospermic and azospermic patients revealed hormonal patterns which were significantly higher than in the fertile group. Hyperprolactinemia was found in most cases of both infertile groups indicating that PRL has a significant role. (author)

  17. The PTEN/NRF2 Axis Promotes Human Carcinogenesis

    DEFF Research Database (Denmark)

    Rojo, Ana I; Rada, Patricia; Mendiola, Marta

    2014-01-01

    and tumorigenic advantage. Tissue microarrays from endometrioid carcinomas showed that 80% of PTEN-negative tumors expressed high levels of NRF2 or its target heme oxygenase-1 (HO-1). INNOVATION: These results uncover a new mechanism of oncogenic activation of NRF2 by loss of its negative regulation by PTEN/GSK-3....../β-TrCP that may be relevant to a large number of tumors, including endometrioid carcinomas. CONCLUSION: Increased activity of NRF2 due to loss of PTEN is instrumental in human carcinogenesis and represents a novel therapeutic target. Antioxid. Redox Signal. 21, 2498-2514....

  18. A low cortisol response to acute stress is related to worse basal memory performance in older people

    Directory of Open Access Journals (Sweden)

    Mercedes eAlmela

    2014-07-01

    Full Text Available Age-related memory decline has been associated with a faulty regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis. The aim of this study was to investigate whether the magnitude of the stress-induced cortisol increase is related to memory performance when memory is measured in non-stressful conditions. To do so, declarative and working memory performance were measured in 31 men and 35 women between 55 and 77 years of age. On a different day, the magnitude of their cortisol response to acute psychosocial stress was measured. The relationship between the cortisol response and memory performance was U shaped: a low cortisol response to stress was related to poorer declarative and working memory performance, whereas those who did not increase their cortisol levels and those who had the largest cortisol increase had better declarative and working memory capabilities. Sex did not moderate these relationships. These results suggest that a low cortisol response to stress could reflect a defective HPA-axis response to stressors that is accompanied by poorer memory performance. Conversely, a high cortisol response seems to reflect a correct functioning of the HPA-axis and may protect against memory deficits in the later stages of human life.

  19. GH/IGF-I axis and matrix adaptation of the musculotendinous tissue to exercise in humans

    DEFF Research Database (Denmark)

    Heinemeier, K M; Mackey, Abigail; Doessing, S

    2012-01-01

    cells (satellite cells), as increased satellite cell numbers are found in human muscle with increased GH/IGF-I levels, despite no change in myofibrillar protein synthesis. Although advanced age is associated with both a reduction in the GH/IGF-I axis activity, and in skeletal muscle mass (sarcopenia...

  20. Nystagmus responses in a group of normal humans during earth-horizontal axis rotation

    Science.gov (United States)

    Wall, Conrad, III; Furman, Joseph M. R.

    1989-01-01

    Horizontal eye movement responses to earth-horizontal yaw axis rotation were evaluated in 50 normal human subjects who were uniformly distributed in age (20-69 years) and each age group was then divided by gender. Subjects were rotated with eyes open in the dark, using clockwise and counter-clockwise 60 deg velocity trapezoids. The nystagmus slow component velocity is analyzed. It is shown that, despite large intersubject variability, parameters which describe earth-horizontal yaw axis responses are loosely interrelated, and some of them vary significantly with gender and age.

  1. Stress, memory, and the hippocampus.

    Science.gov (United States)

    Wingenfeld, Katja; Wolf, Oliver T

    2014-01-01

    Stress hormones, i.e. cortisol in human and cortisone in rodents, influence a wide range of cognitive functions, including hippocampus-based declarative memory performance. Cortisol enhances memory consolidation, but impairs memory retrieval. In this context glucocorticoid receptor sensitivity and hippocampal integrity play an important role. This review integrates findings on the relationships between the hypothalamus-pituitary-adrenal (HPA) axis, one of the main coordinators of the stress response, hippocampus, and memory. Findings obtained in healthy participants will be compared with selected mental disorders, including major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). These disorders are characterized by alterations of the HPA axis and hippocampal dysfunctions. Interestingly, the acute effects of stress hormones on memory in psychiatric patients are different from those found in healthy humans. While cortisol administration has failed to affect memory retrieval in patients with MDD, patients with PTSD and BPD have been found to show enhanced rather than impaired memory retrieval after hydrocortisone. This indicates an altered sensitivity to stress hormones in these mental disorders. © 2014 S. Karger AG, Basel

  2. Rapid stress system drives chemical transfer of fear from sender to receiver.

    Directory of Open Access Journals (Sweden)

    Jasper H B de Groot

    Full Text Available Humans can register another person's fear not only with their eyes and ears, but also with their nose. Previous research has demonstrated that exposure to body odors from fearful individuals elicited implicit fear in others. The odor of fearful individuals appears to have a distinctive signature that can be produced relatively rapidly, driven by a physiological mechanism that has remained unexplored in earlier research. The apocrine sweat glands in the armpit that are responsible for chemosignal production contain receptors for adrenalin. We therefore expected that the release of adrenalin through activation of the rapid stress response system (i.e., the sympathetic-adrenal medullary system is what drives the release of fear sweat, as opposed to activation of the slower stress response system (i.e., hypothalamus-pituitary-adrenal axis. To test this assumption, sweat was sampled while eight participants prepared for a speech. Participants had higher heart rates and produced more armpit sweat in the fast stress condition, compared to baseline and the slow stress condition. Importantly, exposure to sweat from participants in the fast stress condition induced in receivers (N = 31 a simulacrum of the state of the sender, evidenced by the emergence of a fearful facial expression (facial electromyography and vigilant behavior (i.e., faster classification of emotional facial expressions.

  3. Stressed lungs: unveiling the role of circulating stress ...

    Science.gov (United States)

    Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction with lung lining components causing local oxidative changes, which then leads to cell damage and recruitment of inflammatory cells. It is postulated that the spillover of reactive intermediates and pro-inflammatory molecules from lung to systemic circulation mediates extra-pulmonary effects. However, recent work from our laboratory supports an alternative hypothesis that circulating stress hormones, such as epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects. We have shown in rats and humans that ozone increases the levels of circulating stress hormones through activation of the hypothalamus- pituitary-adrenal (HPA) axis before any measurable effects are observed in the lung. The surgical removal of adrenals diminishes circulating stress hormones and at the same time, the pulmonary effects of ozone suggesting a significant contribution of these hormones in ozone-induced lung injury and inflammation. While ozone effects in the lung have been extensively studied, the contribution of central nervous system -mediated hormonal stress response has not been examined. In order to understand the signaling pathways that might be involved in ozone-induced lun

  4. Psychosocial Stress-Induced Analgesia: An Examination of Effects on Heat Pain Threshold and Tolerance and of Neuroendocrine Mediation.

    Science.gov (United States)

    Gaab, Jens; Jiménez, Julia; Voneschen, Livia; Oschwald, Daniel; Meyer, Andrea H; Nater, Urs M; Krummenacher, Peter

    2016-01-01

    Stress-induced analgesia (SIA) is an adaptive response of reduced nociception following demanding acute internal and external stressors. Although a psychobiological understanding of this phenomenon is of importance for stress-related psychiatric and pain conditions, comparably little is known about the psychobiological mechanisms of SIA in humans. The aim of this study was to investigate the effects of acute psychosocial stress on heat pain perception and its possible neuroendocrine mediation by salivary cortisol levels and α-amylase activity in healthy men. Employing an intra-individual assessment of heat pain parameters, acute psychosocial stress did not influence heat pain threshold but significantly, albeit slightly, increased heat pain tolerance. Using linear mixed-model analysis, this effect of psychosocial stress on heat pain tolerance was not mediated by increases of salivary cortisol and state anxiety levels or by the activity of α-amylase. These results show that while psychosocial stress is selectively analgesic for heat pain tolerance, this observed effect is not mediated by stress-induced increases of salivary cortisol and α-amylase activity, as proxies of both the hypothalamus-pituitary-adrenal axis and the autonomic nervous system activation. © 2017 S. Karger AG, Basel.

  5. Timing is critical for effective glucocorticoid receptor mediated repression of the cAMP-induced CRH gene.

    Directory of Open Access Journals (Sweden)

    Siem van der Laan

    Full Text Available Glucocorticoid negative feedback of the hypothalamus-pituitary-adrenal axis is mediated in part by direct repression of gene transcription in glucocorticoid receptor (GR expressing cells. We have investigated the cross talk between the two main signaling pathways involved in activation and repression of corticotrophin releasing hormone (CRH mRNA expression: cyclic AMP (cAMP and GR. We report that in the At-T20 cell-line the glucocorticoid-mediated repression of the cAMP-induced human CRH proximal promoter activity depends on the relative timing of activation of both signaling pathways. Activation of the GR prior to or in conjunction with cAMP signaling results in an effective repression of the cAMP-induced transcription of the CRH gene. In contrast, activation of the GR 10 minutes after onset of cAMP treatment, results in a significant loss of GR-mediated repression. In addition, translocation of ligand-activated GR to the nucleus was found as early as 10 minutes after glucocorticoid treatment. Interestingly, while both signaling cascades counteract each other on the CRH proximal promoter, they synergize on a synthetic promoter containing 'positive' response elements. Since the order of activation of both signaling pathways may vary considerably in vivo, we conclude that a critical time-window exists for effective repression of the CRH gene by glucocorticoids.

  6. The food-gut human axis: the effects of diet on gut microbiota and metabolome.

    Science.gov (United States)

    De Angelis, Maria; Garruti, Gabriella; Minervini, Fabio; Bonfrate, Leonilde; Portincasa, Piero; Gobbetti, Marco

    2017-04-27

    Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. Within the dietary components, polymers (mainly fibers, proteins, fat and polyphenols) that are not hydrolyzed by human enzymes seem to be the main leads of the metabolic pathways of gut microbiota, which in turn directly influences the human metabolome. Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established. Dietary treatments with fibers are the most effective to benefit the metabolome profile, by improving the synthesis of short chain fatty acids and decreasing the level of molecules, such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, involved in disease state. Based on the axis diet-microbiota-health, this review aims at describing the most recent knowledge oriented towards a profitable use of diet to provide benefits to human health, both directly and indirectly, through the activity of gut microbiota. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. GPR39 (zinc receptor) knockout mice exhibit depression-like behavior and CREB/BDNF down-regulation in the hippocampus

    DEFF Research Database (Denmark)

    Młyniec, Katarzyna; Budziszewska, Bogusława; Holst, Birgitte

    2015-01-01

    Background: Zinc may act as a neurotransmitter in the central nervous system by activation of the GPR39 metabotropic receptors. Methods: In the present study, we investigated whether GPR39 knockout would cause depressive-like and/or anxiety-like behavior, as measured by the forced swim test, tail...... investigated activity in the hypothalamus-pituitary-adrenal axis under both zinc- and GPR39-deficient conditions. Zinc-deficient mice had higher serum corticosterone levels and lower glucocorticoid receptor levels in the hippocampus and frontal cortex. Conclusions: There were no changes in the GPR39 knockout...

  8. 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.

  9. Effects of drugs on beta-endorphin and cortisol in smokers

    International Nuclear Information System (INIS)

    Du Tongxin; Wang Zizheng; Wang Shukui

    2001-01-01

    The authors observed the effects of drugs on beta-endorphin and cortisol in smokers and their correlation. The levels of plasma beta-endorphin and cortisol of smokers before and after cigarette withdrawal were detected by radioimmunoassay (RIA). The Levels of plasma beta-endorphin and cortisol in smokers is significantly higher than in controls. After natural withdrawal, the levels of plasma cortisol increased significantly, while beta-endorphin decreased significantly. After drug treatment, the levels of beta-endorphin and cortisol balanced. The drugs may play the role of cigarette withdrawal by improving the secretion of endogenous opium and the axis of hypothalamus-pituitary adrenal

  10. Beyond the HPA axis: progesterone-derived neuroactive steroids in human stress and emotion

    Directory of Open Access Journals (Sweden)

    Michelle eWirth

    2011-08-01

    Full Text Available Stress and social isolation are well-known risk factors for psychopathology. However, more research is needed as to the physiological mechanisms by which social support buffers the impacts of stress. Research in animal models suggests important roles for progesterone (P and its product, the neuroactive steroid allopregnanolone (ALLO, in stress and psychopathology. These hormones are produced in brain and periphery during stress in rodents, and down-regulate anxiety behavior and HPA axis activity. Human clinical populations, including depressed patients, have alterations in ALLO levels, but it is unclear whether these basal hormone level differences have clinical import. To begin to address this question, this review examines the role of P and ALLO in stress physiology, and the impact of these hormones on mood, in healthy humans. Evidence largely supports that P and ALLO increase during stress in humans. However, P/ALLO administration appears to cause only mild effects on mood and subjective anxiety, while exerting effects consistent with GABA receptor modulation. Additionally, P is linked to motivation for affiliation / social contact; P (and ALLO release may be especially responsive to social rejection. These observations lead to the novel hypothesis that stress-related P/ALLO production functions not only to down-regulate stress and anxiety, but also to promote social contact as a long-term coping strategy. Malfunctioning of the P/ALLO system could therefore underlie depression partly by decreasing propensity to affiliate with others.

  11. In vivo near-infrared dual-axis confocal microendoscopy in the human lower gastrointestinal tract

    Science.gov (United States)

    Piyawattanametha, Wibool; Ra, Hyejun; Qiu, Zhen; Friedland, Shai; Liu, Jonathan T. C.; Loewke, Kevin; Kino, Gordon S.; Solgaard, Olav; Wang, Thomas D.; Mandella, Michael J.; Contag, Christopher H.

    2012-02-01

    Near-infrared confocal microendoscopy is a promising technique for deep in vivo imaging of tissues and can generate high-resolution cross-sectional images at the micron-scale. We demonstrate the use of a dual-axis confocal (DAC) near-infrared fluorescence microendoscope with a 5.5-mm outer diameter for obtaining clinical images of human colorectal mucosa. High-speed two-dimensional en face scanning was achieved through a microelectromechanical systems (MEMS) scanner while a micromotor was used for adjusting the axial focus. In vivo images of human patients are collected at 5 frames/sec with a field of view of 362×212 μm2 and a maximum imaging depth of 140 μm. During routine endoscopy, indocyanine green (ICG) was topically applied a nonspecific optical contrasting agent to regions of the human colon. The DAC microendoscope was then used to obtain microanatomic images of the mucosa by detecting near-infrared fluorescence from ICG. These results suggest that DAC microendoscopy may have utility for visualizing the anatomical and, perhaps, functional changes associated with colorectal pathology for the early detection of colorectal cancer.

  12. Compressed sensing method for human activity recognition using tri-axis accelerometer on mobile phone

    Institute of Scientific and Technical Information of China (English)

    Song Hui; Wang Zhongmin

    2017-01-01

    The diversity in the phone placements of different mobile users' dailylife increases the difficulty of recognizing human activities by using mobile phone accelerometer data.To solve this problem,a compressed sensing method to recognize human activities that is based on compressed sensing theory and utilizes both raw mobile phone accelerometer data and phone placement information is proposed.First,an over-complete dictionary matrix is constructed using sufficient raw tri-axis acceleration data labeled with phone placement information.Then,the sparse coefficient is evaluated for the samples that need to be tested by resolving L1 minimization.Finally,residual values are calculated and the minimum value is selected as the indicator to obtain the recognition results.Experimental results show that this method can achieve a recognition accuracy reaching 89.86%,which is higher than that of a recognition method that does not adopt the phone placement information for the recognition process.The recognition accuracy of the proposed method is effective and satisfactory.

  13. Implicaciones de la crianza en la regulación del estrés

    Directory of Open Access Journals (Sweden)

    María Cristina García

    2011-10-01

    Full Text Available The purpose of this article is to revise evidence from human and animal research around the stressregulation pathway. The data from research studies are based on the hypothalamus-pituitary-adrenal gland system andon the way stress early experiences can condition the circuit reactivity. The role of sensible rearing practices to promote the development of adequate self-regulatory systems. Te risk of negligent experiences as well as chronic stress on early childhood.Finally base on existing evidence we propose activities to prevent chronic stress on early childhood.

  14. Multi-Axis Force Sensor for Human-Robot Interaction Sensing in a Rehabilitation Robotic Device.

    Science.gov (United States)

    Grosu, Victor; Grosu, Svetlana; Vanderborght, Bram; Lefeber, Dirk; Rodriguez-Guerrero, Carlos

    2017-06-05

    Human-robot interaction sensing is a compulsory feature in modern robotic systems where direct contact or close collaboration is desired. Rehabilitation and assistive robotics are fields where interaction forces are required for both safety and increased control performance of the device with a more comfortable experience for the user. In order to provide an efficient interaction feedback between the user and rehabilitation device, high performance sensing units are demanded. This work introduces a novel design of a multi-axis force sensor dedicated for measuring pelvis interaction forces in a rehabilitation exoskeleton device. The sensor is conceived such that it has different sensitivity characteristics for the three axes of interest having also movable parts in order to allow free rotations and limit crosstalk errors. Integrated sensor electronics make it easy to acquire and process data for a real-time distributed system architecture. Two of the developed sensors are integrated and tested in a complex gait rehabilitation device for safe and compliant control.

  15. Seasonal variation in hormonal responses of timber rattlesnakes (Crotalus horridus) to reproductive and environmental stressors.

    Science.gov (United States)

    Lutterschmidt, William I; Lutterschmidt, Deborah I; Mason, Robert T; Reinert, Howard K

    2009-08-01

    Data addressing adrenocortical modulation across taxonomic groups are limited, especially with regard to how female reproductive condition influences the sensitivity of the hypothalamus-pituitary-adrenal axis. We investigated seasonal and reproductive variation in basal and stress-induced hormone profiles in a population of free-ranging timber rattlesnakes (Crotalus horridus) in north-central Pennsylvania during spring (i.e., May), summer (i.e., July), and early fall (i.e., September). Baseline corticosterone concentrations varied seasonally and were significantly lower during the summer sampling period in July. We observed a significant negative relationship between baseline corticosterone and testosterone in male snakes, while baseline corticosterone and estradiol tended to be positively correlated in females. Treatment of snakes with 1 h of capture stress significantly increased corticosterone across all seasons. However, there was a significant interaction between corticosterone responses to capture stress and season, suggesting that adrenocortical function is modulated seasonally. Because elevated corticosterone may be associated with reproduction, we asked whether hormonal stress responses vary with female reproductive condition. Although sample sizes are low, reproductive snakes had significantly higher baseline and stress-induced corticosterone concentrations than non-reproductive or post-parturient females. Further, despite similar baseline corticosterone concentrations between non-reproductive and post-parturient rattlesnakes, post-parturient females responded to capture stress with a significantly higher increase in corticosterone. Collectively, these data suggest that the sensitivity of the hypothalamus-pituitary-adrenal axis varies both seasonally and with changing reproductive states.

  16. Mapping the organization of axis of motion selective features in human area MT using high-field fMRI.

    Directory of Open Access Journals (Sweden)

    Jan Zimmermann

    Full Text Available Functional magnetic resonance imaging (fMRI at high magnetic fields has made it possible to investigate the columnar organization of the human brain in vivo with high degrees of accuracy and sensitivity. Until now, these results have been limited to the organization principles of early visual cortex (V1. While the middle temporal area (MT has been the first identified extra-striate visual area shown to exhibit a columnar organization in monkeys, evidence of MT's columnar response properties and topographic layout in humans has remained elusive. Research using various approaches suggests similar response properties as in monkeys but failed to provide direct evidence for direction or axis of motion selectivity in human area MT. By combining state of the art pulse sequence design, high spatial resolution in all three dimensions (0.8 mm isotropic, optimized coil design, ultrahigh field magnets (7 Tesla and novel high resolution cortical grid sampling analysis tools, we provide the first direct evidence for large-scale axis of motion selective feature organization in human area MT closely matching predictions from topographic columnar-level simulations.

  17. Targeting the ecology within: The role of the gut-brain axis and human microbiota in drug addiction.

    Science.gov (United States)

    Skosnik, Patrick D; Cortes-Briones, Jose A

    2016-08-01

    Despite major advances in our understanding of the brain using traditional neuroscience, reliable and efficacious treatments for drug addiction have remained elusive. Hence, the time has come to utilize novel approaches, particularly those drawing upon contemporary advances in fields outside of established neuroscience and psychiatry. Put another way, the time has come for a paradigm shift in the addiction sciences. Apropos, a revolution in the area of human health is underway, which is occurring at the nexus between enteric microbiology and neuroscience. It has become increasingly clear that the human microbiota (the vast ecology of bacteria residing within the human organism), plays an important role in health and disease. This is not surprising, as it has been estimated that bacteria living in the human body (approximately 1kg of mass, roughly equivalent to that of the human brain) outnumber human cells 10 to 1. While advances in the understanding of the role of microbiota in other areas of human health have yielded intriguing results (e.g., Clostridium difficile, irritable bowel syndrome, autism, etc.), to date, no systematic programs of research have examined the role of microbiota in drug addiction. The current hypothesis, therefore, is that gut dysbiosis plays a key role in addictive disorders. In the context of this hypothesis, this paper provides a rationale for future research to target the "gut-brain axis" in addiction. A brief background of the gut-brain axis is provided, along with a series of hypothesis-driven ideas outlining potential treatments for addiction via manipulations of the "ecology within." Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Circadian Clock Dysfunction and Psychiatric Disease: Could Fruit Flies have a Say?

    Science.gov (United States)

    Zordan, Mauro Agostino; Sandrelli, Federica

    2015-01-01

    There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system leads to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here, we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e., a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia, and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes, which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions, and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease.

  19. Circadian clock dysfunction and psychiatric disease: could fruit flies have a say?

    Directory of Open Access Journals (Sweden)

    Mauro Agostino Zordan

    2015-04-01

    Full Text Available There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system lead to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e. a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease.

  20. Positive and negative social support and HPA-axis hyperactivity: Evidence from glucocorticoids in human hair.

    Science.gov (United States)

    Iob, Eleonora; Kirschbaum, Clemens; Steptoe, Andrew

    2018-06-12

    While positive social support is associated with lower prevalence of disease and better treatment outcomes, negative social relationships can instead have unfavourable consequences for several physical and mental health conditions. However, the specific mechanisms by which this nexus might operate remain poorly understood. Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity owing to psychosocial stress has been proposed as a potential pathway underlying the link between social support and health. Hair glucocorticoids such as cortisol and cortisone are emerging as promising biomarkers of long-term retrospective HPA activation. Therefore, the aim of this investigation was to examine the effects of positive and negative experiences of social support within key relationships (i.e. spouse/partner, children, other family members, and friends) on cortisol and cortisone. These associations were tested in a sample of 2520 older adults (mean age 68.1) from the English Longitudinal Study of Ageing. Hair samples were collected in wave 6 (2012/13). To understand the impact of cumulative exposure to poor social support, the analysis used self-reported data from waves 4 (2008/09) and 6. Covariates included demographic, socioeconomic, lifestyle, and hair characteristics. In cross sectional analyses, lower positive support from all sources and specifically from children were associated with higher cortisol. Additionally, lower positive support from children was positively associated with cortisone. Similarly, higher overall negative support was related to higher cortisol, and greater negative support from children was also positively associated with cortisone. In longitudinal analyses, there was evidence for positive associations between hair glucocorticoids and cumulative exposure to poorer social support. Experiences of low positive and high negative social support, particularly from children, were both related to higher hair glucocorticoids. Hence, social relationships of

  1. Stress in the zoo: Tracking the impact of stress on memory formation over time.

    Science.gov (United States)

    Vogel, Susanne; Schwabe, Lars

    2016-09-01

    Although stress is well known to modulate human memory, precisely how memory formation is altered by a stressful encounter remains unclear. Stress effects on cognition are mainly mediated by the rapidly acting sympathetic nervous system, resulting in the release of catecholamines, and the slower acting hypothalamus-pituitary-adrenal axis secreting cortisol, which induces its effects on cognition through fast, non-genomic actions and delayed, genomic actions. Importantly, these different waves of the physiological stress response are thought to dynamically alter neural processing in brain regions important for memory such as the amygdala and the hippocampus. However, the precise time course of stress effects on memory formation is still unclear. To track the development of stress effects on memory over time, we tested individuals who underwent a stressful experience or a control procedure before a 2-h walk through a zoo, while an automatic camera continuously photographed the events they encoded. In a recognition memory test one week later, participants were presented with target photographs of their own zoo tour and lure photographs from an alternate tour. Stressed participants showed better memory for the experimental treatment than control participants, and this memory enhancement for the stressful encounter itself was directly linked to the sympathetic stress response. Moreover, stress enhanced memory for events encoded 41-65min after stressor onset, which was associated with the cortisol stress response, most likely arising from non-genomic cortisol actions. However, memory for events encoded long after the stressor, when genomic cortisol actions had most likely developed, remained unchanged. Our findings provide novel insights into how stress effects on memory formation develop over time, depending on the activity of major physiological stress response systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The combined propranolol/TSST paradigm--a new method for psychoneuroendocrinology.

    Directory of Open Access Journals (Sweden)

    Julie Andrews

    Full Text Available Upon perception of a stimulus as stressful, the human brain reacts with the activation of the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system (SNS, to mobilize energy resources to better cope with the stressor. Since the perception of the stressor is the initial stimulus, a synchronicity between the subjective perception of stress and the physiological stress reactivity should be expected. However, according to a recent meta-analysis, these associations are weak and inconsistent. The goal of the current study was to investigate the interaction between the SNS, HPA and subjective stress perceptions, by introducing an experimental manipulation of this interaction. For this purpose, we combined the SNS inhibitor propranolol with the Trier Social Stress Test, and measured endocrinological and psychological responses to the stressor. Thirty healthy male participants were recruited and randomly assigned to either a propranolol (PROP; n = 15 or placebo (PLC; n = 15 group. All subjects were administered 80 mg of propranolol 60 minutes prior to exposure to psychosocial stress. Salivary cortisol and alpha amylase (sAA, heart rate, blood pressure and subjective stress responses were assessed throughout the study. We observed significantly reduced sAA levels and heart rate increases in the PROP group in response to stress, with no effects of the drug on systolic or diastolic blood pressure changes. In line with previous studies, a significant increase in cortisol was seen in response to the stress exposure. Importantly, the cortisol increase was significantly higher in the PROP group. A typical increase in subjective stress could be seen in both groups, with no significant group differences emerging. Complementing previous work, this study further demonstrates a significant interaction between the HPA and the SNS during acute stress. The HPA activity was found to be elevated in the presence of a suppressed SNS in

  3. Evaluating the stress response as a bioindicator of sub-lethal effects of crude oil exposure in wild house sparrows (Passer domesticus.

    Directory of Open Access Journals (Sweden)

    Christine R Lattin

    Full Text Available Petroleum can disrupt endocrine function in humans and wildlife, and interacts in particularly complex ways with the hypothalamus-pituitary-adrenal (HPA axis, responsible for the release of the stress hormones corticosterone and cortisol (hereafter CORT. Ingested petroleum can act in an additive fashion with other stressors to cause increased mortality, but it is not clear exactly why--does petroleum disrupt feedback mechanisms, stress hormone production, or both? This laboratory study aimed to quantify the effects of ingested Gulf of Mexico crude oil on the physiological stress response of house sparrows (Passer domesticus. We examined baseline and stress-induced CORT, negative feedback, and adrenal sensitivity in house sparrows given a 1% oil or control diet (n = 12 in each group. We found that four weeks on a 1% oil diet did not alter baseline CORT titers or efficacy of negative feedback, but significantly reduced sparrows' ability to secrete CORT in response to a standardized stressor and adrenocorticotropin hormone injection, suggesting that oil damages the steroid-synthesizing cells of the adrenal. In another group of animals on the same 1% oil (n = 9 or control diets (n = 8, we examined concentrations of eight different blood chemistry parameters, and CORT in feathers grown before and during the feeding experiments as other potential biomarkers of oil exposure. None of the blood chemistry parameters differed between birds on the oil and control diets after two or four weeks of feeding, nor did feather CORT differ between the two groups. Overall, this study suggests that the response of CORT to stressors, but not baseline HPA function, may be a particularly sensitive bioindicator of sub-lethal chronic effects of crude oil exposure.

  4. Evaluating the stress response as a bioindicator of sub-lethal effects of crude oil exposure in wild house sparrows (Passer domesticus).

    Science.gov (United States)

    Lattin, Christine R; Ngai, Heather M; Romero, L Michael

    2014-01-01

    Petroleum can disrupt endocrine function in humans and wildlife, and interacts in particularly complex ways with the hypothalamus-pituitary-adrenal (HPA) axis, responsible for the release of the stress hormones corticosterone and cortisol (hereafter CORT). Ingested petroleum can act in an additive fashion with other stressors to cause increased mortality, but it is not clear exactly why--does petroleum disrupt feedback mechanisms, stress hormone production, or both? This laboratory study aimed to quantify the effects of ingested Gulf of Mexico crude oil on the physiological stress response of house sparrows (Passer domesticus). We examined baseline and stress-induced CORT, negative feedback, and adrenal sensitivity in house sparrows given a 1% oil or control diet (n = 12 in each group). We found that four weeks on a 1% oil diet did not alter baseline CORT titers or efficacy of negative feedback, but significantly reduced sparrows' ability to secrete CORT in response to a standardized stressor and adrenocorticotropin hormone injection, suggesting that oil damages the steroid-synthesizing cells of the adrenal. In another group of animals on the same 1% oil (n = 9) or control diets (n = 8), we examined concentrations of eight different blood chemistry parameters, and CORT in feathers grown before and during the feeding experiments as other potential biomarkers of oil exposure. None of the blood chemistry parameters differed between birds on the oil and control diets after two or four weeks of feeding, nor did feather CORT differ between the two groups. Overall, this study suggests that the response of CORT to stressors, but not baseline HPA function, may be a particularly sensitive bioindicator of sub-lethal chronic effects of crude oil exposure.

  5. Systematic Review of the Neurobiological Relevance of Chemokines to Psychiatric Disorders.

    Science.gov (United States)

    Stuart, Michael J; Singhal, Gaurav; Baune, Bernhard T

    2015-01-01

    Psychiatric disorders are highly prevalent and disabling conditions of increasing public health relevance. Much recent research has focused on the role of cytokines in the pathophysiology of psychiatric disorders; however, the related family of immune proteins designated chemokines has been relatively neglected. Chemokines were originally identified as having chemotactic function on immune cells; however, recent evidence has begun to elucidate novel, brain-specific functions of these proteins of relevance to the mechanisms of psychiatric disorders. A systematic review of both human and animal literature in the PubMed and Google Scholar databases was undertaken. After application of all inclusion and exclusion criteria, 157 references were remained for the review. Some early mechanistic evidence does associate select chemokines with the neurobiological processes, including neurogenesis, modulation of the neuroinflammatory response, regulation of the hypothalamus-pituitary-adrenal axis, and modulation of neurotransmitter systems. This early evidence however does not clearly demonstrate any specificity for a certain psychiatric disorder, but is primarily relevant to mechanisms which are shared across disorders. Notable exceptions include CCL11 that has recently been shown to impair hippocampal function in aging - of distinct relevance to Alzheimer's disease and depression in the elderly, and pre-natal exposure to CXCL8 that may disrupt early neurodevelopmental periods predisposing to schizophrenia. Pro-inflammatory chemokines, such as CCL2, CCL7, CCL8, CCL12, and CCL13, have been shown to drive chemotaxis of pro-inflammatory cells to the inflamed or injured CNS. Likewise, CX3CL has been implicated in promoting glial cells activation, pro-inflammatory cytokines secretion, expression of ICAM-1, and recruitment of CD4+ T-cells into the CNS during neuroinflammatory processes. With further translational research, chemokines may present novel diagnostic and

  6. Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.

    Science.gov (United States)

    Cacciaglia, Raffaele; Nees, Frauke; Grimm, Oliver; Ridder, Stephanie; Pohlack, Sebastian T; Diener, Slawomira J; Liebscher, Claudia; Flor, Herta

    2017-02-01

    Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Individual variations in maternal care early in life correlate with later life decision-making and c-fos expression in prefrontal subregions of rats.

    Directory of Open Access Journals (Sweden)

    Felisa N van Hasselt

    Full Text Available Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology--e.g. depression, anxiety and schizophrenia--later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG, correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT. In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures.

  8. Functional correlates of the position of the axis of rotation of the mandible during chewing in non-human primates.

    Science.gov (United States)

    Iriarte-Diaz, Jose; Terhune, Claire E; Taylor, Andrea B; Ross, Callum F

    2017-10-01

    The location of the axis of rotation (AoR) of the mandible was quantified using the helical axis (HA) in eight individuals from three species of non-human primates: Papio anubis, Cebus apella, and Macaca mulatta. These data were used to test three hypotheses regarding the functional significance of anteroposterior condylar translation - an AoR located inferior to the temporomandibular joint (TMJ) - during chewing: minimizing impingement of the gonial region on cervical soft tissue structures during jaw opening; avoiding stretching of the inferior alveolar neurovascular bundle (IANB); and increasing jaw-elevator muscle torques. The results reveal that the HA is located near the occlusal plane in Papio and Cebus, but closer to the condyle in Macaca; is located anteroinferior to the TMJ during both opening and closing in Papio, as well as during opening in Macaca and Cebus; and varies in its location during closing in Macaca and Cebus. The impingement hypothesis is not supported by interspecific variation in HA location: species with larger gonial angles like Cebus do not have more inferiorly located HAs than species with more obtuse mandibular angles like Papio. However, intraspecific variation provides some support for the impingement hypothesis. The HA seldom passes near or through the lingula, falsifying the hypothesis that its location is determined by the sphenomandibular ligament, and the magnitudes of strain associated with a HA at the TMJ would not be large enough to cause problematic stretching of the IANB. HA location does affect muscle moment arms about the TMJ, with implications for the torque generation capability of the jaw-elevator muscles. In Cebus, a HA farther away from the TMJ is associated with larger jaw-elevator muscle moment arms about the joint than if it were at the TMJ. The effects of HA location on muscle strain and muscle moment arms are largest at large gapes and smallest at low gapes, suggesting that if HA location is of functional

  9. The PDL1-PD1 Axis Converts Human Th1 Cells Into Regulatory T Cells

    Science.gov (United States)

    Amarnath, Shoba; Mangus, Courtney W.; Wang, James C.M.; Wei, Fang; He, Alice; Kapoor, Veena; Foley, Jason E.; Massey, Paul R.; Felizardo, Tania C.; Riley, James L.; Levine, Bruce L.; June, Carl H.; Medin, Jeffrey A.; Fowler, Daniel H.

    2011-01-01

    Immune surveillance by T helper type 1 (Th1) cells is critical for the host response to tumors and infection, but also contributes to autoimmunity and graft-versus-host disease (GvHD) after transplantation. The inhibitory molecule programmed death ligand-1 (PDL1) has been shown to anergize human Th1 cells, but other mechanisms of PDL1-mediated Th1 inhibition such as the conversion of Th1 cells to a regulatory phenotype have not been well characterized. We hypothesized that PDL1 may cause Th1 cells to manifest differentiation plasticity. Conventional T cells or irradiated K562 myeloid tumor cells overexpressing PDL1 converted TBET+ Th1 cells into FOXP3+ regulatory T cells (TREGS) in vivo, thereby preventing human-into-mouse xenogeneic GvHD (xGvHD). Either blocking PD1 expression on Th1 cells by siRNA targeting or abrogation of PD1 signaling by SHP1/2 pharmacologic inhibition stabilized Th1 cell differentiation during PDL1 challenge and restored the capacity of Th1 cells to mediate lethal xGVHD. PD1 signaling therefore induces human Th1 cells to manifest in vivo plasticity, resulting in a TREG phenotype that severely impairs cell-mediated immunity. Converting human Th1 cells to a regulatory phenotype with PD1 signaling provides a potential way to block GvHD after transplantation. Moreover, because this conversion can be prevented by blocking PD1 expression or pharmacologically inhibiting SHP1/2, this pathway provides a new therapeutic direction for enhancing T cell immunity to cancer and infection. PMID:22133721

  10. Regulation of MT1-MMP/MMP-2/TIMP-2 axis in human placenta

    Directory of Open Access Journals (Sweden)

    Vincent ZL

    2015-10-01

    Full Text Available Zoë L Vincent,1,2 Murray D Mitchell,l,3 Anna P Ponnampalam1,2 1Liggins Institute, 2Gravida: National Centre for Growth and Development, University of Auckland, Auckland, New Zealand; 3University of Queensland Centre for Clinical Research, Brisbane, QLD, Australia Abstract: Matrix metalloproteinases (MMPs and specific endogenous tissue inhibitors of metalloproteinases (TIMPs mediate rupture of the fetal membranes in both physiological and pathological conditions. MMPs and TIMPs are subject to regulation by DNA methylation in human malignancies and pre-eclampsia. To determine if membrane type 1 MMP (MT1-MMP, MMP2, and TIMP2 are regulated by DNA methylation in human placentas, we employed an in vitro model where human placental tissues were collected at term gestation and cultured with methylation inhibiting agent 5-aza-2′deoxycytidine (AZA and lipopolysaccharide. The results suggest that DNA methylation is not directly involved in the regulation of MT1-MMP in placental tissue; however, remodeling of chromatin by a pharmacologic agent such as AZA potentiates an infection-related increase in MT1-MMP. MT1-MMP is a powerful activator of MMP2 and this action, coupled with either no change or a decrease in TIMP2 concentrations, favors a gelatinolytic state leading to extracellular matrix degradation, which could predispose fetal membranes to rupture prematurely during inflammation. Keywords: placenta, epigenetic regulation, DNA methylation, MMPs, labor

  11. microRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells

    DEFF Research Database (Denmark)

    Hamam, D; Ali, D; Vishnubalaji, R

    2014-01-01

    The molecular mechanisms promoting lineage-specific commitment of human mesenchymal (skeletal or stromal) stem cells (hMSCs) into adipocytes (ADs) are not fully understood. Thus, we performed global microRNA (miRNA) and gene expression profiling during adipocytic differentiation of h...... differentiation and accelerated formation of mature ADs in ex vivo cultures. Integrated analysis of bioinformatics and global gene expression profiling in miR-320c overexpressing cells and during adipocytic differentiation of hMSC identified several biologically relevant gene targets for miR-320c including RUNX2...

  12. Mir-452-3p: A Potential Tumor Promoter That Targets the CPEB3/EGFR Axis in Human Hepatocellular Carcinoma

    Science.gov (United States)

    Tang, Hui; Zhang, Jianwen; Yu, Zhenyu; Ye, Linsen; Li, Kun; Ding, Fan; Feng, Xiao

    2017-01-01

    Purpose: We proposed to investigate the effects of miR-452-3p on the proliferation and mobility of hepatocellular carcinoma (HCC) cells by targeting cytoplasmic polyadenylation element binding protein 3/estimated glomerular filtration rate (CPEB3/EGFR) axis. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-452-3p expression in 84 pairs of HCC tissues and adjacent tissues. Luciferase reporter assay was employed to examine the relationship between miR-452-3p and CPEB3. Microculture tetrazolium (MTT) assay, colony formation assay, flow cytometry detection, wound healing assay, and transwell assay were used to detect cell proliferation, cycle arrest, apoptosis, and mobility, respectively, in HCC, HepG2, and Huh-7. Western blot was used to detect protein expression levels in EGFR signaling pathway. Kaplan-Meier survival analysis was conducted to analyze the correlation between the miR-452-3p and CPEB3 expression levels and the survival of patients with HCC. Results: MiRNA-452-3p was found significantly upregulated in 84 human HCC sample tissues and cells in comparison with adjacent tissues and normal liver epithelial cells (P < .01). Luciferase reporter assay demonstrated that CPEB3 was a direct target of miR-452-3p. Overexpression of miR-452-3p promoted cell proliferation and mobility and suppressed apoptosis. MiR-452-3p enhanced EGFR and phosphorylated AKT (pAKT) expression but inhibited p21 expression level. Conclusion: MiR-452-3p promoted HCC cell proliferation and mobility by directly targeting the CPEB3/EGFR axis. PMID:29332449

  13. Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity.

    Science.gov (United States)

    Grassi, G; Seravalle, G; Dell'Oro, R; Turri, C; Pasqualinotto, L; Colombo, M; Mancia, G

    2001-12-01

    Previous studies have shown that hypothalamic and hypophyseal factors are involved in the acute sympathoexcitation induced by a variety of laboratory stimuli. Whether a chronic condition of sympathetic activation, such as that characterizing human obesity, is also dependent on these factors has never been investigated. In 40 normotensive obese subjects ([mean+/-SEM] age, 39.1+/-0.8 years) we measured blood pressure (Finapres), heart rate (ECG), and postganglionic muscle sympathetic nerve activity (MSNA) (microneurography). In 20 subjects measurements were repeated, according to a double-blind randomized sequence, after a midnight oral dose of dexamethasone (1 mg) (n=10) or placebo (n=10), while in the remaining subjects they were performed again after 1 week of a daily evening oral administration of 1 mg of dexamethasone (n=10) or placebo (n=10). The same protocol was performed in 16 age-matched lean normotensives. In both groups acute dexamethasone administration markedly reduced plasma cortisol (radioimmunoassay), without affecting hemodynamic and neural variables. In contrast to the acute administration, in obese subjects prolonged dexamethasone administration, although not affecting blood pressure and heart rate, significantly reduced both plasma cortisol (from 16.0+/-1.3 to 0.7+/-0.1 microg/dL; P<0.01) and MSNA (from 59.5+/-2.8 to 39.6+/-2.9 bursts per 100 heartbeats; P<0.02; -33.1+/-4.1%). This was not the case in lean subjects, in which the dexamethasone-induced reduction in plasma cortisol was associated with a slight and nonsignificant MSNA decrease. In both lean and obese subjects, placebo administration caused no change in any variable. Thus, prolonged dexamethasone administration exerts in obese subjects marked sympathoinhibitory effects that are not detectable in lean individuals. This suggests that hypothalamic and hypophyseal factors substantially contribute to the sympathoexcitation of obesity.

  14. Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1

    Directory of Open Access Journals (Sweden)

    Junichiro Miyazaki

    2017-04-01

    Full Text Available Renal cell carcinoma (RCC is the most lethal urological malignancy with high risk of recurrence; thus, new prognostic biomarkers are needed. In this study, a new RCC antigen, PTPL1 associated RhoGAP1 (PARG1, was identified by using serological identification of recombinant cDNA expression cloning with sera from RCC patients. PARG1 protein was found to be differentially expressed in RCC cells among patients. High PARG1 expression is significantly correlated with various clinicopathological factors relating to cancer cell proliferation and invasion, including G3 percentage (P = .0046, Ki-67 score (p expression is also correlated with high recurrence of N0M0 patients (P = .0084 and poor prognosis in RCC patients (P = .0345. Multivariate analysis has revealed that high PARG1 expression is an independent factor for recurrence (P = .0149 of N0M0 RCC patients. In in vitro studies, depletion of PARG1by siRNA in human RCC cell lines inhibited their proliferation through inducing G1 cell cycle arrest via upregulation of p53 and subsequent p21Cip1/Waf1, which are mediated by increased RhoA-ROCK activities. Similarly, PARG1 depletion cells inhibited invasion ability via increasing RhoA-ROCK activities in the RCC cell lines. Conversely, overexpression of PARG1 on human embryonic kidney cell line HEK293T promotes its cell proliferation and invasion. These results indicate that PARG1 plays crucial roles in progression of human RCC in increasing cell proliferation and invasion ability via inhibition of the RhoA-ROCK axis, and PARG1 is a poor prognostic marker, particularly for high recurrence of N0M0 RCC patients.

  15. Puberty and Perimenopause: Reproductive Transitions and their Implications for Women's Health

    Science.gov (United States)

    Hoyt, Lindsay T.; Falconi, April

    2015-01-01

    This scoping review synthesizes existing research on two major transitions in females’ lives: puberty and perimenopause. These two periods of vast physiological change demarcate the beginning and the end of the reproductive life cycle and are associated with major neuroendocrine reorganization across two key systems, the hypothalamic-pituitary-gonadal (HPG) axis the hypothalamus-pituitary-adrenal (HPA) axis. Despite growing evidence suggesting that the timing and experience of puberty and perimenopause are related to various physical and mental health outcomes (e.g., mood disorders, metabolism, cardiovascular health, autoimmune conditions and cancer), these two processes are rarely examined together. In this paper, we bridge these disparate literatures to highlight similarities, isolate inconsistencies, and identify important areas for future research in women’s health. PMID:25797100

  16. The gastrointestinal-brain axis in humans as an evolutionary advance of the root-leaf axis in plants: A hypothesis linking quantum effects of light on serotonin and auxin.

    Science.gov (United States)

    Tonello, Lucio; Gashi, Bekim; Scuotto, Alessandro; Cappello, Glenda; Cocchi, Massimo; Gabrielli, Fabio; Tuszynski, Jack A

    2018-01-01

    Living organisms tend to find viable strategies under ambient conditions that optimize their search for, and utilization of, life-sustaining resources. For plants, a leading role in this process is performed by auxin, a plant hormone that drives morphological development, dynamics, and movement to optimize the absorption of light (through branches and leaves) and chemical "food" (through roots). Similarly to auxin in plants, serotonin seems to play an important role in higher animals, especially humans. Here, it is proposed that morphological and functional similarities between (i) plant leaves and the animal/human brain and (ii) plant roots and the animal/human gastro-intestinal tract have general features in common. Plants interact with light and use it for biological energy, whereas, neurons in the central nervous system seem to interact with bio-photons and use them for proper brain function. Further, as auxin drives roots "arborescence" within the soil, similarly serotonin seems to facilitate enteric nervous system connectivity within the human gastro-intestinal tract. This auxin/serotonin parallel suggests the root-branches axis in plants may be an evolutionary precursor to the gastro-intestinal-brain axis in humans. Finally, we hypothesize that light might be an important factor, both in gastro-intestinal dynamics and brain function. Such a comparison may indicate a key role for the interaction of light and serotonin in neuronal physiology (possibly in both the central nervous system and the enteric nervous system), and according to recent work, mind and consciousness.

  17. Establishment of one-axis vibration test system for measurement of biodynamic response of human hand-arm system.

    Science.gov (United States)

    Shibata, Nobuyuki; Hosoya, Naoki; Maeda, Setsuo

    2008-12-01

    Prolonged exposure to hand-arm vibration (HAV) due to use of hand-held power tools leads to an increased occurrence of symptoms of disorders in the vascular, neurological, and osteo-articular systems of the upper limbs called hand-arm vibration syndrome (HAVS). Biodynamic responses of the hand-arm system to vibration can be suggestive parameters that give us better assessment of exposure to HAV and fundamental data for design of low-vibration-exposure power tools. Recently, a single axis hand-arm vibration system has been installed in the Japan National Institute of Occupational Safety and Health (NIOSH). The aims of this study were to obtain the fundamental dynamic characteristics of an instrumented handle and to validate the performance and measurement accuracy of the system applied to dynamic response measurement. A pseudo-random vibration signal with a frequency range of 5-1,250 Hz and a power spectrum density of 1.0 (m/s2)2/Hz was used in this study. First the dynamic response of the instrumented handle without any weight was measured. After this measurement, the dynamic response measurement of the handle with weights mounted on the handle was performed. The apparent mass of a weight itself was obtained by using the mass cancellation method. The mass of the measuring cap on the instrumented handle was well compensated by using the mass cancellation method. Based on the 10% error tolerance, this handle can reliably measure the dynamic response represented by an apparent mass with a minimum weight of 2.0 g in a frequency range of 10.0 to 1,000 Hz. A marked increase in the AM magnitude of the weights of 15 g and 20 g in frequency ranges greater than 800 Hz is attributed not to the fundamental resonance frequency of the handle with weights, but to the fixation of the weight to the measuring cap. In this aspect, the peak of the AM magnitude can be reduced and hence should not be an obstacle to the biodynamic response measurement of the human hand-arm system. On the

  18. Differential effect of glucocorticoids on tumour necrosis factor production in mice: up-regulation by early pretreatment with dexamethasone.

    Science.gov (United States)

    Fantuzzi, G; Demitri, M T; Ghezzi, P

    1994-04-01

    Glucocorticoids (GC) are well known inhibitors of tumour necrosis factor (TNF) production. We investigated the role of endogenous GC in the regulation of TNF production in mice treated with lipopolysaccharide (LPS) using a pretreatment with dexamethasone (DEX) to down-regulate the hypothalamus-pituitary-adrenal axis (HPA). Short-term DEX pretreatment (up to 12 h before LPS) inhibited TNF production, but earlier (24-48 h) pretreatments potentiated it. This up-regulating effect was not observed in adrenalectomized mice or when GC synthesis was inhibited with cyanoketone (CK). This effect could not be explained only by the suppression of LPS-induced corticosterone (CS) levels induced by DEX, since a 48-h pretreatment potentiated TNF production without affecting LPS-induced CS levels. On the other hand, mice chronically pretreated with DEX were still responsive to its inhibitory effect on TNF production, thus ruling out the possibility of a decreased responsiveness to GC.

  19. Extra-adrenal glucocorticoid synthesis: immune regulation and aspects on local organ homeostasis.

    Science.gov (United States)

    Talabér, Gergely; Jondal, Mikael; Okret, Sam

    2013-11-05

    Systemic glucocorticoids (GCs) mainly originate from de novo synthesis in the adrenal cortex under the control of the hypothalamus-pituitary-adrenal (HPA)-axis. However, research during the last 1-2 decades has revealed that additional organs express the necessary enzymes and have the capacity for de novo synthesis of biologically active GCs. This includes the thymus, intestine, skin and the brain. Recent research has also revealed that locally synthesized GCs most likely act in a paracrine or autocrine manner and have significant physiological roles in local homeostasis, cell development and immune cell activation. In this review, we summarize the nature, regulation and known physiological roles of extra-adrenal GC synthesis. We specifically focus on the thymus in which GC production (by both developing thymocytes and epithelial cells) has a role in the maintenance of proper immunological function. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

    Directory of Open Access Journals (Sweden)

    Itaru Kato

    Full Text Available In acute lymphoblastic leukemia (ALL patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis.

  1. Relationships between 24-hour urinary free cortisol concentrations and metabolic syndrome in obese children.

    Science.gov (United States)

    Reinehr, Thomas; Kulle, Alexandra; Wolters, Barbara; Knop, Caroline; Lass, Nina; Welzel, Maik; Holterhus, Paul-Martin

    2014-07-01

    Clinical features of Metabolic Syndrome (MetS) and Cushing's Syndrome are similar, suggesting a pathogenetic role of hypothalamus-pituitary-adrenal axis in MetS. The aim of the study was to determine whether MetS diagnosis and specific clusters of MetS components (waist circumference, dyslipidemia, hypertension, and impaired glucose metabolism) are associated with serum cortisol (SC) or 24-h urinary free cortisol (UFC) levels. We conducted cross-sectional analyses of data from our obesity cohort. We studied 264 obese children (age, 11.0 ± 2.8 years; male, 48%; BMI, 28.2 ± 5.4 kg/m(2)). We examined UFC, SC, homeostasis model assessment (HOMA), and features of MetS (waist circumference, blood pressure, fasting lipids, and glucose). Slightly increased UFC concentrations were measured in 30.7% of the children. Obese children with MetS had significantly (P = .003) higher UFC levels compared with obese children without MetS. Girls demonstrated significantly higher UFC concentrations compared with boys independent of pubertal stage. UFC and SC levels were significantly related to features of MetS, but the associations were stronger for UFC. In multivariate analyses adjusted for age, sex, and body mass index, none of the features of MetS but HOMA index was correlated with UFC, whereas SC demonstrated no significant association to any parameter of MetS or HOMA. Our findings support the hypothesis that changes in the hypothalamus-pituitary-adrenal axis are related to MetS in obesity. UFC seems to be a suitable marker for this relationship. Norm values for UFC adapted to obese children may help to avoid unnecessary dexamethasone suppression tests.

  2. GPR39 (zinc receptor) knockout mice exhibit depression-like behavior and CREB/BDNF down-regulation in the hippocampus.

    Science.gov (United States)

    Młyniec, Katarzyna; Budziszewska, Bogusława; Holst, Birgitte; Ostachowicz, Beata; Nowak, Gabriel

    2014-10-31

    Zinc may act as a neurotransmitter in the central nervous system by activation of the GPR39 metabotropic receptors. In the present study, we investigated whether GPR39 knockout would cause depressive-like and/or anxiety-like behavior, as measured by the forced swim test, tail suspension test, and light/dark test. We also investigated whether lack of GPR39 would change levels of cAMP response element-binding protein (CREB),brain-derived neurotrophic factor (BDNF) and tropomyosin related kinase B (TrkB) protein in the hippocampus and frontal cortex of GPR39 knockout mice subjected to the forced swim test, as measured by Western-blot analysis. In this study, GPR39 knockout mice showed an increased immobility time in both the forced swim test and tail suspension test, indicating depressive-like behavior and displayed anxiety-like phenotype. GPR39 knockout mice had lower CREB and BDNF levels in the hippocampus, but not in the frontal cortex, which indicates region specificity for the impaired CREB/BDNF pathway (which is important in antidepressant response) in the absence of GPR39. There were no changes in TrkB protein in either structure. In the present study, we also investigated activity in the hypothalamus-pituitary-adrenal axis under both zinc- and GPR39-deficient conditions. Zinc-deficient mice had higher serum corticosterone levels and lower glucocorticoid receptor levels in the hippocampus and frontal cortex. There were no changes in the GPR39 knockout mice in comparison with the wild-type control mice, which does not support a role of GPR39 in hypothalamus-pituitary-adrenal axis regulation. The results of this study indicate the involvement of the GPR39 Zn(2+)-sensing receptor in the pathophysiology of depression with component of anxiety. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  3. Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome.

    Science.gov (United States)

    Prete, Alessandro; Paragliola, Rosa Maria; Bottiglieri, Filomena; Rota, Carlo Antonio; Pontecorvi, Alfredo; Salvatori, Roberto; Corsello, Salvatore Maria

    2017-03-01

    Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus-pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary-adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of

  4. If It Goes up, Must It Come Down? Chronic Stress and the Hypothalamic-Pituitary Adrenocortical Axis in Humans

    Science.gov (United States)

    Miller, Gregory E.; Chen, Edith; Zhou, Eric S.

    2007-01-01

    The notion that chronic stress fosters disease by activating the hypothalamic-pituitary adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed…

  5. In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines

    Directory of Open Access Journals (Sweden)

    Antecka Emilia

    2007-11-01

    Full Text Available Abstract Purpose The CXCR4/CXCL12 chemokine axis may play a critical role in guiding CXCR4+ circulating malignant cells to organ specific locations that actively secrete its ligand CXCL12 (SDF-1 such as bone, brain, liver, and lungs. We sought to characterize the presence of the CXCR4/CXCL12 axis in five uveal melanoma (UM cell lines in vitro. The ability of TN14003, a synthetic peptide inhibitor that targets the CXCR4 receptor complex, to inhibit this axis was also assessed. Methods Immunocytochemistry was performed against CXCR4 to confirm expression of this chemokine receptor in all five UM cell lines. Flow cytometry was preformed to evaluate CXCR4 cell surface expression on all five UM cell lines. A proliferation assay was also used to test effects TN14003 would have on cellular proliferation. Inhibition of cellular migration by specifically inhibiting the CXCR4/CXCL12 axis with TN14003 was also investigated. The binding efficacy of TN14003 to the CXCR4 receptor was assessed through flow cytometric methods. Results The CXCR4 receptor was present on all five UM cell lines. All five cell lines expressed different relative levels of surface CXCR4. TN14003 did not affect the proliferation of the five cell lines (p > 0.05. All cell lines migrated towards the chemokine CXCL12 at a level greater than the negative control (p Conclusion Interfering with the CXCR4/CXCL12 axis, using TN14003 was shown to effectively down regulate UM cell migration in vitro. Knowing that UM expresses the CXCR4 receptor, these CXCR4+ cells may be less likely to colonize distant organs that secrete the CXCL12 ligand, if treated with an inhibitor that binds CXCR4. Further studies should be pursued in order to test TN14003 efficacy in vivo.

  6. How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans.

    Science.gov (United States)

    Frodl, Thomas; O'Keane, Veronica

    2013-04-01

    There is evidence that excessive stress exposure of the brain, mediated through the neurotoxic effects of cortisol and possibly neuroinflammation, causes damage to brain structure and function: the glucocorticoid cascade hypothesis. Functional changes of hypothalamic-pituitary-adrenal (HPA) axis as well as alterations in brain structures like the hippocampus have been consistently reported in major depression. However, there has not been a lot of emphasis on bringing findings from studies on early childhood stress, HPA axis functioning and hippocampal imaging together. This is the subject for this systematic review of the literature on how developmental stress, specifically childhood maltreatment, may impact on HPA axis function and hippocampal structure. We will also review the literature on the relationship between HPA axis function and hippocampal volume in healthy, depressed and other disease states. There is evidence that prenatal stress and childhood maltreatment is associated with an abnormally developing HPA system, as well as hippocampal volume reduction. Smaller hippocampal volumes are associated with increased cortisol secretion during the day. We conclude that a model integrating childhood maltreatment, cortisol abnormalities and hippocampal volume may need to take other factors into account, such as temperament, genetics or the presence of depression; to provide a cohesive explanation of all the findings. Finally, we have to conclude that the cascade hypothesis, mainly based on preclinical studies, has not been translated enough into humans. While there is evidence that early life maltreatment results in structural hippocampal changes and these are in turn more prominent in subjects with higher continuous cortisol secretion it is less clear which role early life maltreatment plays in HPA axis alteration. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Human otolith-ocular reflexes during off-vertical axis rotation: effect of frequency on tilt-translation ambiguity and motion sickness

    Science.gov (United States)

    Wood, Scott J.; Paloski, W. H. (Principal Investigator)

    2002-01-01

    The purpose of this study was to examine how the modulation of tilt and translation otolith-ocular responses during constant velocity off-vertical axis rotation varies as a function of stimulus frequency. Eighteen human subjects were rotated in darkness about their longitudinal axis 30 degrees off-vertical at stimulus frequencies between 0.05 and 0.8 Hz. The modulation of torsion decreased while the modulation of horizontal slow phase velocity (SPV) increased with increasing frequency. It is inferred that the ambiguity of otolith afferent information is greatest in the frequency region where tilt (torsion) and translational (horizontal SPV) otolith-ocular responses crossover. It is postulated that the previously demonstrated peak in motion sickness susceptibility during linear accelerations around 0.3 Hz is the result of frequency segregation of ambiguous otolith information being inadequate to distinguish between tilt and translation.

  8. Characterisation of adiponectin multimers and the IGF axis in humans with a heterozygote mutation in the tyrosine kinase domain of the insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning; Flyvbjerg, Allan

    2012-01-01

    Objective: Low levels of adiponectin, IGF-binding protein (IGFBP)-1, and IGFBP-2, and high levels of leptin correlate with several indices of insulin resistance and risk of type 2 diabetes. However, in insulin receptoropathies plasma adiponectin is paradoxically increased despite severe insulin...... resistance, whereas the IGF-axis is sparsely described. Here, we aimed to characterize the multimeric distribution of adiponectin and the IGF-axis in humans with a heterozygous INSR mutation (Arg1174Gln).Methods: Blood samples obtained in six Arg1174Gln-carriers and 10 lean, healthy controls before and after...... an euglycemic-hyperinsulinemic clamp were examined for plasma adiponectin multimers, leptin, total IGF-I, IGF-II, free IGF-I, IGFBP-1 and IGFBP-2.Results: Despite 10-fold elevated fasting insulin and marked insulin resistance in Arg1174Gln-carriers, the levels of total adiponectin, leptin, IGFBP-1 and IGFBP-2...

  9. Vergence-mediated changes in the axis of eye rotation during the human vestibulo-ocular reflex can occur independent of eye position.

    Science.gov (United States)

    Migliaccio, Americo A; Cremer, Phillip D; Aw, Swee T; Halmagyi, G Michael; Curthoys, Ian S; Minor, Lloyd B; Todd, Michael J

    2003-07-01

    The aim of this study was to determine whether vergence-mediated changes in the axis of eye rotation in the human vestibulo-ocular reflex (VOR) would obey Listing's Law (normally associated with saccadic eye movements) independent of the initial eye position. We devised a paradigm for disassociating the saccadic velocity axis from eye position by presenting near and far targets that were centered with respect to one eye. We measured binocular 3-dimensional eye movements using search coils in ten normal subjects and 3-dimensional linear head acceleration using Optotrak in seven normal subjects. The stimuli consisted of passive, unpredictable, pitch head rotations with peak acceleration of approximately 2000 degrees /s(2 )and amplitude of approximately 20 degrees. During the pitch head rotation, each subject fixated straight ahead with one eye, whereas the other eye was adducted 4 degrees during far viewing (94 cm) and 25 degrees during near viewing (15 cm). Our data showed expected compensatory pitch rotations in both eyes, and a vergence-mediated horizontal rotation only in the adducting eye. In addition, during near viewing we observed torsional eye rotations not only in the adducting eye but also in the eye looking straight ahead. In the straight-ahead eye, the change in torsional eye velocity between near and far viewing, which began approximately 40 ms after the start of head rotation, was 10+/-6 degrees /s (mean +/- SD). This change in torsional eye velocity resulted in a 2.4+/-1.5 degrees axis tilt toward Listing's plane in that eye. In the adducting eye, the change in torsional eye velocity between near and far viewing was 16+/-6 degrees /s (mean +/- SD) and resulted in a 4.1+/-1.4 degrees axis tilt. The torsional eye velocities were conjugate and both eyes partially obeyed Listing's Law. The axis of eye rotation tilted in the direction of the line of sight by approximately one-third of the angle between the line of sight and a line orthogonal to Listing

  10. PRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells By Enhancing the PI3K/AKT/SOX2 Axis.

    Science.gov (United States)

    Jeong, Ho-Chang; Park, Soon-Jung; Choi, Jong-Jin; Go, Young-Hyun; Hong, Soon-Ki; Kwon, Ok-Seon; Shin, Joong-Gon; Kim, Rae-Kwon; Lee, Mi-Ok; Lee, Su-Jae; Shin, Hyoung Doo; Moon, Sung-Hwan; Cha, Hyuk-Jin

    2017-09-01

    Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferase 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions. Direct interaction of membrane-localized PRMT8 with p85, a regulatory subunit of PI3K, was associated with accumulation of phosphoinositol 3-phosphate and consequently high AKT activity. Furthermore, the SOX2 induction, which was controlled by the PRMT8/PI3K/AKT axis, was linked to mesodermal lineage differentiation. Thus, we propose that PRMT8 in hESCs plays an important role not only in maintaining pluripotency but also in controlling mesodermal differentiation through bFGF signaling toward the PI3K/AKT/SOX2 axis. Stem Cells 2017;35:2037-2049. © 2017 AlphaMed Press.

  11. Atorvastatin Inhibits the HIF1α-PPAR Axis, Which Is Essential for Maintaining the Function of Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Nakashima, Yoshiki; Miyagi-Shiohira, Chika; Noguchi, Hirofumi; Omasa, Takeshi

    2018-06-19

    We herein report a novel mechanism of action of statin preparations using a new drug discovery method. Milk fat globule-EGF factor 8 protein (MFG-E8) was identified from the secretory component of mouse embryonic fibroblast (MEF) as a cell adhesion-promoting factor effective for screening active cellular agents of human induced pluripotent stem cells (hiPSCs) in vitro using electrochemical impedance. Our analyses showed that atorvastatin did not cause death in myocardial cells differentiated from hiPSCs but reduced the pluripotent cell survival in vitro when using serum- and albumin-free media, and inhibited the ability to form teratomas in mice. This result could have been already the cytopathic effect of atorvastatin, and complete elimination of hiPSCs was confirmed in the xenotransplantation assay. The administration of atorvastatin to hiPSCs caused the expression of hypoxia inducible factor (HIF)1α mRNA to be unchanged at 6 hr and downregulated at 24 hr. In addition, the inhibition of the survival of hiPSCs was confirmed by HIF1α-peroxisome proliferator-activated receptor (PPAR) axis inhibition. These results suggest that the addition of atorvastatin to hiPSC cultures reduces the survival of pluripotent cells by suppressing the HIF1α-PPAR axis. In summary, the HIF1α-PPAR axis has an important role in maintaining the survival of pluripotent hiPSCs. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Glucocorticoid receptor haplotypes conferring increased sensitivity (BclI and N363S) are associated with faster progression of multiple sclerosis

    DEFF Research Database (Denmark)

    Melief, Jeroen; Koper, Jan W; Endert, Erik

    2016-01-01

    As high cortisol levels are implicated in suppressed disease activity of multiple sclerosis (MS), glucocorticoid receptor (GR) polymorphisms that affect glucocorticoid (GC) sensitivity may impact on this by changing local immunomodulation or regulation of the hypothalamus-pituitary-adrenal (HPA...

  13. Direct analysis of δ2H and δ18O in natural and enriched human urine using laser-based, Off-Axis Integrated Cavity Output Spectroscopy

    Science.gov (United States)

    Berman, Elena S.F.; Fortsona, Susan L.; Snaith, Steven P.; Gupta, Manish; Baer, Douglas S.; Chery, Isabelle; Blanc, Stephane; Melanson, Edward L.; Thomson, Peter J; Speakman, John R.

    2012-01-01

    The stable isotopes of hydrogen (δ2H) and oxygen (δ18O) in human urine are measured during studies of total energy expenditure by the doubly labeled water method, measurement of total body water, and measurement of insulin resistance by glucose disposal among other applications. An ultrasensitive laser absorption spectrometer based on off-axis integrated cavity output spectroscopy was demonstrated for simple and inexpensive measurement of stable isotopes in natural isotopic abundance and isotopically enriched human urine. Preparation of urine for analysis was simple and rapid (approx. 25 samples per hour), requiring no decolorizing or distillation steps. Analysis schemes were demonstrated to address sample-to-sample memory while still allowing analysis of 45 natural or 30 enriched urine samples per day. The instrument was linear over a wide range of water isotopes (δ2H = −454 to +1702 ‰ and δ18O= −58.3 to +265 ‰). Measurements of human urine were precise to better than 0.65 ‰ 1σ for δ2H and 0.09 ‰ 1σ for δ18O for natural urines, 1.1 ‰ 1σ for δ2H and 0.13 ‰ 1σ for δ18O for low enriched urines, and 1.0 ‰ 1σ for δ2H and 0.08 ‰ 1σ for δ18O for high enriched urines. Furthermore, the accuracy of the isotope measurements of human urines was verified to better than ±0.81 ‰ in δ2H and ±0.13 ‰ in δ18O (average deviation) against three independent IRMS laboratories. The ability to immediately and inexpensively measure the stable isotopes of water in human urine is expected to increase the number and variety of experiments which can be undertaken. PMID:23075099

  14. Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

    Science.gov (United States)

    Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

    2016-07-01

    Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR. ©2016 American

  15. Bovine lactoferricin induces TIMP-3 via the ERK1/2-Sp1 axis in human articular chondrocytes.

    Science.gov (United States)

    Yan, Dongyao; Chen, Di; Hawse, John R; van Wijnen, Andre J; Im, Hee-Jeong

    2013-03-15

    Bovine lactoferricin (LfcinB) is a heparan sulfate-binding peptide with multiple bioactivities. In human articular cartilage, LfcinB antagonizes interleukin-1 β (IL-1β) and fibroblast growth factor 2 (FGF-2) in proteoglycan metabolism, catabolic protease expression, and induction of pro-inflammatory mediators. LfcinB specifically activates ERK1/2, p38 and Akt, but whether these signaling pathways control the expression of LfcinB target genes remained unknown. In this report, we characterized a novel aspect of LfcinB-mediated genetic response in human articular chondrocytes, tissue inhibitor of metalloproteinase 3 (TIMP-3) induction. Inhibition of individual signaling pathways revealed that ERK1/2 functions as the major pathway in TIMP-3 expression, whereas Akt plays a minor role. Further investigation identified Sp1 as a critical transcriptional activator in TIMP-3 regulation, and Sp1 activity is modulated by ERK1/2, not Akt. Comparative quantification indicates that significant downregulation of TIMP-3 occurs in OA chondrocytes, suggesting a beneficial role of LfcinB in OA pathogenesis. Our results collectively provide new insights into the mechanism of action of LfcinB, and support the candidacy of LfcinB as a chondroprotective agent. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. c-FLIP and the NOXA/Mcl-1 axis participate in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells.

    Science.gov (United States)

    Zhao, Xiaofei; Kong, Feng; Wang, Lei; Zhang, Han

    2017-01-01

    Choroidal melanoma is the most common primary malignant intraocular tumor, and very few effective therapies are available to treat it. Our study aimed to understand whether pemetrexed plus cisplatin exerts a beneficial synergistic effect in human choroidal melanoma cells and to delineate the underlying molecular mechanism. To accomplish these aims, we treated choroidal melanoma cells with pemetrexed and cisplatin and assessed cell survival with SRB and MTT assays. Proteins were detected using western blotting analysis. NOXA and CHOP were knocked down with siRNA. We found that pemetrexed or cisplatin alone inhibited survival and induced apoptosis in human choroidal melanoma cells. Furthermore, the expression levels of c-FLIP, an anti-apoptotic protein in the extrinsic apoptosis pathway, and Mcl-1, an anti-apoptotic protein in the intrinsic apoptosis pathway, were decreased by pemetrexed or cisplatin respectively, while the expression of a pro-apoptotic protein in the intrinsic apoptosis pathway, NOXA, was up-regulated. Moreover, pemetrexed or cisplatin alone increased the protein expression of the endoplasmic reticulum stress markers IRE1α, Bip and CHOP. Silencing CHOP expression reduced NOXA expression. These findings suggest that the pemetrexed or cisplatin induced intrinsic apoptosis via activation of the ER stress response. Importantly, combining the two compounds more strongly induced apoptosis. Following the cotreatment, CHOP and NOXA expression increased, while c-FLIP and Mcl-1 expression decreased, and these effects were more pronounced than when using either compound alone. This result suggests that pemetrexed and cisplatin synergistically activate ER stress response-induced apoptosis in choroidal melanoma cells. To summarize, the c-FLIP and NOXA/Mcl-1 axis participated in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells. Intrinsic apoptosis was induced via activation of the ER stress response. Our study provides

  17. ATP Induces IL-1β Secretion in Neisseria gonorrhoeae-Infected Human Macrophages by a Mechanism Not Related to the NLRP3/ASC/Caspase-1 Axis

    Directory of Open Access Journals (Sweden)

    Killen García

    2016-01-01

    Full Text Available Neisseria gonorrhoeae (Ngo has developed multiple immune evasion mechanisms involving the innate and adaptive immune responses. Recent findings have reported that Ngo reduces the IL-1β secretion of infected human monocyte-derived macrophages (MDM. Here, we investigate the role of adenosine triphosphate (ATP in production and release of IL-1β in Ngo-infected MDM. We found that the exposure of Ngo-infected MDM to ATP increases IL-1β levels about ten times compared with unexposed Ngo-infected MDM (P0.05 and caspase-1 (CASP1, P>0.05. In addition, ATP was not able to modify caspase-1 activity in Ngo-infected MDM but was able to increase pyroptosis (P>0.01. Notably ATP treatment defined an increase of positive staining for IL-1β with a distinctive intracellular pattern of distribution. Collectively, these data demonstrate that ATP induces IL-1β secretion by a mechanism not related to the NLRP3/ASC/caspase-1 axis and likely is acting at the level of vesicle trafficking or pore formation.

  18. Protective Macroautophagy Is Involved in Vitamin E Succinate Effects on Human Gastric Carcinoma Cell Line SGC-7901 by Inhibiting mTOR Axis Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Liying Hou

    Full Text Available Vitamin E succinate (VES, a potential cancer therapeutic agent, potently induces apoptosis and inhibits the growth of various cancer cells. Autophagy has been supposed to promote cancer cell survival or trigger cell death, depending on particular cancer types and tumor microenvironments. The role of autophagy in the growth suppressive effect of VES on gastric cancer cell is basically unknown. We aimed to determine whether and how autophagy affected the VES-induced inhibition of SGC-7901 human gastric carcinoma cell growth. SGC-7901 cells were treated with VES or pre-treated with autophagy inhibitor, chloroquine (CQ and 3-methyladenine (3-MA. Electron microscopy, fluorescence microscopy and Western blot were used to study whether VES induced autophagy reaction in SGC-7901 cells. Western blot evaluated the activities of the mammalian target of rapamycin (mTOR axis. Then we used 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and flow cytometry to detect the level of cell viability and apoptosis. Collectively, our data indeed strongly support our hypothesis that VES treatment produced cytological variations that depict autophagy, increased the amount of intracellular green fluorescent protein-microtubule associated protein 1 light chain 3 (GFP-LC3 punctate fluorescence and the number of autophagic vacuoles. It altered the expression of endogenous autophagy marker LC3. VES activated the suppression of mTOR through inhibiting upstream regulators p38 MAPK and Akt. mTOR suppression consequently inhibited the activation of mTOR downstream targets p70S6K and 4E-BP-1. The activation of the upstream mTOR inhibitor AMPK had been up-regulated by VES. The results showed that pre-treatment SGC-7901 with autophagy inhibitors before VES treatment could increase the capacity of VES to reduce cell viability and to provoke apoptosis. In conclusion, VES-induced autophagy participates in SGC-7901 cell protection by inhibiting mTOR axis

  19. Fucoidan Elevates MicroRNA-29b to Regulate DNMT3B-MTSS1 Axis and Inhibit EMT in Human Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Ming-De Yan

    2015-09-01

    Full Text Available Accumulating evidence has revealed that fucoidan exhibits anti-tumor activities by arresting cell cycle and inducing apoptosis in many types of cancer cells including hepatocellular carcinoma (HCC. Exploring its effect on microRNA expression, we found that fucoidan markedly upregulated miR-29b of human HCC cells. The induction of miR-29b was accompanied with suppression of its downstream target DNMT3B in a dose-dependent manner. The reduction of luciferase activity of DNMT3B 3′-UTR reporter by fucoidan was as markedly as that by miR-29b mimic, indicating that fucoidan induced miR-29b to suppress DNMT3B. Accordingly, the mRNA and protein levels of MTSS1 (metastasis suppressor 1, a target silenced by DNMT3B, were increased after fucoidan treatment. Furthermore, fucoidan also down-regulated TGF-β receptor and Smad signaling of HCC cells. All these effects leaded to the inhibition of EMT (increased E-cadherin and decreased N-cadherin and prevention of extracellular matrix degradation (increased TIMP-1 and decreased MMP2, 9, by which the invasion activity of HCC cells was diminished. Our results demonstrate the profound effect of fucoidan not only on the regulation of miR-29b-DNMT3B-MTSS1 axis but also on the inhibition of TGF-β signaling in HCC cells, suggesting the potential of using fucoidan as integrative therapeutics against invasion and metastasis of HCC.

  20. The angiotensin-(1-7/Mas axis counteracts angiotensin II-dependent and –independent pro-inflammatory signaling in human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Laura A Villalobos

    2016-12-01

    Full Text Available Background and aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7 is a member of the renin-angiotensin system (RAS that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7 to counteract human aortic smooth muscle cell (HASMC inflammation triggered by RAS-dependent and –independent stimuli, such as Ang II or interleukin (IL-1.Methods and Results: In cultured HASMC, the expression of iNOS and the release of nitric oxide were stimulated by both Ang II and IL-1, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7 in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7, suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and NF-B. Indeed, Ang-(1-7 markedly inhibited the activation of the NADPH oxidase and subsequently of NF-B, as determined by lucigenin-derived chemiluminiscence and electromobility shift assay, respectively.Conclusion: Ang-(1-7 can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  1. A CD8 T Cell/Indoleamine 2,3-Dioxygenase Axis Is Required for Mesenchymal Stem Cell Suppression of Human Systemic Lupus Erythematosus

    Science.gov (United States)

    Wang, Dandan; Feng, Xuebing; Lu, Lin; Konkel, Joanne E; Zhang, Huayong; Chen, Zhiyong; Li, Xia; Gao, Xiang; Lu, Liwei; Shi, Songtao; Chen, Wanjun; Sun, Lingyun

    2014-01-01

    Objective Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients. Methods The effects of allogeneic umbilical cord–derived MSCs (UC-MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real-time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC–mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC-MSC transplantation. Results Allogeneic UC-MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3-dioxygenase (IDO). We further found that interferon-γ (IFNγ), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK-2/STAT signaling pathways. Intriguingly, bone marrow–derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFNγ and allogeneic CD8+ T cell stimulation. After allogeneic UC-MSC transplantation, serum IDO activity increased in lupus patients. Conclusion We found a previously unrecognized CD8+ T cell/IFNγ/IDO axis that mediates the therapeutic effects of allogeneic MSCs in lupus patients. PMID:24756936

  2. The effects of dietary fatty acids on the postprandial triglyceride-rich lipoprotein/apoB48 receptor axis in human monocyte/macrophage cells.

    Science.gov (United States)

    Varela, Lourdes M; Ortega-Gomez, Almudena; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G; Bermudez, Beatriz

    2013-12-01

    Intestinally produced triglyceride-rich lipoproteins (TRL) play an important role in the progression of atherosclerosis. In this study, we investigated the relevance of monounsaturated fatty acid (MUFA) and saturated fatty acid (SFA) in postprandial TRL in affecting the transcriptional activity of the apolipoprotein-B48 receptor (ApoB48R) and its functionality in human monocyte/macrophage cells. Healthy male volunteers were administered four standardized high-fat meals containing butter, high-palmitic sunflower oil, olive oil (ROO) or a mixture of vegetable and fish oils (50 g/m(2) body surface area) to obtain a panel of postprandial TRL with gradual MUFA oleic acid-to-SFA palmitic acid ratios. The increase in this ratio was linearly associated with a decrease of ApoB48R up-regulation and lipid accumulation in THP-1 and primary monocytes. ApoB48R mRNA levels and intracellular triglycerides were also lower in the monocytes from volunteers after the ingestion of the ROO meal when compared to the ingestion of the butter meal. In THP-1 macrophages, the increase in the MUFA oleic acid-to-SFA palmitic acid ratio in the postprandial TRL was linearly correlated with an increase in ApoB48R down-regulation and a decrease in lipid accumulation. We also revealed that the nuclear receptor transcription factors PPARα, PPARβ/δ, and PPARγ and the PPAR-RXR transcriptional complex were involved in sensing the proportion of MUFA oleic acid and SFA palmitic acid, and these were also involved in adjusting the transcriptional activity of ApoB48R. The results of this study support the notion that MUFA-rich dietary fats may prevent excessive lipid accumulation in monocyte/macrophage cells by targeting the postprandial TRL/ApoB48R axis. © 2013.

  3. The Significance of SDF-1α-CXCR4 Axis in in vivo Angiogenic Ability of Human Periodontal Ligament Stem Cells.

    Science.gov (United States)

    Bae, Yoon-Kyung; Kim, Gee-Hye; Lee, Jae Cheoun; Seo, Byoung-Moo; Joo, Kyeung-Min; Lee, Gene; Nam, Hyun

    2017-06-30

    Periodontal ligament stem cells (PDLSCs) are multipotent stem cells derived from periodontium and have mesenchymal stem cell (MSC)-like characteristics. Recently, the perivascular region was recognized as the developmental origin of MSCs, which suggests the in vivo angiogenic potential of PDLSCs. In this study, we investigated whether PDLSCs could be a potential source of perivascular cells, which could contribute to in vivo angiogenesis. PDLSCs exhibited typical MSC-like characteristics such as the expression pattern of surface markers (CD29, CD44, CD73, and CD105) and differentiation potentials (osteogenic and adipogenic differentiation). Moreover, PDLSCs expressed perivascular cell markers such as NG2, αsmooth muscle actin, platelet-derived growth factor receptor β, and CD146. We conducted an in vivo Matrigel plug assay to confirm the in vivo angiogenic potential of PDLSCs. We could not observe significant vessel-like structures with PDLSCs alone or human umbilical vein endothelial cells (HU-VECs) alone at day 7 after injection. However, when PDLSCs and HUVECs were co-injected, there were vessel-like structures containing red blood cells in the lumens, which suggested that anastomosis occurred between newly formed vessels and host circulatory system. To block the SDF-1α and CXCR4 axis between PDLSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into the Matrigel plug. After day 3 and day 7 after injection, there were no significant vessel-like structures. In conclusion, we demonstrated the peri-vascular characteristics of PDLSCs and their contribution to in vivo angiogenesis, which might imply potential application of PDLSCs into the neovascularization of tissue engineering and vascular diseases.

  4. Dissociative symptoms and neuroendocrine dysregulation in depression.

    Science.gov (United States)

    Bob, Petr; Fedor-Freybergh, Peter; Jasova, Denisa; Bizik, Gustav; Susta, Marek; Pavlat, Josef; Zima, Tomas; Benakova, Hana; Raboch, Jiri

    2008-10-01

    Dissociative symptoms are traditionally attributed to psychological stressors that produce dissociated memories related to stressful life events. Dissociative disorders and dissociative symptoms including psychogenic amnesia, fugue, dissociative identity-disorder, depersonalization, derealization and other symptoms or syndromes have been reported as an epidemic psychiatric condition that may be coexistent with various psychiatric diagnoses such as depression, schizophrenia, borderline personality disorder or anxiety disorders. According to recent findings also the somatic components of dissociation may occur and influence brain, autonomic and neuroendocrine functions. At this time there are only few studies examining neuroendocrine response related to dissociative symptoms that suggest significant dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. The aim of the present study is to perform examination of HPA axis functioning indexed by basal cortisol and prolactin and test their relationship to psychic and somatoform dissociative symptoms. Basal cortisol and prolactin and psychic and somatoform dissociative symptoms were assessed in 40 consecutive inpatients with diagnosis of unipolar depression mean age 43.37 (SD=12.21). The results show that prolactin and cortisol as indices of HPA axis functioning manifest significant relationship to dissociative symptoms. Main results represent highly significant correlations obtained by simple regression between psychic dissociative symptoms (DES) and serum prolactin (R=0.55, p=0.00027), and between somatoform dissociation (SDQ-20) and serum cortisol (R=-0.38, p=0.015). These results indicate relationship between HPA-axis reactivity and dissociative symptoms in unipolar depressive patients that could reflect passive coping behavior and disengagement.

  5. Positive modulation of a neutral declarative memory by a threatening social event.

    Science.gov (United States)

    Fernández, Rodrigo S; Bavassi, Luz; Campos, Jorge; Allegri, Ricardo F; Molina, Victor A; Forcato, Cecilia; Pedreira, María E

    2015-12-01

    Memories can be altered by negative or arousing experiences due to the activation of the stress-responsive sympatho-adrenal-medullary axis (SYM). Here, we used a neutral declarative memory that was acquired during multi-trial training to determine the effect of a threatening event on memory without emotional valence. To this end, participants received a new threatening social protocol before learning pairs of meaningless syllables and were tested either 15 min, 2 days or 8 days after acquisition. We first demonstrated that this threatening social situation activates not only the SYM axis (Experiment 1) and the hypothalamus-pituitary-adrenal axis (HPA; Experiment 2), but also, it improves the acquisition or early consolidation of the syllable pairs (Experiment 3). This improvement is not a transient effect; it can be observed after the memory is consolidated. Furthermore, this modulation increases the persistence of memory (Experiment 4). Thus, it is possible to affect memories with specific events that contain unrelated content and a different valence. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Basal hypercortisolism and trauma in patients with psychogenic nonepileptic seizures.

    Science.gov (United States)

    Bakvis, Patricia; Spinhoven, Philip; Giltay, Erik J; Kuyk, Jarl; Edelbroek, Peter M; Zitman, Frans G; Roelofs, Karin

    2010-05-01

    Several studies have indicated that psychogenic nonepileptic seizures (PNES) are associated with psychological trauma, but only a few studies have examined the associations with neurobiologic stress systems, such as the hypothalamus-pituitary-adrenal (HPA) axis and its end-product cortisol. We tested several relevant HPA-axis functions in patients with PNES and related them to trauma history. Cortisol awakening curve, basal diurnal cortisol, and negative cortisol feedback (using a 1 mg dexamethasone suppression test) were examined in 18 patients with PNES and 19 matched healthy controls (HCs) using saliva cortisol sampling on two consecutive days at 19 time points. Concomitant sympathetic nervous system (SNS) activity was assessed by analyzing saliva alpha-amylase (sAA). Patients with PNES showed significantly increased basal diurnal cortisol levels compared to HCs. This effect was driven mainly by patients reporting sexual trauma who showed a trend toward higher cortisol levels as compared to patients without a sexual trauma report. Importantly, the increased basal diurnal cortisol levels in patients were not explained by depression, medication, or smoking, or by current seizures or group differences in SNS activity. This is the first study showing that basal hypercortisolism in patients with PNES is independent of the acute occurrence of seizures. In addition, basal hypercortisolism was more pronounced in traumatized patients with PNES as compared to nontraumatized patients with PNES. These findings suggest that HPA-axis activity provides a significant neurobiologic marker for PNES.

  7. Free cortisol and salivary alpha-amylase levels during a six-hour-water immersion in healthy young men

    Science.gov (United States)

    Rohleder, N.; Wirth, D.; Fraßl, W.; Kowoll, R.; Schlemmer, M.; Vogler, S.; Kirsch, K. A.; Kirschbaum, C.; Gunga, H.-C.

    2005-08-01

    Limited data are available on the response of stress systems to microgravity. Increased activity of stress systems is reported during space flight, but unchanged or decreased activity during simulated microgravity. We here investigated the impact of head-out water immersion on the activity of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary (SAM) system.Eight healthy young men were exposed to a six-hour water immersion in a thermo neutral bath and a control condition. Saliva samples were taken before, during, and after interventions to assess cortisol as an index for HPA axis activity, and salivary α-amylase as an index for SAM system activity.Cortisol levels uniformly decreased during both conditions. Amylase levels increased during both conditions, but were significantly lower during the first half of water immersion compared to the control condition.In conclusion, the HPA axis is not influenced by simulated microgravity, while SAM system activity shows initial decreases during water immersion.

  8. Neonatal handling induces anovulatory estrous cycles in rats

    Directory of Open Access Journals (Sweden)

    Gomes C.M.

    1999-01-01

    Full Text Available Since previous work has shown that stimulation early in life decreases sexual receptiveness as measured by the female lordosis quotient, we suggested that neonatal handling could affect the function of the hypothalamus-pituitary-gonadal axis. The effects of neonatal handling on the estrous cycle and ovulation were analyzed in adult rats. Two groups of animals were studied: intact (no manipulation, N = 10 and handled (N = 11. Pups were either handled daily for 1 min during the first 10 days of life or left undisturbed. At the age of 90 days, a vaginal smear was collected daily at 9:00 a.m. and analyzed for 29 days; at 9:00 a.m. on the day of estrus, animals were anesthetized with thiopental (40 mg/kg, ip, the ovaries were removed and the oviduct was dissected and squashed between 2 glass slides. The number of oocytes of both oviductal ampullae was counted under the microscope. The average numbers for each phase of the cycle (diestrus I, diestrus II, proestrus and estrus during the period analyzed were compared between the two groups. There were no significant differences between intact and handled females during any of the phases. However, the number of handled females that showed anovulatory cycles (8 out of 11 was significantly higher than in the intact group (none out of 10. Neonatal stimulation may affect not only the hypothalamus-pituitary-adrenal axis, as previously demonstrated, but also the hypothalamus-pituitary-gonadal axis in female rats.

  9. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Francesco Orio

    2014-01-01

    Full Text Available Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo- and autologous- (auto- stem cell transplant (HSCT. This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma, gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.

  10. CRF1 receptor-deficiency increases cocaine reward.

    Science.gov (United States)

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

    2017-05-01

    Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF 1 receptor-deficient (CRF 1 -/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF 1 -/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF 1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF 1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF 1 -/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF 1 -/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF 1 -/- mice by exogenous corticosterone does not affect CRF 1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF 1 receptor in cocaine reward, independently of the closely related HPA axis activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Acute stress impairs recall after interference in older people, but not in young people.

    Science.gov (United States)

    Hidalgo, Vanesa; Almela, Mercedes; Villada, Carolina; Salvador, Alicia

    2014-03-01

    Stress has been associated with negative changes observed during the aging process. However, very little research has been carried out on the role of age in acute stress effects on memory. We aimed to explore the role of age and sex in the relationship between hypothalamus-pituitary-adrenal axis (HPA-axis) and sympathetic nervous system (SNS) reactivity to psychosocial stress and short-term declarative memory performance. To do so, sixty-seven participants divided into two age groups (each group with a similar number of men and women) were exposed to the Trier Social Stress Test (TSST) and a control condition in a crossover design. Memory performance was assessed by the Rey Auditory Verbal Learning Test (RAVLT). As expected, worse memory performance was associated with age; but more interestingly, the stressor impaired recall after interference only in the older group. In addition, this effect was negatively correlated with the alpha-amylase over cortisol ratio, which has recently been suggested as a good marker of stress system dysregulation. However, we failed to find sex differences in memory performance. These results show that age moderates stress-induced effects on declarative memory, and they point out the importance of studying both of the physiological systems involved in the stress response together. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Exploring longitudinal associations between neighborhood disadvantage and cortisol levels in early childhood.

    Science.gov (United States)

    Finegood, Eric D; Rarick, Jason R D; Blair, Clancy

    2017-12-01

    Children who grow up in poverty are more likely to experience chronic stressors that generate "wear" on stress regulatory systems including the hypothalamus-pituitary-adrenal (HPA) axis. This can have long-term consequences for health and well-being. Prior research has examined the role of proximal family and home contributions to HPA axis functioning. However, there is evidence to suggest that more distal levels of context, including neighborhoods, also matter. Prior evidence has primarily focused on adolescents and adults, with little evidence linking the neighborhood context with HPA activity in infancy and toddlerhood. We tested whether neighborhood disadvantage (indexed by US Census data) was associated with basal salivary cortisol levels at 7, 15, and 24 months of child age in a large sample of families (N = 1,292) residing in predominately low-income and rural communities in the United States. Multilevel models indicated that neighborhood disadvantage was positively associated with salivary cortisol levels and that this effect emerged across time. This effect was moderated by the race/ethnicity of children such that the association was only observed in White children in our sample. Findings provide preliminary evidence that the neighborhood context is associated with stress regulation during toddlerhood, elucidating a need for future work to address possible mechanisms.

  13. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

    Science.gov (United States)

    Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

    2016-04-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Respiratory Effects and Systemic Stress Response Following ...

    Science.gov (United States)

    Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically impaired models. We examined respiratory and systemic effects following exposure to a sensory irritant acrolein to elucidate the systemic and pulmonary consequences in healthy and diabetic rat models. Male Wistar and Goto Kakizaki (GK) rats, a nonobese type II diabetic Wistar-derived model, were exposed by inhalation to 0, 2, or 4 ppm acrolein, 4 h/d for 1 or 2 days. Exposure at 4 ppm significantly increased pulmonary and nasal inflammation in both strains with vascular protein leakage occurring only in the nose. Acrolein exposure (4 ppm) also caused metabolic impairment by inducing hyperglycemia and glucose intolerance (GK > Wistar). Serum total cholesterol (GKs only), low-density lipoprotein (LDL) cholesterol (both strains), and free fatty acids (GK > Wistar) levels increased; however, no acrolein-induced changes were noted in branched-chain amino acid or insulin levels. These responses corresponded with a significant increase in corticosterone and modest but insignificant increases in adrenaline in both strains, suggesting activation of the HPA axis. Collectively, these data demonstrate that acrolein exposure has a profound effect on nasal and pulmonary inflammation, as well as glucose and lipid metabolis

  15. Palatable food avoidance and acceptance learning with different stressors in female rats.

    Science.gov (United States)

    Liang, N-C; Smith, M E; Moran, T H

    2013-04-03

    Stress activates the hypothalamus-pituitary-adrenal (HPA) axis leading to the release of glucocorticoids (GC). Increased activity of the HPA axis and GC exposure has been suggested to facilitate the development of obesity and metabolic syndrome. Nonetheless, different stressors can produce distinct effects on food intake and may support different directions of food learning e.g. avoidance or acceptance. This study examined whether interoceptive (LiCl and exendin-4) and restraint stress (RS) support similar or distinct food learning. Female rats were exposed to different stressors after their consumption of a palatable food (butter icing). After four palatable food-stress pairings, distinct intakes of the butter icing were observed in rats treated with different stressors. Rats that received butter icing followed by intraperitoneal injections of LiCl (42.3mg/kg) and exendin-4 (10μg/kg) completely avoided the palatable food with subsequent presentations. In contrast, rats experiencing RS paired with the palatable food increased their consumption of butter icing across trials and did so to a greater degree than rats receiving saline injections. These data indicate that interoceptive and psychosocial stressors support conditioned food avoidance and acceptance, respectively. Examination of c-Fos immunoreactivity revealed distinct neural activation by interoceptive and psychosocial stressors that could provide the neural basis underlying opposite direction of food acceptance learning. Published by Elsevier Ltd.

  16. The Cortisol Response to Anticipated Intergroup Interactions Predicts Self-Reported Prejudice

    Science.gov (United States)

    Bijleveld, Erik; Scheepers, Daan; Ellemers, Naomi

    2012-01-01

    Objectives While prejudice has often been shown to be rooted in experiences of threat, the biological underpinnings of this threat–prejudice association have received less research attention. The present experiment aims to test whether activations of the hypothalamus-pituitary-adrenal (HPA) axis, due to anticipated interactions with out-group members, predict self-reported prejudice. Moreover, we explore potential moderators of this relationship (i.e., interpersonal similarity; subtle vs. blatant prejudice). Methodology/Principal findings Participants anticipated an interaction with an out-group member who was similar or dissimilar to the self. To index HPA activation, cortisol responses to this event were measured. Then, subtle and blatant prejudices were measured via questionnaires. Findings indicated that only when people anticipated an interaction with an out-group member who was dissimilar to the self, their cortisol response to this event significantly predicted subtle (r = .50) and blatant (r = .53) prejudice. Conclusions These findings indicate that prejudicial attitudes are linked to HPA-axis activity. Furthermore, when intergroup interactions are interpreted to be about individuals (and not so much about groups), experienced threat (or its biological substrate) is less likely to relate to prejudice. This conclusion is discussed in terms of recent insights from social neuroscience. PMID:22442709

  17. Clinical applications of cortisol measurements in hair.

    Science.gov (United States)

    Wester, Vincent L; van Rossum, Elisabeth F C

    2015-10-01

    Cortisol measurements in blood, saliva and urine are frequently used to examine the hypothalamus-pituitary-adrenal (HPA) axis in clinical practice and in research. However, cortisol levels are subject to variations due to acute stress, the diurnal rhythm and pulsatile secretion. Cortisol measurements in body fluids are not always a reflection of long-term cortisol exposure. The analysis of cortisol in scalp hair is a relatively novel method to measure cumulative cortisol exposure over months up to years. Over the past years, hair cortisol concentrations (HCC) have been examined in association with a large number of somatic and mental health conditions. HCC can be used to evaluate disturbances of the HPA axis, including Cushing's syndrome, and to evaluate hydrocortisone treatment. Using HCC, retrospective timelines of cortisol exposure can be created which can be of value in diagnosing cyclic hypercortisolism. HCC have also been shown to increase with psychological stressors, including major life events, as well as physical stressors, such as endurance exercise and shift work. Initial studies show that HCC may be increased in depression, but decreased in general anxiety disorder. In posttraumatic stress disorder, changes in HCC seem to be dependent on the type of traumatic experience and the time since traumatization. Increased hair cortisol is consistently linked to obesity, metabolic syndrome and cardiovascular disease. Potentially, HCC could form a future marker for cardiovascular risk stratification, as well as serve as a treatment target. © 2015 European Society of Endocrinology.

  18. The cortisol response to anticipated intergroup interactions predicts self-reported prejudice.

    Science.gov (United States)

    Bijleveld, Erik; Scheepers, Daan; Ellemers, Naomi

    2012-01-01

    While prejudice has often been shown to be rooted in experiences of threat, the biological underpinnings of this threat-prejudice association have received less research attention. The present experiment aims to test whether activations of the hypothalamus-pituitary-adrenal (HPA) axis, due to anticipated interactions with out-group members, predict self-reported prejudice. Moreover, we explore potential moderators of this relationship (i.e., interpersonal similarity; subtle vs. blatant prejudice). Participants anticipated an interaction with an out-group member who was similar or dissimilar to the self. To index HPA activation, cortisol responses to this event were measured. Then, subtle and blatant prejudices were measured via questionnaires. Findings indicated that only when people anticipated an interaction with an out-group member who was dissimilar to the self, their cortisol response to this event significantly predicted subtle (r = .50) and blatant (r = .53) prejudice. These findings indicate that prejudicial attitudes are linked to HPA-axis activity. Furthermore, when intergroup interactions are interpreted to be about individuals (and not so much about groups), experienced threat (or its biological substrate) is less likely to relate to prejudice. This conclusion is discussed in terms of recent insights from social neuroscience.

  19. Respiratory Effects and Systemic Stress Response Following ...

    Science.gov (United States)

    Previous studies have demonstrated that exposure to ozone, a pulmonary irritant, causes myriad systemic metabolic and pulmonary effects that are attributed to neuronal and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically-impaired models. In order to elucidate the systemic consequences and the contribution of the HPA axis in mediating metabolic and respiratory effects of acrolein, a sensory irritant, we examined pulmonary, nasal, and systemic effects in rats following exposure. Male, 10 week old Wistar and Goto Kakizaki (GK) rats, a non-obese type II diabetic Wistar-derived model, were exposed to 0, 2 or 4 ppm acrolein, 4h/day for 1 or 2 days. Acrolein exposure at 4 ppm significantly increased pulmonary and nasal damage in both strains as demonstrated by increased inspiratory and expiratory times indicating labored breathing, elevated biomarkers of injury, and neutrophilic inflammation. Overall, at both time points acrolein exposure caused noticeably more damage in the nasal passages as opposed to the lung with vascular protein leakage occurring only in the nose. Acrolein exposure (4 ppm) also led to metabolic impairment by inducing hyperglycemia and glucose intolerance (GK>Wistar) as indicated by glucose tolerance testing. In addition, serum total cholesterol (GKs only), LDL cholesterol (both strains), and free fatty acids (GK>Wistar) levels increased; however, no acrolein-induced changes were noted in branched-c

  20. Neuroendocrine Alterations in Obese Patients with Sleep Apnea Syndrome

    Directory of Open Access Journals (Sweden)

    Fabio Lanfranco

    2010-01-01

    Full Text Available Obstructive sleep apnea syndrome (OSAS is a serious, prevalent condition that has significant morbidity and mortality when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. Obese patients with OSAS show a reduction of both spontaneous and stimulated growth hormone (GH secretion coupled to reduced insulin-like growth factor-I (IGF-I concentrations and impaired peripheral sensitivity to GH. Hypoxemia and chronic sleep fragmentation could affect the sleep-entrained prolactin (PRL rhythm. A disrupted Hypothalamus-Pituitary-Adrenal (HPA axis activity has been described in OSAS. Some derangement in Thyroid-Stimulating Hormone (TSH secretion has been demonstrated by some authors, whereas a normal thyroid activity has been described by others. Changes of gonadal axis are common in patients with OSAS, who frequently show a hypogonadotropic hypogonadism. Altogether, hormonal abnormalities may be considered as adaptive changes which indicate how a local upper airway dysfunction induces systemic consequences. The understanding of the complex interactions between hormones and OSAS may allow a multi-disciplinary approach to obese patients with this disturbance and lead to an effective management that improves quality of life and prevents associated morbidity or death.

  1. Triple axis spectrometers

    International Nuclear Information System (INIS)

    Clausen, K.N.

    1997-01-01

    Conventional triple-axis neutron spectroscopy was developed by Brockhouse over thirty years ago' and remains today a versatile and powerful tool for probing the dynamics of condensed matter. The original design of the triple axis spectrometer is technically simple and probes momentum and energy space on a point-by-point basis. This ability to systematically probe the scattering function in a way which only requires a few angles to be moved under computer control and where the observed data in general can be analysed using a pencil and graph paper or a simple fitting routine, has been essential for the success of the method. These constraints were quite reasonable at the time the technique was developed. Advances in computer based data acquisition, neutron beam optics, and position sensitive area detectors have been gradually implemented on many triple axis spectrometer spectrometers, but the full potential of this has not been fully exploited yet. Further improvement in terms of efficiency (beyond point by point inspection) and increased sensitivity (use of focusing optics whenever the problem allows it) could easily be up to a factor of 10-20 over present instruments for many problems at a cost which is negligible compared to that of increasing the flux of the source. The real cost will be in complexity - finding the optimal set-up for a given scan and interpreting the data as the they are taken. On-line transformation of the data for an appropriate display in Q, ω space and analysis tools will be equally important for this task, and the success of these new ideas will crucially depend on how well we solve these problems. (author)

  2. The microbiota-gut-brain axis as a key regulator of neural function and the stress response: Implications for human and animal health.

    Science.gov (United States)

    Wiley, N C; Dinan, T G; Ross, R P; Stanton, C; Clarke, G; Cryan, J F

    2017-07-01

    The brain-gut-microbiota axis comprises an extensive communication network between the brain, the gut, and the microbiota residing there. Development of a diverse gut microbiota is vital for multiple features of behavior and physiology, as well as many fundamental aspects of brain structure and function. Appropriate early-life assembly of the gut microbiota is also believed to play a role in subsequent emotional and cognitive development. If the composition, diversity, or assembly of the gut microbiota is impaired, this impairment can have a negative impact on host health and lead to disorders such as obesity, diabetes, inflammatory diseases, and even potentially neuropsychiatric illnesses, including anxiety and depression. Therefore, much research effort in recent years has focused on understanding the potential of targeting the intestinal microbiota to prevent and treat such disorders. This review aims to explore the influence of the gut microbiota on host neural function and behavior, particularly those of relevance to stress-related disorders. The involvement of microbiota in diverse neural functions such as myelination, microglia function, neuronal morphology, and blood-brain barrier integrity across the life span, from early life to adolescence to old age, will also be discussed. Nurturing an optimal gut microbiome may also prove beneficial in animal science as a means to manage stressful situations and to increase productivity of farm animals. The implications of these observations are manifold, and researchers are hopeful that this promising body of preclinical work can be successfully translated to the clinic and beyond.

  3. Vertical axis wind turbines

    Science.gov (United States)

    Krivcov, Vladimir [Miass, RU; Krivospitski, Vladimir [Miass, RU; Maksimov, Vasili [Miass, RU; Halstead, Richard [Rohnert Park, CA; Grahov, Jurij [Miass, RU

    2011-03-08

    A vertical axis wind turbine is described. The wind turbine can include a top ring, a middle ring and a lower ring, wherein a plurality of vertical airfoils are disposed between the rings. For example, three vertical airfoils can be attached between the upper ring and the middle ring. In addition, three more vertical airfoils can be attached between the lower ring and the middle ring. When wind contacts the vertically arranged airfoils the rings begin to spin. By connecting the rings to a center pole which spins an alternator, electricity can be generated from wind.

  4. Vertical axis wind turbine

    International Nuclear Information System (INIS)

    Obretenov, V.; Tsalov, T.; Chakarov, T.

    2012-01-01

    In recent years, the interest in wind turbines with vertical axis noticeably increased. They have some important advantages: low cost, relatively simple structure, reliable packaging system of wind aggregate long period during which require no maintenance, low noise, independence of wind direction, etc.. The relatively low efficiency, however, makes them applicable mainly for small facilities. The work presents a methodology and software for approximately aerodynamic design of wind turbines of this type, and also analyzed the possibility of improving the efficiency of their workflow

  5. [Systemic biopsychological perspective of basic emotions].

    Science.gov (United States)

    Poisson, Benoît

    the peripheral nervous system. The latter is divided into two: the sympathetic (norepinephrine) that accelerates the motor response and the parasympathetic (acetylcholine), which slows it down. These two systems work in tandem. As for the second release of information, it is endocrine, thus it will follow the hypothalamus-pituitary-adrenal axis to cortisol, the hypothalamus-pituitary axis to endorphin and oxytocin and the hypothalamus-pineal axis to melatonin. The different emotional behaviours result from one of these two sources of information or from a combination of these two and are then managed by the limbic system, which is in continuous connection with the neocortex.In short, no specific centre totally controls human behaviour. Control is achieved through a group of brain structures and relays, permitting adaptive behaviour and maintenance of balance by means of permanent exchanges. Anger, for instance, is a survival emotion, which allows protecting one's physical integrity. It is very useful as an immediate response in an emergency situation, but it can also be harmful if it is used extensively in all situations, giving way to conduct disorders. Thus, the other neurohormonal circuits will regulate anger.Emotions are an integral part of human behaviour. They allow the individual to constantly adapt to the physical and social environment. This approach brings a new perspective to understand how each person maintains balance to avoid the onset of clinical disorders. The understanding of neurochemical mechanisms underlying basic emotions opens up the door to several clinical applications.

  6. Protective effect of ciliary neurotrophic factor (CNTF) in a model of endotoxic shock: action mechanisms and role of CNTF receptor alpha.

    Science.gov (United States)

    Demitri, M T; Benigni, F; Meazza, C; Zinetti, M; Fratelli, M; Villa, P; Acheson, A; Panayotatos, N; Ghezzi, P

    1998-01-01

    Ciliary neurotrophic factor (CNTF) inhibits the production of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-treated mice and protects against LPS lethality when coadministered with its soluble receptor (sCNTFR alpha). Both of these activities are abolished in adrenalectomized (ADX) mice. LPS-induced pulmonary polymorphonuclear neutrophil (PMN) infiltration and nitric oxide (NO) production were also inhibited by CNTF + sCNTFR alpha but not by CNTF alone. sCNTFR alpha did not alter the clearance or tissue distribution of CNTF. Furthermore, CNTF variants coadministered with sCNTFR alpha protected against LPS toxicity in a manner related to their affinity for the beta components of CNTFR. Thus, inhibition of TNF production and protection against LPS lethality by CNTF/sCNTFR alpha require an intact hypothalamus-pituitary-adrenal axis (HPAA) and may be mediated by endogenous glucocorticoids. This protective effect is, at least in part, due to the inhibition of PMN infiltration and NO production, and appears to be mediated by cells displaying only beta-receptor subtypes.

  7. NUR TRANSCRIPTION FACTORS IN STRESS AND ADDICTION

    Directory of Open Access Journals (Sweden)

    Danae eCampos-Melo

    2013-12-01

    Full Text Available The Nur transcription factors Nur77 (NGFI-B, NR4A1, Nurr1 (NR4A2 and Nor-1 (NR4A3 are a sub-family of orphan members of the nuclear receptor superfamily. These transcription factors are products of immediate early genes, whose expression is rapidly and transiently induced in the central nervous system by several types of stimuli. Nur factors are present throughout the hypothalamus-pituitary-adrenal axis where are prominently induced in response to stress. Drugs of abuse and stress also induce the expression of Nur factors in nuclei of the motivation/reward circuit of the brain, indicating their participation in the process of drug addiction and in non-hypothalamic responses to stress. Repeated use of addictive drugs and chronic stress induce long-lasting dysregulation of the brain motivation/reward circuit, due to reprogramming of gene expression and enduring alterations in neuronal function. Here, we review the data supporting that Nur transcription factors are key players in the molecular basis of the dysregulation of neuronal circuits involved in chronic stress and addiction.

  8. Genetic variation of the porcine NR5A1 is associated with meat color.

    Science.gov (United States)

    Görres, Andreas; Ponsuksili, Siriluck; Wimmers, Klaus; Muráni, Eduard

    2016-02-01

    Because of the central role of Steroidogenic factor 1 in the regulation of the development and function of steroidogenic tissues, including the adrenal gland, we chose the encoding gene NR5A1 as a candidate for stress response, meat quality and carcass composition in the domestic pig. To identify polymorphisms of the porcine NR5A1 we comparatively sequenced the coding, untranslated and regulatory regions in four commercial pig lines. Single nucleotide polymorphisms could be found in the 3' UTR and in an intronic enhancer, whereas no polymorphisms were detected in the proximal promoter and coding region. A subset of the detected polymorphisms was genotyped in Piétrain x (German Large White x German Landrace) and German Landrace pigs. For the same animals, carcass composition traits, meat quality characteristics and parameters of adrenal function were recorded. Associations with meat color were found for two of the discovered SNPs in Piétrain x (German Large White x German Landrace) and German Landrace pigs but no connections to parameters of adrenal function could be established. We conclude that NR5A1 variations influence meat color in a hypothalamus-pituitary-adrenal axis independent manner and that further regulatory regions need to be analyzed for genetic variations to understand the discovered effects.

  9. Association between changes in heart rate variability during the anticipation of a stressful situation and the stress-induced cortisol response.

    Science.gov (United States)

    Pulopulos, Matias M; Vanderhasselt, Marie-Anne; De Raedt, Rudi

    2018-08-01

    Vagal activity - reflecting the activation of stress regulatory mechanisms and prefrontal cortex activation - is thought to play an inhibitory role in the regulation of the hypothalamus-pituitary-adrenal axis. However, most studies investigating the association between stress-induced changes in heart rate variability (HRV, an index of cardiac vagal tone) and cortisol have shown a non-significant relationship. It has been proposed that physiological changes observed during anticipation of a stressor allow individuals to make behavioral, cognitive, and physiological adjustments that are necessary to deal with the upcoming actual stressor. In this study, in a large sample of 171 healthy adults (96 men and 75 women; mean age = 29.98, SD = 11.07), we investigated whether the cortisol response to a laboratory-based stress task was related to anticipation-induced or stress task-induced changes in HRV. As expected, regression analyses showed that a larger decrease in HRV during the anticipation of a stress task was related to higher stress task-induced cortisol increase, but not cortisol recovery. In line with prior research, the stress task-induced change in HRV was not significantly related to cortisol increase or recovery. Our results show for the first time that anticipatory HRV (reflecting differences in stress regulation and prefrontal activity before the encounter with the stressor) is important to understand the stress-induced cortisol increase. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    F. Azevedo-Silva

    2010-03-01

    Full Text Available Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL. The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

  11. Cortisol responses to chronic stress in adult macaques: moderation by a polymorphism in the serotonin transporter gene.

    Science.gov (United States)

    Qin, Dongdong; Rizak, Joshua; Feng, Xiaoli; Yang, Shangchuan; Yang, Lichuan; Fan, Xiaona; Lü, Longbao; Chen, Lin; Hu, Xintian

    2015-02-01

    Accumulating evidence has shown that a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) moderates the association between stress and depressive symptoms. However, the exact etiologies underlying this moderation are not well understood. Here it is reported that among adult female rhesus macaques, an orthologous polymorphism (rh5-HTTLPR) exerted an influence on cortisol responses to chronic stress. It was found that females with two copies of the short allele were associated with increased cortisol responses to chronic stress in comparison to their counterparts who have one or two copies of the long allele. In the absence of stress, no differences related to genotype were observed in these females. This genetic moderation was found without a genetic influence on exposure to stressful situations. Rather it was found to be a genetic modulation of cortisol responses to chronic stress. These findings indicate that the rh5-HTTLPR polymorphism is closely related to hypothalamus-pituitary-adrenal (HPA) axis reactivity, which may increase susceptibility to depression in females with low serotonin transporter efficiency and a history of stress. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Cortisol responses to naturalistic and laboratory stress in student teachers: comparison with a non-stress control day.

    Science.gov (United States)

    Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

    2013-04-01

    Ambulatory assessments of hypothalamus-pituitary-adrenal axis responses to acute natural stressors yield evidence on stress regulation with high ecological validity. Sampling of salivary cortisol is a standard technique in this field. In 21 healthy student teachers, we assessed cortisol responses to a demonstration lesson. On a control day, sampling was repeated at analogous times. Additionally, the cortisol awakening response (CAR) was assessed on both days. Participants were also exposed to a laboratory stressor, the Trier Social Stress Test, and rated their individual levels of chronic work stress. In pre-to-post-stress assessment, cortisol levels declined after the lesson. However, post-stress cortisol levels were significantly higher compared with those on the control day. Also, the Trier Social Stress Test yielded higher cortisol responses when using the control day as reference baseline. Associations between the CAR and chronic stress measures were observed solely on the control day. There were no significant associations between cortisol responses to the natural and laboratory stressors. Our results indicate that a control day might be an important complement in laboratory but especially in ambulatory stress research. Furthermore, associations between chronic stress measures and the CAR might be obscured by acute stress exposure. Finally, responses to the laboratory stressor do not seem to mirror natural stress responses. Copyright © 2012 John Wiley & Sons, Ltd.

  13. Salivary cortisol and α-amylase: subclinical indicators of stress as cardiometabolic risk.

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    Cozma, S; Dima-Cozma, L C; Ghiciuc, C M; Pasquali, V; Saponaro, A; Patacchioli, F R

    2017-02-06

    Currently, the potential for cardiovascular (CV) stress-induced risk is primarily based on the theoretical (obvious) side effects of stress on the CV system. Salivary cortisol and α-amylase, produced respectively by the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary (SAM) system during stress response, are still not included in the routine evaluation of CV risk and require additional and definitive validation. Therefore, this article overviews studies published between 2010 and 2015, in which salivary cortisol and α-amylase were measured as stress biomarkers to examine their associations with CV/CMR (cardiometabolic risk) clinical and subclinical indicators. A comprehensive search of PubMed, Web of Science and Scopus electronic databases was performed, and 54 key articles related to the use of salivary cortisol and α-amylase as subclinical indicators of stress and CV/CMR factors, including studies that emphasized methodological biases that could influence the accuracy of study outcomes, were ultimately identified. Overall, the biological impact of stress measured by salivary cortisol and α-amylase was associated with CV/CMR factors. Results supported the use of salivary cortisol and α-amylase as potential diagnostic tools for detecting stress-induced cardiac diseases and especially to describe the mechanisms by which stress potentially contributes to the pathogenesis and outcomes of CV diseases.

  14. Intention retrieval and deactivation following an acute psychosocial stressor.

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    Moritz Walser

    Full Text Available We often form intentions but have to postpone them until the appropriate situation for retrieval and execution has come, an ability also referred to as event-based prospective memory. After intention completion, our cognitive system has to deactivate no-more-relevant intention representations from memory to avoid interference with subsequent tasks. In everyday life, we frequently rely on these abilities also in stressful situations. Surprisingly, little is known about potential stress effects on these functions. Therefore, the present study aimed to examine the reliability of event-based prospective memory and of intention deactivation in conditions of acute psychosocial stress. To this aim, eighty-two participants underwent the Trier Social Stress Test, a standardized stress protocol, or a standardized control situation. Following this treatment, participants performed a computerized event-based prospective memory task with non-salient and focal prospective memory cues in order to assess prospective memory performance and deactivation of completed intentions. Although the stress group showed elevated levels of salivary cortisol as marker of a stress-related increase in hypothalamus-pituitary-adrenal axis activity throughout the cognitive testing period compared to the no-stress group, prospective memory performance and deactivation of completed intentions did not differ between groups. Findings indicate that cognitive control processes subserving intention retrieval and deactivation after completion may be mostly preserved even under conditions of acute stress.

  15. Anti-stress and neuronal cell differentiation induction effects of Rosmarinus officinalis L. essential oil.

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    Villareal, Myra O; Ikeya, Ayumi; Sasaki, Kazunori; Arfa, Abdelkarim Ben; Neffati, Mohamed; Isoda, Hiroko

    2017-12-22

    Mood disorder accounts for 13 % of global disease burden. And while therapeutic agents are available, usually orally administered, most have unwanted side effects, and thus making the inhalation of essential oils (EOs) an attractive alternative therapy. Rosmarinus officinalis EO (ROEO), Mediterranean ROEO reported to improve cognition, mood, and memory, the effect on stress of which has not yet been determined. Here, the anti-stress effect of ROEO on stress was evaluated in vivo and in vitro. Six-week-old male ICR mice were made to inhale ROEO and subjected to tail suspension test (TST). To determine the neuronal differentiation effect of ROEO in vitro, induction of ROEO-treated PC12 cells differentiation was observed. Intracellular acetylcholine and choline, as well as the Gap43 gene expression levels were also determined. Inhalation of ROEO significantly decreased the immobility time of ICR mice and serum corticosterone level, accompanied by increased brain dopamine level. Determination of the underlying mechanism in vitro revealed a PC12 differentiation-induction effect through the modulation of intracellular acetylcholine, choline, and Gap43 gene expression levels. ROEO activates the stress response system through the NGF pathway and the hypothalamus-pituitary-adrenal axis, promoting dopamine production and secretion. The effect of ROEO may be attributed to its bioactive components, specifically to α-pinene, one of its major compounds that has anxiolytic property. The results of this study suggest that ROEO inhalation has therapeutic potential against stress-related psychiatric disorders.

  16. The cortisol awakening response and memory performance in older men and women.

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    Almela, Mercedes; van der Meij, Leander; Hidalgo, Vanesa; Villada, Carolina; Salvador, Alicia

    2012-12-01

    The activity and regulation of the hypothalamus-pituitary-adrenal axis has been related to cognitive decline during aging. This study investigated whether the cortisol awakening response (CAR) is related to memory performance among older adults. The sample was composed of 88 participants (44 men and 44 women) from 55 to 77 years old. The memory assessment consisted of two tests measuring declarative memory (a paragraph recall test and a word list learning test) and two tests measuring working memory (a spatial span test and a spatial working memory test). Among those participants who showed the CAR on two consecutive days, we found that a greater CAR was related to poorer declarative memory performance in both men and women, and to better working memory performance only in men. The results of our study suggest that the relationship between CAR and memory performance is negative in men and women when memory performance is largely dependent on hippocampal functioning (i.e. declarative memory), and positive, but only in men, when memory performance is largely dependent on prefrontal cortex functioning (i.e. working memory). Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Endocannabinoid System and Synaptic Plasticity: Implications for Emotional Responses

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    María-Paz Viveros

    2007-01-01

    Full Text Available The endocannabinoid system has been involved in the regulation of anxiety, and proposed as an inhibitory modulator of neuronal, behavioral and adrenocortical responses to stressful stimuli. Brain regions such as the amygdala, hippocampus and cortex, which are directly involved in the regulation of emotional behavior, contain high densities of cannabinoid CB1 receptors. Mutant mice lacking CB1 receptors show anxiogenic and depressive-like behaviors as well as an altered hypothalamus pituitary adrenal axis activity, whereas enhancement of endocannabinoid signaling produces anxiolytic and antidepressant-like effects. Genetic and pharmacological approaches also support an involvement of endocannabinoids in extinction of aversive memories. Thus, the endocannabinoid system appears to play a pivotal role in the regulation of emotional states. Endocannabinoids have emerged as mediators of short- and long- term synaptic plasticity in diverse brain structures. Despite the fact that most of the studies on this field have been performed using in vitro models, endocannabinoid-mediated plasticity might be considered as a plausible candidate underlying some of the diverse physiological functions of the endogenous cannabinoid system, including developmental, affective and cognitive processes. In this paper, we will focus on the functional relevance of endocannabinoid-mediated plasticity within the framework of emotional responses. Alterations of the endocannabinoid system may constitute an important factor in the aetiology of certain neuropsychiatric disorders, and, in turn, enhancers of endocannabinoid signaling could represent a potential therapeutical tool in the treatment of both anxiety and depressive symptoms.

  18. Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder.

    Science.gov (United States)

    Martín-Blanco, Ana; Ferrer, Marc; Soler, Joaquim; Salazar, Juliana; Vega, Daniel; Andión, Oscar; Sanchez-Mora, Cristina; Arranz, Maria Jesús; Ribases, Marta; Feliu-Soler, Albert; Pérez, Víctor; Pascual, Juan Carlos

    2014-10-01

    The hypothalamus-pituitary-adrenal axis (HPA) is essential in the regulation of stress responses. Increased methylation of the promoter region of the glucocorticoid receptor gene (NR3C1) has been described both in subjects with history of childhood trauma and in patients with Borderline Personality Disorder (BPD). However, no data on the possible association between a higher methylation of this gene and clinical severity is available. The aim of this study was to evaluate the association between NR3C1 methylation status, the history of childhood trauma, and current clinical severity in subjects with BPD. A sample of 281 subjects with BPD (diagnosed by SCID-II and DIB-R semi-structured diagnostic interviews) was recruited. Clinical variables included previous hospitalizations, self-injurious behavior, and self-reported history of childhood trauma. DNA was extracted from peripheral blood. The results indicated a significant positive correlation between NR3C1 methylation status and childhood maltreatment (specifically physical abuse). In addition, a positive correlation between methylation status and clinical severity (DIB-R total score and hospitalizations) was observed. These findings suggest that NR3C1 methylation in subjects with BPD may be associated not only with childhood trauma but also with clinical severity, adding new evidence to the involvement of gene-environment interactions in this disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Neuroendocrine and behavioral consequences of untreated and treated depression in pregnancy and lactation.

    Science.gov (United States)

    Csaszar, Eszter; Melichercikova, Kristina; Dubovicky, Michal

    2014-01-01

    Depression during pregnancy and in the post partum period is a significant health issue in modern society. The estimated prevalence of depression in pregnancy ranges from 13-20%. The major dilemma for gynecologists is to treat or not to treat depression during gestation and lactation. Consequences of untreated depression can be so serious that the benefit of antidepressant therapy may overweigh the possible risk for injury of fetal/neonatal development. Currently, selective serotonin re-uptake inhibitors (SSRIs) and serotonin and noradrenaline re-uptake inhibitors (SNRIs) are commonly used for treatment of maternal depression. The review article brings up-to-date knowledge on effects of maternal adversity (depression) and/or antidepressants on the development of the hypothalamus-pituitary-adrenal axis of the offspring in relation to postnatal behavior and reactivity to stressful stimuli. Treated as well as untreated maternal depression presents a risk for the developing fetus and neonate. The authors stress the need to evaluate the relative safety of SNRIs/SNRIs by means of relevant experimental models to assess if these drugs can be assigned to treat pregnant and lactating depressive women.

  20. Serum brain-derived neurotrophic factor and glucocorticoid receptor levels in lymphocytes as markers of antidepressant response in major depressive patients: a pilot study.

    Science.gov (United States)

    Rojas, Paulina Soledad; Fritsch, Rosemarie; Rojas, Romina Andrea; Jara, Pablo; Fiedler, Jenny Lucy

    2011-09-30

    Depressive patients often have altered cortisol secretion, an effect that likely derives from impaired activity of the glucocorticoid receptor (GR), the main regulator of the hypothalamus-pituitary-adrenal (HPA) axis. Glucocorticoids reduce the levels of brain-derived neurotrophic factor (BDNF), a downstream target of antidepressants. Antidepressants promote the transcriptional activity of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), a regulator of BDNF expression. To identify potential biomarkers for the onset of antidepressant action in depressive patients, GR and phospho-CREB (pCREB) levels in lymphocytes and serum BDNF levels were repeatedly measured during the course of antidepressant treatment. Thirty-four depressed outpatients (10 male and 24 female) were treated with venlafaxine (75mg/day), and individuals exhibiting a 50% reduction in their baseline 17-Item Hamilton Depression Rating Scale score by the 6th week of treatment were considered responders. Responders showed an early improvement in parallel with a rise in BDNF levels during the first two weeks of treatment. Non-responders showed increased GR levels by the third week and reduced serum BDNF by the sixth week of treatment. In contrast, venlafaxine did not affect levels of pCREB. We conclude that levels of BDNF in serum and GR levels in lymphocytes may represent biomarkers that could be used to predict responses to venlafaxine treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. The Anti-Inflammatory Effects of Acupuncture and Their Relevance to Allergic Rhinitis: A Narrative Review and Proposed Model

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    John L. McDonald

    2013-01-01

    Full Text Available Classical literature indicates that acupuncture has been used for millennia to treat numerous inflammatory conditions, including allergic rhinitis. Recent research has examined some of the mechanisms underpinning acupuncture's anti-inflammatory effects which include mediation by sympathetic and parasympathetic pathways. The hypothalamus-pituitary-adrenal (HPA axis has been reported to mediate the antioedema effects of acupuncture, but not antihyperalgesic actions during inflammation. Other reported anti-inflammatory effects of acupuncture include an antihistamine action and downregulation of proinflammatory cytokines (such as TNF-α, IL-1β, IL-6, and IL-10, proinflammatory neuropeptides (such as SP, CGRP, and VIP, and neurotrophins (such as NGF and BDNF which can enhance and prolong inflammatory response. Acupuncture has been reported to suppress the expression of COX-1, COX-2, and iNOS during experimentally induced inflammation. Downregulation of the expression and sensitivity of the transient receptor potential vallinoid 1 (TRPV1 after acupuncture has been reported. In summary, acupuncture may exert anti-inflammatory effects through a complex neuro-endocrino-immunological network of actions. Many of these generic anti-inflammatory effects of acupuncture are of direct relevance to allergic rhinitis; however, more research is needed to elucidate specifically how immune mechanisms might be modulated by acupuncture in allergic rhinitis, and to this end a proposed model is offered to guide further research.

  2. Adrenal gland volume, intra-abdominal and pericardial adipose tissue in major depressive disorder.

    Science.gov (United States)

    Kahl, Kai G; Schweiger, Ulrich; Pars, Kaweh; Kunikowska, Alicja; Deuschle, Michael; Gutberlet, Marcel; Lichtinghagen, Ralf; Bleich, Stefan; Hüper, Katja; Hartung, Dagmar

    2015-08-01

    Major depressive disorder (MDD) is associated with an increased risk for the development of cardio-metabolic diseases. Increased intra-abdominal (IAT) and pericardial adipose tissue (PAT) have been found in depression, and are discussed as potential mediating factors. IAT and PAT are thought to be the result of a dysregulation of the hypothalamus-pituitary-adrenal axis (HPAA) with subsequent hypercortisolism. Therefore we examined adrenal gland volume as proxy marker for HPAA activation, and IAT and PAT in depressed patients. Twenty-seven depressed patients and 19 comparison subjects were included in this case-control study. Adrenal gland volume, pericardial, intraabdominal and subcutaneous adipose tissue were measured by magnetic resonance imaging. Further parameters included factors of the metabolic syndrome, fasting cortisol, fasting insulin, and proinflammatory cytokines. Adrenal gland and pericardial adipose tissue volumes, serum concentrations of cortisol and insulin, and serum concentrations tumor-necrosis factor-α were increased in depressed patients. Adrenal gland volume was positively correlated with intra-abdominal and pericardial adipose tissue, but not with subcutaneous adipose tissue. Our findings point to the role of HPAA dysregulation and hypercortisolism as potential mediators of IAT and PAT enlargement. Further studies are warranted to examine whether certain subtypes of depression are more prone to cardio-metabolic diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders.

    Science.gov (United States)

    Gu, Simeng; Wang, Wei; Wang, Fushun; Huang, Jason H

    2016-01-01

    Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC)/norepinephrine (NE) system is regarded as a critical part of the central "stress circuitry," whose major function is to induce "fight or flight" behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty). The reason for this discrepancy might be that NE is not only for flight (fear), but also for fight (anger). Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. "Adrenaline rush or norepinephrine rush" and fear and anger emotion might act as biomarkers for mental disorders.

  4. Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders

    Directory of Open Access Journals (Sweden)

    Simeng Gu

    2016-01-01

    Full Text Available Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC/norepinephrine (NE system is regarded as a critical part of the central “stress circuitry,” whose major function is to induce “fight or flight” behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty. The reason for this discrepancy might be that NE is not only for flight (fear, but also for fight (anger. Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. “Adrenaline rush or norepinephrine rush” and fear and anger emotion might act as biomarkers for mental disorders.

  5. Exploring the link between depression and accelerated cellular aging: telomeres hold the key

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    Yu R

    2015-12-01

    Full Text Available Ruby Yu, Jean Woo Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China Abstract: Accumulating evidence suggests that telomeres may be a marker for biological aging and telomere length may be affected by multifactorial influences, including cumulative exposure to depression. Associations with telomere length have been reported for major depressive disorder, lifetime duration of depression, higher depression severity, and history of depression. The exact underling mechanisms for these associations have yet to be fully elucidated; however, oxidative stress, chronic inflammation, dysregulated hypothalamus-pituitary-adrenal axis, and altered cortisol levels may be important biochemical mediators. These mediators could also be influenced by psychological stress, unhealthy lifestyle behaviors, or other potential factors, such as childhood abuse, post-traumatic stress disorder, and anxiety that are commonly associated with depression. As such, stress reduction and lifestyle interventions that may affect the telomere maintenance system should be considered for individuals with depression.Keywords: depression, telomere length, biomarkers, cellular ageing

  6. Central administration of dipeptides, beta-alanyl-BCAAs, induces hyperactivity in chicks

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    Denbow D Michael

    2007-05-01

    Full Text Available Abstract Background Carnosine (β-alanyl-L-histidine is a putative neurotransmitter and has a possible role in neuron-glia cell interactions. Previously, we reported that carnosine induced hyperactivity in chicks when intracerebroventricularly (i.c.v. administered. In the present study, we focused on other β-alanyl dipeptides to determine if they have novel functions. Results In Experiment 1, i.c.v. injection of β-alanyl-L-leucine, but not β-alanyl-glycine, induced hyperactivity behavior as observed with carnosine. Both carnosine and β-alanyl-L-leucine stimulated corticosterone release. Thus, dipeptides of β-alanyl-branched chain amino acids were compared in Experiment 2. The i.c.v. injection of β-alanyl-L-isoleucine caused a similar response as β-alanyl-L-leucine, but β-alanyl-L-valine was somewhat less effective than the other two dipeptides. β-Alanyl-L-leucine strongly stimulated, and the other two dipeptides tended to stimulate, corticosterone release. Conclusion These results suggest that central β-alanyl-branched chain amino acid stimulates activity in chicks through the hypothalamus-pituitary-adrenal axis. We named β-alanyl-L-leucine, β-alanyl-L-isoleucine and β-alanyl-L-valine as Excitin-1, Excitin-2 and Excitin-3, respectively.

  7. Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity.

    Science.gov (United States)

    Quarta, Carmelo; Clemmensen, Christoffer; Zhu, Zhimeng; Yang, Bin; Joseph, Sini S; Lutter, Dominik; Yi, Chun-Xia; Graf, Elisabeth; García-Cáceres, Cristina; Legutko, Beata; Fischer, Katrin; Brommage, Robert; Zizzari, Philippe; Franklin, Bernardo S; Krueger, Martin; Koch, Marco; Vettorazzi, Sabine; Li, Pengyun; Hofmann, Susanna M; Bakhti, Mostafa; Bastidas-Ponce, Aimée; Lickert, Heiko; Strom, Tim M; Gailus-Durner, Valerie; Bechmann, Ingo; Perez-Tilve, Diego; Tuckermann, Jan; Hrabě de Angelis, Martin; Sandoval, Darleen; Cota, Daniela; Latz, Eicke; Seeley, Randy J; Müller, Timo D; DiMarchi, Richard D; Finan, Brian; Tschöp, Matthias H

    2017-10-03

    Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Signs of chronic stress in women with recurrent candida vulvovaginitis.

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    Ehrström, Sophia M; Kornfeld, Dan; Thuresson, Jessica; Rylander, Eva

    2005-10-01

    The purpose of this study was to determine whether there is an association between recurrent vulvovaginal candida and chronic stress. Chronic stress affects the hypothalamus-pituitary-adrenal axis, which influences the immune function. Recurrent candida vulvovaginitis is increasing. Women with recurrent vulvovaginal candida (n = 35) and age-matched healthy control subjects (n = 35) collected saliva for the analysis of cortisol. Hormone analyses of blood samples and vulvovaginal examinations were performed. A questionnaire was completed. Morning rise cortisol level was significantly blunted among patients compared with control subjects (P vulvovaginal candida, compared with control subjects. More patients than control subjects reported a history of condyloma, bacterial vaginosis, and herpes genitalis. No differences were seen between patients and control subjects regarding sexual hormone binding globulin, dihydroepiandrosterone, testosterone or Hemoglobin A1c. Morning rise salivary cortisol level is blunted in women with recurrent vulvovaginal candida, which indicates signs of chronic stress. The higher incidence of vulvovaginal infections in these women compared with control subjects may reflect impaired immunity, which may be due to chronic stress.

  9. An aberrant parasympathetic response: a new perspective linking chronic stress and itch.

    Science.gov (United States)

    Kim, Hei Sung; Yosipovitch, Gil

    2013-04-01

    Perceived stress has long been known to alter the dynamic equilibrium established between the nervous, endocrine and immune system and is widely recognised to trigger or enhance pruritus. However, the exact mechanism of how the major stress response systems, such as the hypothalamus-pituitary adrenal (HPA) axis and the autonomic nervous system induce or aggravate chronic itch, has not been elucidated. The limbic regions of the brain such as the prefrontal cortex and hippocampus are deeply involved in the regulation of the stress response and intersect with circuits that are responsible for memory and reward. According to the 'Polyvagal Theory', certain limbic structures that serve as a 'higher brain equivalent of the parasympathetic nervous system' play a foremost role in maintaining body homoeostasis by functioning as an active vagal brake. In addition, the limbic system has been postulated to regulate two distinct, yet related aspects of itch: (i) the sensory-discriminative aspect; and (ii) the affective-cognitive aspect. Chronic stress-induced itch is hypothesised to be caused by stress-related changes in limbic structure with subsequent rewiring of both the peripheral and central pruriceptive circuits. Herein, we review data suggesting that a dysfunctional parasympathetic nervous system associated with chronic stress may play a critical role in the regulatory control of key candidate molecules, receptors and brain structures involved in chronic itch. © 2012 John Wiley & Sons A/S.

  10. A link between sleep loss, glucose metabolism and adipokines

    Directory of Open Access Journals (Sweden)

    H.G. Padilha

    2011-10-01

    Full Text Available The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

  11. Inverse correlation between morning plasma cortisol levels and MMPI psychasthenia and depression scale scores in victims of mobbing with adjustment disorders.

    Science.gov (United States)

    Rocco, Antonio; Martocchia, Antonio; Frugoni, Patrizia; Baldini, Rossella; Sani, Gabriele; Di Simone Di Giuseppe, Barbara; Vairano, Andrea; Girardi, Paolo; Monaco, Edoardo; Tatarelli, Roberto; Falaschi, Paolo

    2007-10-01

    Evidence in the literature suggests stress-related changes of hypothalamus-pituitary-adrenal (HPA) axis in mobbing. We investigated the association between HPA activity and psychological profiles in mobbing, using a multidisciplinary approach. Forty-eight victims of mobbing were evaluated by a working group of the Departments of Occupational Medicine, Psychiatry and Internal Medicine. After an informed consent, a detailed occupational history, a psychiatric interview with Minnesota Multiphasic Personality Inventory 2 (MMPI-2) administration and a blood sample (8:00 AM) for the determination of basal adrenocorticotropin (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS) plasma levels were collected. Twenty-six patients received an overnight dexamethasone (dex) test. Mean ACTH, cortisol and DHEAS levels were within normal ranges. The dex-test response was normal, with a significant hormone suppression (ACTH pmobbing with adjustment disorders was observed. A larger group of patients is necessary to identify and validate a cut-off cortisol level that may become an innovative biological parameter for the diagnosis and follow-up in victims of mobbing.

  12. Incoordination among Subcellular Compartments Is Associated with Depression-Like Behavior Induced by Chronic Mild Stress

    Science.gov (United States)

    Xu, Aiping; Cui, Shan

    2016-01-01

    Background: Major depressive disorder is characterized as persistent low mood. A chronically stressful life in genetically susceptible individuals is presumably the major etiology that leads to dysfunctions of monoamine and hypothalamus-pituitary-adrenal axis. These pathogenic factors cause neuron atrophy in the limbic system for major depressive disorder. Cell-specific pathophysiology is unclear, so we investigated prelimbic cortical GABAergic neurons and their interaction with glutamatergic neurons in depression-like mice. Methods: Mice were treated with chronic unpredictable mild stress for 3 weeks until they expressed depression-like behaviors confirmed by sucrose preference, Y-maze, and forced swimming tests. The structures and functions of GABAergic and glutamatergic units in prelimbic cortices were studied by cell imaging and electrophysiology in chronic unpredictable mild stress-induced depression mice vs controls. Results: In depression-like mice, prelimbic cortical GABAergic neurons show incoordination among the subcellular compartments, such as decreased excitability and synaptic outputs as well as increased reception from excitatory inputs. GABAergic synapses on glutamatergic cells demonstrate decreased presynaptic innervation and increased postsynaptic responsiveness. Conclusions: Chronic unpredictable mild stress-induced incoordination in prelimbic cortical GABAergic and glutamatergic neurons dysregulates their target neurons, which may be the pathological basis for depressive mood. The rebalance of compatibility among subcellular compartments would be an ideal strategy to treat neural disorders. PMID:26506857

  13. Diurnal Variation of Plasma Brain-Derived Neurotrophic Factor Levels in Women with Functional Hypothalamic Amenorrhea.

    Science.gov (United States)

    Drakopoulos, Panagiotis; Casarosa, Elena; Bucci, Fiorella; Piccinino, Manuela; Wenger, Jean-Marie; Nappi, Rossella Elena; Polyzos, Nicholas; Genazzani, Andrea Riccardo; Pluchino, Nicola

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is strongly related to hormonal networks and is modulated by hypothalamic activity. To evaluate plasma BDNF concentration in patients with functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm, and to assess whether the duration of amenorrhea might influence the BDNF:F ratio in FHA. This was an observational study evaluating 36 amenorrheic and 30 eumenorrheic women. Basal values of BDNF and hormones were examined in blood samples collected from 7:00 to 9:00 h in all the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8:00, 12:00, 16:00, 20:00, and 24:00 h. BDNF plasma levels are significantly lower in amenorrheic women (p 0.05), sex steroids, and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated with duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower when compared to the control group, and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups. Interactions between BDNF, the hypothalamus-pituitary-adrenal axis, and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA. © 2015 S. Karger AG, Basel.

  14. Recent Updates on the Systemic and Local Safety of Intranasal Steroids.

    Science.gov (United States)

    Jang, Tae Young; Kim, Young Hyo

    2016-01-01

    Allergic rhinitis is a global health problem, and its prevalence rate and socioeconomic burden continue to increase. Intranasal steroid (INS) is the first treatment choice in the majority of patients, because of its ability to effectively control allergic symptoms. However, patients and clinicians are concerned about the potential adverse effects of prolonged INS use. We performed to review for evaluating systemic and local safety of INS use, by searching MEDLINE, EMBASE, and Cochrane Library database for identification of relevant articles. In the present study, the systemic bioavailabilities of several commercially available INSs were researched, and then systemic safeties were reviewed with focus on suppression of the hypothalamus-pituitary-adrenal axis and their effects on pediatric growth. In addition, local adverse effects, such as, epistaxis and nasal septal perforation, were investigated. Finally, the authors proposed some techniques in order to avoid these complications. INSs offer a safe, effective means of treating allergic rhinitis in the short- and long-term with no or minimal adverse systemic and local effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Dopamine D1 receptors are responsible for stress-induced emotional memory deficit in mice.

    Science.gov (United States)

    Wang, Yongfu; Wu, Jing; Zhu, Bi; Li, Chaocui; Cai, Jing-Xia

    2012-03-01

    It is established that stress impairs spatial learning and memory via the hypothalamus-pituitary-adrenal axis response. Dopamine D1 receptors were also shown to be responsible for a stress-induced deficit of working memory. However, whether stress affects the subsequent emotional learning and memory is not elucidated yet. Here, we employed the well-established one-trial step-through task to study the effect of an acute psychological stress (induced by tail hanging for 5, 10, or 20 min) on emotional learning and memory, and the possible mechanisms as well. We demonstrated that tail hanging induced an obvious stress response. Either an acute tail-hanging stress or a single dose of intraperitoneally injected dopamine D1 receptor antagonist (SCH23390) significantly decreased the step-through latency in the one-trial step-through task. However, SCH23390 prevented the acute tail-hanging stress-induced decrease in the step-through latency. In addition, the effects of tail-hanging stress and/or SCH23390 on the changes in step-through latency were not through non-memory factors such as nociceptive perception and motor function. Our data indicate that the hyperactivation of dopamine D1 receptors mediated the stress-induced deficit of emotional learning and memory. This study may have clinical significance given that psychological stress is considered to play a role in susceptibility to some mental diseases such as depression and post-traumatic stress disorder.

  16. Enhancing effects of acute psychosocial stress on priming of non-declarative memory in healthy young adults.

    Science.gov (United States)

    Hidalgo, Vanesa; Villada, Carolina; Almela, Mercedes; Espín, Laura; Gómez-Amor, Jesús; Salvador, Alicia

    2012-05-01

    Social stress affects cognitive processes in general, and memory performance in particular. However, the direction of these effects has not been clearly established, as it depends on several factors. Our aim was to determine the impact of the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) reactivity to psychosocial stress on short-term non-declarative memory and declarative memory performance. Fifty-two young participants (18 men, 34 women) were subjected to the Trier Social Stress Task (TSST) and a control condition in a crossover design. Implicit memory was assessed by a priming test, and explicit memory was assessed by the Rey Auditory Verbal Learning Test (RAVLT). The TSST provoked greater salivary cortisol and salivary alpha-amylase (sAA) responses than the control task. Men had a higher cortisol response to stress than women, but no sex differences were found for sAA release. Stress was associated with an enhancement of priming but did not affect declarative memory. Additionally, the enhancement on the priming test was higher in those whose sAA levels increased more in response to stress (r(48) = 0.339, p = 0.018). Our results confirm an effect of acute stress on priming, and that this effect is related to SNS activity. In addition, they suggest a different relationship between stress biomarkers and the different memory systems.

  17. Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis.

    Science.gov (United States)

    Novotna, Aneta; Dvorak, Zdenek

    2014-01-01

    Benzimidazole drugs lansoprazole and omeprazole are used for treatment of various gastrointestinal pathologies. Both compounds cause drug-drug interactions because they activate aryl hydrocarbon receptor and induce CYP1A genes. In the current paper, we examined the effects of lansoprazole and omeprazole enantiomers on the expression of key drug-metabolizing enzyme CYP3A4 in human hepatocytes and human cancer cell lines. Lansoprazole enantiomers, but not omeprazole, were equipotent inducers of CYP3A4 mRNA in HepG2 cells. All forms (S-, R-, rac-) of lansoprazole and omeprazole induced CYP3A4 mRNA and protein in human hepatocytes. The quantitative profiles of CYP3A4 induction by individual forms of lansoprazole and omeprazole exerted enantiospecific patterns. Lansoprazole dose-dependently activated pregnane X receptor PXR in gene reporter assays, and slightly modulated rifampicin-inducible PXR activity, with similar potency for each enantiomer. Omeprazole dose-dependently activated PXR and inhibited rifampicin-inducible PXR activity. The effects of S-omeprazole were much stronger as compared to those of R-omeprazole. All forms of lansoprazole, but not omeprazole, slightly activated glucocorticoid receptor and augmented dexamethasone-induced GR transcriptional activity. Omeprazole and lansoprazole influenced basal and ligand inducible expression of tyrosine aminotransferase, a GR-target gene, in HepG2 cells and human hepatocytes. Overall, we demonstrate here that omeprazole and lansoprazole enantiomers induce CYP3A4 in HepG2 cells and human hepatocytes. The induction comprises differential interactions of omeprazole and lansoprazole with transcriptional regulators PXR and GR, and some of the effects were enantiospecific. The data presented here might be of toxicological and clinical importance, since the effects occurred in therapeutically relevant concentrations.

  18. The Activin A-Peroxisome Proliferator-Activated Receptor Gamma Axis Contributes to the Transcriptome of GM-CSF-Conditioned Human Macrophages.

    Science.gov (United States)

    Nieto, Concha; Bragado, Rafael; Municio, Cristina; Sierra-Filardi, Elena; Alonso, Bárbara; Escribese, María M; Domínguez-Andrés, Jorge; Ardavín, Carlos; Castrillo, Antonio; Vega, Miguel A; Puig-Kröger, Amaya; Corbí, Angel L

    2018-01-01

    GM-CSF promotes the functional maturation of lung alveolar macrophages (A-MØ), whose differentiation is dependent on the peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor. In fact, blockade of GM-CSF-initiated signaling or deletion of the PPARγ-encoding gene PPARG leads to functionally defective A-MØ and the onset of pulmonary alveolar proteinosis. In vitro , macrophages generated in the presence of GM-CSF display potent proinflammatory, immunogenic and tumor growth-limiting activities. Since GM-CSF upregulates PPARγ expression, we hypothesized that PPARγ might contribute to the gene signature and functional profile of human GM-CSF-conditioned macrophages. To verify this hypothesis, PPARγ expression and activity was assessed in human monocyte-derived macrophages generated in the presence of GM-CSF [proinflammatory GM-CSF-conditioned human monocyte-derived macrophages (GM-MØ)] or M-CSF (anti-inflammatory M-MØ), as well as in ex vivo isolated human A-MØ. GM-MØ showed higher PPARγ expression than M-MØ, and the expression of PPARγ in GM-MØ was found to largely depend on activin A. Ligand-induced activation of PPARγ also resulted in distinct transcriptional and functional outcomes in GM-MØ and M-MØ. Moreover, and in the absence of exogenous activating ligands, PPARγ knockdown significantly altered the GM-MØ transcriptome, causing a global upregulation of proinflammatory genes and significantly modulating the expression of genes involved in cell proliferation and migration. Similar effects were observed in ex vivo isolated human A-MØ, where PPARγ silencing led to enhanced expression of genes coding for growth factors and chemokines and downregulation of cell surface pathogen receptors. Therefore, PPARγ shapes the transcriptome of GM-CSF-dependent human macrophages ( in vitro derived GM-MØ and ex vivo isolated A-MØ) in the absence of exogenous activating ligands, and its expression is primarily regulated by activin A

  19. Shifting the IGF-axis: An age-related decline in human tear IGF-1 correlates with clinical signs of dry eye.

    Science.gov (United States)

    Patel, Roshni; Zhu, Meifang; Robertson, Danielle M

    2018-02-06

    The human corneal epithelium expresses both the insulin-like growth factor type 1 receptor (IGF-1R) and the IGF-1R/insulin receptor (INSR) hybrid. Despite the previous identification of IGF-1 in human tear fluid, little is known regarding the regulation of IGF-1 in tear fluid and its role in corneal epithelial homeostasis. In the present study, we investigated the impact of biological parameters on the concentration of human tear levels of IGF-1. Tear levels of IGF-1 were measured in 41 healthy, human volunteers without any reported symptoms of dry eye. All volunteers underwent standard biomicroscopic examination of the cornea and tear film. In a subgroup of volunteers, corneal staining with sodium fluorescein, tear film break up time and tear production using a Schirmer's test strip were measured to assess clinical signs of dry eye. Tears were collected from the inferior tear meniscus using glass microcapillary tubes and IGF-1 levels were measured using a solid phase sandwich ELISA. Tear levels of IGF-1 were highest in young adults and significantly decreased in older adults (P = 0.003). There were no differences in tear IGF-1 between males and females (P = 0.628). Tear IGF-1 levels were correlated with tear film break up time (R = 0.738) and tear production (R = 0.826). These data indicate that there is a progressive decline in tear IGF-1 due to aging that is associated with clinical signs of dry eye. This effect is likely due to age-related changes in the lacrimal gland. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice.

    Science.gov (United States)

    Nakata, Daisuke; Masaki, Tsuneo; Tanaka, Akira; Yoshimatsu, Mie; Akinaga, Yumiko; Asada, Mari; Sasada, Reiko; Takeyama, Michiyasu; Miwa, Kazuhiro; Watanabe, Tatsuya; Kusaka, Masami

    2014-01-15

    TAK-385 (relugolix) is a novel, non-peptide, orally active gonadotropin-releasing hormone (GnRH) antagonist, which builds on previous work with non-peptide GnRH antagonist TAK-013. TAK-385 possesses higher affinity and more potent antagonistic activity for human and monkey GnRH receptors compared with TAK-013. Both TAK-385 and TAK-013 have low affinity for the rat GnRH receptor, making them difficult to evaluate in rodent models. Here we report the human GnRH receptor knock-in mouse as a humanized model to investigate pharmacological properties of these compounds on gonadal function. Twice-daily oral administration of TAK-013 (10mg/kg) for 4 weeks decreased the weights of testes and ventral prostate in male knock-in mice but not in male wild-type mice, demonstrating the validity of this model to evaluate antagonists for the human GnRH receptor. The same dose of TAK-385 also reduced the prostate weight to castrate levels in male knock-in mice. In female knock-in mice, twice-daily oral administration of TAK-385 (100mg/kg) induced constant diestrous phases within the first week, decreased the uterus weight to ovariectomized levels and downregulated GnRH receptor mRNA in the pituitary after 4 weeks. Gonadal function of TAK-385-treated knock-in mice began to recover after 5 days and almost completely recovered within 14 days after drug withdrawal in both sexes. Our findings demonstrate that TAK-385 acts as an antagonist for human GnRH receptor in vivo and daily oral administration potently, continuously and reversibly suppresses the hypothalamic-pituitary-gonadal axis. TAK-385 may provide useful therapeutic interventions in hormone-dependent diseases including endometriosis, uterine fibroids and prostate cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Localization of the aromatase enzyme expression in the human pituitary gland and its effect on growth hormone, prolactin, and thyroid stimulating hormone axis.

    Science.gov (United States)

    Caglar, Asli Sezgin; Kapucu, Aysegul; Dar, Kadriye Akgun; Ozkaya, Hande Mefkure; Caglar, Erkan; Ince, Haluk; Kadioglu, Pinar

    2015-08-01

    The aim of this study is to evaluate aromatase expression in prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) secreting cells. Nontumoral human pituitary specimens were obtained from autopsy samples. Aromatase co-expression was determined by double immunohistochemical staining and assessed using H scores. H scores for GH-aromatase co-expression (GH-aromatase), TSH-aromatase co-expression (TSH-aromatase), and PRL-aromatase co-expression (PRL-aromatase) were 83.1 ± 13.1, 95.6 ± 16.1, and 83.7 ± 14.5, respectively. TSH producing cells exhibited the highest H score for co-expression of aromatase (p 0.05 for all). There was a negative correlation between the H scores for aromatase and PRL-aromatase, GH-aromatase and TSH-aromatase, respectively (r = -0.592, p 0.05 for all). Age was negatively correlated with PRL-aromatase H score (r = -0.373, p = 0.008). Our study demonstrated significant aromatase co-expression in PRL, GH, and TSH secreting cells of the human anterior pituitary gland. The mutual paracrinal regulation between aromatase and three adenohypophyseal hormones indicates that aromatase may have a regulatory role on the synthesis and secretion of these hormones.

  2. Central nervous system lipocalin-type prostaglandin D2-synthase is correlated with orexigenic neuropeptides, visceral adiposity and markers of the hypothalamic-pituitary-adrenal axis in obese humans.

    Science.gov (United States)

    Elias, E; Benrick, A; Behre, C J; Ekman, R; Zetterberg, H; Stenlöf, K; Wallenius, V

    2011-06-01

    Lipocalin-type prostaglandin D2-synthase (L-PGDS) is the main producer of prostaglandin D2 (PGD2) in the central nervous system (CNS). Animal data suggest effects of central nervous L-PGDS in the regulation of food intake and obesity. No human data are available. We hypothesised that a role for CNS L-PGDS in metabolic function in humans would be reflected by correlations with known orexigenic neuropeptides. Cerebrospinal fluid (CSF) and serum samples were retrieved from 26 subjects in a weight loss study, comprising a 3-week dietary lead-in followed by 12-weeks of leptin or placebo treatment. At baseline, CSF L-PGDS was positively correlated with neuropeptide Y (NPY) (ρ = 0.695, P fat distribution and central HPA axis mediators. The importance of these findings is unclear but could suggest a role for CSF L-PGDS in the regulation of visceral obesity by interaction with the neuroendocrine circuits regulating appetite and fat distribution. Further interventional studies will be needed to characterise these interactions in more detail. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  3. Insulin Promotes the Proliferation of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells by Activating the Akt-Cyclin D1 Axis

    Directory of Open Access Journals (Sweden)

    Peng Li

    2017-01-01

    Full Text Available Background. The functions of insulin in mesenchymal stem cells (MSC remain poorly understood. Methods. MSC from human umbilical cord matrix (UCM cultured in serum-free media (SFM with or without insulin were subjected to various molecular biological analyses to determine their proliferation and growth states, expression levels of Akt-cyclin D1 signaling molecules, and in vitro differentiation capacities. Results. Insulin accelerated the G1-S cell cycle progression of UCM-MSC and significantly stimulated their proliferation and growth in SFM. The pro-proliferative action of insulin was associated with augmented cyclin D1 and phosphorylated Akt expression levels. Akt inactivation remarkably abrogated insulin-induced increases in cyclin D1 expression and cell proliferation, indicating that insulin enhances the proliferation of UCM-MSC via acceleration of the G1-S transition mediated by the Akt-cyclin D1 pathway. Additionally, the UCM-MSC propagated in SFM supplemented with insulin exhibited similar specific surface antigen profiles and differentiation capacities as those generated in conventional media containing fetal bovine serum. Conclusions. These findings suggest that insulin acts solely to promote UCM-MSC proliferation without affecting their immunophenotype and differentiation potentials and thus have important implications for utilizing insulin to expand clinical-grade MSC in vitro.

  4. Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor 2 Axis Can Promote Mouse and Human Primary Mast Cell Angiogenic Potential through Upregulation of Vascular Endothelial Growth Factor-A and Matrix Metalloproteinase-2

    Directory of Open Access Journals (Sweden)

    Alena Chumanevich

    2016-01-01

    Full Text Available Mast cells (MC are present in most vascularized tissues around the vasculature likely exerting immunomodulatory functions. Endowed with diverse mediators, resident MC represent first-line fine-tuners of local microenvironment. Sphingosine-1-phosphate (S1P functions as a pluripotent signaling sphingolipid metabolite in health and disease. S1P formation occurs at low levels in resting MC and is upregulated upon activation. Its export can result in type 2 S1P receptor- (S1PR2- mediated stimulation of MC, further fueling inflammation. However, the role of S1PR2 ligation in proangiogenic vascular endothelial growth factor- (VEGF- A and matrix metalloproteinase- (MMP- 2 release from MC is unknown. Using a preclinical MC-dependent model of acute allergic responses and in vitro stimulated primary mouse bone marrow-derived MC (BMMC or human primary skin MC, we report that S1P signaling resulted in substantial amount of VEGF-A release. Similar experiments using S1pr2-deficient mice or BMMC or selective S1P receptor agonists or antagonists demonstrated that S1P/S1PR2 ligation on MC is important for VEGF-A secretion. Further, we show that S1P stimulation triggered transcriptional upregulation of VEGF-A and MMP-2 mRNA in human but not in mouse MC. S1P exposure also triggered MMP-2 secretion from human MC. These studies identify a novel proangiogenic axis encompassing MC/S1P/S1PR2 likely relevant to inflammation.

  5. CART peptide is a potential endogenous antioxidant and preferentially localized in mitochondria.

    Directory of Open Access Journals (Sweden)

    Peizhong Mao

    Full Text Available The multifunctional neuropeptide Cocaine and Amphetamine Regulated Transcript (CART is secreted from hypothalamus, pituitary, adrenal gland and pancreas. It also can be found in circulatory system. This feature suggests a general role for CART in different cells. In the present study, we demonstrate that CART protects mitochondrial DNA (mtDNA, cellular proteins and lipids against the oxidative action of hydrogen peroxide, a widely used oxidant. Using cis-parinaric acid as a sensitive reporting probe for peroxidation in membranes, and a lipid-soluble azo initiator of peroxyl radicals, 2,2'-azobis(2,4-dimethylvaleronitrile we found that CART is an antioxidant. Furthermore, we found that CART localized to mitochondria in cultured cells and mouse brain neuronal cells. More importantly, pretreatment with CART by systemic injection protects against a mouse oxidative stress model, which mimics the main features of Parkinson's disease. Given the unique molecular structure and biological features of CART, we conclude that CART is an antioxidant peptide (or antioxidant hormone. We further propose that it may have strong therapeutic properties for human diseases in which oxidative stress is strongly involved such as Parkinson's disease.

  6. A novel role for a major component of the vitamin D axis: vitamin D binding protein-derived macrophage activating factor induces human breast cancer cell apoptosis through stimulation of macrophages.

    Science.gov (United States)

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Fiore, Maria Giulia; Magherini, Stefano; Branca, Jacopo J V; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco; Pacini, Stefania

    2013-07-08

    The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH)(2)D3), its two binding proteins that are the vitamin D receptor (VDR) and the vitamin D-binding protein-derived macrophage activating factor (GcMAF). In this study we demonstrate that GcMAF stimulates macrophages, which in turn attack human breast cancer cells, induce their apoptosis and eventually phagocytize them. These results are consistent with the observation that macrophages infiltrated implanted tumors in mice after GcMAF injections. In addition, we hypothesize that the last 23 hydrophobic amino acids of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF located at the external part of the plasma membrane. This allows 1,25(OH)(2)D3 and oleic acid to become sandwiched between the two vitamin D-binding proteins, thus postulating a novel molecular mode of interaction between GcMAF and VDR. Taken together, these results support and reinforce the hypothesis that GcMAF has multiple biological activities that could be responsible for its anti-cancer effects, possibly through molecular interaction with the VDR that in turn is responsible for a multitude of non-genomic as well as genomic effects.

  7. A Novel Role for a Major Component of the Vitamin D Axis: Vitamin D Binding Protein-Derived Macrophage Activating Factor Induces Human Breast Cancer Cell Apoptosis through Stimulation of Macrophages

    Directory of Open Access Journals (Sweden)

    Marco Ruggiero

    2013-07-01

    Full Text Available The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH(2D3, its two binding proteins that are the vitamin D receptor (VDR and the vitamin D-binding protein-derived macrophage activating factor (GcMAF. In this study we demonstrate that GcMAF stimulates macrophages, which in turn attack human breast cancer cells, induce their apoptosis and eventually phagocytize them. These results are consistent with the observation that macrophages infiltrated implanted tumors in mice after GcMAF injections. In addition, we hypothesize that the last 23 hydrophobic amino acids of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF located at the external part of the plasma membrane. This al1ows 1,25(OH(2D3 and oleic acid to become sandwiched between the two vitamin D-binding proteins, thus postulating a novel molecular mode of interaction between GcMAF and VDR. Taken together, these results support and reinforce the hypothesis that GcMAF has multiple biological activities that could be responsible for its anti-cancer effects, possibly through molecular interaction with the VDR that in turn is responsible for a multitude of non-genomic as well as genomic effects.

  8. Construction and application of a bovine immune-endocrine cDNA microarray.

    Science.gov (United States)

    Tao, Wenjing; Mallard, Bonnie; Karrow, Niel; Bridle, Byram

    2004-09-01

    A variety of commercial DNA arrays specific for humans and rodents are widely available; however, microarrays containing well-characterized genes to study pathway-specific gene expression are not as accessible for domestic animals, such as cattle, sheep and pigs. Therefore, a small-scale application-targeted bovine immune-endocrine cDNA array was developed to evaluate genetic pathways involved in the immune-endocrine axis of cattle during periods of altered homeostasis provoked by physiological or environmental stressors, such as infection, vaccination or disease. For this purpose, 167 cDNA sequences corresponding to immune, endocrine and inflammatory response genes were collected and categorized. Positive controls included 5 housekeeping genes (glyceraldehydes-3-phosphate dehydrogenase, hypoxanthine phosphoribosyltransferase, ribosomal protein L19, beta-actin, beta2-microglobulin) and bovine genomic DNA. Negative controls were a bacterial gene (Rhodococcus equi 17-kDa virulence-associated protein) and a partial sequence of the plasmid pACYC177. In addition, RNA extracted from un-stimulated, as well as superantigen (Staphylococcus aureus enterotoxin-A, S. aureus Cowan Pansorbin Cells) and mitogen-stimulated (LPS, ConA) bovine blood leukocytes was mixed, reverse transcribed and PCR amplified using gene-specific primers. The endocrine-associated genes were amplified from cDNA derived from un-stimulated bovine hypothalamus, pituitary, adrenal and thyroid gland tissues. The array was constructed in 4 repeating grids of 180 duplicated spots by coupling the PCR amplified 213-630 bp gene fragments onto poly-l-lysine coated glass slides. The bovine immune-endocrine arrays were standardized and preliminary gene expression profiles generated using Cy3 and Cy5 labelled cDNA from un-stimulated and ConA (5 microg/ml) stimulated PBMC of 4 healthy Holstein cows (2-4 replicate arrays/cow) in a time course study. Mononuclear cell-derived cytokine and chemokine (IL-2, IL-1alpha

  9. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  10. The adrenocortical response of tufted puffin chicks to nutritional deficits

    Science.gov (United States)

    Kitaysky, A.S.; Romano, Marc D.; Piatt, John F.; Wingfield, J.C.; Kikuchi, M.

    2005-01-01

    In several seabirds, nutritional state of a nest-bound chick is negatively correlated with the activity of its hypothalamus-pituitary-adrenal (HPA) axis. Increased corticosterone (cort) secretion has been shown to facilitate changes in behavior that allow hungry chicks to obtain more food from parents. However, if parents are not willing/able to buffer their young from temporary food shortages, increased cort secretion could be detrimental to undernourished chicks. In a system where parents are insensitive to chick demands, low benefits and high costs of activation of the HPA-axis in hungry chicks should lead to a disassociation of the nutritional state of the young and the activity of its HPA-axis. We tested this novel hypothesis for the tufted puffin (Fratercula cirrhata), a seabird with intermittent provisioning of a nest-bound semi-precocial chick. We examined the HPA-axis activity of captive chicks exposed to the following: (1) a short-term (24 h) food deprivation; and (2) an array of prolonged (3 weeks) restrictions in feeding regimens. We found that in response to a short-term food deprivation chicks decreased baseline levels of cort and thyroid hormones. In response to prolonged restrictions, food-limited chicks exhibited signs of nutritional deficit: they had lower body mass, endogenous lipid reserves, and thyroid hormone titers compared to chicks fed ad libitum. However, baseline and maximum acute stress-induced levels of cort were also lower in food-restricted chicks compared to those of chicks fed ad libitum. These results support a major prediction of the study hypothesis that puffin chicks suppress HPA-axis activity in response to short- and long-term nutritional deficits. This physiological adaptation may allow a chick to extend its development in the nest, while eluding detrimental effects of chronic cort elevation. 

  11. Late-Onset Cognitive Impairments after Early-Life Stress Are Shaped by Inherited Differences in Stress Reactivity

    Science.gov (United States)

    McIlwrick, Silja; Pohl, Tobias; Chen, Alon; Touma, Chadi

    2017-01-01

    Early-life stress (ELS) has been associated with lasting cognitive impairments and with an increased risk for affective disorders. A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, the body’s main stress response system, is critically involved in mediating these long-term consequences of adverse early-life experience. It remains unclear to what extent an inherited predisposition for HPA axis sensitivity or resilience influences the relationship between ELS and cognitive impairments, and which neuroendocrine and molecular mechanisms may be involved. To investigate this, we exposed animals of the stress reactivity mouse model, consisting of three independent lines selectively bred for high (HR), intermediate (IR), or low (LR) HPA axis reactivity to a stressor, to ELS and assessed their cognitive performance, neuroendocrine function and hippocampal gene expression in early and in late adulthood. Our results show that HR animals that were exposed to ELS exhibited an HPA axis hyper-reactivity in early and late adulthood, associated with cognitive impairments in hippocampus-dependent tasks, as well as molecular changes in transcript levels involved in the regulation of HPA axis activity (Crh) and in neurotrophic action (Bdnf). In contrast, LR animals showed intact cognitive function across adulthood, with no change in stress reactivity. Intriguingly, LR animals that were exposed to ELS even showed significant signs of enhanced cognitive performance in late adulthood, which may be related to late-onset changes observed in the expression of Crh and Crhr1 in the dorsal hippocampus of these animals. Collectively, our findings demonstrate that the lasting consequences of ELS at the level of cognition differ as a function of inherited predispositions and suggest that an innate tendency for low stress reactivity may be protective against late-onset cognitive impairments after ELS. PMID:28261058

  12. An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development

    Science.gov (United States)

    Boman, Bruce M.; Fields, Jeremy Z.

    2013-01-01

    APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT) that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs) at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside). WNT signaling, in contrast, is high at the bottom (where SCs reside) and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g., survivin) are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric). APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly proliferating cells) during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes. PMID:24224156

  13. Vertical axis wind turbine airfoil

    Science.gov (United States)

    Krivcov, Vladimir; Krivospitski, Vladimir; Maksimov, Vasili; Halstead, Richard; Grahov, Jurij Vasiljevich

    2012-12-18

    A vertical axis wind turbine airfoil is described. The wind turbine airfoil can include a leading edge, a trailing edge, an upper curved surface, a lower curved surface, and a centerline running between the upper surface and the lower surface and from the leading edge to the trailing edge. The airfoil can be configured so that the distance between the centerline and the upper surface is the same as the distance between the centerline and the lower surface at all points along the length of the airfoil. A plurality of such airfoils can be included in a vertical axis wind turbine. These airfoils can be vertically disposed and can rotate about a vertical axis.

  14. Helical axis stellarator equilibrium model

    International Nuclear Information System (INIS)

    Koniges, A.E.; Johnson, J.L.

    1985-02-01

    An asymptotic model is developed to study MHD equilibria in toroidal systems with a helical magnetic axis. Using a characteristic coordinate system based on the vacuum field lines, the equilibrium problem is reduced to a two-dimensional generalized partial differential equation of the Grad-Shafranov type. A stellarator-expansion free-boundary equilibrium code is modified to solve the helical-axis equations. The expansion model is used to predict the equilibrium properties of Asperators NP-3 and NP-4. Numerically determined flux surfaces, magnetic well, transform, and shear are presented. The equilibria show a toroidal Shafranov shift

  15. Restoring the salivary cortisol awakening response through nasal continuous positive airway pressure therapy in obstructive sleep apnea.

    Science.gov (United States)

    Ghiciuc, Cristina Mihaela; Dima Cozma, Lucia Corina; Bercea, Raluca Mihaela; Lupusoru, Catalina Elena; Mihaescu, Traian; Szalontay, Andreea; Gianfreda, Angela; Patacchioli, Francesca Romana

    2013-10-01

    Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP.

  16. Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults.

    Science.gov (United States)

    Sasayama, Daimei; Hori, Hiroaki; Iijima, Yoshimi; Teraishi, Toshiya; Hattori, Kotaro; Ota, Miho; Fujii, Takashi; Higuchi, Teruhiko; Amano, Naoji; Kunugi, Hiroshi

    2011-07-05

    Recently, hypothalamus-pituitary-adrenal (HPA) axis function assessed with the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test has been shown to be associated with response to antidepressant treatment. A polymorphism (rs16944) in the interleukin-1beta (IL-1β) gene has also been reported to be associated with the medication response in depression. These findings prompted us to examine the possible association between IL-1β gene polymorphisms and HPA axis function assessed with the DEX/CRH test. DEX/CRH test was performed in 179 healthy volunteers (45 males: mean age 40.5 ± 15.8 years; 134 females: mean age 47.1 ± 13.2 years). Five tagging single nucleotide polymorphisms (SNPs) of IL-1β gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were selected at an r2 threshold of 0.80 with a minor allele frequency > 0.1. Genotyping was performed by the TaqMan allelic discrimination assay. A two-way factorial analysis of variance (ANOVA) was performed with the DEX/CRH test results as the dependent variable and genotype and gender as independent variables. To account for multiple testing, P values rs16944 (P = 0.00049) and rs1143633 (P = 0.0060), with no significant gender effect or genotype × gender interaction. On the other hand, cortisol levels after CRH administration (DEX/CRH-Cortisol) were affected by gender but were not significantly influenced by the genotype of the examined SNPs, with no significant genotype × gender interaction. Our results suggest that genetic variations in the IL-1β gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the IL-1β gene polymorphisms with the DEX/CRH-Cortisol were observed. Confirmation of our findings in futures studies may add new insight into the communication between the immune system and the HPA axis.

  17. The GH/IGF-1 axis in ageing and longevity

    Science.gov (United States)

    List, Edward O.; Berryman, Darlene E.; Murrey, John W.

    2014-01-01

    Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the ‘somatopause’, has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans. PMID:23591370

  18. Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

    Science.gov (United States)

    Dreiling, Michelle; Schiffner, Rene; Bischoff, Sabine; Rupprecht, Sven; Kroegel, Nasim; Schubert, Harald; Witte, Otto W; Schwab, Matthias; Rakers, Florian

    2018-01-01

    Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

  19. Habitual sleep quality and diurnal rhythms of salivary cortisol and dehydroepiandrosterone in postmenopausal women.

    Science.gov (United States)

    Huang, Tianyi; Poole, Elizabeth M; Vetter, Celine; Rexrode, Kathryn M; Kubzansky, Laura D; Schernhammer, Eva; Rohleder, Nicolas; Hu, Frank B; Redline, Susan; Tworoger, Shelley S

    2017-10-01

    Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a potential mechanism linking sleep and cardiometabolic disorders. However, the associations of two primary outputs of the HPA axis, cortisol and its antagonist dehydroepiandrosterone (DHEA), with sleep are less well studied. In the Nurses' Health Study II, 233 postmenopausal women provided five timed saliva samples over one day (immediately upon waking, 45min, 4h, and 10h after waking, and prior to going to sleep) to measure cortisol and DHEA. Of these, 209 completed assessment of their habitual sleep patterns using the Pittsburgh Sleep Quality Index (PSQI). We used piecewise linear mixed models to compare cross-sectional associations of slopes reflecting diurnal cortisol and DHEA rhythms with overall sleep quality and with seven sub-components. Overall, we observed no differences in the diurnal patterns of cortisol or DHEA between good versus poor sleepers as assessed by the global PSQI score. However, longer sleep latency was associated with significantly reduced cortisol awakening rise (p=0.02). Poorer subjective sleep quality (p=0.02), shorter sleep duration (p=0.02), and lower sleep efficiency (p=0.03) were associated with slower rate of cortisol decline later in the day. Women reporting daytime dysfunction had a sharper cortisol decline early in the day (p=0.03) but a flattened decline later in the day (p=0.01). The differences in diurnal patterns of DHEA between good versus poor sleepers, though less pronounced, were similar in direction to those of cortisol. Self-reported sleep duration, efficiency, latency and daytime dysfunction were associated with altered diurnal rhythms of cortisol and, to a lesser extent, DHEA. These findings provide support for the interplay between sleep and the HPA axis that may contribute to cardiometabolic disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Hair cortisol concentration (HCC) as a measure for prenatal psychological distress - A systematic review.

    Science.gov (United States)

    Mustonen, Paula; Karlsson, Linnea; Scheinin, Noora M; Kortesluoma, Susanna; Coimbra, Bárbara; Rodrigues, Ana João; Karlsson, Hasse

    2018-06-01

    Prenatal environment reportedly affects the programming of developmental trajectories in offspring and the modification of risks for later morbidity. Among the increasingly studied prenatal exposures are maternal psychological distress (PD) and altered maternal hypothalamus-pituitary-adrenal (HPA) axis functioning. Both prenatal PD and maternal short-term cortisol concentrations as markers for HPA axis activity have been linked to adverse child outcomes and it has been assumed that maternal PD affects the offspring partially via altered cortisol secretion patterns. Yet, the existing literature on the interrelations between these two measures is conflicting. The assessment of cortisol levels by using hair cortisol concentration (HCC) has gained interest, as it offers a way to assess long-term cortisol levels with a single non-invasive sampling. According to our review, 6 studies assessing the associations between maternal HCC during pregnancy and various types of maternal PD have been published so far. Measures of prenatal PD range from maternal symptoms of depression or anxiety to stress related to person's life situation or pregnancy. The aim of this systematic review is to critically evaluate the potential of HCC as a biomarker for maternal PD during pregnancy. We conclude that HCC appears to be inconsistently associated with self-reported symptoms of prenatal PD, especially in the range of mild to moderate symptom levels. Self-reports on PD usually cover short time periods and they seem to depict partly different phenomena than HCC. Thus, methodological aspects are in a key role in future studies evaluating the interconnections across different types of prenatal PD and maternal HPA axis functioning. Further, studies including repetitive measurements of both HCC and PD during the prenatal period are needed, as timing of the assessments is one important source of variation among current studies. The significance of prenatal HCC in the context of offspring outcomes

  1. History of stress-related health changes: a cue to pursue a diagnosis of latent primary adrenal insufficiency.

    Science.gov (United States)

    Yamamoto, Toshihide

    2014-01-01

    Routine delays in the diagnosis of primary adrenal insufficiency (PAI) are well known and conceivably attributable to the absence of cues, other than anti-adrenal autoantibodies, to pursue subclinical PAI. Subclinical PAI is latent unless the afflicted patient encounters stress such as an acute illness, surgery, psychosocial burden, etc. It remains to be demonstrated whether a history of stress-related health changes is a useful cue to pursue a diagnosis of latent PAI. The patients were selected for a history of recurrent symptoms, i.e., gastrointestinal symptoms, fatigue, or lassitude, aggravated by stress and alleviated by the removal of stress, and signs, i.e., weight loss, hypotension, and hyperpigmentation. As the early morning cortisol levels were low or low-normal and the adrenocorticotropic hormone (ACTH) levels were within the reference ranges, provocation tests, i.e., insulin-induced hypoglycemia tests and low-dose (1 μg) corticotropin tests (LDTs), were used to estimate the hypothalamus-pituitary-adrenal (HPA) axis status. Patients with the HPA axis dysfunction on two provocation tests were supplemented with physiologic doses of glucocorticoids (GCs). The effects of GC supplementation on stress-related health changes were observed. The ACTH levels after insulin-induced hypoglycemia were higher and the cortisol levels were lower in the patients than in the control subjects. The cortisol levels in the patients were increased less significantly by LDT than those observed in the control subjects. Stress-related health changes ceased to recur and signs, i.e., a low body weight, hypotension, and hyperpigmentation, were ameliorated following GC supplementation. A history of stress-related health changes is useful as a cue to pursue latent PAI in patients with low or low-normal early morning cortisol levels.

  2. Cipadesin A, a bioactive ingredient of Xylocarpus granatum, produces antidepressant-like effects in adult mice.

    Science.gov (United States)

    Gao, Qiang; Gao, Yuan; Song, Han; Li, Jianli; Wu, Yibing; Shi, Xiaowei; Shi, Haishui; Ma, Yuxia

    2016-10-28

    Xylocarpus granatum Koenig, widely used in folk medicine in southeast countries, has been reported to exert neuropharmacological activities as well as mood regulation. The neuroprotective activities of limonoids, riches in X. granatum, are poorly understood. To investigate the potential antidepressant-like effects and the underlying mechanisms of cipadesin A, one limonoid component, extracted from X. granatum, in acute stress-induced depression mouse models. Antidepressant-like effects of cipadesin A were investigated through behavioral tests, and potential mechanism was assessed by neuroendocrine system. Antidepressant-like effects of cipadesin A (5, 15, 50mg/kg/day for 7days, intragastrically) were estimated through forced-swimming test (FST), tail suspension test (TST) and open field test (OFT). Effects of cipadesin A on hypothalamus-pituitary- adrenal (HPA) axis were evaluated by analysis of serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) using enzyme-linked immunosorbent assay (ELISA). Cipadesin A administration significantly reduced the floating time in the FST and immobility time in the TST (15-50mg/kg). Cipadesin A dose-dependently increased the time in the central zone in the OFT (5-50mg/kg), without altering the locomotor activity. Moreover, repeated cipadesin A treatment significantly inhibited the increase levels of serum CORT (5-50mg/kg), ACTH (15-50mg/kg) following the forced swimming, but not in the absence of stress. Cipadesin A has antidepressant-like activities in acute stressed mice model of depression, which likely occurs by inhibiting the HPA axis activity response to stress. These data support further exploration for developing cipadesin A as a potential agent to treat depression and anxiety disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Cooper, Odelia; Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

    2017-06-01

    Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Prospective controlled study in an outpatient clinic. Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm 3 [standard deviation (SD), 227.3 mm 3 ] in PTSD subjects vs 835.2 mm 3 (SD, 302.8 mm 3 ) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects ( P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches.

  4. Effects of prenatal stress on anxiety- and depressive-like behaviors are sex-specific in prepubertal rats.

    Science.gov (United States)

    Iturra-Mena, Ann Mary; Arriagada-Solimano, Marcia; Luttecke-Anders, Ariane; Dagnino-Subiabre, Alexies

    2018-05-17

    The fetal brain is highly susceptible to stress in late pregnancy, with lifelong effects of stress on physiology and behavior. The aim of this study was to determine the physiological and behavioral effects of prenatal stress during the prepubertal period of female and male rats. We subjected pregnant Sprague-Dawley rats to a restraint stress protocol from gestational day 14 until 21, a critical period for fetal brain susceptibility to stress effects. Male and female offspring were subsequently assessed at postnatal day 24 for anxiety- and depressive-like behaviors, and spontaneous social interaction. We also assessed maternal behaviors and two stress markers: basal vs. acute-evoked stress levels of serum corticosterone and body weight gain. Prenatal stress did not affect the maternal behavior, while both female and male offspring had higher body weight gain. On the other hand, lower levels of corticosterone after acute stress stimulation as well as anxiety- and depressive-like behaviors were only evident in stressed males compared to control males. These results suggest that prenatal stress induced sex-specific effects on the hypothalamus-pituitary-adrenal (HPA) axis activity and on behavior during prepuberty. The HPA axis of prenatally stressed male rats was less active compared to control males, as well as they were more anxious and experienced depressive-like behaviors. Our results can be useful to study the neurobiological basis of childhood depression at a pre-clinical level. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Chicken domestication changes expression of stress-related genes in brain, pituitary and adrenals

    Directory of Open Access Journals (Sweden)

    Pia Løtvedt

    2017-12-01

    Full Text Available Domesticated species have an attenuated behavioral and physiological stress response compared to their wild counterparts, but the genetic mechanisms underlying this change are not fully understood. We investigated gene expression of a panel of stress response-related genes in five tissues known for their involvement in the stress response: hippocampus, hypothalamus, pituitary, adrenal glands and liver of domesticated White Leghorn chickens and compared it with the wild ancestor of all domesticated breeds, the Red Junglefowl. Gene expression was measured both at baseline and after 45 min of restraint stress. Most of the changes in gene expression related to stress were similar to mammals, with an upregulation of genes such as FKBP5, C-FOS and EGR1 in hippocampus and hypothalamus and StAR, MC2R and TH in adrenal glands. We also found a decrease in the expression of CRHR1 in the pituitary of chickens after stress, which could be involved in negative feedback regulation of the stress response. Furthermore, we observed a downregulation of EGR1 and C-FOS in the pituitary following stress, which could be a potential link between stress and its effects on reproduction and growth in chickens.We also found changes in the expression of important genes between breeds such as GR in the hypothalamus, POMC and PC1 in the pituitary and CYP11A1 and HSD3B2 in the adrenal glands. These results suggest that the domesticated White Leghorn may have a higher capacity for negative feedback of the HPA axis, a lower capacity for synthesis of ACTH in the pituitary and a reduced synthesis rate of corticosterone in the adrenal glands compared to Red Junglefowl. All of these findings could explain the attenuated stress response in the domesticated birds. Keywords: Animal domestication, Stress response, HPA axis, Glucocorticoid receptor, Gene expression, Chicken

  6. The combined dexamethasone/TSST paradigm--a new method for psychoneuroendocrinology.

    Directory of Open Access Journals (Sweden)

    Julie Andrews

    Full Text Available The two main physiological systems involved in the regulation of the stress response are the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system (SNS. However, the interaction of these systems on the stress response remains poorly understood. To better understand the cross-regulatory effects of the different systems involved in stress regulation, we developed a new stress paradigm that keeps the activity of the HPA constant when exposing subjects to psychosocial stress. Thirty healthy male participants were recruited and randomly assigned to either a dexamethasone (DEX; n = 15 or placebo (PLC; n = 15 group. All subjects were instructed to take the Dexamethasone (2 mg or Placebo pill the night before coming to the laboratory to undergo the Trier Social Stress Task (TSST. Salivary cortisol, salivary alpha amylase (sAA, heart rate, blood pressure and subjective stress were assessed throughout the protocol. As expected, the DEX group presented with suppressed cortisol levels. In comparison, their heart rate was elevated by approximately ten base points compared to the PLC group, with increases throughout the protocol and during the TSST. Neither sAA, nor systolic or diastolic blood pressures showed significant group differences. Subjective stress levels significantly increased from baseline, and were found to be higher before and after the TSST after DEX compared to placebo. These results demonstrate a significant interaction between the HPA and the SNS during acute stress. The SNS activity was found to be elevated in the presence of a suppressed HPA axis, with some further effects on subjective levels of stress. The method to suppress the HPA prior to inducing stress was found to completely reliable, without any adverse side effects. Therefore, we propose this paradigm as a new method to investigate the interaction of the two major stress systems in the regulation of the stress response.

  7. Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms

    Science.gov (United States)

    Iliadis, Stavros I.; Comasco, Erika; Sylvén, Sara; Hellgren, Charlotte; Sundström Poromaa, Inger; Skalkidou, Alkistis

    2015-01-01

    Background The biology of peripartum depression remains unclear, with altered stress and the Hypothalamus-Pituitary-Adrenal axis response having been implicated in its pathophysiology. Methods The current study was undertaken as a part of the BASIC project (Biology, Affect, Stress, Imaging, Cognition), a population-based longitudinal study of psychological wellbeing during pregnancy and the postpartum period in Uppsala County, Sweden, in order to assess the association between evening salivary cortisol levels and depressive symptoms in the peripartum period. Three hundred and sixty-five pregnant women from the BASIC cohort were recruited at pregnancy week 18 and instructed to complete a Swedish validated version of the Edinburgh Postnatal Depression Scale at the 36th week of pregnancy as well as the sixth week after delivery. At both times, they were also asked to provide evening salivary samples for cortisol analysis. A comprehensive review of the relevant literature is also provided. Results Women with postpartum EPDS score ≥ 10 had higher salivary evening cortisol at six weeks postpartum compared to healthy controls (median cortisol 1.19 vs 0.89 nmol/L). A logistic regression model showed a positive association between cortisol levels and depressive symptoms postpartum (OR = 4.1; 95% CI 1.7–9.7). This association remained significant even after controlling for history of depression, use of tobacco, partner support, breastfeeding, stressful life events, and sleep problems, as possible confounders (aOR = 4.5; 95% CI 1.5–14.1). Additionally, women with postpartum depressive symptoms had higher postpartum cortisol levels compared to both women with depressive symptoms antenatally and controls (p = 0.019 and p = 0.004, respectively). Conclusions Women with depressive symptoms postpartum had higher postpartum cortisol levels, indicating an altered response of the HPA-axis in postpartum depression. PMID:26322643

  8. Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid.

    Science.gov (United States)

    Chen, Jiao; Wang, Zhen-zhen; Zuo, Wei; Zhang, Shuai; Chu, Shi-feng; Chen, Nai-hong

    2016-02-01

    Major depression is thought to originate from maladaptation to adverse events, particularly when impairments occur in mood-related brain regions. Hypothalamus-pituitary-adrenal (HPA) axis is one of the major systems involved in physiological stress response. HPA axis dysfunction and high glucocorticoid concentrations play an important role in the pathogenesis of depression. In addition, astrocytic disability and dysfunction of neurotrophin brain-derived neurotrophin factor (BDNF) greatly influence the development of depression and anxiety disorders. Therefore, we investigated whether depressive-like and anxiety-like behaviors manifest in the absence of glucocorticoid production and circulation in adrenalectomized (ADX) rats after chronic mild stress (CMS) exposure and its potential molecular mechanisms. The results demonstrate that glucocorticoid-controlled rats showed anxiety-like behaviors but not depression-like behaviors after CMS. Molecular and cellular changes included the decreased BDNF in the hippocampus, astrocytic dysfunction with connexin43 (cx43) decreasing and abnormality in gap junction in prefrontal cortex (PFC). Interestingly, we did not find any changes in glucocorticoid receptor (GR) or its chaperone protein FK506 binding protein 51 (FKBP5) expression in the hippocampus or PFC in ADX rats subjected to CMS. In conclusion, the production and circulation of glucocorticoids are one of the contributing factors in the development of depression-like behaviors in response to CMS. In contrast, the effects of CMS on anxiety-like behaviors are independent of the presence of circulating glucocorticoids. Meanwhile, stress decreased GR expression and enhanced FKBP5 expression via higher glucocorticoid exposure. Gap junction dysfunction and changes in BDNF may be associated with anxiety-like behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Prenatal exposure to noise stress: anxiety, impaired spatial memory, and deteriorated hippocampal plasticity in postnatal life.

    Science.gov (United States)

    Barzegar, Marzieh; Sajjadi, Fatemeh Sadat; Talaei, Sayyed Alireza; Hamidi, Gholamali; Salami, Mahmoud

    2015-02-01

    Sound pollution is known as an annoying phenomenon in modern life. Especially, development of organisms during fetal life is more sensitive to environmental tensions. To address a link between the behavioral and electrophysiological aspects of brain function with action of hypothalamus-pituitary-adrenal (HPA) axis in stressed animals, this study was carried out on the male Wistar rats prenatally exposed to sound stress. Groups of pregnant rats were exposed to noise stress for 1, 2, and 4 hour(s). The degree of anxiety and the spatial memory were evaluated by elevated plus maze and Morris water maze, respectively. Basic synaptic activity and long-term potentiation (LTP) induction were assessed in the CA3-CA1 pathway of hippocampus. The serum level of corticosterone was measured in the pregnant mothers and the offspring. The behavioral experiments appeared that the stressed animals performed considerably weaker than the control rats. The prenatal stress negatively affected the basic synaptic responses and led to a lower level of LTP. The pregnant animals showed an increased serum corticosterone in comparison with the nonpregnant females. Also the offspring exposed to the noise stress had a more elevated level of corticosterone than the control rats. Our findings indicate that the corticosterone concentration changes markedly coincides the results of behavioral and electrophysiological experiments. We conclude that, similar to other environmental stresses, the sound stress during fetal life efficiently disturbs both cognitive abilities and synaptic activities. The changes in action of HPA axis may contribute to problems of the brain function in the prenatally stress exposed animals. © 2014 Wiley Periodicals, Inc.

  10. Stretching the stress boundary: Linking air pollution health effects to a neurohormonal stress response.

    Science.gov (United States)

    Kodavanti, Urmila P

    2016-12-01

    Inhaled pollutants produce effects in virtually all organ systems in our body and have been linked to chronic diseases including hypertension, atherosclerosis, Alzheimer's and diabetes. A neurohormonal stress response (referred to here as a systemic response produced by activation of the sympathetic nervous system and hypothalamus-pituitary-adrenal (HPA)-axis) has been implicated in a variety of psychological and physical stresses, which involves immune and metabolic homeostatic mechanisms affecting all organs in the body. In this review, we provide new evidence for the involvement of this well-characterized neurohormonal stress response in mediating systemic and pulmonary effects of a prototypic air pollutant - ozone. A plethora of systemic metabolic and immune effects are induced in animals exposed to inhaled pollutants, which could result from increased circulating stress hormones. The release of adrenal-derived stress hormones in response to ozone exposure not only mediates systemic immune and metabolic responses, but by doing so, also modulates pulmonary injury and inflammation. With recurring pollutant exposures, these effects can contribute to multi-organ chronic conditions associated with air pollution. This review will cover, 1) the potential mechanisms by which air pollutants can initiate the relay of signals from respiratory tract to brain through trigeminal and vagus nerves, and activate stress responsive regions including hypothalamus; and 2) the contribution of sympathetic and HPA-axis activation in mediating systemic homeostatic metabolic and immune effects of ozone in various organs. The potential contribution of chronic environmental stress in cardiovascular, neurological, reproductive and metabolic diseases, and the knowledge gaps are also discussed. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Published by Elsevier B.V.

  11. Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

    Science.gov (United States)

    Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

    2017-01-01

    Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Design: Prospective controlled study in an outpatient clinic. Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches. PMID:29264511

  12. 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.

  13. Effect of Relative Marker Movement on the Calculation of the Foot Torsion Axis Using a Combined Cardan Angle and Helical Axis Approach

    Directory of Open Access Journals (Sweden)

    Eveline S. Graf

    2012-01-01

    Full Text Available The two main movements occurring between the forefoot and rearfoot segment of a human foot are flexion at the metatarsophalangeal joints and torsion in the midfoot. The location of the torsion axis within the foot is currently unknown. The purpose of this study was to develop a method based on Cardan angles and the finite helical axis approach to calculate the torsion axis without the effect of flexion. As the finite helical axis method is susceptible to error due to noise with small helical rotations, a minimal amount of rotation was defined in order to accurately determine the torsion axis location. Using simulation, the location of the axis based on data containing noise was compared to the axis location of data without noise with a one-sample t-test and Fisher's combined probability score. When using only data with helical rotation of seven degrees or more, the location of the torsion axis based on the data with noise was within 0.2 mm of the reference location. Therefore, the proposed method allowed an accurate calculation of the foot torsion axis location.

  14. Effect of Relative Marker Movement on the Calculation of the Foot Torsion Axis Using a Combined Cardan Angle and Helical Axis Approach

    Science.gov (United States)

    Graf, Eveline S.; Wright, Ian C.; Stefanyshyn, Darren J.

    2012-01-01

    The two main movements occurring between the forefoot and rearfoot segment of a human foot are flexion at the metatarsophalangeal joints and torsion in the midfoot. The location of the torsion axis within the foot is currently unknown. The purpose of this study was to develop a method based on Cardan angles and the finite helical axis approach to calculate the torsion axis without the effect of flexion. As the finite helical axis method is susceptible to error due to noise with small helical rotations, a minimal amount of rotation was defined in order to accurately determine the torsion axis location. Using simulation, the location of the axis based on data containing noise was compared to the axis location of data without noise with a one-sample t-test and Fisher's combined probability score. When using only data with helical rotation of seven degrees or more, the location of the torsion axis based on the data with noise was within 0.2 mm of the reference location. Therefore, the proposed method allowed an accurate calculation of the foot torsion axis location. PMID:22666303

  15. Anterior fixation of the axis.

    Science.gov (United States)

    Traynelis, Vincent C; Fontes, Ricardo B V

    2010-09-01

    Although anterior fixation of the axis is not commonly performed, plate fixation of C2 is an important technique for treating select upper cervical traumatic injuries and is also useful in the surgical management of spondylosis. To report the technique and outcomes of C2 anterior plate fixation for a series of patients in which the majority presented with symptomatic degenerative spondylosis. Forty-six consecutive patients underwent single or multilevel fusions over a 7-year period; 30 of these had advanced degenerative disease manifested by myelopathy or deformity. Exposure was achieved with rostral extension of the standard anterior cervical exposure via careful soft tissue dissection, mobilization of the superior thyroid artery, and the use of a table-mounted retractor. It was not necessary to remove the submandibular gland, section the digastric muscle, or make additional skin incisions. Screws were placed an average of 4.6 mm (+/- 2.3 mm) from the inferior C2 endplate with a mean sagittal trajectory of 15.7 degrees (+/- 7.6 degrees). Short- and long-term procedure-related mortality was 4.4%, and perioperative morbidity was 8.9%. Patients remained intubated an average of 2.5 days following surgery. Dysphagia was initially reported by 15.2% of patients but resolved by the 8th postoperative week in all patients. Arthrodesis was achieved in all patients available for long-term follow-up. Multilevel fusions were not associated with longer hospitalization or morbidity. Anterior plate fixation of the axis for degenerative disease can be accomplished with acceptable morbidity employing an extension of the standard anterolateral route.

  16. Phytochemicals for taming agitated immune-endocrine-neural axis.

    Science.gov (United States)

    Patel, Seema

    2017-07-01

    Homeostasis of immune-endocrine-neural axis is paramount for human health. If this axis gets agitated due to age, genetic variations, environmental exposures or lifestyle assaults, a cascade of adverse reactions occurs in human body. Cytokines, hormones and neurotransmitters, the effector molecules of this axis behave erratically, leading to a gamut of neural, endocrine, autoimmune, and metabolic diseases. Current panel of drugs can tackle some of them but not in a sustainable, benign way as a myriad of side effects, causal of them have been documented. In this context, phytochemicals, the secondary metabolites of plants seem beneficial. These bioactive constituents encompassing polyphenols, alkaloids, flavonoids, terpenoids, tannins, lignans, stilbenoids (resveratrol), saponins, polysaccharides, glycosides, and lectins etc. have been proven to exert antioxidant, anti-inflammatory, hypolipidemic, hypotensive, antidiabetic, anticancer, immunomodulatory, anti-allergic, analgesic, hepatoprotective, neuroprotective, dermatoprotective, and antimicrobial properties, among a litany of other biological effects. This review presents a holistic perspective of common afflictions resultant of immune-endocrine-neural axis disruption, and the phytochemicals capable of restoring their normalcy and mitigating the ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity.

    Science.gov (United States)

    Schwaiger, Marion; Grinberg, Marianna; Moser, Dirk; Zang, Johannes C S; Heinrichs, Markus; Hengstler, Jan G; Rahnenführer, Jörg; Cole, Steve; Kumsta, Robert

    2016-09-01

    Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.

  18. Chronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis.

    Science.gov (United States)

    de Andrade, J S; Céspedes, I C; Abrão, R O; Dos Santos, T B; Diniz, L; Britto, L R G; Spadari-Bratfisch, R C; Ortolani, D; Melo-Thomas, L; da Silva, R C B; Viana, M B

    2013-08-01

    Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. In unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. In stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. In stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Pharmacological activities, mechanisms of action, and safety of salidroside in the central nervous system

    Directory of Open Access Journals (Sweden)

    Zhong ZF

    2018-05-01

    Full Text Available Zhifeng Zhong,1 Jing Han,1 Jizhou Zhang,1 Qing Xiao,1 Juan Hu,1,2 Lidian Chen1,2 1Institute of Materia Medica, Fujian Academy of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 2School of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China Abstract: The primary objective of this review article was to summarize comprehensive information related to the neuropharmacological activity, mechanisms of action, toxicity, and safety of salidroside in medicine. A number of studies have revealed that salidroside exhibits neuroprotective activities, including anti-Alzheimer’s disease, anti-Parkinson’s disease, anti-Huntington’s disease, anti-stroke, anti-depressive effects, and anti-traumatic brain injury; it is also useful for improving cognitive function, treating addiction, and preventing epilepsy. The mechanisms underlying the potential protective effects of salidroside involvement are the regulation of oxidative stress response, inflammation, apoptosis, hypothalamus-pituitary-adrenal axis, neurotransmission, neural regeneration, and the cholinergic system. Being free of side effects makes salidroside potentially attractive as a candidate drug for the treatment of neurological disorders. It is evident from the available published literature that salidroside has potential use as a beneficial therapeutic medicine with high efficacy and low toxicity to the central nervous system. However, the definite target protein molecules remain unclear, and clinical trials regarding this are currently insufficient; thus, guidance for further research on the molecular mechanisms and clinical applications of salidroside is urgent. Keywords: salidroside, Alzheimer’s disease, Parkinson’s disease, stroke, cognitive impairment, clinical trials

  20. Height, shape and anterior-posterior diameter of pituitary gland on magnetic resonance imaging among patients with multiple sclerosis compared to normal individuals.

    Science.gov (United States)

    Saba, Mohammad; Ebrahimi, Hossein Ali; Ahmadi-Pour, Habibeh; Khodadoust, Mohammad

    2017-10-07

    Background: Several studies indicate contribution of hypothalamus-pituitary-adrenal (HPA) axis in multiple sclerosis (MS) disease. This study was designed to determine whether there is an effective difference in pituitary height, shape, and anterior-posterior diameter (APD) between patients with MS and the control group. Methods: In this study, sagittal pituitary height and APD of 134 men and women (64 patients with MS and 70 healthy subjects as control group) were measured by T1 sequence magnetic resonance imaging (MRI). All the subjects were free of sellar or parasellar pathology without a history of surgical intervention or prolactin affecting drugs like bromocriptine and cabergoline or corticosteroid consumption. Results: Mean height of pituitary gland was 6.62 ± 1.43 and 5.78 ± 1.15 mm for patients and the control group, respectively, and the difference between the two groups was statistically significant (P = 0.001). Mean APD was 10.40 ± 1.29 mm for the group of patients and 10.25 ± 1.41 mm for the control group, respectively, without significant differences. 46.9%, 37.5%, and 15.6% of patients had flat, convex, and concave hypophyseal surfaces, respectively. This rate was 50%, 30%, and 20% among the control group, respectively. There was no significant difference between our measurements among patients on whom imaging study was performed at time of disease onset with others. Conclusion: Mean height of pituitary gland among patients with MS was significantly greater than the control group (P = 0.001). So can we consider the same etiology for pituitary hypertrophy among patients with MS as a hypothesis?

  1. Interactive effects of genetic polymorphisms and childhood adversity on brain morphologic changes in depression.

    Science.gov (United States)

    Kim, Yong-Ku; Ham, Byung-Joo; Han, Kyu-Man

    2018-03-10

    The etiology of depression is characterized by the interplay of genetic and environmental factors and brain structural alteration. Childhood adversity is a major contributing factor in the development of depression. Interactions between childhood adversity and candidate genes for depression could affect brain morphology via the modulation of neurotrophic factors, serotonergic neurotransmission, or the hypothalamus-pituitary-adrenal (HPA) axis, and this pathway may explain the subsequent onset of depression. Childhood adversity is associated with structural changes in the hippocampus, amygdala, anterior cingulate cortex (ACC), and prefrontal cortex (PFC), as well as white matter tracts such as the corpus callosum, cingulum, and uncinate fasciculus. Childhood adversity showed an interaction with the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism, serotonin transporter-linked promoter region (5-HTTLPR), and FK506 binding protein 51 (FKBP5) gene rs1360780 in brain morphologic changes in patients with depression and in a non-clinical population. Individuals with the Met allele of BDNF Val66Met and a history of childhood adversity had reduced volume in the hippocampus and its subfields, amygdala, and PFC and thinner rostral ACC in a study of depressed patients and healthy controls. The S allele of 5-HTTLPR combined with exposure to childhood adversity or a poorer parenting environment was associated with a smaller hippocampal volume and subsequent onset of depression. The FKBP5 gene rs160780 had a significant interaction with childhood adversity in the white matter integrity of brain regions involved in emotion processing. This review identified that imaging genetic studies on childhood adversity may deepen our understanding on the neurobiological background of depression by scrutinizing complicated pathways of genetic factors, early psychosocial environments, and the accompanying morphologic changes in emotion-processing neural circuitry. Copyright

  2. A SYSTEMATIC REVIEW OF NON-INVASIVE BRAIN STIMULATION THERAPIES AND CARDIOVASCULAR RISK: IMPLICATIONS FOR THE TREATMENT OF MAJOR DEPRESSIVE DISORDER.

    Directory of Open Access Journals (Sweden)

    Leonardo Augusto Negreiros Parente Capela Sampaio

    2012-10-01

    Full Text Available Major depressive disorder (MDD and cardiovascular diseases are intimately associated. Depression is an independent risk factor for mortality in cardiovascular samples. Neuroendocrine dysfunctions in MDD are related to an overactive hypothalamus-pituitary-adrenal (HPA axis and increased sympathetic activity. Novel intervention strategies for MDD include the non-invasive brain stimulation (NIBS techniques such as repetitive transcranial magnetic stimulation (rTMS and transcranial direct current stimulation (tDCS. In fact, although these techniques have being increasingly used as a treatment for MDD, their cardiovascular effects were not sufficiently investigated, which would be important considering the dyad MDD/cardiovascular disorders. We investigated this issue through a systematic review for published articles from the first date available to May 2012 in MEDLINE and other databases, looking for main risk factors and surrogate markers for cardiovascular disease such as: cortisol, heart rate variability, alcohol, smoking, obesity, hypertension, glucose. We identified 37 articles (981 subjects according to our eligibility criteria. Our main findings were that NIBS techniques might be effective strategies for down-regulating HPA activity and regulating food, alcohol and cigarette consumption. NIBS’s effects on HRV and blood pressure presented mixed findings, with studies suggesting that HRV values can decrease or remain unchanged after NIBS, while one study found that rTMS increased blood pressure levels. Also, a single study showed that glucose levels decrease after tDCS. However, most studies tested the acute effects after one single session of rTMS/tDCS; therefore further studies are necessary to investigate whether NIBS modifies cardiovascular risk factors in the long-term. In fact, considering the burden of cardiac disease, further trials in cardiovascular, depressed and nondepressed samples using NIBS should be performed.

  3. Gender differences in serum testosterone and cortisol in patients with major depressive disorder compared with controls.

    Science.gov (United States)

    Matsuzaka, Hisashi; Maeshima, Hitoshi; Kida, Sayaka; Kurita, Hirofumi; Shimano, Takahisa; Nakano, Yoshiyuki; Baba, Hajime; Suzuki, Toshihito; Arai, Heii

    2013-01-01

    Testosterone may have a role distinct from cortisol in the pathophysiology of depression. The hypothalamus-pituitary-adrenal (HPA) axis affects the functions of sex steroid hormones through interaction with corticotropin-releasing hormone (CRH) and gonadotropin-releasing hormone (GnRH). The objective of this study was to investigate differences in serum levels of testosterone and cortisol in male and female patients with major depressive disorder (MDD). Participants included 87 inpatients with MDD at Juntendo University Koshigaya Hospital. Serum levels of testosterone and cortisol were assessed at admission. Matched controls included 128 healthy individuals. Data from MDD patients and controls were compared separately for men and women. Correlations between serum hormone levels and scores on the Hamilton Rating Scale for Depression (HAM-D) of patients were assessed by sex. Effects of various factors on testosterone and cortisol were analyzed using multiple regression analysis. In male patients with MDD, a significant negative correlation was seen between testosterone levels and the "retardation" score of HAM-D. However, serum testosterone levels were not significantly different in either male or female MDD patients compared with controls. Serum testosterone was negatively associated with the number of depressive episodes in male patients with MDD. Serum cortisol levels in female patients were significantly increased compared with female controls with no significant correlations between cortisol levels and HAM-D scores. The negative correlation between the sub-score of the HAM-D and testosterone may be associated with the biological pathophysiology of male depression. Findings of serum cortisol levels in women may suggest distinct characteristics of these hormones in men and women with MDD.

  4. Immediate recall influences the effects of pre-encoding stress on emotional episodic long-term memory consolidation in healthy young men.

    Science.gov (United States)

    Wolf, Oliver T

    2012-05-01

    The stress-associated activation of the hypothalamus-pituitary-adrenal axis influences memory. Several studies have supported the notion that post-learning stress enhances memory consolidation, while pre-retrieval stress impairs retrieval. Findings regarding the effects of pre-encoding stress, in contrast, have been rather inconsistent. In the current two studies, the impact of an immediate retrieval task on these effects was explored. In the first study, 24 healthy young male participants were exposed to a psychosocial laboratory stressor (Trier Social Stress Test) or a control condition before viewing positive, negative, and neutral photographs, which were accompanied by a brief narrative. Immediate as well as delayed (24 h later) free recall was assessed. Stress was expected to enhance emotional long-term memory without affecting immediate recall performance. Stress caused a significant increase in salivary cortisol concentrations but had no significant effects on immediate or delayed retrieval performance, even though a trend toward poorer memory of the stress group was apparent. Based on these findings, the second experiment tested the hypothesis that the beneficial effects of stress on emotional long-term memory performance might be abolished by an immediate recall test. In the second study (n = 32), the same design was used, except for the omission of the immediate retrieval test. This time stressed participants recalled significantly more negative photographs compared to the control group. The present study indicates that an immediate retrieval attempt of material studied after stress exposure can prevent or even reverse the beneficial effects of pre-encoding stress on emotional long-term memory consolidation.

  5. Exposure to retrieval cues improves retention performance and induces changes in ACTH and corticosterone release.

    Science.gov (United States)

    Gisquet-Verrier, Pascale; Botreau, Fanny; Venero, Cesar; Sandi, Carmen

    2004-05-01

    Memory retrieval can be facilitated by pretest exposure to cues associated with the original training. The present series of experiments was aimed at investigating whether the effectiveness of the retrieval cues might be due to their emotional value and thus be associated to a particular pattern of activation of stress systems. Therefore, the effects of exposing rats to different cueing conditions were investigated both on retention performance and on the level of different stress hormones (ACTH, corticosterone and glucose; the latter as an indirect index of adrenergic/sympathetic nervous system activation). Rats trained in a brightness avoidance discrimination task exhibited an enhancement of the retention performance following exposure to the light discriminative stimulus when delivered 1-day after training and not after 21 days, while exposure to contextual cues led to opposite effects on the retention performance, confirming our previous results. Analyses of the level of stress hormones at the time of testing indicated that when the retrieval cues were effective at the behavioral level, cued rats exhibited higher ACTH plasmatic levels than controls, but did not differ in their glucose or corticosterone levels. Further experiments showed that one day after training, both ACTH and corticosterone levels were elevated in light-cued rats if hormone samples were taken 15 min after cueing. These results show that exposure to an effective retrieval cue is accompanied by the activation of the hypothalamus-pituitary-adrenal axis. The possible involvement of the Corticotropin Releasing Factor at the level of the hypothalamus and amygdala (particularly the central nucleus) on the facilitating effect on retention performance following exposure to aversive training-associated cues is discussed. The present results strengthen the notion that emotion can interact with retrieval processes.

  6. Working memory is differentially affected by stress in men and women.

    Science.gov (United States)

    Schoofs, Daniela; Pabst, Stephan; Brand, Matthias; Wolf, Oliver T

    2013-03-15

    Stress has been shown to influence working memory. However, sex differences and the potential impact of stimulus emotionality have not received much attention. In a first experiment the effects of stress on a neutral working memory (WM) paradigm were tested in male and female participants (Experiment 1). Experiment 2 employed the same paradigm but used emotional stimuli. For this purpose, healthy participants were exposed either to a stressful (Trierer Social Stress Test (TSST)) or to a non-stressful control condition. Subsequently, WM performance in an n-back task was assessed. In Experiment 1, single digits were used as stimuli, while in Experiment 2 neutral and negative pictures were additionally employed. Salivary cortisol and Alpha-Amylase (sAA) were measured before and three times after the treatment as a marker of hypothalamus-pituitary-adrenal (HPA) axis- and sympathetic nervous system (SNS) activity. In both experiments, stress caused a substantial cortisol and sAA increase. For WM performance (response time) a stress by sex interaction was apparent. Stress enhanced performance in men, while impairing it in women. In both experiments stress had no effect on response accuracy. No modulating effect of the emotional quality of stimuli on n-back performance was observed (study 2). The results indicate that the effect of acute stress on n-back performance differs between the sexes. In contrast to long-term memory, the influence of stress on WM appears not to be modulated by the emotionality of the employed stimuli if stimuli are potential targets as it is the case in the n-back task. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Progesterone modulation of alpha5 nAChR subunits influences anxiety-related behavior during estrus cycle.

    Science.gov (United States)

    Gangitano, D; Salas, R; Teng, Y; Perez, E; De Biasi, M

    2009-06-01

    Smokers often report an anxiolytic effect of cigarettes. In addition, stress-related disorders such as anxiety, post-traumatic stress syndrome and depression are often associated with chronic nicotine use. To study the role of the alpha5 nicotinic acetylcholine receptor subunit in anxiety-related responses, control and alpha5 subunit null mice (alpha5(-/-)) were subjected to the open field activity (OFA), light-dark box (LDB) and elevated plus maze (EPM) tests. In the OFA and LDB, alpha5(-/-) behaved like wild-type controls. In the EPM, female alpha5(-/-) mice displayed an anxiolytic-like phenotype, while male alpha5(-/-) mice were undistinguishable from littermate controls. We studied the hypothalamus-pituitary-adrenal axis by measuring plasma corticosterone and hypothalamic corticotropin-releasing factor. Consistent with an anxiolytic-like phenotype, female alpha5(-/-) mice displayed lower basal corticosterone levels. To test whether gonadal steroids regulate the expression of alpha5, we treated cultured NTera 2 cells with progesterone and found that alpha5 protein levels were upregulated. In addition, brain levels of alpha5 mRNA increased upon progesterone injection into ovariectomized wild-type females. Finally, we tested anxiety levels in the EPM during the estrous cycle. The estrus phase (when progesterone levels are low) is anxiolytic-like in wild-type mice, but no cycle-dependent fluctuations in anxiety levels were found in alpha5(-/-) females. Thus, alpha5-containing neuronal nicotinic acetylcholine receptors may be mediators of anxiogenic responses, and progesterone-dependent modulation of alpha5 expression may contribute to fluctuations in anxiety levels during the ovarian cycle.

  8. Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: A pilot investigation.

    Science.gov (United States)

    Harb, H; González-de-la-Vara, M; Thalheimer, L; Klein, U; Renz, H; Rose, M; Kruse, J; Potaczek, D P; Peters, E M J

    2017-12-01

    To study pathogenic stress-effects in health and disease, it is paramount to define easy access parameters for non-invasive analysis of biological change in response to stress. Hair samples successfully provide this access for the study of hypothalamus-pituitary-adrenal axis (HPA) changes. In this study, we assess the hair expression and corresponding epigenetic changes of a neurotrophin essential for autonomic nervous system function and mental health: brain derived neurotrophic factor (BDNF). In three independent studies in healthy academic volunteers (study I: German students, N=36; study II, German academic population sample, N=28; study III: Mexican students, N=115), BDNF protein expression or BDNF gene (BDNF) histone acetylation was determined. Simultaneously, mental distress and distress-associated somatic complaints were assessed by self-report. In study I, we found a negative correlation between hair-BDNF protein level and hair-cortisol as well as between hair-BDNF and somatic complaints, while hair-cortisol correlated positively with mental distress. In study II, we found a negative correlation between H4 histone acetylation at the BDNF gene P4-promoter and somatic complaints. Regression analysis confirmed confounder stability of associations in both studies. In study III, we confirmed study I and found lower hair-BDNF protein level in volunteers with high somatic complaints, who also reported higher mental distress during the end of term exams. The results indicate that BDNF protein levels can be detected in clipped hair and are associated with somatic complaints and stress in life. In addition, we concluded that plucked hair can provide material for the study of epigenetic changes in stress-affected tissues. These tools can prove valuable for future studies on distress, both under experimental and field conditions. Copyright © 2017. Published by Elsevier Ltd.

  9. Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

    Science.gov (United States)

    Villa, R F; Ferrari, F; Gorini, A

    2012-12-27

    Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

  10. FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.

    Science.gov (United States)

    Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E; Fiely, Miranda K; Mosley, Brianne E; Brown, Callie M; Duffy, Tessa J; Scharf, Amanda R; Earley, McKenna B; Rorabaugh, Boyd R

    2017-03-01

    FK506 binding protein 51 (FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Vels Lotte

    2008-09-01

    Full Text Available Abstract Background Liver plays a profound role in the acute phase response (APR observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli. To gain an insight into the genes and pathways involved in hepatic APR of dairy cows we performed a global gene expression analysis of liver tissue sampled at different time points before and after intra-mammary (IM exposure to E. coli lipopolysaccharide (LPS treatment. Results Approximately 20% target transcripts were differentially expressed and eight co-expression clusters were identified. Each cluster had a unique time-dependent expression profile and consisted of genes involved in different biological processes. Our findings suggest that APR in the liver is triggered by the activation of signaling pathways that are involved with common and hepatic-specific transcription factors and pro-inflammatory cytokines. These mediators in turn stimulated or repressed the expression of genes encoding acute phase proteins (APP, collectins, complement components, chemokines, cell adhesion molecules and key metabolic enzymes during the APR. Hormones, anti-inflammatory and other hypothalamus-pituitary-adrenal axis (HPAA linked mediators also seemed to participate in APR. Conclusion Performing global gene expression analysis on liver tissue from IM LPS treated cows verified that the liver plays a major role in the APR of E. coli mastitis, and that the bovine hepatic APR follows the same pattern as other mammals when they are challenged with LPS. Our work presents the first insight into the dynamic changes in gene expression in the liver that influences the induction, kinetics and clinical outcome of the APR in dairy cows.

  12. 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.

  13. Gut vagal afferents differentially modulate innate anxiety and learned fear.

    Science.gov (United States)

    Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs

    2014-05-21

    Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior. Copyright © 2014 the authors 0270-6474/14/347067-10$15.00/0.

  14. Effects of Qiangji Jianli Yin on the hypothalamus CRH contents and plasma ACTH, cortisol levels in rat models of kidney-yang deficiency syndrome

    International Nuclear Information System (INIS)

    Zhao Hui; Chen Zhixi; Chen Jinyan; Li Zhiqiang; He Zanhou

    2007-01-01

    Objective: To investigate the effects of qiangji jianli yin on hypothalamus CRH contents and plasma ACTH, Cortisol levels in rat models with kidney-yang deficiency syndrome. Methods: Rat models of kidney-yang deficiency syndrome were prepared with intramuscular injuection of hydroeortisone and divided into 5 groups: (1) no further treatment, n=13 (2) treated with high dosage d qiangji jiandi yin, n=12 (3) treated with medium dosage of qiangji jianli yin, n=12 (4) treated with low dosage of qiangji jianli yin n=12, (5) treated with yougui wan, n=12. Ten rats injuected with intramuscular distilled water only served as controls. The animals were sacrificied 14 days later and the hypothalamus CRH contents as well as plasma AOM and cortisol levels were measured with RIA. The thymus gland weight index and the adrenal gland index were calculated. Results: (1) The hypothalamus CRH contents and plasma ACTH, cortisol levels were significantly lower (P<0.01) in the rat models of kidney-yang deficiency syndrome without any treatment thas those in controls rats; the thymus and adrenal gland weight index were significantly decreased too (P <0.01). The CRH conteats and ACTH, cortisol levels in all the three group of rat model treated with different dosage of qiangji jianli yin were significantly higher than those in the models without any treatment (P<0.05-0.01). Conclusion: In rat models of kidney-yang deficiency syndrome, dysfunction of the hypothalamus-pituitary-adrenal axis (HPAA) led to decreased secretion of related hormones. The HPAA function might be partially restored with administation of qiangji jianli yin. (authors)

  15. Comparison of the neurobiological effects of attribution retraining group therapy with those of selective serotonin reuptake inhibitors

    Directory of Open Access Journals (Sweden)

    C. Wang

    2013-03-01

    Full Text Available The aim of this study was to compare the effectiveness of attribution retraining group therapy (ARGT with selective serotonin reuptake inhibitors (SSRIs in the treatment of major depressive disorder (MDD, generalized anxiety disorder (GAD, and obsessive-compulsive disorder (OCD. Subjects were sequentially recruited and randomized into two groups, one receiving ARGT (n = 63 and the other SSRIs (n = 66 for 8 weeks. Fifty-four ARGT outpatients with MDD (n = 19, GAD (n = 19, and OCD (n = 16 and 55 SSRI outpatients with MDD (n = 19, GAD (n = 19, and OCD (n = 17 completed the study. All subjects were assessed using the Hamilton Depression Scale and Hamilton Anxiety Scale before and after treatment. The 10-item Yale-Brown Obsessive Compulsive Scale was employed only for OCD subjects. Plasma levels of serotonin, norepinephrine, cortisol, and adrenocorticotropic hormone were also measured at baseline and 8 weeks after completion of treatment. Symptom scores were significantly reduced (P < 0.001 in both the ARGT and SSRI groups at the end of treatment. However, MDD, GAD and OCD patients in the ARGT group had significantly lower plasma cortisol concentrations compared to baseline (P < 0.05, whereas MDD and OCD patients receiving SSRIs showed significantly increased plasma levels of serotonin (P < 0.05. These findings suggest that ARGT may modulate plasma cortisol levels and affect the hypothalamus-pituitary-adrenal axis as opposed to SSRIs, which may up-regulate plasma serotonin levels via a different pathway to produce an overall improvement in the clinical condition of the patients.

  16. Comparison of the neurobiological effects of attribution retraining group therapy with those of selective serotonin reuptake inhibitors

    Directory of Open Access Journals (Sweden)

    C. Wang

    Full Text Available The aim of this study was to compare the effectiveness of attribution retraining group therapy (ARGT with selective serotonin reuptake inhibitors (SSRIs in the treatment of major depressive disorder (MDD, generalized anxiety disorder (GAD, and obsessive-compulsive disorder (OCD. Subjects were sequentially recruited and randomized into two groups, one receiving ARGT (n = 63 and the other SSRIs (n = 66 for 8 weeks. Fifty-four ARGT outpatients with MDD (n = 19, GAD (n = 19, and OCD (n = 16 and 55 SSRI outpatients with MDD (n = 19, GAD (n = 19, and OCD (n = 17 completed the study. All subjects were assessed using the Hamilton Depression Scale and Hamilton Anxiety Scale before and after treatment. The 10-item Yale-Brown Obsessive Compulsive Scale was employed only for OCD subjects. Plasma levels of serotonin, norepinephrine, cortisol, and adrenocorticotropic hormone were also measured at baseline and 8 weeks after completion of treatment. Symptom scores were significantly reduced (P < 0.001 in both the ARGT and SSRI groups at the end of treatment. However, MDD, GAD and OCD patients in the ARGT group had significantly lower plasma cortisol concentrations compared to baseline (P < 0.05, whereas MDD and OCD patients receiving SSRIs showed significantly increased plasma levels of serotonin (P < 0.05. These findings suggest that ARGT may modulate plasma cortisol levels and affect the hypothalamus-pituitary-adrenal axis as opposed to SSRIs, which may up-regulate plasma serotonin levels via a different pathway to produce an overall improvement in the clinical condition of the patients.

  17. Blubber cortisol: a potential tool for assessing stress response in free-ranging dolphins without effects due to sampling.

    Directory of Open Access Journals (Sweden)

    Nicholas M Kellar

    Full Text Available When paired with dart biopsying, quantifying cortisol in blubber tissue may provide an index of relative stress levels (i.e., activation of the hypothalamus-pituitary-adrenal axis in free-ranging cetacean populations while minimizing the effects of the act of sampling. To validate this approach, cortisol was extracted from blubber samples collected from beach-stranded and bycaught short-beaked common dolphins using a modified blubber steroid isolation technique and measured via commercially available enzyme immunoassays. The measurements exhibited appropriate quality characteristics when analyzed via a bootstraped stepwise parallelism analysis (observed/expected = 1.03, 95%CI: 99.6 - 1.08 and showed no evidence of matrix interference with increasing sample size across typical biopsy tissue masses (75-150 mg; r(2 = 0.012, p = 0.78, slope = 0.022 ng(cortisol deviation/ul(tissue extract added. The relationships between blubber cortisol and eight potential cofactors namely, 1 fatality type (e.g., stranded or bycaught, 2 specimen condition (state of decomposition, 3 total body length, 4 sex, 5 sexual maturity state, 6 pregnancy status, 7 lactation state, and 8 adrenal mass, were assessed using a Bayesian generalized linear model averaging technique. Fatality type was the only factor correlated with blubber cortisol, and the magnitude of the effect size was substantial: beach-stranded individuals had on average 6.1-fold higher cortisol levels than those of bycaught individuals. Because of the difference in conditions surrounding these two fatality types, we interpret this relationship as evidence that blubber cortisol is indicative of stress response. We found no evidence of seasonal variation or a relationship between cortisol and the remaining cofactors.

  18. Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.

    Science.gov (United States)

    Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie-Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania

    2015-12-01

    Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Non-infant adoption from care: lessons for safeguarding children.

    Science.gov (United States)

    Rees, C A; Selwyn, J

    2009-07-01

    responsibilities in supporting it need to be acknowledged and adequately resourced. Dysfunctional hypothalamus-pituitary-adrenal axis programming may contribute to persisting difficulties. Supporting substitute care should be considered integral to safeguarding children.

  20. Characterisation of CART-containing neurons and cells in the porcine pancreas, gastro-intestinal tract, adrenal and thyroid glands

    Directory of Open Access Journals (Sweden)

    Gunnarsdóttir Anna

    2007-07-01

    Full Text Available Abstract Background The peptide CART is widely expressed in central and peripheral neurons, as well as in endocrine cells. Known peripheral sites of expression include the gastrointestinal (GI tract, the pancreas, and the adrenal glands. In rodent pancreas CART is expressed both in islet endocrine cells and in nerve fibers, some of which innervate the islets. Recent data show that CART is a regulator of islet hormone secretion, and that CART null mutant mice have islet dysfunction. CART also effects GI motility, mainly via central routes. In addition, CART participates in the regulation of the hypothalamus-pituitary-adrenal-axis. We investigated CART expression in porcine pancreas, GI-tract, adrenal glands, and thyroid gland using immunocytochemistry. Results CART immunoreactive (IR nerve cell bodies and fibers were numerous in pancreatic and enteric ganglia. The majority of these were also VIP IR. The finding of intrinsic CART containing neurons indicates that pancreatic and GI CART IR nerve fibers have an intrinsic origin. No CART IR endocrine cells were detected in the pancreas or in the GI tract. The adrenal medulla harboured numerous CART IR endocrine cells, most of which were adrenaline producing. In addition CART IR fibers were frequently seen in the adrenal cortex and capsule. The capsule also contained CART IR nerve cell bodies. The majority of the adrenal CART IR neuronal elements were also VIP IR. CART IR was also seen in a substantial proportion of the C-cells in the thyroid gland. The majority of these cells were also somatostatin IR, and/or 5-HT IR, and/or VIP IR. Conclusion CART is a major neuropeptide in intrinsic neurons of the porcine GI-tract and pancreas, a major constituent of adrenaline producing adrenomedullary cells, and a novel peptide of the thyroid C-cells. CART is suggested to be a regulatory peptide in the porcine pancreas, GI-tract, adrenal gland and thyroid.

  1. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

    Science.gov (United States)

    Quigley, Eamonn M M

    2017-10-17

    The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

  2. Nanoparticle Delivered Human Biliverdin Reductase-Based Peptide Increases Glucose Uptake by Activating IRK/Akt/GSK3 Axis: The Peptide Is Effective in the Cell and Wild-Type and Diabetic Ob/Ob Mice

    Directory of Open Access Journals (Sweden)

    Peter E. M. Gibbs

    2016-01-01

    Full Text Available Insulin’s stimulation of glucose uptake by binding to the IRK extracellular domain is compromised in diabetes. We have recently described an unprecedented approach to stimulating glucose uptake. KYCCSRK (P2 peptide, corresponding to the C-terminal segment of hBVR, was effective in binding to and inducing conformational change in the IRK intracellular kinase domain. Although myristoylated P2, made of L-amino acids, was effective in cell culture, its use for animal studies was unsuitable. We developed a peptidase-resistant formulation of the peptide that was efficient in both mice and cell culture systems. The peptide was constructed of D-amino acids, in reverse order, and blocked at both termini. Delivery of the encapsulated peptide to HepG2 and HSKM cells was confirmed by its prolonged effect on stimulation of glucose uptake (>6 h. The peptide improved glucose clearance in both wild-type and Ob/Ob mice; it lowered blood glucose levels and suppressed glucose-stimulated insulin secretion. IRK activity was stimulated in the liver of treated mice and in cultured cells. The peptide potentiated function of IRK’s downstream effector, Akt-GSK3-(α,β axis. Thus, P2-based approach can be used for improving glucose uptake by cells. Also, it allows for screening peptides in vitro and in animal models for treatment of diabetes.

  3. UMAPRM: Uniformly sampling the medial axis

    KAUST Repository

    Yeh, Hsin-Yi Cindy

    2014-05-01

    © 2014 IEEE. Maintaining clearance, or distance from obstacles, is a vital component of successful motion planning algorithms. Maintaining high clearance often creates safer paths for robots. Contemporary sampling-based planning algorithms That utilize The medial axis, or The set of all points equidistant To Two or more obstacles, produce higher clearance paths. However, They are biased heavily Toward certain portions of The medial axis, sometimes ignoring parts critical To planning, e.g., specific Types of narrow passages. We introduce Uniform Medial Axis Probabilistic RoadMap (UMAPRM), a novel planning variant That generates samples uniformly on The medial axis of The free portion of Cspace. We Theoretically analyze The distribution generated by UMAPRM and show its uniformity. Our results show That UMAPRM\\'s distribution of samples along The medial axis is not only uniform but also preferable To other medial axis samplers in certain planning problems. We demonstrate That UMAPRM has negligible computational overhead over other sampling Techniques and can solve problems The others could not, e.g., a bug Trap. Finally, we demonstrate UMAPRM successfully generates higher clearance paths in The examples.

  4. Actuator assembly including a single axis of rotation locking member

    Science.gov (United States)

    Quitmeyer, James N.; Benson, Dwayne M.; Geck, Kellan P.

    2009-12-08

    An actuator assembly including an actuator housing assembly and a single axis of rotation locking member fixedly attached to a portion of the actuator housing assembly and an external mounting structure. The single axis of rotation locking member restricting rotational movement of the actuator housing assembly about at least one axis. The single axis of rotation locking member is coupled at a first end to the actuator housing assembly about a Y axis and at a 90.degree. angle to an X and Z axis providing rotation of the actuator housing assembly about the Y axis. The single axis of rotation locking member is coupled at a second end to a mounting structure, and more particularly a mounting pin, about an X axis and at a 90.degree. angle to a Y and Z axis providing rotation of the actuator housing assembly about the X axis. The actuator assembly is thereby restricted from rotation about the Z axis.

  5. Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal-axis (HPA-axis)

    OpenAIRE

    Lee, Richard; Sawa, Akira

    2014-01-01

    In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the hypothalamic-pituitary-adrenal axis (HPA)-axis function and behavior. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA-axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, duration, and intensity during di...

  6. Nitric oxide in the stress axis.

    Science.gov (United States)

    López-Figueroa, M O; Day, H E; Akil, H; Watson, S J

    1998-10-01

    In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.

  7. Neutral axis as damage sensitive feature

    International Nuclear Information System (INIS)

    Sigurdardottir, D H; Glisic, B

    2013-01-01

    Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature. (paper)

  8. Neutral axis as damage sensitive feature

    Science.gov (United States)

    Sigurdardottir, D. H.; Glisic, B.

    2013-07-01

    Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature.

  9. Aeroelastically coupled blades for vertical axis wind turbines

    Science.gov (United States)

    Paquette, Joshua; Barone, Matthew F.

    2016-02-23

    Various technologies described herein pertain to a vertical axis wind turbine blade configured to rotate about a rotation axis. The vertical axis wind turbine blade includes at least an attachment segment, a rear swept segment, and optionally, a forward swept segment. The attachment segment is contiguous with the forward swept segment, and the forward swept segment is contiguous with the rear swept segment. The attachment segment includes a first portion of a centroid axis, the forward swept segment includes a second portion of the centroid axis, and the rear swept segment includes a third portion of the centroid axis. The second portion of the centroid axis is angularly displaced ahead of the first portion of the centroid axis and the third portion of the centroid axis is angularly displaced behind the first portion of the centroid axis in the direction of rotation about the rotation axis.

  10. Theoretical tool movement required to diamond turn an off-axis paraboloid on axis

    International Nuclear Information System (INIS)

    Thompson, D.C.

    1976-01-01

    Current techniques for manufacturing off-axis paraboloids are both expensive and insufficiently accurate. An alternative method, turning the workpiece about its axis on a diamond-turning machine, is presented, and the equations describing the necessary tool movement are derived. A discussion of a particular case suggests that the proposed technique is feasible

  11. New Urban Vertical Axis Wind Turbine Design

    Directory of Open Access Journals (Sweden)

    Alexandru-Mihai CISMILIANU

    2015-12-01

    Full Text Available This paper develops a different approach for enhancing the performance of Vertical Axis Wind Turbines for the use in the urban or rural environment and remote isolated residential areas. Recently the vertical axis wind turbines (VAWT have become more attractive due to the major advantages of this type of turbines in comparison to the horizontal axis wind turbines. We aim to enhance the overall performance of the VAWT by adding a second set of blades (3 x 2=6 blades following the rules of biplane airplanes. The model has been made to operate at a maximum power in the range of the TSR between 2 to 2.5. The performances of the VAWT were investigated numerically and experimentally and justify the new proposed design.

  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. RITA: The reinvented triple axis spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Mason, T.E. [Toronto Univ., ON (Canada). Dept. of Physics; Clausen, K.N.; Aeppli, G.; McMorrow, D.R.; Kjems, J.K. [Risoe National Lab., Roskilde (Denmark)

    1995-11-01

    Risoe National Laboratory was reported to be in the process of developing a new spectrometer design, RITA, based on the triple axis design. The spectrometer will attempt to incorporate more recent innovations such as multilayer supermirrors and microstrip proportional counters into a rethinking of the triple-axis spectrometer. By optimizing the beam optics, using supermirrors and extending the analyser to map regions of (Q, {omega}) space using an array of independently controllable pyrolytic graphite crystals focussed on an area detector, it was hoped that the efficiency of single-crystal inelastic experiments could be increased by as much as a factor of 20. 7 figs., 20 refs.

  14. Equilibrium studies of helical axis stellarators

    International Nuclear Information System (INIS)

    Hender, T.C.; Carreras, B.A.; Garcia, L.; Harris, J.H.; Rome, J.A.; Cantrell, J.L.; Lynch, V.E.

    1984-01-01

    The equilibrium properties of helical axis stellarators are studied with a 3-D equilibrium code and with an average method (2-D). The helical axis ATF is shown to have a toroidally dominated equilibrium shift and good equilibria up to at least 10% peak beta. Low aspect ratio heliacs, with relatively large toroidal shifts, are shown to have low equilibrium beta limits (approx. 5%). Increasing the aspect ratio and number of field periods proportionally is found to improve the equilibrium beta limit. Alternatively, increasing the number of field periods at fixed aspect ratio which raises and lowers the toroidal shift improves the equilibrium beta limit

  15. Insulin-Like Growth Factor Axis Expression in Dental Pulp Cells Derived From Carious Teeth

    Directory of Open Access Journals (Sweden)

    Hanaa Esa Alkharobi

    2018-04-01

    Full Text Available The insulin-like growth factor (IGF axis plays an important role in dental tissue regeneration and most components of this axis are expressed in human dental pulp cells (DPCs. In our previous study, we analyzed IGF axis gene expression in DPCs and demonstrated a novel role of IGF binding protein (IGFBP-2 and -3 in coordinating mineralized matrix formation in differentiating DPCs. A more recent study from our laboratory partially characterized dental pulp stem cells from teeth with superficial caries (cDPCs and showed that their potential to differentiate odontoblasts and/or into osteoblasts is enhanced by exposure to the mild inflammatory conditions characteristic of superficial caries. In the present study, we examine whether changes apparent in IGF axis expression during osteogenic differentiation of healthy DPCs are also apparent in DPCs derived from carious affected teeth.

  16. Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions

    DEFF Research Database (Denmark)

    Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A

    2015-01-01

    OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched...... for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation...... of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. DESIGN: Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls...

  17. Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition II: Computational Modeling

    Science.gov (United States)

    ABSTRACT Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We developed a mechanistic mathematical model of the hypothalamic­ pituitary-gonadal (HPG) axis in female fathead minnows to predic...

  18. The role of the vascular endothelial growth factor/vascular endothelial growth factor receptors axis mediated angiogenesis in curcumin-loaded nanostructured lipid carriers induced human HepG2 cells apoptosis

    Directory of Open Access Journals (Sweden)

    Fengling Wang

    2015-01-01

    Full Text Available Background: Curcumin (diferuloylmethane, the active constituent of turmeric extract has potent anti-cancer properties have been demonstrated in hepatocellular carcinoma (HCC. However, its underlying molecular mechanism of therapeutic effects remains unclear. Vascular endothelial growth factor (VEGF and its receptors (VEGFRs have crucial roles in tumor angiogenesis. Purpose: The goal of this study was to investigate the role of the VEGF/VEGFRs mediated angiogenesis during the proliferation and apoptosis of human HepG2 hepatoma cell line and the effect of curcumin-loaded nanostructured lipid carriers (Cur-NLC. Materials and Methods: The proliferation of HepG2 cells was determined by methyl thiazolyl tetrazolium after exposure to Cur-NLC and native curcumin. Apoptosis was quantified by flow cytometry with annexin V-fluorescein isothiocyanate and propidium iodide staining. Cellular internalization of Cur-NLC was observed by fluorescent microscope. The level of VEGF was detected by enzyme-linked immunosorbent assay kits. The expression of VEGFRs was quantified by Western blotting. Results: Cur-NLC was more effective in inhibiting the proliferation and enhancing the apoptosis of HepG2 cells than native curcumin. Fluorescent microscope analysis showed that HepG2 cells internalized Cur-NLC more effectively than native curcumin. Furthermore, Cur-NLC down-regulated the level of VEGF and the expression of VEGFR-2, but had a slight effect on VEGFR-1. Conclusion: These results clearly demonstrated that Cur-NLC was more effective in anti-cancer activity than the free form of curcumin. These studies demonstrate for the 1 st time that Cur-NLC exerts an antitumor effect on HepG2 cells by modulating VEGF/VEGFRs signaling pathway.

  19. Evolution of hypothalamus-pituitary growth axis among fish, amphibian, birds and mammals

    Directory of Open Access Journals (Sweden)

    Moaeen-Ud-Din M.

    2015-01-01

    Full Text Available Hypothalamus-pituitary growth axis (HP growth axis regulates animal growth and development in pre-natal and post natal life governed by many factors. However, until recently, the evolutionary history of this axis among lineages is not understood. Aim of the present study was to understand the major events in evolution and evolutionary history and trend of HP growth axis. The diversity among Homo sapience, Mus musculus, Rattus norvegicus, Gallus gallus, Danio rerio and Xenopus laevis was determined for genes involved in HP growth axis in current study. Sequences of HP growth axis genes were retrieved from NCBI (http://www.ncbi.nlm.nih.gov/. Nucleotide diversity using Kimura’s two-parameter method; codon-based test of positive selection using the Nei-Gojobori; equality of evolutionary rate with Tajima's relative rate test and phylogenetic history using the RelTime method were estimated in MEGA6. Estimates of the coefficients of evolutionary differentiation based on nucleotides and amino acids substitution patterns of HP growth axis genes showed contrasting evolutionary patterns among the lineages. The results demonstrated that although these genes might have crucial functional roles in each of the species, however, their sequence divergence did not necessarily reflect similar molecular evolution among the species. Codon-based test of positive selection revealed that Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat had similar and higher non synonymous substitutions (P > 0.05. Higher rate of non-synonymous substitutions at similar orthologs level among species indicated a similar positive selection pressure in these species. Results for relative rate test assessed with the chi-squared test showed difference on unique mutations among lineages at synonymous and non synonymous sites except Chicken vs Mouse, Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat. This indicated that the mutagenic process that generates

  20. Triple-axis spectrometer DruechaL

    International Nuclear Information System (INIS)

    Buehrer, W.; Keller, P.

    1996-01-01

    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs

  1. Vortex capturing vertical axis wind turbine

    International Nuclear Information System (INIS)

    Zannetti, L; Gallizio, F; Ottino, G

    2007-01-01

    An analytical-numerical study is presented for an innovative lift vertical axis turbine whose blades are designed with vortex trapping cavities that act as passive flow control devices. The unsteady flow field past one-bladed and two-bladed turbines is described by a combined analytical and numerical method based on conformal mapping and on a blob vortex method

  2. The Trading Axis in Irkutsk Downtown

    Directory of Open Access Journals (Sweden)

    Elena Grigoryeva

    2016-10-01

    Full Text Available The article reveals a linear concentration of the trading function in the historical center of Irkutsk. It features historical prerequisites and continuation of the tradition in the post-Soviet period, given the conversion of plants and factories. The article analyses the current state and prospects of modernization of the trading axis with its transformation into a modern public space.

  3. Triple-axis spectrometer DruechaL

    Energy Technology Data Exchange (ETDEWEB)

    Buehrer, W; Keller, P [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs.

  4. Reframing the Teenage Wasteland: Adolescent Microbiota-Gut-Brain Axis.

    Science.gov (United States)

    McVey Neufeld, Karen-Anne; Luczynski, Pauline; Dinan, Timothy G; Cryan, John F

    2016-04-01

    Human adolescence is arguably one of the most challenging periods of development. The young adult is exposed to a variety of stressors and environmental stimuli on a backdrop of significant physiological change and development, which is especially apparent in the brain. It is therefore unsurprising that many psychiatric disorders are first observable during this time. The human intestine is inhabited by trillions of microorganisms, and evidence from both preclinical and clinical research focusing on the established microbiota-gut-brain axis suggests that the etiology and pathophysiology of psychiatric disorders may be influenced by intestinal dysbiosis. Provocatively, many if not all of the challenges faced by the developing teen have a documented impact on these intestinal commensal microbiota. In this review, we briefly summarize what is known about the developing adolescent brain and intestinal microbiota, discuss recent research investigating the microbiota-gut-brain axis during puberty, and propose that pre- and probiotics may prove useful in both the prevention and treatment of psychiatric disorders specifically benefitting the young adult. © The Author(s) 2016.

  5. METHODOLOGY FOR CROSS-CURRICULAR THEME OF THE ENVIRONMENTAL AXIS

    Directory of Open Access Journals (Sweden)

    José Luis Aparicio López

    2015-04-01

    Full Text Available This article introduces a methodology to identify the presence of the environmental axis in educational programs in Bachelors in the Universidad Autónoma de Guerrero, Mexico. It is sustained on competency-based education and constructionism, due to they appeal to humanism to deal current problems. It is composed of four phases: committee conformation, theoretical and conceptual concerning analysis, construction and application of instruments on a PE, and identification of the cross-curricular theme level. Even though the proposed methodology is applied to the environment, it is feasible to adapt to other axes, such as human rights, multiculturalism, and poverty, relevant to the educational context of the state of Guerrero.

  6. UARS PEM Level 2 AXIS 2 V001 (UARPE2AXIS2) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 2 daily product contains the X-ray high-resolution spectral...

  7. UARS PEM Level 2 AXIS 1 V001 (UARPE2AXIS1) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 1 daily product contains the X-ray high-resolution spectral...

  8. Food and the circadian activity of the hypothalamic-pituitary-adrenal axis

    Directory of Open Access Journals (Sweden)

    A.M.O. Leal

    1997-12-01

    Full Text Available Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or" zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states

  9. Does the GH/IGF-1 axis contribute to skeletal sexual dimorphism? Evidence from mouse studies.

    Science.gov (United States)

    Liu, Zhongbo; Mohan, Subburaman; Yakar, Shoshana

    2016-04-01

    The contribution of the gonadotropic axis to skeletal sexual dimorphism (SSD) was clarified in recent years. Studies with animal models of estrogen receptor (ER) or androgen receptor (AR) null mice, as well as mice with bone cell-specific ablation of ER or AR, revealed that both hormones play major roles in skeletal acquisition, and that estrogen regulates skeletal accrual in both sexes. The growth hormone (GH) and its downstream effector, the insulin-like growth factor-1 (IGF-1) are also major determinants of peak bone mass during puberty and young adulthood, and play important roles in maintaining bone integrity during aging. A few studies in both humans and animal models suggest that in addition to the differences in sex steroid actions on bone, sex-specific effects of GH and IGF-1 play essential roles in SSD. However, the contributions of the somatotropic (GH/IGF-1) axis to SSD are controversial and data is difficult to interpret. GH/IGF-1 are pleotropic hormones that act in an endocrine and autocrine/paracrine fashion on multiple tissues, affecting body composition as well as metabolism. Thus, understanding the contribution of the somatotropic axis to SSD requires the use of mouse models that will differentiate between these two modes of action. Elucidation of the relative contribution of GH/IGF-1 axis to SSD is significant because GH is approved for the treatment of normal children with short stature and children with congenital growth disorders. Thus, if the GH/IGF-1 axis determines SSD, treatment with GH may be tailored according to sex. In the following review, we give an overview of the roles of sex steroids in determining SSD and how they may interact with the GH/IGF-1 axis in bone. We summarize several mouse models with impaired somatotropic axis and speculate on the possible contribution of that axis to SSD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Resolution of a triple axis spectrometer

    DEFF Research Database (Denmark)

    Nielsen, Mourits; Bjerrum Møller, Hans

    1969-01-01

    A new method for obtaining the resolution function for a triple-axis neutron spectrometer is described, involving a combination of direct measurement and analytical calculation. All factors which contribute to the finite resolution of the instrument may be taken into account, and Gaussian...... or experimentally determined probability distributions may be used. The application to the study of the dispersion relation for excitations in a crystal is outlined...

  11. Interplay between tilted and principal axis rotation

    International Nuclear Information System (INIS)

    Datta, Pradip; Roy, Santosh; Chattopadhyay, S.

    2014-01-01

    At IUAC-INGA, our group has studied four neutron rich nuclei of mass-110 region, namely 109,110 Ag and 108,110 Cd. These nuclei provide the unique platform to study the interplay between Tilted and Principal axis rotation since these are moderately deformed and at the same time, shears structures are present at higher spins. The salient features of the high spin behaviors of these nuclei will be discussed which are the signatures of this interplay

  12. Interplay between tilted and principal axis rotation

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Pradip [Ananda Mohan College, 102/1 Raja Rammohan Sarani, Kolkata 700 009 (India); Roy, Santosh; Chattopadhyay, S. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700 064 (India)

    2014-08-14

    At IUAC-INGA, our group has studied four neutron rich nuclei of mass-110 region, namely {sup 109,110}Ag and {sup 108,110}Cd. These nuclei provide the unique platform to study the interplay between Tilted and Principal axis rotation since these are moderately deformed and at the same time, shears structures are present at higher spins. The salient features of the high spin behaviors of these nuclei will be discussed which are the signatures of this interplay.

  13. Evidence of a liver-alpha cell axis in humans

    DEFF Research Database (Denmark)

    Wewer Albrechtsen, Nicolai J; Færch, Kristine; Jensen, Troels M

    2018-01-01

    . In this cohort, we have previously reported insulin resistance to be accompanied by increased plasma concentrations of glucagon. We now measure plasma levels of amino acids in the same cohort. HOMA-IR was calculated as a marker of hepatic insulin resistance. RESULTS: Fasting levels of glucagonotropic amino acids...

  14. Psychological traits and the cortisol awakening response: results from the Netherlands Study of Depression and Anxiety.

    Science.gov (United States)

    van Santen, Aafke; Vreeburg, Sophie A; Van der Does, A J Willem; Spinhoven, Philip; Zitman, Frans G; Penninx, Brenda W J H

    2011-02-01

    Hypothalamus-Pituitary-Adrenal (HPA) axis dysregulation is often seen in major depression, and is thought to represent a trait vulnerability - rather than merely an illness marker - for depressive disorder and possibly anxiety disorder. Vulnerability traits associated with stress-related disorders might reflect increased sensitivity for the development of psychopathology through an association with HPA axis activity. Few studies have examined the association between psychological trait factors and the cortisol awakening response, with inconsistent results. The present study examined the relationship between multiple psychological trait factors and the cortisol awakening curve, including both the dynamic of the CAR and overall cortisol awakening levels, in a sample of persons without psychopathology, hypothesizing that persons scoring high on vulnerability traits demonstrate an elevated cortisol awakening curve. From 2981 participants of the Netherlands Study of Depression and Anxiety (NESDA), baseline data from 381 controls (aged 18-65) without previous, current and parental depression and anxiety disorders were analyzed. Psychological measures included the Big Five personality traits (neuroticism, extraversion, openness to experience, conscientiousness, and agreeableness) measured using the NEO-FFI, anxiety sensitivity assessed by the Anxiety Sensitivity Index, cognitive reactivity to sadness (hopelessness, acceptance/coping, aggression, control/perfectionism, risk aversion, and rumination) as measured by the LEIDS-R questionnaire, and mastery, assessed using the Pearlin and Schooler Mastery scale. Salivary cortisol levels were measured at awakening, and 30, 45, and 60 min afterwards. In adjusted analyses, high scores of hopelessness reactivity (β=.13, p=.02) were consistently associated with a higher cortisol awakening response. In addition, although inconsistent across analyses, persons scoring higher on extraversion, control/perfectionism reactivity, and

  15. Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults

    Directory of Open Access Journals (Sweden)

    Ota Miho

    2011-07-01

    Full Text Available Abstract Background Recently, hypothalamus-pituitary-adrenal (HPA axis function assessed with the combined dexamethasone (DEX/corticotropin releasing hormone (CRH test has been shown to be associated with response to antidepressant treatment. A polymorphism (rs16944 in the interleukin-1beta (IL-1β gene has also been reported to be associated with the medication response in depression. These findings prompted us to examine the possible association between IL-1β gene polymorphisms and HPA axis function assessed with the DEX/CRH test. Methods DEX/CRH test was performed in 179 healthy volunteers (45 males: mean age 40.5 ± 15.8 years; 134 females: mean age 47.1 ± 13.2 years. Five tagging single nucleotide polymorphisms (SNPs of IL-1β gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944 were selected at an r2 threshold of 0.80 with a minor allele frequency > 0.1. Genotyping was performed by the TaqMan allelic discrimination assay. A two-way factorial analysis of variance (ANOVA was performed with the DEX/CRH test results as the dependent variable and genotype and gender as independent variables. To account for multiple testing, P values Results The cortisol levels after DEX administration (DST-Cortisol showed significant associations with the genotypes of rs16944 (P = 0.00049 and rs1143633 (P = 0.0060, with no significant gender effect or genotype × gender interaction. On the other hand, cortisol levels after CRH administration (DEX/CRH-Cortisol were affected by gender but were not significantly influenced by the genotype of the examined SNPs, with no significant genotype × gender interaction. Conclusions Our results suggest that genetic variations in the IL-1β gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the IL-1β gene polymorphisms with the DEX/CRH-Cortisol were observed. Confirmation of our findings in futures studies may add new insight into

  16. Congenital axis dysmorphism in a medieval skeleton : …secunda a vertendo epistropheus….

    Science.gov (United States)

    Travan, Luciana; Saccheri, Paola; Toso, Francesco; Crivellato, Enrico

    2013-05-01

    We describe here the axis dysmorphism that we observed in the skeletal remains of a human child dug up from a fifteenth century cemetery located in north-eastern Italy. This bone defect is discussed in the light of pertinent literature. We performed macroscopical examination and CT scan analysis of the axis. Axis structure was remarkably asymmetric. Whilst the left half exhibited normal morphology, the right one was smaller than normal, and its lateral articular surface showed horizontal orientation. In addition, the odontoid process appeared leftward deviated and displayed a supplementary articular-like facet situated on the right side of its surface. These findings suggest a diagnosis of unilateral irregular segmentation of atlas and axis, a rare dysmorphism dependent upon disturbances of notochordal development in early embryonic life. Likewise other malformations of the craniovertebral junction, this axis defect may alter the delicate mechanisms of upper neck movements and cause a complex series of clinical symptoms. This is an emblematic case whereby human skeletal remains may provide valuable information on the anatomical defects of craniovertebral junction.

  17. Adaptive Response in Female Modeling of the Hypothalamic-pituitary-gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

  18. Six-axis force–torque sensor with a large range for biomechanical applications

    International Nuclear Information System (INIS)

    + Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" data-affiliation=" (MESA+ Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" >Brookhuis, R A; + Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" data-affiliation=" (MESA+ Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" >Droogendijk, H; + Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" data-affiliation=" (MESA+ Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" >De Boer, M J; + Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" data-affiliation=" (MESA+ Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" >Sanders, R G P; + Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" data-affiliation=" (MESA+ Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" >Lammerink, T S J; + Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" data-affiliation=" (MESA+ Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" >Wiegerink, R J; + Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" data-affiliation=" (MESA+ Institute for Nanotechnology, University of Twente, Enschede (Netherlands))" >Krijnen, G J M

    2014-01-01

    A silicon six-axis force–torque sensor is designed and realized to be used for measurement of the power transfer between the human body and the environment. Capacitive read-out is used to detect all axial force components and all torque components simultaneously. Small electrode gaps in combination with mechanical amplification by the sensor structure result in a high sensitivity. The miniature sensor has a wide force range of up to 50 N in normal direction, 10 N in shear direction and 25 N mm of maximum torque around each axis. (paper)

  19. Theoretical tool movement required to diamond turn an off-axis paraboloid on axis

    International Nuclear Information System (INIS)

    Thompson, D.C.

    1975-01-01

    High-quality, off-axis parabolic reflectors, required by the CTR and laser-fusion programs at Lawrence Livermore Laboratory (LLL) and other ERDA laboratories, are currently manufactured by hand. There are several drawbacks to this method, including lead times of up to a year, costs in excess of dollars 75,000 for a small reflector, and unsatisfactory limits to the tolerances obtainable. This situation has led to a search for cheaper and more accurate methods of manufacturing off-axis paraboloids. An alternative method, turning the workpiece about its axis on a diamond-turning machine, is presented, and the equations describing the necessary tool movement are derived. A discussion of a particular case suggests that the proposed technique is feasible

  20. The Triple Axis and SPINS Spectrometers.

    Science.gov (United States)

    Trevino, S F

    1993-01-01

    In this paper are described the triple axis and spin polarized inelastic neutron scattering (SPINS) spectrometers which are installed at the NIST Cold Neutron Research Facility (CNRF). The general principle of operation of these two instruments is described in sufficient detail to allow the reader to make an informed decision as to their usefulness for his needs. However, it is the intention of the staff at the CNRF to provide the expert resources for their efficient use in any given situation. Thus, this work is not intended as a user manual but rather as a guide into the range of applicability of the two instruments.

  1. Equilibrium calculations for helical axis stellarators

    International Nuclear Information System (INIS)

    Hender, T.C.; Carreras, B.A.

    1984-04-01

    An average method based on a vacuum flux coordinate system is presented. This average method permits the study of helical axis stellarators with toroidally dominated shifts. An ordering is introduced, and to lowest order the toroidally averaged equilibrium equations are reduced to a Grad-Shafranov equation. Also, to lowest order, a Poisson-type equation is obtained for the toroidally varying corrections to the equilibium. By including these corrections, systems that are toroidally dominated, but with significant helical distortion to the equilibrium, may be studied. Numerical solutions of the average method equations are shown to agree well with three-dimensional calculations

  2. Three-axis asymmetric radiation detector system

    Science.gov (United States)

    Martini, Mario Pierangelo; Gedcke, Dale A.; Raudorf, Thomas W.; Sangsingkeow, Pat

    2000-01-01

    A three-axis radiation detection system whose inner and outer electrodes are shaped and positioned so that the shortest path between any point on the inner electrode and the outer electrode is a different length whereby the rise time of a pulse derived from a detected radiation event can uniquely define the azimuthal and radial position of that event, and the outer electrode is divided into a plurality of segments in the longitudinal axial direction for locating the axial location of a radiation detection event occurring in the diode.

  3. Extracellular matrix dynamics during vertebrate axis formation.

    Science.gov (United States)

    Czirók, András; Rongish, Brenda J; Little, Charles D

    2004-04-01

    The first evidence for the dynamics of in vivo extracellular matrix (ECM) pattern formation during embryogenesis is presented below. Fibrillin 2 filaments were tracked for 12 h throughout the avian intraembryonic mesoderm using automated light microscopy and algorithms of our design. The data show that these ECM filaments have a reproducible morphogenic destiny that is characterized by directed transport. Fibrillin 2 particles initially deposited in the segmental plate mesoderm are translocated along an unexpected trajectory where they eventually polymerize into an intricate scaffold of cables parallel to the anterior-posterior axis. The cables coalesce near the midline before the appearance of the next-formed somite. Moreover, the ECM filaments define global tissue movements with high precision because the filaments act as passive motion tracers. Quantification of individual and collective filament "behaviors" establish fate maps, trajectories, and velocities. These data reveal a caudally propagating traveling wave pattern in the morphogenetic movements of early axis formation. We conjecture that within vertebrate embryos, long-range mechanical tension fields are coupled to both large-scale patterning and local organization of the ECM. Thus, physical forces or stress fields are essential requirements for executing an emergent developmental pattern-in this case, paraxial fibrillin cable assembly.

  4. VERITAS: Versatile Triple-Axis Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il

    2006-04-15

    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, {approx} 5 m Curved Guide, {approx} 26 m w/ R 1500 m Straight Guide before the Instrument, {approx} 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world.

  5. VERITAS: Versatile Triple-Axis Spectrometer

    International Nuclear Information System (INIS)

    Park, Sung Il

    2006-04-01

    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, ∼ 5 m Curved Guide, ∼ 26 m w/ R 1500 m Straight Guide before the Instrument, ∼ 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world

  6. Anatomy of an eradication effort: Removing Hawaii's illegally introduced axis deer

    Science.gov (United States)

    Hess, Steven C.; Muise, Jake; Schipper, Jan

    2015-01-01

    In February 2011, a rancher in the rural southern part of Hawaii Island reported a large mammal on her land. Her call mobilized several agencies led by the Big Island Invasive Species Committee (BIISC), a partnership to prevent, detect, and control the establishment and spread of invasive species, to sit up and take notice. Agency biologists installed camera traps to identify the animal, and a few months later verified the diagnostic field marks of a chervid with spots. The animal in questions was a chital, or axis deer (Axis axis)--a species native to tropical and subtropical India. Although the deer are abundant on the islands of Molokai, Lānai, and Maui, officials knew they weren't capable of swimming across the notoriously treacherous ʻAlenuihāhā channel, and subsequently suspected human intervention.

  7. Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review.

    Science.gov (United States)

    Azuma, Kagaku; Zhou, Qian; Niwa, Masami; Kubo, Kin-Ya

    2017-08-03

    Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity.

  8. The Proline Regulatory Axis and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Phang, James Ming; Liu, Wei; Hancock, Chad; Christian, Kyle J., E-mail: phangj@mail.nih.gov [Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States)

    2012-06-21

    Studies in metabolism and cancer have characterized changes in core pathways involving glucose and glutamine, emphasizing the provision of substrates for building cell mass. But recent findings suggest that pathways previously considered peripheral may play a critical role providing mechanisms for cell regulation. Several of these mechanisms involve the metabolism of non-essential amino acids, for example, the channeling of glycolytic intermediates into the serine pathway for one-carbon transfers. Historically, we proposed that the proline biosynthetic pathway participated in a metabolic interlock with glucose metabolism. The discovery that proline degradation is activated by p53 directed our attention to the initiation of apoptosis by proline oxidase/dehydrogenase. Now, however, we find that the biosynthetic mechanisms and the metabolic interlock may depend on the pathway from glutamine to proline, and it is markedly activated by the oncogene MYC. These findings add a new dimension to the proline regulatory axis in cancer and present attractive potential targets for cancer treatment.

  9. Polarized triple-axis spectrometer TASP

    Energy Technology Data Exchange (ETDEWEB)

    Boeni, P; Keller, P [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    The polarized triple-axis spectrometer TASP at SINQ has been optimized for measuring magnetic cross sections in condensed matter. The neutrons are polarized or analyzed either by means of benders or Heusler monochromators. The beam divergence, i.e. the intensity, and the spectral range of the neutrons is rather large because of the supermirror coatings of the feeding neutron guide. The intensity can be further increased at the sample position by means of a focussing monochromator and a focussing anti-trumpet. The end position of TASP allows the tailoring of the neutron beam already before the monochromator and to scatter neutrons over very wide ranges of angles. (author) 6 figs., 1 tab., 8 refs.

  10. A Portable Single Axis Magnetic Gradiometer

    DEFF Research Database (Denmark)

    Merayo, José M.G.; Petersen, Jan Raagaard; Nielsen, Otto V

    2001-01-01

    not provide vector information about the magnetic field. Secondly, one of the sensors measures the ambient magnetic field and is used to compensate for the main field at both sensors. Several methods have been developed for characterization of the 2 gradiometer, and the calibration of the gradient......The single axis magnetic gradiometer based on two compact detector compensation (CDC) fluxgate ringcore sensors separated 20 cm is described. Despite its high stability and precision better than 1 nT, the calibration procedures are not straightforward. Firstly, the mono-axial measurement does...... measurements is achieved by using a magnetic dipole of strength 2 mAm(2). In a coil facility, the gradient can be determined with an accuracy of 0.3 nT/m(RMS)....

  11. RITA-type triple axis spectrometers

    International Nuclear Information System (INIS)

    Roennow, H.M.

    2001-01-01

    The RITA spectrometer at Risoe National Laboratory was the first to incorporate a complete re-thinking of the neutron-path from source, through detector to analysis. Since then, other RITA-type spectrometers such as SPINS at NIST, RITA-II at PSI have been built, and several new spectrometers around the world are adapting the same philosophy. The main novelty of RITA was the introduction of a single back-end tank featuring both an analyser block with multiple individually turnable analyser blades and a 2D position sensitive detector. Several new triple-axis spectrometers are presently being built at existing and future sources, and almost all of them have learnt from the experience with RITA. (R.P.)

  12. Analysis and design of a vertical axis wind turbine

    OpenAIRE

    Goyena Iriso, Joseba

    2011-01-01

    The main objective of this project is to design a new vertical axis wind turbine, specifically one Giromill wind turbine. The project development requires performing a previous study of the vertical axis wind turbines currently development. This study has to be performed before starting to design the wind turbine. Other very important aim is the development of a new vertical axis wind turbine. The after analyses that will result in the final design of the wind turbine will b...

  13. Self-starting aerodynamics analysis of vertical axis wind turbine

    OpenAIRE

    Jianyang Zhu; Hailin Huang; Hao Shen

    2015-01-01

    Vertical axis wind turbine is a special type of wind-force electric generator which is capable of working in the complicated wind environment. The self-starting aerodynamics is one of the most important considerations for this kind of turbine. This article aims at providing a systematic synthesis on the self-starting aerodynamic characteristics of vertical axis wind turbine based on the numerical analysis approach. First, the physical model of vertical axis wind turbine and its parameter defi...

  14. Concept of a Programmable Fixture for 3-Axis CNC

    Directory of Open Access Journals (Sweden)

    Ahmad Dalloul

    2017-09-01

    Full Text Available CNC machine is the one of the major reasons for industrial advancement in recent decades for its ability of producing accurate parts. The most commen CNC machines are of 3-axis and adopted widely in the industrial sector. However, for producing more complicated parts 5-axis CNC machines are required. Although the introduction of the 5-axis machine came after the 3-axis CNC machine has established itself and many manufacturers did not make the move toward the newer model and its high pricing compared to the 3-axis model did not help either. In this time the development of a fixture or a platform to help transfer the 3-axis to a 5-axis to some degree. This paper discusses the concept of a programmable fixture that gives 3-axis CNC machine the freedom to act in similar manner as the 5-axis. The paper describes the mechanism with some initial results of the testing. Result showed that the platform moves in translation manner with an average error of 5.58 % and 7.303% average error for rotation movement.

  15. Suicidal behavior on Axis VI: clinical data supporting a sixth Axis for DSM-V.

    Science.gov (United States)

    Van Orden, Kimberly A; Witte, Tracy K; Holm-Denoma, Jill; Gordon, Kathryn H; Joiner, Thomas E

    2011-01-01

    Oquendo and colleagues (Oquendo, Baca-García, Mann, & Giner, 2008; Oquendo & Currier, 2009) recommend that DSM-V emphasize suicide risk assessment on a sixth axis, thereby increasing regularity of suicide risk assessments. We propose that evidence of nonredundancy with Axis V - Global Assessment of Functioning (GAF) is one piece of data that can serve as a starting point for a line of research establishing incremental predictive utility for a separate suicide risk assessment in the DSM framework. A standardized suicide risk assessment protocol, measures of depressive, anxious, and eating disordered symptomatology, as well as an index of comorbidity were administered to a sample of 412 adult outpatients. Our data indicate that data from standardized suicide risk assessments are associated with indices of symptomatology severity as well as comorbidity, controlling for GAF. These results support the nonredundancy of the assessments and suggest the utility of longitudinal investigations of the predictive utility of a sixth DSM axis in the assessment of suicide risk.

  16. Effective solidity in vertical axis wind turbines

    Science.gov (United States)

    Parker, Colin M.; Leftwich, Megan C.

    2016-11-01

    The flow surrounding vertical axis wind turbines (VAWTs) is investigated using particle imaging velocimetry (PIV). This is done in a low-speed wind tunnel with a scale model that closely matches geometric and dynamic properties tip-speed ratio and Reynolds number of a full size turbine. Previous results have shown a strong dependance on the tip-speed ratio on the wake structure of the spinning turbine. However, it is not clear whether this is a speed or solidity effect. To determine this, we have measured the wakes of three turbines with different chord-to-diameter ratios, and a solid cylinder. The flow is visualized at the horizontal mid-plane as well as the vertical mid-plane behind the turbine. The results are both ensemble averaged and phase averaged by syncing the PIV system with the rotation of the turbine. By keeping the Reynolds number constant with both chord and diameter, we can determine how each effects the wake structure. As these parameters are varied there are distinct changes in the mean flow of the wake. Additionally, by looking at the vorticity in the phase averaged profiles we can see structural changes to the overall wake pattern.

  17. Mitochondrial–Lysosomal Axis in Acetaminophen Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Anna Moles

    2018-05-01

    Full Text Available Acetaminophen (APAP toxicity is the most common cause of acute liver failure and a major indication for liver transplantion in the United States and Europe. Although significant progress has been made in understanding the molecular mechanisms underlying APAP hepatotoxicity, there is still an urgent need to find novel and effective therapies against APAP-induced acute liver failure. Hepatic APAP metabolism results in the production of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI, which under physiological conditions is cleared by its conjugation with glutathione (GSH to prevent its targeting to mitochondria. APAP overdose or GSH limitation leads to mitochondrial NAPQI-protein adducts formation, resulting in oxidative stress, mitochondrial dysfunction, and necrotic cell death. As mitochondria are a major target of APAP hepatotoxicity, mitochondrial quality control and clearance of dysfunctional mitochondria through mitophagy, emerges as an important strategy to limit oxidative stress and the engagement of molecular events leading to cell death. Recent evidence has indicated a lysosomal–mitochondrial cross-talk that regulates APAP hepatotoxicity. Moreover, as lysosomal function is essential for mitophagy, impairment in the fusion of lysosomes with autophagosomes-containing mitochondria may compromise the clearance of dysfunctional mitochondria, resulting in exacerbated APAP hepatotoxicity. This review centers on the role of mitochondria in APAP hepatotoxicity and how the mitochondrial/lysosomal axis can influence APAP-induced liver failure.

  18. Yaw dynamics of horizontal axis wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, A.C. (Utah Univ., Salt Lake City, UT (United States))

    1992-05-01

    Designers of a horizontal axis wind turbine yaw mechanism are faced with a difficult decision. They know that if they elect to use a yaw- controlled rotor then the system will suffer increased initial cost and increased inherent maintenance and reliability problems. On the other hand, if they elect to allow the rotor to freely yaw they known they will have to account for unknown and random, though bounded, yaw rates. They will have a higher-risk design to trade-off against the potential for cost savings and reliability improvement. The risk of a yaw-free system could be minimized if methods were available for analyzing and understanding yaw behavior. The complexity of yaw behavior has, until recently, discouraged engineers from developing a complete yaw analysis method. The objectives of this work are to (1) provide a fundamental understanding of free-yaw mechanics and the design concepts most effective at eliminating yaw problems, and (2) provide tested design tools and guidelines for use by free-yaw wind systems manufacturers. The emphasis is on developing practical and sufficiently accurate design methods.

  19. Six axis force feedback input device

    Science.gov (United States)

    Ohm, Timothy (Inventor)

    1998-01-01

    The present invention is a low friction, low inertia, six-axis force feedback input device comprising an arm with double-jointed, tendon-driven revolute joints, a decoupled tendon-driven wrist, and a base with encoders and motors. The input device functions as a master robot manipulator of a microsurgical teleoperated robot system including a slave robot manipulator coupled to an amplifier chassis, which is coupled to a control chassis, which is coupled to a workstation with a graphical user interface. The amplifier chassis is coupled to the motors of the master robot manipulator and the control chassis is coupled to the encoders of the master robot manipulator. A force feedback can be applied to the input device and can be generated from the slave robot to enable a user to operate the slave robot via the input device without physically viewing the slave robot. Also, the force feedback can be generated from the workstation to represent fictitious forces to constrain the input device's control of the slave robot to be within imaginary predetermined boundaries.

  20. Creating a Multi-axis Machining Postprocessor

    Directory of Open Access Journals (Sweden)

    Petr Vavruška

    2012-01-01

    Full Text Available This paper focuses on the postprocessor creation process. When using standard commercially available postprocessors it is often very difficult to modify its internal source code, and it is a very complex process, in many cases even impossible, to implement the newly-developed functions. It is therefore very important to have a method for creating a postprocessor for any CAM system, which allows CL data (Cutter Location data to be generated to a separate text file. The goal of our work is to verify the proposed method for creating a postprocessor. Postprocessor functions for multi-axis machiningare dealt with in this work. A file with CL data must be translated by the postprocessor into an NC program that has been customized for a specific production machine and its control system. The postprocessor is therefore verified by applications for machining free-form surfaces of complex parts, and by executing the NC programs that are generated on real machine tools. This is also presented here.

  1. Factors affecting fecal glucocorticoid levels in semi-free-ranging female mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Setchell, Joanna M; Smith, Tessa; Wickings, E Jean; Knapp, Leslie A

    2008-11-01

    Subordinate female cercopithecine primates often experience decreased reproductive success in comparison with high-ranking females, with a later age at sexual maturity and first reproduction and/or longer interbirth intervals. One explanation that has traditionally been advanced to explain this is high levels of chronic social stress in subordinates, resulting from agonistic and aggressive interactions and leading to higher basal levels of glucocorticoids. We assessed the relationships among fecal cortisol levels and reproductive condition, dominance rank, degree of social support, and fertility in female mandrills (Mandrillus sphinx) living in a semi-free-ranging colony in Franceville, Gabon. Lower-ranking females in this colony have a reproductive disadvantage relative to higher-ranking females, and we were interested in determining whether this relationship between dominance rank and reproductive success is mediated through stress hormones. We analyzed 340 fecal samples from 19 females, collected over a 14-month period. We found that pregnant females experienced higher fecal cortisol levels than cycling or lactating females. This is similar to results for other primate species and is likely owing to increased metabolic demands and interactions between the hypothalamus-pituitary-adrenal axis, estrogen, and placental production of corticotrophin releasing hormones during pregnancy. There was no influence of dominance rank on fecal cortisol levels, suggesting that subordinate females do not suffer chronic stress. This may be because female mandrills have a stable social hierarchy, with low levels of aggression and high social support. However, we found no relationship between matriline size, as a measure of social support, and fecal cortisol levels. Subordinates may be able to avoid aggression from dominants in the large enclosure or may react only transiently to specific aggressive events, rather than continuously expecting them. Finally, we found no relationship

  2. Early experience of a novel-environment in isolation primes a fearful phenotype characterized by persistent amygdala activation.

    Science.gov (United States)

    Daskalakis, Nikolaos P; Diamantopoulou, Anastasia; Claessens, Sanne E F; Remmers, Elisa; Tjälve, Marika; Oitzl, Melly S; Champagne, Danielle L; de Kloet, E Ronald

    2014-01-01

    Prolonged maternal separation (MS) activates the neonate's hypothalamus-pituitary-adrenal axis causing elevated basal and stress-induced corticosterone levels that may initiate amygdala-dependent fear learning. Here we test the hypothesis that the adult fearful phenotype is programmed by the pup's stressful experience during prolonged MS rather than by prolonged maternal absence per se. For this purpose, Wistar rat pups were exposed, on postnatal-day (pnd) 3, to: (i) repeated-MS in home-environment (HOME-SEP), 8h-MS daily for three days with the pups remaining together in the home-cage; (ii) repeated-MS in a novel-environment (NOVEL-SEP), with the same separation procedure, but now the pups were individually housed in a novel-environment during the 8h dam's absence; (iii) repeated handling, which consisted of daily brief (15 min instead of 8h) MS in the home-altogether or in a novel-environment individually (HOME-HAN and NOVEL-HAN, respectively); (iv) no-separation/no-handling (NON-SEP/NON-HAN) control condition, in which pups were left undisturbed in their home-cage. Compared to HOME-SEP rats, the NOVEL-SEP rats showed one day after the last MS enhanced stress-induced amygdala c-Fos expression and ACTH-release, despite of reduced adrenal corticosterone secretion. The higher amygdala c-Fos expression, ACTH-release and reduced corticosterone output observed postnatally, persisted into adulthood of the NOVEL-SEP animals. Behaviorally, NOVEL-SEP juvenile rats displayed deficits in social play, had intact spatial memory in the peri-pubertal period and showed more contextual fear memory compared to HOME-SEP in adulthood. Finally, NOVEL-HAN, compared to HOME-HAN, displayed increased stress-induced corticosterone output, no deficits in social play and reduced contextual fear. In conclusion, programming of an adult fearful phenotype linked to amygdala priming develops if pups are repeatedly isolated from peers in a novel-environment, while away from the dam for a prolonged

  3. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica = Expression of genes related to the adrenocortical function in the neoplastic cachexia process

    Directory of Open Access Journals (Sweden)

    Nicole de Angelis Scripes

    2009-04-01

    Full Text Available A glândula adrenal tem papel fundamental na resposta neuroendócrina,especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4 foram sacrificados dez dias após a inoculação de células tumorais e a glândula adrenal foi removida. O RNA foi extraído para o estudo da expressão de genes relacionados ao controle da esteroidogênese por RT-PCR semiquantitativa. A análise dos dados demonstrou expressão significativamente reduzida dos genes MC2R (receptor tipo 2 para melacortina, 3ßHSD I (3β-hidroxiesteroidedesidrogenase tipo I e TSPO (proteína translocadora em animais com caquexia neoplásica(valores de P=0,037; 0,0097 e 0,052, respectivamente, revelando falência do córtex da adrenal.The adrenal gland plays a crucial role in the neuroendocrine response, especially in situations where homeostasis is disturbed. In the neoplastic cachexia process, there is homeostasis impairment by nutritional and metabolic alterations of advanced-stage cancer, involving hypothalamus-pituitary-adrenal axis response. In thisassignment, an experimental model of cachexia induced by Walker-256 tumor was performed in Wistar rats. Animals (n=4 were sacrificed 10 days after inoculation of tumor cells, and the adrenal glands were excised. The RNA was isolated for the study of gene expression related to the steroidogenesis control by semi-quantitative RT-PCR. Data analysis showed a significant reduced expression of MC2R (melancortin type 2 receptor, 3ßHSD I (3-beta-hydroxysteroid dehydrogenase type I and TSPO (translocator protein genes in animals with neoplastic cachexia (P=0.037, 0.0097 and 0.052, respectively, revealing

  4. Expressão de genes relacionados à função adrenocortical no estado de caquexia neoplásica - DOI: 10.4025/actascihealthsci.v31i2.6759 Expression of genes related to the adrenocortical function in the neoplastic cachexia process- DOI: 10.4025/actascihealthsci.v31i2.6759

    Directory of Open Access Journals (Sweden)

    Maria Angélica Ehara Watanabe

    2009-09-01

    Full Text Available A glândula adrenal tem papel fundamental na resposta neuroendócrina, especialmente em situações em que há comprometimento da homeostasia. No processo de caquexia neoplásica, há prejuízo da homeostasia por alterações nutricionais e metabólicas do câncer em estágio avançado, envolvendo a resposta do eixo hipotálamo-hipófise-adrenal. Neste trabalho, foi utilizado um modelo animal de caquexia induzida pelo tumor de Walker-256 em ratos Wistar. Os animais (n=4 foram sacrificados dez dias após a inoculação de células tumorais e a glândula adrenal foi removida. O RNA foi extraído para o estudo da expressão de genes relacionados ao controle da esteroidogênese por RT-PCR semiquantitativa. A análise dos dados demonstrou expressão significativamente reduzida dos genes MC2R (receptor tipo 2 para melacortina, 3ßHSD I (3ß-hidroxiesteroide-desidrogenase tipo I e TSPO (proteína translocadora em animais com caquexia neoplásica (valores de P=0,037; 0,0097 e 0,052, respectivamente, revelando falência do córtex da adrenal.The adrenal gland plays a crucial role in the neuroendocrine response, especially in situations where homeostasis is disturbed. In the neoplastic cachexia process, there is homeostasis impairment by nutritional and metabolic alterations of advanced-stage cancer, involving hypothalamus-pituitary-adrenal axis response. In this assignment, an experimental model of cachexia induced by Walker-256 tumor was performed in Wistar rats. Animals (n=4 were sacrificed 10 days after inoculation of tumor cells, and the adrenal glands were excised. The RNA was isolated for the study of gene expression related to the steroidogenesis control by semi-quantitative RT-PCR. Data analysis showed a significant reduced expression of MC2R (melancortin type 2 receptor, 3ßHSD I (3-beta-hydroxysteroid dehydrogenase type I and TSPO (translocator protein genes in animals with neoplastic cachexia (P=0.037, 0.0097 and 0.052, respectively, revealing

  5. Diurnal patterns and associations among salivary cortisol, DHEA and alpha-amylase in older adults.

    Science.gov (United States)

    Wilcox, Rand R; Granger, Douglas A; Szanton, Sarah; Clark, Florence

    2014-04-22

    Cortisol and dehydroepiandrosterone (DHEA) are considered to be valuable markers of the hypothalamus-pituitary-adrenal (HPA) axis, while salivary alpha-amylase (sAA) reflects the autonomic nervous system. Past studies have found certain diurnal patterns among these biomarkers, with some studies reporting results that differ from others. Also, some past studies have found an association among these three biomarkers while other studies have not. This study investigates these patterns and associations in older adults by taking advantage of modern statistical methods for dealing with non-normality, outliers and curvature. Basic characteristics of the data are reported as well, which are relevant to understanding the nature of any patterns and associations. Boxplots were used to check on the skewness and presence of outliers, including the impact of using simple transformations for dealing with non-normality. Diurnal patterns were investigated using recent advances aimed at comparing medians. When studying associations, the initial step was to check for curvature using a non-parametric regression estimator. Based on the resulting fit, a robust regression estimator was used that is designed to deal with skewed distributions and outliers. Boxplots indicated highly skewed distributions with outliers. Simple transformations (such as taking logs) did not deal with this issue in an effective manner. Consequently, diurnal patterns were investigated using medians and found to be consistent with some previous studies but not others. A positive association between awakening cortisol levels and DHEA was found when DHEA is relatively low; otherwise no association was found. The nature of the association between cortisol and DHEA was found to change during the course of the day. Upon awakening, cortisol was found to have no association with sAA when DHEA levels are relatively low, but otherwise there is a negative association. DHEA was found to have a positive association with s

  6. Prospective, randomized, double-blind, placebo-controlled phase IIa clinical trial on the effects of an estrogen-progestin combination as add-on to inpatient psychotherapy in adult female patients suffering from anorexia nervosa.

    Science.gov (United States)

    Paslakis, Georgios; Maas, Stefanie; Gebhardt, Bernd; Mayr, Andreas; Rauh, Manfred; Erim, Yesim

    2018-04-10

    There is a need for novel treatment approaches in anorexia nervosa (AN). While there is broad knowledge with regard to altered appetite regulation and neuropsychological deficits in AN patients on the one hand, and the effects of estrogen replacement upon neuropsychological performance in healthy subjects on the other, up to now, no study has implemented estrogen replacement in AN patients, in order to examine its effects upon AN-associated and general psychopathology, neuropsychological performance and concentrations of peptide components of the hypothalamus-pituitary-adrenal (HPA) axis and within appetite-regulating circuits. This is a randomized placebo-controlled clinical trial on the effects of a 10-week oral estrogen replacement (combination of ethinyl estradiol 0.03 mg and dienogest 2 mg) in adult female AN patients. The primary target is the assessment of the impact of sex hormone replacement upon neuropsychological performance by means of a neuropsychological test battery consisting of a test for verbal intelligence, the Trail making test A and B, a Go/No-go paradigm with food cues and the Wisconsin Card Sorting Test. Secondary targets include a) the examination of safety and tolerability (as mirrored by the number of adverse events), b) assessments of the impact upon eating disorder-specific psychopathology by means of the Eating Disorder Examination Questionnaire (EDE-Q) and the Eating Disorder Inventory-2 (EDI-2), c) the influence upon anxiety using the State-Trait-Anxiety Inventory (STAI), d) assessments of plasma cortisol levels during a dexamethasone-suppression test and appetite-regulating plasma peptides (ghrelin, leptin, insulin, glucose) during an oral glucose tolerance test and, e) a possible impact upon the prescription of antidepressants. This is the first study of its kind. There are no evidence-based psychopharmacological options for the treatment of AN. Thus, the results of this clinical trial may have a relevant impact on future

  7. Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

    Science.gov (United States)

    Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

    2014-01-01

    Crohn's disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

  8. Relationship between Vagal Tone, Cortisol, TNF-Alpha, Epinephrine and Negative Affects in Crohn’s Disease and Irritable Bowel Syndrome

    Science.gov (United States)

    Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

    2014-01-01

    Crohn’s disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8∶00 AM and 10∶00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r = −0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r = −0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases. PMID

  9. Age Dependent Hypothalamic and Pituitary Responses to Novel Environment Stress or Lipopolysaccharide in Rats

    Directory of Open Access Journals (Sweden)

    Sandy Koenig

    2018-03-01

    cells. In the old rats, this specific cytokine interaction could not be detected. Overall, the present results revealed strong differences in the activation patterns and pathways between old and young rats after both stressors. The prolonged hyperthermic and inflammatory response seen in aged animals seems to be linked to dysregulated pituitary cytokine interactions and brain cell activation (NF-IL6 in the hypothalamus-pituitary-adrenal axis.

  10. Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Sonia Pellissier

    Full Text Available Crohn's disease (CD and irritable bowel syndrome (IBS involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls. The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients. The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI and depressive symptoms (CES-D. After 30 min of rest, ECG was recorded for heart rate variability (HRV analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05 was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05. No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

  11. Distortion definition and correction in off-axis systems

    Science.gov (United States)

    Da Deppo, Vania; Simioni, Emanuele; Naletto, Giampiero; Cremonese, Gabriele

    2015-09-01

    Off-axis optical configurations are becoming more and more used in a variety of applications, in particular they are the most preferred solution for cameras devoted to Solar System planets and small bodies (i.e. asteroids and comets) study. Off-axis designs, being devoid of central obstruction, are able to guarantee better PSF and MTF performance, and thus higher contrast imaging capabilities with respect to classical on-axis designs. In particular they are suitable for observing extended targets with intrinsic low contrast features, or scenes where a high dynamical signal range is present. Classical distortion theory is able to well describe the performance of the on-axis systems, but it has to be adapted for the off-axis case. A proper way to deal with off-axis distortion definition is thus needed together with dedicated techniques to accurately measure and hence remove the distortion effects present in the acquired images. In this paper, a review of the distortion definition for off-axis systems will be given. In particular the method adopted by the authors to deal with the distortion related issues (definition, measure, removal) in some off-axis instruments will be described in detail.

  12. Late Presentation of a Type III Axis Fracture with Spondyloptosis

    Science.gov (United States)

    Jayakumar, Prakash; Choi, David; Casey, Adrian

    2008-01-01

    A 58-year-old man presented with an undiagnosed Effendi type III classification fracture and spondyloptosis of the axis with remarkably normal neurology. We discuss his surgery 4 years since the initial injury, and the presentation, features and management of fractures of the axis. PMID:18430325

  13. Axis: Generating Explanations at Scale with Learnersourcing and Machine Learning

    Science.gov (United States)

    Williams, Joseph Jay; Kim, Juho; Rafferty, Anna; Heffernan, Neil; Maldonado, Samuel; Gajos, Krzysztof Z.; Lasecki, Walter S.; Heffernan, Neil

    2016-01-01

    While explanations may help people learn by providing information about why an answer is correct, many problems on online platforms lack high-quality explanations. This paper presents AXIS (Adaptive eXplanation Improvement System), a system for obtaining explanations. AXIS asks learners to generate, revise, and evaluate explanations as they solve…

  14. Angular momentum projection of tilted axis rotating states

    Energy Technology Data Exchange (ETDEWEB)

    Oi, M; Onishi, N; Tajima, N [Tokyo Univ. (Japan); Horibata, T

    1998-03-01

    We applied an exact angular momentum projection to three dimensional cranked HFB (3d-CHFB) states. Tilted axis rotating states (TAR) and principal axis rotating states (PAR) are compared. It is shown that TAR is more adequate than PAR for description of the back bending phenomena driven by tilted rotation or wobbling motion. (author)

  15. The Performance Characteristics of a Closed Loop, One Axis ...

    African Journals Online (AJOL)

    This paper presents a closed loop one axis solar tracking device of the polar axis type, which achieves an accurate tracking of the sun with a steady state error of less, than 2%. This prototype uses a photo-sensing system to generate an error signal. This error signal switches on a relay, which actuates an electromechanical ...

  16. Identification of Time-Varying Pilot Control Behavior in Multi-Axis Control Tasks

    Science.gov (United States)

    Zaal, Peter M. T.; Sweet, Barbara T.

    2012-01-01

    Recent developments in fly-by-wire control architectures for rotorcraft have introduced new interest in the identification of time-varying pilot control behavior in multi-axis control tasks. In this paper a maximum likelihood estimation method is used to estimate the parameters of a pilot model with time-dependent sigmoid functions to characterize time-varying human control behavior. An experiment was performed by 9 general aviation pilots who had to perform a simultaneous roll and pitch control task with time-varying aircraft dynamics. In 8 different conditions, the axis containing the time-varying dynamics and the growth factor of the dynamics were varied, allowing for an analysis of the performance of the estimation method when estimating time-dependent parameter functions. In addition, a detailed analysis of pilots adaptation to the time-varying aircraft dynamics in both the roll and pitch axes could be performed. Pilot control behavior in both axes was significantly affected by the time-varying aircraft dynamics in roll and pitch, and by the growth factor. The main effect was found in the axis that contained the time-varying dynamics. However, pilot control behavior also changed over time in the axis not containing the time-varying aircraft dynamics. This indicates that some cross coupling exists in the perception and control processes between the roll and pitch axes.

  17. An augmented reality C-arm for intraoperative assessment of the mechanical axis: a preclinical study.

    Science.gov (United States)

    Fallavollita, Pascal; Brand, Alexander; Wang, Lejing; Euler, Ekkehard; Thaller, Peter; Navab, Nassir; Weidert, Simon

    2016-11-01

    Determination of lower limb alignment is a prerequisite for successful orthopedic surgical treatment. Traditional methods include the electrocautery cord, alignment rod, or axis board which rely solely on C-arm fluoroscopy navigation and are radiation intensive. To assess a new augmented reality technology in determining lower limb alignment. A camera-augmented mobile C-arm (CamC) technology was used to create a panorama image consisting of hip, knee, and ankle X-rays. Twenty-five human cadaver legs were used for validation with random varus or valgus deformations. Five clinicians performed experiments that consisted in achieving acceptable mechanical axis deviation. The applicability of the CamC technology was assessed with direct comparison to ground-truth CT. A t test, Pearson's correlation, and ANOVA were used to determine statistical significance. The value of Pearson's correlation coefficient R was 0.979 which demonstrates a strong positive correlation between the CamC and ground-truth CT data. The analysis of variance produced a p value equal to 0.911 signifying that clinician expertise differences were not significant with regard to the type of system used to assess mechanical axis deviation. All described measurements demonstrated valid measurement of lower limb alignment. With minimal effort, clinicians required only 3 X-ray image acquisitions using the augmented reality technology to achieve reliable mechanical axis deviation.

  18. The hypothalamo-pituitary-adrenal axis in major affective disorder

    DEFF Research Database (Denmark)

    Christensen, M V; Kessing, L V

    2001-01-01

    disorder. The HPA axis is a complex neuroendocrine network with multiple integrated levels of control, and it is likely that the dysregulation involves abnormalities at several sites within the axis. At present, it is not clear whether the abnormalities are related to the affective episodes only......This paper reviews studies of the hypothalamo-pituitary-adrenal (HPA)-axis activity in patients with affective disorders. It is concluded that, despite methodological drawbacks in most studies, dysregulation of the HPA axis seems to be a consistent finding in a proportion of patients with affective...... or to the disorder itself. There is a need for prospective studies of larger samples of patients to be followed during successive affective episodes with a combination of measurements of the HPA-axis activity and brain imaging....

  19. Shot H3837: Darht's First Dual-Axis Explosive Experiment

    Science.gov (United States)

    Mendez, Jacob; McNeil, Wendy Vogan; Harsh, James; Hull, Lawrence

    2011-06-01

    Test H3837 was the first explosive shot performed in front of both flash x-ray axes at the Los Alamos Dual Axis Radiographic HydroTest (DARHT) facility. Executed in November 2009, the shot was an explosively-driven metal flyer plate in a series of experiments designed to explore equation-of-state properties of shocked materials. Imaging the initial shock wave traveling through the flyer plate, DARHT Axis II captured the range of motion from the shock front emergence in the flyer to breakout at the free surface; the Axis I pulse provided a perpendicular perspective of the shot at a time coinciding with the third pulse of Axis II. Since the days of the Manhattan Project, penetrating radiography with multiple frames from different viewing angles has remained a high-profile goal at the Laboratory. H3837 is merely the beginning of a bright future for two-axis penetrating radiography.

  20. Three-Axis Ground Reaction Force Distribution during Straight Walking.

    Science.gov (United States)

    Hori, Masataka; Nakai, Akihito; Shimoyama, Isao

    2017-10-24

    We measured the three-axis ground reaction force (GRF) distribution during straight walking. Small three-axis force sensors composed of rubber and sensor chips were fabricated and calibrated. After sensor calibration, 16 force sensors were attached to the left shoe. The three-axis force distribution during straight walking was measured, and the local features of the three-axis force under the sole of the shoe were analyzed. The heel area played a role in receiving the braking force, the base area of the fourth and fifth toes applied little vertical or shear force, the base area of the second and third toes generated a portion of the propulsive force and received a large vertical force, and the base area of the big toe helped move the body's center of mass to the other foot. The results demonstrate that measuring the three-axis GRF distribution is useful for a detailed analysis of bipedal locomotion.

  1. Theoretical performance of cross-wind axis turbines with results for a catenary vertical axis configuration

    Science.gov (United States)

    Muraca, R. J.; Stephens, M. V.; Dagenhart, J. R.

    1975-01-01

    A general analysis capable of predicting performance characteristics of cross-wind axis turbines was developed, including the effects of airfoil geometry, support struts, blade aspect ratio, windmill solidity, blade interference and curved flow. The results were compared with available wind tunnel results for a catenary blade shape. A theoretical performance curve for an aerodynamically efficient straight blade configuration was also presented. In addition, a linearized analytical solution applicable for straight configurations was developed. A listing of the computer program developed for numerical solutions of the general performance equations is included in the appendix.

  2. Effective shunt impedance comparison between s-band standing wave accelerators with on-axis and off-axis couplers

    International Nuclear Information System (INIS)

    Schriber, S.O.; Funk, L.W.; Hutcheon, R.M.

    1976-01-01

    The effective shunt impedances of a side-coupled S-band standing wave accelerating structure and a structure employing on-axis couplers have been compared by measuring the energy of accelerated electrons. Criteria for choosing an on-axis coupled structure compared to side-coupled and ''disk and washer'' accelerating structures are given. (author)

  3. The Oncogenic STP Axis Promotes Triple-Negative Breast Cancer via Degradation of the REST Tumor Suppressor

    Directory of Open Access Journals (Sweden)

    Kristen L. Karlin

    2014-11-01

    Full Text Available Defining the molecular networks that drive breast cancer has led to therapeutic interventions and improved patient survival. However, the aggressive triple-negative breast cancer subtype (TNBC remains recalcitrant to targeted therapies because its molecular etiology is poorly defined. In this study, we used a forward genetic screen to discover an oncogenic network driving human TNBC. SCYL1, TEX14, and PLK1 (“STP axis” cooperatively trigger degradation of the REST tumor suppressor protein, a frequent event in human TNBC. The STP axis induces REST degradation by phosphorylating a conserved REST phospho-degron and bridging REST interaction with the ubiquitin-ligase βTRCP. Inhibition of the STP axis leads to increased REST protein levels and impairs TNBC transformation, tumor progression, and metastasis. Expression of the STP axis correlates with low REST protein levels in human TNBCs and poor clinical outcome for TNBC patients. Our findings demonstrate that the STP-REST axis is a molecular driver of human TNBC.

  4. Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition: Computational Modeling

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We developed a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (DRTC)...

  5. Predicting Adaptive Response to Fadrozole Exposure:Computational Model of the Fathead MinnowsHypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict doseresponse and time-course (...

  6. Adaptive Response in Female Fathead Minnows Exposed to an Aromatase Inhibitor: Computational Modeling of the Hypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

  7. Predicting Adaptive Response to Fadrozole Exposure: Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (...

  8. Thoughts on the so-called 'radius-capitellum axis'

    International Nuclear Information System (INIS)

    Schild, H.; Mueller, H.A.; Wagner, H.; Baetz, W.; Mainz Univ.

    1982-01-01

    We have studied 438 patients radiologically in order to observe the so-called 'radius-capitellum axis'. In about a quarter of people with normal elbows the axis passes lateral to the middle portion of the capitellum, so that even when there is marked deviation, there is no certainty that the humero-radial joint is abnormal. Deviation of the axis can be caused by changes in the shape of the capitellum or of the radius, or by distension of the capsule of the elbow joint, or by various changes in muscular pull. (orig.) [de

  9. Thoughts on the so-called radius-capitellum axis

    Energy Technology Data Exchange (ETDEWEB)

    Schild, H; Mueller, H A; Wagner, H; Baetz, W

    1982-02-01

    We have studied 438 patients radiologically in order to observe the so-called 'radius-capitellum axis'. In about a quarter of people with normal elbows the axis passes lateral to the middle portion of the capitellum, so that even when there is marked deviation, there is no certainty that the humero-radial joint is abnormal. Deviation of the axis can be caused by changes in the shape of the capitellum or of the radius, or by distension of the capsule of the elbow joint, or by various changes in muscular pull.

  10. [Localization and registration of the hinge axis in black Africans].

    Science.gov (United States)

    Assi, K D; N'Guessan, K S; N'Dindin, C; Bamba, A

    2003-06-01

    The study of the cinematic method using "SAM" and "Quick Axis of FAG" added to mandibular condyle palpation for the hinge axis limited points, show that the Black Africans mandibular condyle rotation axis position is higher (3.5 mm) and backer (2 mm) than the Caucasians. The axial points are located to between 11 and 12 mm in front of the tragus and between 7 and 8 mm below on the perpendicular line to the furrow defining the tragus superior side to the Ectocanthus.

  11. Targeting the IL-33/IL-13 Axis for Respiratory Viral Infections.

    Science.gov (United States)

    Donovan, Chantal; Bourke, Jane E; Vlahos, Ross

    2016-04-01

    Lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are highly prevalent worldwide. One of the major factors that limits the efficacy of current medication in these patients are viral infections, leading to exacerbations of symptoms and decreased quality of life. Current pharmacological strategies targeting virus-induced lung disease are problematic due to antiviral resistance and the requirement for strain-specific vaccination. Thus, new therapeutic strategies are urgently required. In this Opinion article, we provide state-of-the-art evidence from humans and preclinical animal models implicating the interleukin (IL)-33/IL-13 axis in virus-induced lung disease. Thus, targeting the IL-33/IL-13 axis may be a feasible way to overcome the limitations of current therapy used to treat virus-induced exacerbations of lung disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. A Method for Modeling of Floating Vertical Axis Wind Turbine

    DEFF Research Database (Denmark)

    Wang, Kai; Hansen, Martin Otto Laver; Moan, Torgeir

    2013-01-01

    It is of interest to investigate the potential advantages of floating vertical axis wind turbine (FVAWT) due to its economical installation and maintenance. A novel 5MW vertical axis wind turbine concept with a Darrieus rotor mounted on a semi-submersible support structure is proposed in this paper....... In order to assess the technical and economic feasibility of this novel concept, a comprehensive simulation tool for modeling of the floating vertical axis wind turbine is needed. This work presents the development of a coupled method for modeling of the dynamics of a floating vertical axis wind turbine....... This integrated dynamic model takes into account the wind inflow, aerodynamics, hydrodynamics, structural dynamics (wind turbine, floating platform and the mooring lines) and a generator control. This approach calculates dynamic equilibrium at each time step and takes account of the interaction between the rotor...

  13. design and implementation of a microcontroller based dual axis

    African Journals Online (AJOL)

    user

    In this paper, an efficient microcontroller-based dual axis solar radiation tracker which can be used to align a single photovoltaic (PV) ... replaced them with wind turbine generating stations. ... tracker which has both horizontal and vertical axle.

  14. The effects of lateral head tilt on ocular astigmatic axis

    Directory of Open Access Journals (Sweden)

    Hamid Fesharaki

    2014-01-01

    Conclusion: Any minimal angle of head tilt may cause erroneous measurement of astigmatic axis and should be avoided during refraction. One cannot rely on the compensatory function of ocular counter-torsion during the refraction.

  15. Particle orbit analysis for LHD helical axis configurations

    International Nuclear Information System (INIS)

    Guasp, J.; Yamazaki, K.; Motojima, O.

    1993-04-01

    Fast ion orbits for helical magnetic axis configurations in LHD (Large Helical Device) are analyzed and compared with the standard circular axis case. Boundaries between passing and helically trapped particle regions show clear differences: in the non-planar axis case the helically trapped region spreads, near the magnetic axis, over a much wider band across the 90deg pitch angle value and shows a very marked asymmetry. The locally trapped particle region is also wider than in the standard case. The differences in the loss cone boundaries of the two cases are rather small, however, the effects of re-entering criteria are very important in both cases. On the contrary, effects of finite coil size are not significant. (author)

  16. Space/Flight Operable Miniature Six Axis Transducer, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — FUTEK will fully design and manufacture a sensor capable of measuring forces in and about each axis. The unit will measure forces up to 300 Newton's in the principle...

  17. Off-axis vortex breakdown in a shallow whirlpool.

    Science.gov (United States)

    Herrada, Miguel A; Shtern, Vladimir N; López-Herrera, José María

    2013-06-01

    The off-axis emergence of vortex breakdown (VB) is revealed. The steady axisymmetric flow in a vertical sealed cylinder, which is partially filled with water and the rest is filled with air, is driven by the rotating bottom disk. The numerical simulations show that VB can emerge away from the rotation axis, interface, and walls. As the rotation intensifies, VB first develops in the water region. If the water height is less (larger) than nearly one half of the cylinder radius, VB emerges off (on) the axis. As the rotation further increases, the off-axis VB ring touches the interface and then a thin countercirculation layer develops in the air flow above the water VB domain. This two-fluid VB ring shrinks (it even disappears in a very shallow whirlpool) as the interface approaches the bottom disk.

  18. Helical-axis stellarators with noninterlocking planar coils

    International Nuclear Information System (INIS)

    Reiman, A.; Boozer, A.

    1983-08-01

    The properties of helical axis stellarator fields generated by unlinked, planar coils are described. It is shown that such fields can have a magnetic well and large rotational transform, implying large equilibrium and stability beta limits

  19. Helical-axis stellarators with noninterlocking planar coils

    Energy Technology Data Exchange (ETDEWEB)

    Reiman, A.; Boozer, A.

    1983-08-01

    The properties of helical axis stellarator fields generated by unlinked, planar coils are described. It is shown that such fields can have a magnetic well and large rotational transform, implying large equilibrium and stability beta limits.

  20. Design of a Three-Axis Machine Tool Module

    National Research Council Canada - National Science Library

    Childers, Marshal

    2003-01-01

    This report documents the design improvement process of the components in a tool module for a three-axis machine tool, which occurred during the period of March-April 2002 in support of a critical U.S...

  1. Proper time axis of a closed relativistic system

    International Nuclear Information System (INIS)

    Chernikov, N.A.; Fadeev, N.G.; Shavokhina, N.S.

    1997-01-01

    The definition of a proper time axis of a closed relativistic system of colliding particles is given. The solution of the proper time axis problem is presented. If the light velocity c equals the imaginary unit i, then in the case of a plane motion of the system the problem about the proper time axis turns out to be equivalent to the known in engineering mechanics problem about the reduction of any system of forces, applied to a rigid body, to the dynamic screw. In the general case, when c=i, the problem about the proper time axis turns out to be equivalent to the problem about the reduction to the dynamic screw of a system of forces, applied to a rigid body in a four-dimensional Euclidean space

  2. UARS PEM Level 2 AXIS 1 V001

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 1 daily product contains the X-ray high-resolution spectral...

  3. UARS PEM Level 2 AXIS 2 V001

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 2 daily product contains the X-ray high-resolution spectral...

  4. Dual Axis Controller for Extreme Environments, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The Dual Axis Controller for Extreme Environments (DACEE) addresses a critical need of NASA's future exploration plans to investigate extreme environments within our...

  5. Three-Axis Gasless Sounding Rocket Payload Attitude Control

    Data.gov (United States)

    National Aeronautics and Space Administration — Gas released by current sounding rocket payload attitude control systems (ACS) has the potential to interfere with some types of science instruments. A single-axis...

  6. Microbiota-gut-brain axis and the central nervous system

    OpenAIRE

    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

    2017-01-01

    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated ...

  7. Self-starting aerodynamics analysis of vertical axis wind turbine

    Directory of Open Access Journals (Sweden)

    Jianyang Zhu

    2015-12-01

    Full Text Available Vertical axis wind turbine is a special type of wind-force electric generator which is capable of working in the complicated wind environment. The self-starting aerodynamics is one of the most important considerations for this kind of turbine. This article aims at providing a systematic synthesis on the self-starting aerodynamic characteristics of vertical axis wind turbine based on the numerical analysis approach. First, the physical model of vertical axis wind turbine and its parameter definitions are presented. Secondary, the interaction model between the vertical axis wind turbine and fluid is developed by using the weak coupling approach; the numerical data of this model are then compared with the wind tunnel experimental data to show its feasibility. Third, the effects of solidity and fixed pitch angle on the self-starting aerodynamic characteristics of the vertical axis wind turbine are analyzed systematically. Finally, the quantification effects of the solidity and fixed pitch angle on the self-starting performance of the turbine can be obtained. The analysis in this study will provide straightforward physical insight into the self-starting aerodynamic characteristics of vertical axis wind turbine.

  8. Energy Efficient Hybrid Dual Axis Solar Tracking System

    Directory of Open Access Journals (Sweden)

    Rashid Ahammed Ferdaus

    2014-01-01

    Full Text Available This paper describes the design and implementation of an energy efficient solar tracking system from a normal mechanical single axis to a hybrid dual axis. For optimizing the solar tracking mechanism electromechanical systems were evolved through implementation of different evolutional algorithms and methodologies. To present the tracker, a hybrid dual-axis solar tracking system is designed, built, and tested based on both the solar map and light sensor based continuous tracking mechanism. These light sensors also compare the darkness and cloudy and sunny conditions assisting daily tracking. The designed tracker can track sun’s apparent position at different months and seasons; thereby the electrical controlling device requires a real time clock device for guiding the tracking system in seeking solar position for the seasonal motion. So the combination of both of these tracking mechanisms made the designed tracker a hybrid one. The power gain and system power consumption are compared with a static and continuous dual axis solar tracking system. It is found that power gain of hybrid dual axis solar tracking system is almost equal to continuous dual axis solar tracking system, whereas the power saved in system operation by the hybrid tracker is 44.44% compared to the continuous tracking system.

  9. Design and optimize of 3-axis filament winding machine

    Science.gov (United States)

    Quanjin, Ma; Rejab, M. R. M.; Idris, M. S.; Bachtiar, B.; Siregar, J. P.; Harith, M. N.

    2017-10-01

    Filament winding technique is developed as the primary process for composite cylindrical structures fabrication at low cost. Fibres are wound on a rotating mandrel by a filament winding machine where resin impregnated fibres pass through a pay-out eye. This paper aims to develop and optimize a 3-axis, lightweight, practical, efficient, portable filament winding machine to satisfy the customer demand, which can fabricate pipes and round shape cylinders with resins. There are 3 main units on the 3-axis filament winding machine, which are the rotary unit, the delivery unit and control system unit. Comparison with previous existing filament winding machines in the factory, it has 3 degrees of freedom and can fabricate more complex shape specimens based on the mandrel shape and particular control system. The machine has been designed and fabricated on 3 axes movements with control system. The x-axis is for movement of the carriage, the y-axis is the rotation of mandrel and the z-axis is the movement of the pay-out eye. Cylindrical specimens with different dimensions and winding angles were produced. 3-axis automated filament winding machine has been successfully designed with simple control system.

  10. Major and minor axis kinematics of 22 ellipticals

    International Nuclear Information System (INIS)

    Franx, M.; Illingworth, G.; Heckman, T.

    1989-01-01

    Rotation curves and velocity dispersion profiles have been determined for the major and the minor axes of 22 elliptical galaxies. Rotation was detected in all but one galaxy, even though the sample was biased toward round ellipticals. Minor axis rotation larger than major axis rotation was measured in two galaxies, NGC 4406 and NGC 7507. Roughly 10 percent of ellipticals may show large minor axis velocities relative to those on the major axis. A simple model is used to derive a rotational axis from the observed minor and major axis velocities to a typical accuracy of 6 deg. The rotational and photometric minor axes aligned to better than 10 deg for 60 percent of the sample, implying that the direction of the angular momentum is related to the orientation of the figure of the galaxy. IC 1459 has a kinematically distinct core with its angular momentum opposite to the angular momentum of the outer parts, and NGC 4406 has a core with its angular momentum perpendicular to that of the outer parts. 46 refs

  11. Optic axis-driven new horizons for hyperbolic metamaterials

    Directory of Open Access Journals (Sweden)

    Boardman Allan D.

    2015-01-01

    Full Text Available The broad assertion here is that the current hyperbolic metamaterial world is only partially served by investigations that incorporate only some limited version of anisotropy. Even modest deviations of the optic axis from the main propagation axis lead to new phase shifts, which not only compete with those created by absorption but end up dominating them. Some progress has been attempted in the literature by introducing the terms “asymmetric hyperbolic media”, but it appears that this kind of asymmetry only involves an optic axis at an angle to the interface of a uniaxial crystal. From a device point of view, many new prospects should appear and the outcomes of the investigations presented here yield a new general theory. It is emphasised that the orientation of the optic axis is a significant determinant in the resulting optical properties. Whereas for conventional anisotropic waveguides homogeneous propagating waves occur over a limited range of angular dispositions of the optic axis it is shown that for a hyperbolic guide a critical angular setting exists, above which the guided waves are always homogeneous. This has significant implications for metawaveguide designs. The resulting structures are more tolerant to optic axis misalignment.

  12. Psychoneuromedulator role of corticotrophin releasing hormone in PCOS

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2016-10-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is a common complex condition in women associated with reproductive and metabolic systems and also psychological disorders. There is considerable evidence to suggest that the sympathetic nervous system is involved in PCO and metabolic syndromes. Noradrenalin (NA, corticotrophin releasing hormone (CRH and nerve growth factor (NGF are the strong stimulants for two axes: hypothalamic-pituitary-adrenal (HPA and hypothalamic-pituitary-ovarian (HPO axes which are regulators for the female reproductive system. Following previous studies on sympathetic nervous system over activity in PCOS, the main purpose of this study is to evaluate the role of CRH and NGF as two important findings from the perspective of the psycho-emotional. Methods: This case-control study was conducted in Reproductive Health Research Center of Imam Khomeini Hospital, Tehran, Iran in the September of 2011. 170 women participated in this study. The diagnosis of PCOS was made according to the joint criteria of the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine (ESHRE/ASRM. All women have 20-40 years of age and body mass index (BMI of less than 28. Demographic questionnaire was used in this study and blood sample was obtained from all participants before 8AM. All analysis was done in SPSS software, version 19 (IBM SPSS, Armonk, NY, USA. P-value less than 0.05 considered as significant level. Results: Serum levels of CRH and NGF in patients with polycystic ovary was significantly lower than the control group (P< 0.001. This reduction can disrupt two neural axes: the sympathetic nervous system (SAS and hypothalamus-pituitary-adrenal (HPA. These axes have a fundamental role in psycho-emotional reactions in women with PCOS. Moreover, using demographic questionnaire quantitative and qualitative characteristics of the population studied, the results of which are reported in the regression

  13. Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

    Science.gov (United States)

    Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Nakamura, Yumi; Koyama, Hidekazu

    2015-01-01

    Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD), which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1), which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2), which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX), an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH), and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease.

  14. Coordinated control of multi-axis tasks

    International Nuclear Information System (INIS)

    Mc Kinnon, G.M.; King, M.L.; Runnings, D.W.

    1987-01-01

    The use of manipulators and the development of manipulator technology has steadily increased in recent years. Consequently, teleoperation of the remote operation of a machine or piece of equipment has also increased. Typically, teleoperation is employed in situations where the environment is dangerous or too remote for humans to work. In space exploration with the use of dextrous manipulators, teleoperation has become a critical component. This paper describes tests carried out to evaluate three man-machine interfaces with two dextrous manipulators. The three interfaces were a master/slave system with force reflection, a master slave system without force reflection, and two six degree of freedom handcontrollers. Results indicated that task accuracy was superior with the handcontrollers

  15. Axis of eye rotation changes with head-pitch orientation during head impulses about earth-vertical.

    Science.gov (United States)

    Migliaccio, Americo A; Schubert, Michael C; Clendaniel, Richard A; Carey, John P; Della Santina, Charles C; Minor, Lloyd B; Zee, David S

    2006-06-01

    The goal of this study was to assess how the axis of head rotation, Listing's law, and eye position influence the axis of eye rotation during brief, rapid head rotations. We specifically asked how the axis of eye rotation during the initial angular vestibuloocular reflex (VOR) changed when the pitch orientation of the head relative to Earth-vertical was varied, but the initial position of the eye in the orbit and the orientation of Listing's plane with respect to the head were fixed. We measured three-dimensional eye and head rotation axes in eight normal humans using the search coil technique during head-and-trunk (whole-body) and head-on-trunk (head-only) "impulses" about an Earth-vertical axis. The head was initially oriented at one of five pitch angles (30 degrees nose down, 15 degrees nose down, 0 degrees, 15 degrees nose up, 30 degrees nose up). The fixation target was always aligned with the nasooccipital axis. Whole-body impulses were passive, unpredictable, manual, rotations with peak-amplitude of approximately 20 degrees , peak-velocity of approximately 80 degrees /s, and peak-acceleration of approximately 1000 degrees /s2. Head-only impulses were also passive, unpredictable, manual, rotations with peak-amplitude of approximately 20 degrees , peak-velocity of approximately 150 degrees /s, and peak-acceleration of approximately 3000 degrees /s2. During whole-body impulses, the axis of eye rotation tilted in the same direction, and by an amount proportional (0.51 +/- 0.09), to the starting pitch head orientation (P rotation could be predicted from vectorial summation of the gains (eye velocity/head velocity) obtained for rotations about the pure yaw and roll head axes. Thus, even when the orientation of Listing's plane and eye position in the orbit are fixed, the axis of eye rotation during the VOR reflects a compromise between the requirements of Listing's law and a perfectly compensatory VOR.

  16. Design Of Single-Axis And Dual-Axis Solar Tracking Systems Protected Against High Wind Speeds

    Directory of Open Access Journals (Sweden)

    Mai Salaheldin Elsherbiny

    2017-09-01

    Full Text Available Solar energy is rapidly gaining ground as an important mean of expanding renewable energy use. Solar tracking is employed in order to maximize collected solar radiation by a photovoltaic panel. In this paper we present a prototype for Automatic solar tracker that is designed using Arduino UNO with Wind sensor to Cease Wind effect on panels if wind speed exceeds certain threshold. The Proposed solar tracker tracks the location of the sun anywhere in any time by calculating the position of the sun. For producing the maximum amount of solar energy a solar panel must always be perpendicular to the source of light. Because the sun motion plane varies daily and during the day it moves from east to west one needs two axis tracking to follow the suns position. Maximum possible power is collected when two axis tracking is done. However two axis tracking is relatively costly and complex. A compromise between maximum power collection and system simplicity is obtained by single axis tracking where the plane North south axis is fixed while the east west motion is accomplished. This work deals with the design of both single and two axis tracking systems. Automatic trackers is also compared to Fixed one in terms of Energy generated Efficiency Cost and System reliability.

  17. Postnatal development of the atlas and axis: CT study

    International Nuclear Information System (INIS)

    Byun, Sung Su; Kim, Hyung Jin; Lim, Myung Kwan; Kim, Won Hong; Jeon, Yong Sun; Kim, Jeong Ho; Kim, Sung Tae

    2003-01-01

    To evaluate normal postnatal development of the atlas and axis by means of CT scanning. We prospectively analyzed CT scans of the developing atlas and axis of 200 normal children aged less than 14, investigating the CT appearance of these regions with particular attenuation to two synchondroses related to the atlas and four synchondroses and one ossification center related to the axis. Fusion varying was categorized as either low (grade1-5) or high (grade4-5), according to the varying degrees of fusion at each synchondrosis of ossification center. Neurocentral synchondrosis of the atlas was low grade in all children less than five, and high grade in all aged nine or more, while posterior synchondrosis of the atlas was low grade in 97% of children less than three and high grade in 99% aged three or more. As for the axis, neurocentral synchondrosis was low grade in all children less than three, and high grade in 97% of children aged five or more. PS of the axis was low grade in both children less than 6 months, and high grade in all aged two years or more. Dentocentral synchondrosis of the axis was low grade in 93% of children less than three and high grade in 96% of those aged at least five. Intradental axial synchondrosis was high grade in all children. Fusion of the terminal ossicle with the remainder of the dens was low in all children less than five and high in 97% of those aged nine of more. CT can help determine the parameters of normal postnatal development of the atlas and axis. A knowledge of normal ossification patterns of these regions may help provide an understanding of developmental anomalies and also help prevent confusion with fractures

  18. Gut-Brain Axis and Behavior.

    Science.gov (United States)

    Martin, Clair R; Mayer, Emeran A

    2017-01-01

    In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

  19. Use of polarization to separate on-axis scattered and unscattered light in red blood cells

    Science.gov (United States)

    Sardar, Dhiraj K.; Nemati, Babak; Barrera, Frederick J.

    1991-06-01

    The separation of on-axis scattered and unscattered transmission through turbid media has been a difficult experimental task in recent years. This study suggests the use of a polarimeter to filter out the contribution of scattered light to the net on-axis transmission. Red blood cells (RBC) were used to produce the scattering effect. The scattering level was varied by: (1) altering the distance of the detector from the sample, (2) using erythrocytes from three different species, e.g., the dog, goat, and human, which are know to have different RBC sizes, and (3) allowing the RBCs from each species to shrink and swell osmotically. An He-Ne laser was used as the source of the radiation so that data were obtained at a wavelength in the spectral region used in oximetry and hemoglobinometry. In each case, the difference in the scattering cross sections obtained for each sample, with and without polarization filtering, gave us a measure of the filtered scattered light. The results obtained were in close agreement with the expected contribution of scattered radiation to the net axial transmission. This method may be used effectively for all studies involving measurements of on-axis transmission through turbid media, such as biological tissue.

  20. Mapping local anisotropy axis for scattering media using backscattering Mueller matrix imaging

    Science.gov (United States)

    He, Honghui; Sun, Minghao; Zeng, Nan; Du, E.; Guo, Yihong; He, Yonghong; Ma, Hui

    2014-03-01

    Mueller matrix imaging techniques can be used to detect the micro-structure variations of superficial biological tissues, including the sizes and shapes of cells, the structures in cells, and the densities of the organelles. Many tissues contain anisotropic fibrous micro-structures, such as collagen fibers, elastin fibers, and muscle fibers. Changes of these fibrous structures are potentially good indicators for some pathological variations. In this paper, we propose a quantitative analysis technique based on Mueller matrix for mapping local anisotropy axis of scattering media. By conducting both experiments on silk sample and Monte Carlo simulation based on the sphere-cylinder scattering model (SCSM), we extract anisotropy axis parameters from different backscattering Mueller matrix elements. Moreover, we testify the possible applications of these parameters for biological tissues. The preliminary experimental results of human cancerous samples show that, these parameters are capable to map the local axis of fibers. Since many pathological changes including early stage cancers affect the well aligned structures for tissues, the experimental results indicate that these parameters can be used as potential tools in clinical applications for biomedical diagnosis purposes.

  1. Craniospinal axis irradiation: an improved electron technique for irradiation of the spinal axis

    International Nuclear Information System (INIS)

    Chun Li; Vijayakumar, S.; Myrianthopoulos, L.C.; Kuchnir, F.T.; Muller-Runkel, R.

    1994-01-01

    The authors review dosimetric features of craniospinal axis irradiation in the areas of matching cranial and spinal fields, with reference to normal structures within the spinal field. The implications of the use of photon or electron modalities for the spinal port were evaluated. A novel method of matching the cranial photon and the spinal electron fields involving a computer-aided junction design is presented, involving moving the photon beam in three steps to degrade its penumbra to match that of the electron field. Thermoluminescent dosimetry in a Rando phantom and computed tomography-based dose-volume histogram study for an illustrative paediatric case were used to compare dose to normal structures within the spinal field. Results show that the use of electrons for the spinal field leads to better sparing of deep seated normal structures. For bone marrow, the use of a customized bolus for the spinal field results in an improved dose distribution, making electrons potentially superior to photons for radiobiological reasons. (author)

  2. Measurement Axis Searching Model for Terrestrial Laser Scans Registration

    Directory of Open Access Journals (Sweden)

    Shaoxing Hu

    2016-01-01

    Full Text Available Nowadays, terrestrial Lidar scans can cover rather a large area; the point densities are strongly varied because of the line-of-sight measurement principle in potential overlaps with scans taken from different viewpoints. Most of the traditional methods focus on registration algorithm and ignore searching model. Sometimes the traditional methods are directly used to align two point clouds; a large critically unsolved problem of the large biases will be created in areas distant from the overlaps while the local overlaps are often aligned well. So a novel measurement axis searching model (MASM has been proposed in this paper. The method includes four steps: (1 the principal axis fitting, (2 the measurement axis generation, (3 low-high-precision search, and (4 result generation. The principal axis gives an orientation to the point cloud; the search scope is limited by the measurement axis. The point cloud orientation can be adjusted gradually until the achievement of the global optimum using low- and high-precision search. We perform some experiments with simulated point clouds and real terrestrial laser scans. The results of simulated point clouds have shown the processing steps of our method, and the results of real terrestrial laser scans have shown the sensitivity of the approach with respect to the indoor and outdoor scenes.

  3. Ankle-foot orthosis bending axis influences running mechanics.

    Science.gov (United States)

    Russell Esposito, Elizabeth; Ranz, Ellyn C; Schmidtbauer, Kelly A; Neptune, Richard R; Wilken, Jason M

    2017-07-01

    Passive-dynamic ankle-foot orthoses (AFOs) are commonly prescribed to improve locomotion for people with lower limb musculoskeletal weakness. The clinical prescription and design process are typically qualitative and based on observational assessment and experience. Prior work examining the effect of AFO design characteristics generally excludes higher impact activities such as running, providing clinicians and researchers limited information to guide the development of objective prescription guidelines. The proximal location of the bending axis may directly influence energy storage and return and resulting running mechanics. The purpose of this study was to determine if the location of an AFO's bending axis influences running mechanics. Marker and force data were recorded as 12 participants with lower extremity weakness ran overground while wearing a passive-dynamic AFO with posterior struts manufactured with central (middle) and off-centered (high and low) bending axes. Lower extremity joint angles, moments, powers, and ground reaction forces were calculated and compared between limbs and across bending axis conditions. Bending axis produced relatively small but significant changes. Ankle range of motion increased as the bending axis shifted distally (pbenefits during running, although individual preference and physical ability should also be considered. Published by Elsevier B.V.

  4. The Microbiome-Gut-Behavior Axis: Crosstalk Between the Gut Microbiome and Oligodendrocytes Modulates Behavioral Responses.

    Science.gov (United States)

    Ntranos, Achilles; Casaccia, Patrizia

    2018-01-01

    Environmental and dietary stimuli have always been implicated in brain development and behavioral responses. The gut, being the major portal of communication with the external environment, has recently been brought to the forefront of this interaction with the establishment of a gut-brain axis in health and disease. Moreover, recent breakthroughs in germ-free and antibiotic-treated mice have demonstrated the significant impact of the microbiome in modulating behavioral responses in mice and have established a more specific microbiome-gut-behavior axis. One of the mechanisms by which this axis affects social behavior is by regulating myelination at the prefrontal cortex, an important site for complex cognitive behavior planning and decision-making. The prefrontal cortex exhibits late myelination of its axonal projections that could extend into the third decade of life in humans, which make it susceptible to external influences, such as microbial metabolites. Changes in the gut microbiome were shown to alter the composition of the microbial metabolome affecting highly permeable bioactive compounds, such as p-cresol, which could impair oligodendrocyte differentiation. Dysregulated myelination in the prefrontal cortex is then able to affect behavioral responses in mice, shifting them towards social isolation. The reduced social interactions could then limit microbial exchange, which could otherwise pose a threat to the survival of the existing microbial community in the host and, thus, provide an evolutionary advantage to the specific microbial community. In this review, we will analyze the microbiome-gut-behavior axis, describe the interactions between the gut microbiome and oligodendrocytes and highlight their role in the modulation of social behavior.

  5. CXCR4/CXCL12/CXCR7 axis is functional in neuroendocrine tumors and signals on mTOR.

    Science.gov (United States)

    Circelli, Luisa; Sciammarella, Concetta; Guadagno, Elia; Tafuto, Salvatore; del Basso de Caro, Marialaura; Botti, Giovanni; Pezzullo, Luciano; Aria, Massimo; Ramundo, Valeria; Tatangelo, Fabiana; Losito, Nunzia Simona; Ieranò, Caterina; D'Alterio, Crescenzo; Izzo, Francesco; Ciliberto, Gennaro; Colao, Annamaria; Faggiano, Antongiulio; Scala, Stefania

    2016-04-05

    To evaluate the possible crosstalk between C-X-C chemokine receptor 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12)/C-X-C chemokine receptor 7 (CXCR7) axis with the mammalian target of rapamycin (mTOR) pathway in neuroendocrine tumors (NETs). Sixty-one human NETs were included into the study. CXCR4/CXCL12/CXCR7 axis and mTOR pathway were assessed by qRT-PCR and immunohistochemistry (IHC). The effect of mTOR inhibitor, RAD001, was evaluated on CXCR4 pathway through proliferation and p-Erk and p-AKT induction. CXCR4/CXCL12/CXCR7 axis and p-mTOR were found to be active and correlated with grading, Ki67 index and tumor stage. mTOR pathway activation significantly correlated with poor prognosis. In human NET cells, CXCL12 induced mTOR signalling while AMD3100 (CXCR4-antagonist) impaired it. The mTOR-antagonist, RAD001, impaired the CXCL12-dependent induction of CXCR4 downstream effectors. Combination of AMD3100 and RAD001 potentiate cell growth inhibition. CXCR4/CXCL12/CXCR7 axis is active in NETs and signals on mTOR. CXCR4 might be considered a prognostic factor in NETs. Combined treatment with AMD3100 and RAD001 may provide clinical benefits in NET patients with drug-resistant.

  6. Role of Met Axis in Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yiru, E-mail: xuyiru@umich.edu; Fisher, Gary J., E-mail: xuyiru@umich.edu [Department of Dermatology, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-11-26

    Head and neck cancer is the sixth most common type of cancer worldwide. Despite advances in aggressive multidisciplinary treatments, the 5-year survival rate for this dreadful disease is only 50%, mostly due to high rate of recurrence and early involvement of regional lymph nodes and subsequent metastasis. Understanding the molecular mechanisms responsible for invasion and metastasis is one of the most pressing goals in the field of head and neck cancer. Met, also known as hepatocyte growth factor receptor (HGFR), is a member of the receptor protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis is dysregulated and plays important roles in tumorigenesis, progression, metastasis, angiogenesis, and drug resistance in head and neck cancer. We describe in this review current understanding of Met axis in head and neck cancer biology and development of therapeutic inhibitors targeting Met axis.

  7. Subquadratic medial-axis approximation in $\\mathbb{R}^3$

    Directory of Open Access Journals (Sweden)

    Christian Scheffer

    2015-09-01

    Full Text Available We present an algorithm that approximates the medial axis of a smooth manifold in $\\mathbb{R}^3$ which is given by a sufficiently dense point sample. The resulting, non-discrete approximation is shown to converge to the medial axis as the sampling density approaches infinity. While all previous algorithms guaranteeing convergence have a running time quadratic in the size $n$ of the point sample, we achieve a running time of at most $\\mathcal{O}(n\\log^3 n$. While there is no subquadratic upper bound on the output complexity of previous algorithms for non-discrete medial axis approximation, the output of our algorithm is guaranteed to be of linear size.

  8. Small Vertical Axis Wind Turbines: aerodynamics and starting behavior

    Directory of Open Access Journals (Sweden)

    Horia DUMITRESCU

    2013-12-01

    Full Text Available In urban areas the wind is very turbulent and unstable with fast changes in direction andvelocity. In these environments, the use of small vertical axis wind turbines (VAWT becomesincreasingly attractive due to several advantages over horizontal axis wind turbines (HAWT.However, such designs have received much less attention than the more common propeller-typedesigns and the understanding of same aspects of their operation remains, to this day, incomplete.This is particularly true of their starting characteristics. Indeed, same authors heuristically maintainthat they cannot start without external assistance. This paper reviews the cause of the inability of thelow solidity fixed pitch vertical axis wind turbines to self-start, and investigates the way ofovercoming this draw back.

  9. Off-axis and inline electron holography: Experimental comparison

    International Nuclear Information System (INIS)

    Latychevskaia, Tatiana; Formanek, Petr; Koch, C.T.; Lubk, Axel

    2010-01-01

    Electron holography is a very powerful technique for mapping static electric and magnetic potentials down to atomic resolution. While electron holography is commonly considered synonymous with its off-axis variant in the high energy electron microscopy community, inline electron holography is widely applied in low-energy electron microscopy, where the realization of the off-axis setup is still an experimental challenge. This paper demonstrates that both inline and off-axis holography may be used to recover amplitude and phase shift of the very same object, in our example latex spheres of 90 and 200 nm in diameter, producing very similar results, provided the object does not charge under the electron beam.

  10. Vertical axis wind turbines: a survey and bibliography

    Energy Technology Data Exchange (ETDEWEB)

    Abramovich, H

    1987-01-01

    The stimulus for the development of modern, big wind turbines has been the world-wide oil crisis during the seventies. Although the horizontal axis wind turbines (HAWT) was the most popular type of wind turbine the Darrieus vertical axis wind turbine (VAWT) has been recognized as a machine with competitive economic potential. The state of the art of the VAWT is reviewed. The wind turbine carrying the name of Darrieus was first proposed by the French inventor in 1925. His original patent covered a range of vertical-axis configurations but the term 'Darrieus' is now generally associated with the curved-blade geometry. In 1966 two researchers at the Canadian NRC again raised the idea of both the straight and curved-blade versions of the Darrieus VAWT.

  11. Study of morphological alterations of the adrenal glands in the neoplastic cachexia Estudo das alterações morfológicas da glândula adrenal na caquexia neoplásica

    Directory of Open Access Journals (Sweden)

    Tânia Longo Mazzuco

    2009-01-01

    Full Text Available Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculation and adrenal glands removal for histopathologic analysis by means of hematoxylin and eosin stain. Nutritional parameters, cachexia index and adrenal glands weight, were evaluated. Animals with tumor presented cachexia index of 16,6 ± 4%. Adrenal glands average weight was significantly higher in the tumor group (40 mg ± 10 than in the control group (25 mg ± 3. Adrenal cortex of animals with cachexia showed hypertrophy of the zona fasciculata and reticular layer, with voluminous spongiocytes; vascular congestion and stasis were observed in the medullar region. Results were similar in the pair and ad libitum-fed groups. Animals with cancer cachexia showed compromised morphology of the adrenal glands which showed alterations related to stress response, suggesting increased cathecolamine secretion and activation of the hypothalamus-pituitary-adrenal axis.   Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculation and adrenal glands removal for histopathologic analysis by means of hematoxylin and eosin stain. Nutritional

  12. Calibration of three-axis magnetometers with differential evolution algorithm

    International Nuclear Information System (INIS)

    Pang, Hongfeng; Zhang, Qi; Wang, Wei; Wang, Junya; Li, Ji; Luo, Shitu; Wan, Chengbiao; Chen, Dixiang; Pan, Mengchun; Luo, Feilu

    2013-01-01

    The accuracy of three-axis magnetometers is influenced by different scale and bias of each axis and nonorthogonality between axes. One limitation of traditional iteration methods is that initial parameters influence the calibration, thus leading to the local optimal or wrong results. In this paper, a new method is proposed to calibrate three-axis magnetometers. To employ this method, a nonmagnetic rotation platform, a proton magnetometer, a DM-050 three-axis magnetometer and the differential evolution (DE) algorithm are used. The performance of this calibration method is analyzed with simulation and experiment. In simulation, the calibration results of DE, unscented Kalman filter (UKF), recursive least squares (RLS) and genetic algorithm (GA) are compared. RMS error using DE is least, which is reduced from 81.233 nT to 1.567 nT. Experimental results show that comparing with UKF, RLS and GA, the DE algorithm has not only the least calibration error but also the best robustness. After calibration, RMS error is reduced from 68.914 nT to 2.919 nT. In addition, the DE algorithm is not sensitive to initial parameters, which is an important advantage compared with traditional iteration algorithms. The proposed algorithm can avoid the troublesome procedure to select suitable initial parameters, thus it can improve the calibration performance of three-axis magnetometers. - Highlights: • The calibration results and robustness of UKF, GA, RLS and DE algorithm are analyzed. • Calibration error of DE is the least in simulation and experiment. • Comparing with traditional calibration algorithms, DE is not sensitive to initial parameters. • It can improve the calibration performance of three-axis magnetometers

  13. 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.

  14. Research on Parameter Design of Multi - axis Hydrostatic Transmission Vehicle

    Directory of Open Access Journals (Sweden)

    Zhao Liang

    2017-01-01

    Full Text Available In order to obtain reasonable parameters in the design of driving system of multi-axis hydrostatic transmission vehicle, the working principle of single-side drive of hydrostatic transmission vehicle is introduced. The matching and control of engine and hydraulic pump are analyzed. According to the driving equation of vehicle, The driving force required for driving system is determined, and the parameters of hydraulic motor, hydraulic pump, system working pressure and braking system are designed and calculated, which provides the parameter design for driving system of multi-axis hydrostatic transmission Reliable theoretical basis.

  15. Microbiota-gut-brain axis and the central nervous system.

    Science.gov (United States)

    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

    2017-08-08

    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

  16. Three axis vector atomic magnetometer utilizing polarimetric technique

    Energy Technology Data Exchange (ETDEWEB)

    Pradhan, Swarupananda, E-mail: spradhan@barc.gov.in, E-mail: pradhans75@gmail.com [Laser and Plasma Technology Division, Bhabha Atomic Research Centre, Mumbai 400085, India and Homi Bhabha National Institute, Department of Atomic Energy, Mumbai 400094 (India)

    2016-09-15

    The three axis vector magnetic field measurement based on the interaction of a single elliptically polarized light beam with an atomic system is described. The magnetic field direction dependent atomic responses are extracted by the polarimetric detection in combination with laser frequency modulation and magnetic field modulation techniques. The magnetometer geometry offers additional critical requirements like compact size and large dynamic range for space application. Further, the three axis magnetic field is measured using only the reflected signal (one polarization component) from the polarimeter and thus can be easily expanded to make spatial array of detectors and/or high sensitivity field gradient measurement as required for biomedical application.

  17. Interpretation and quality of the tilted axis cranking approximation

    International Nuclear Information System (INIS)

    Frauendorf, S.; Meng, J.

    1996-06-01

    Comparing with the exact solutions of the model system of one and two particles coupled to an axial rotor, the quality of the semi classical tilted axis cranking approximation is investigated. Extensive comparisons of the energies and M1 and E2 transition probabilities are carried out for the lowest bands. Very good agreement is found, except near band crossings. Various recipes to take into account finite K within the frame of the usual principal axis cranking are included into the comparison. A set of rules is suggested that permits to construct the excited bands from the cranking configurations, avoiding spurious states. (orig.)

  18. Optical Three-Axis Tactile Sensor for Robotic Fingers

    OpenAIRE

    Ohka, Masahiro; Takata, Jumpei; Kobayashi, Hiroaki; Suzuki, Hirofumi; Morisawa, Nobuyuki; Yussof, Hanafiah Bin

    2008-01-01

    A new three-axis tactile sensor to be mounted on multi-fingered hands is developed based on the principle of an optical waveguide-type tactile sensor comprised of an acrylic hemispherical dome, a light source, an array of rubber sensing elements, and a CCD camera. The sensing element of the present tactile sensor includes one columnar feeler and eight conical feelers. A three-axis force applied to the tip of the sensing element is detected by the contact areas of the conical feelers, which ma...

  19. Experimental characterization of individual pitch controlled vertical axis wind turbine

    NARCIS (Netherlands)

    Leblanc, B.P.; Simao Ferreira, C.

    2017-01-01

    Research into the Vertical Axis Wind Turbine (VAWT) has been progressing over the last few years due to
    the large shift in design constraints for large floating offshore wind turbines by leveraging tools and experience
    from research beginning in the 1970s and lasting until the HAWT

  20. Comparison of aerodynamic models for Vertical Axis Wind Turbines

    DEFF Research Database (Denmark)

    Ferreira, C. Simão; Aagaard Madsen, Helge; Barone, M.

    2014-01-01

    Multi-megawatt Vertical Axis Wind Turbines (VAWTs) are experiencing an increased interest for floating offshore applications. However, VAWT development is hindered by the lack of fast, accurate and validated simulation models. This work compares six different numerical models for VAWTS: a multiple...

  1. Local charge measurement using off-axis electron holography

    DEFF Research Database (Denmark)

    Beleggia, Marco; Gontard, L.C.; Dunin-Borkowski, R.0E.

    2016-01-01

    A model-independent approach based on Gauss’ theorem for measuring the local charge in a specimen from an electron-optical phase image recorded using off-axis electron holography was recently proposed. Here, we show that such a charge measurement is reliable when it is applied to determine the to...

  2. Tilted axis rotation in odd-odd {sup 164}Tm

    Energy Technology Data Exchange (ETDEWEB)

    Reviol, W.; Riedinger, L.L.; Wang, X.Z.; Zhang, J.Y. [Univ. of Tennessee, Knoxville, TN (United States)] [and others

    1996-12-31

    Ten band structures are observed in {sup 164}Tm, among them sets of parallel and anti-parallel couplings of the proton and neutron spins. The Tilted Axis Cranking scheme is applied for the first time to an odd-odd nucleus in a prominent region of nuclear deformation.

  3. An improved computer controlled triple-axis neutron spectrometer

    International Nuclear Information System (INIS)

    Cooper, M.J.; Hall, J.W.; Hutchings, M.T.

    1975-07-01

    A description is given of the computer-controlled triple-axis neutron spectrometer installed at the PLUTO reactor at Harwell. The reasons for an nature of recent major improvements are discussed. Following a general description of the spectrometer, details are then given of the new computerised control system, including the functions of the various programs which are now available to the user. (author)

  4. Lake Malawi cichlid evolution along a benthic/limnetic axis.

    Science.gov (United States)

    Hulsey, C D; Roberts, R J; Loh, Y-H E; Rupp, M F; Streelman, J T

    2013-07-01

    Divergence along a benthic to limnetic habitat axis is ubiquitous in aquatic systems. However, this type of habitat divergence has largely been examined in low diversity, high latitude lake systems. In this study, we examined the importance of benthic and limnetic divergence within the incredibly species-rich radiation of Lake Malawi cichlid fishes. Using novel phylogenetic reconstructions, we provided a series of hypotheses regarding the evolutionary relationships among 24 benthic and limnetic species that suggests divergence along this axis has occurred multiple times within Lake Malawi cichlids. Because pectoral fin morphology is often associated with divergence along this habitat axis in other fish groups, we investigated divergence in pectoral fin muscles in these benthic and limnetic cichlid species. We showed that the eight pectoral fin muscles and fin area generally tended to evolve in a tightly correlated manner in the Lake Malawi cichlids. Additionally, we found that larger pectoral fin muscles are strongly associated with the independent evolution of the benthic feeding habit across this group of fish. Evolutionary specialization along a benthic/limnetic axis has occurred multiple times within this tropical lake radiation and has produced repeated convergent matching between exploitation of water column habitats and locomotory morphology.

  5. The somatotropic axis: Effects on brain and cognitive functions

    NARCIS (Netherlands)

    Quik, E.H.

    2012-01-01

    Both hormones of the somatotropic axis, insulin-like growth factor-1 (IGF-1) and growth hormone (GH) can cross the blood-brain barrier and bind to their receptors in neurons and glia throughout the brain. Features of aging resemble those of GHD and aging is also associated with a decline in the

  6. Locating an axis-parallel rectangle on a Manhattan plane

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Körner, Mark-Christoph

    2014-01-01

    In this paper we consider the problem of locating an axis-parallel rectangle in the plane such that the sum of distances between the rectangle and a finite point set is minimized, where the distance is measured by the Manhattan norm 1. In this way we solve an extension of the Weber problem...

  7. Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Hay-Schmidt, Anders; Kiss, Alexander

    2004-01-01

    Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these recept...

  8. Off-axis electron holography of ferromagnetic multilayer nanowires

    DEFF Research Database (Denmark)

    Akhtari-Zavareh, Azadeh; Carignan, L. P.; Yelon, A.

    2014-01-01

    with respect to the axis of the wires. In thinner Cu/CoFeB ((multilayer, magnetic field vortices were detected, associated with opposing magnetization in neighbouring layers. The measured crystallinity, compositions, and layer thicknesses of individual NWs were found to be significantly different...

  9. On the Turbulent Mixing in Horizontal Axis Wind Turbine Wakes

    NARCIS (Netherlands)

    Lignarolo, L.E.M.

    2016-01-01

    The wake flow of a horizontal axis wind turbine is characterised by lower wind speed and higher turbulence than the free-stream conditions. When clustered in large wind farms, wind turbines regularly operate inside the wake of one or more upstream machines. This is a major cause of energy production

  10. A four-axis hand controller for helicopter flight control

    Science.gov (United States)

    Demaio, Joe

    1993-01-01

    A proof-of-concept hand controller for controlling lateral and longitudinal cyclic pitch, collective pitch and tail rotor thrust was developed. The purpose of the work was to address problems of operator fatigue, poor proprioceptive feedback and cross-coupling of axes associated with many four-axis controller designs. The present design is an attempt to reduce cross-coupling to a level that can be controlled with breakout force, rather than to eliminate it entirely. The cascaded design placed lateral and longitudinal cyclic in their normal configuration. Tail rotor thrust was placed atop the cyclic controller. A left/right twisting motion with the wrist made the control input. The axis of rotation was canted outboard (clockwise) to minimize cross-coupling with the cyclic pitch axis. The collective control was a twist grip, like a motorcycle throttle. Measurement of the amount of cross-coupling involved in pure, single-axis inputs showed cross coupling under 10 percent of full deflection for all axes. This small amount of cross-coupling could be further reduced with better damping and force gradient control. Fatigue was not found to be a problem, and proprioceptive feedback was adequate for all flight tasks executed.

  11. Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry.

    Science.gov (United States)

    Sandhu, Kiran V; Sherwin, Eoin; Schellekens, Harriët; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2017-01-01

    The microbial population residing within the human gut represents one of the most densely populated microbial niche in the human body with growing evidence showing it playing a key role in the regulation of behavior and brain function. The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and the behavior that are often associated with neuropsychiatric conditions. Therefore, research targeting the modulation of this gut microbiota as a novel therapy for the treatment of various neuropsychiatric conditions is gaining interest. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth, and environment. However, it is diet composition and nutritional status that has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota at different time points across the lifespan and under various health conditions. Thus the microbiota is poised to play a key role in nutritional interventions for maintaining brain health. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. The manufacturing and metrology of off-axis mirrors

    Science.gov (United States)

    Penzkofer, Karlheinz; Rascher, Rolf; Küpper, Lutz; Liebl, Johannes

    2015-10-01

    Especially in the area of the large mirror manufacturing only a few manufacturers are capable to produce optical surfaces of high quality. Therefore a deterministic process should be developed in the project IFasO. In the field of telescope optics off-axis optical systems are becoming increasingly important. These systems try to avoid an obstructing of the incoming light by moving the secondary mirror out of the primary mirror's optical axis. This advantage leads to an increasing market for this type of optical surface. Until now off-axis mirrors were difficult or almost impossible to produce. With the processes developed in IFasO, high quality mirrors become possible. For this reason, this paper describes the manufacturing of off-axis surfaces and its problems. The mirror production used in the project IFasO is based on the specific design of the CNC center developed by the company Optotech. This center UPG2000 is capable of grinding, polishing, sagitta measurement and interferometric measurement in one mounting of the specimen. Usually a large optics has to be transported during their manufacturing after every individual process step. There is always a risk of damage of the specimen. The exact orientation of the surface relatively to the tool position is also required. This takes a huge amount of time and makes up most of the production time. In this presentation the use of UPG2000 and the next steps within the process development are described. In the current status the manufacturing of large off-axis elements with a PV < λ/10 rms is reproducible.

  13. GRB 170817A: a short GRB seen off-axis

    Science.gov (United States)

    He, Xin-Bo; Tam, Pak-Hin Thomas; Shen, Rong-Feng

    2018-04-01

    The angular distribution of gamma-ray burst (GRB) jets is not yet clear. The observed luminosity of GRB 170817A is the lowest among all known short GRBs, which is best explained by the fact that our line of sight is outside of the jet opening angle, θ obs > θ j , where θ obs is the angle between our line of sight and the jet axis. As inferred by gravitational wave observations, as well as radio and X-ray afterglow modeling of GRB 170817A, it is likely that θ obs ∼ 20° – 28°. In this work, we quantitatively consider two scenarios of angular energy distribution of GRB ejecta: a top-hat jet and a structured jet with a power law index s. For the top-hat jet model, we get a large θ j (e.g., θ j > 10°), a rather high local (i.e., z 7.5 × 104, keV (∼500, keV for a typical short GRB). For the structured jet model, we use θ obs to give limits on s and θj for typical on-axis luminosity of a short GRB (e.g., 1049 erg s‑1 ∼ 1051 erg s‑1), and a low on-axis luminosity case (e.g., 1049 erg s‑1) gives more reasonable values of s. The structured jet model is more feasible for GRB 170817A than the top-hat jet model due to the rather high local short GRB rate, and the extremely high on-axis E peak,0 almost rules out the top-hat jet model. GRB 170817A is likely a low on-axis luminosity GRB (1049 erg s‑1) with a structured jet.

  14. Analytical Aerodynamic Simulation Tools for Vertical Axis Wind Turbines

    International Nuclear Information System (INIS)

    Deglaire, Paul

    2010-01-01

    Wind power is a renewable energy source that is today the fastest growing solution to reduce CO 2 emissions in the electric energy mix. Upwind horizontal axis wind turbine with three blades has been the preferred technical choice for more than two decades. This horizontal axis concept is today widely leading the market. The current PhD thesis will cover an alternative type of wind turbine with straight blades and rotating along the vertical axis. A brief overview of the main differences between the horizontal and vertical axis concept has been made. However the main focus of this thesis is the aerodynamics of the wind turbine blades. Making aerodynamically efficient turbines starts with efficient blades. Making efficient blades requires a good understanding of the physical phenomena and effective simulations tools to model them. The specific aerodynamics for straight bladed vertical axis turbine flow are reviewed together with the standard aerodynamic simulations tools that have been used in the past by blade and rotor designer. A reasonably fast (regarding computer power) and accurate (regarding comparison with experimental results) simulation method was still lacking in the field prior to the current work. This thesis aims at designing such a method. Analytical methods can be used to model complex flow if the geometry is simple. Therefore, a conformal mapping method is derived to transform any set of section into a set of standard circles. Then analytical procedures are generalized to simulate moving multibody sections in the complex vertical flows and forces experienced by the blades. Finally the fast semi analytical aerodynamic algorithm boosted by fast multipole methods to handle high number of vortices is coupled with a simple structural model of the rotor to investigate potential aeroelastic instabilities. Together with these advanced simulation tools, a standard double multiple streamtube model has been developed and used to design several straight bladed

  15. DARHT Axis-I Diode Simulations II: Geometrical Scaling

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, Carl A. Jr. [Los Alamos National Laboratory

    2012-06-14

    Flash radiography of large hydrodynamic experiments driven by high explosives is a venerable diagnostic technique in use at many laboratories. Many of the largest hydrodynamic experiments study mockups of nuclear weapons, and are often called hydrotests for short. The dual-axis radiography for hydrodynamic testing (DARHT) facility uses two electron linear-induction accelerators (LIA) to produce the radiographic source spots for perpendicular views of a hydrotest. The first of these LIAs produces a single pulse, with a fixed {approx}60-ns pulsewidth. The second axis LIA produces as many as four pulses within 1.6-{micro}s, with variable pulsewidths and separation. There are a wide variety of hydrotest geometries, each with a unique radiographic requirement, so there is a need to adjust the radiographic dose for the best images. This can be accomplished on the second axis by simply adjusting the pulsewidths, but is more problematic on the first axis. Changing the beam energy or introducing radiation attenuation also changes the spectrum, which is undesirable. Moreover, using radiation attenuation introduces significant blur, increasing the effective spot size. The dose can also be adjusted by changing the beam kinetic energy. This is a very sensitive method, because the dose scales as the {approx}2.8 power of the energy, but it would require retuning the accelerator. This leaves manipulating the beam current as the best means for adjusting the dose, and one way to do this is to change the size of the cathode. This method has been proposed, and is being tested. This article describes simulations undertaken to develop scaling laws for use as design tools in changing the Axis-1 beam current by changing the cathode size.

  16. Velocity measurement of model vertical axis wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, D.A.; McWilliam, M. [Waterloo Univ., ON (Canada). Dept. of Mechanical Engineering

    2006-07-01

    An increasingly popular solution to future energy demand is wind energy. Wind turbine designs can be grouped according to their axis of rotation, either horizontal or vertical. Horizontal axis wind turbines have higher power output in a good wind regime than vertical axis turbines and are used in most commercial class designs. Vertical axis Savonius-based wind turbine designs are still widely used in some applications because of their simplistic design and low wind speed performance. There are many design variables that must be considered in order to optimize the power output in a given wind regime in a typical wind turbine design. Using particle image velocimetry, a study of the air flow around five different model vertical axis wind turbines was conducted in a closed loop wind tunnel. A standard Savonius design with two semi-circular blades overlapping, and two variations of this design, a deep blade and a shallow blade design were among the turbine models included in this study. It also evaluated alternate designs that attempt to increase the performance of the standard design by allowing compound blade curvature. Measurements were collected at a constant phase angle and also at random rotor orientations. It was found that evaluation of the flow patterns and measured velocities revealed consistent and stable flow patterns at any given phase angle. Large scale flow structures are evident in all designs such as vortices shed from blade surfaces. An important performance parameter was considered to be the ability of the flow to remain attached to the forward blade and redirect and reorient the flow to the following blade. 6 refs., 18 figs.

  17. Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones.

    Science.gov (United States)

    Stephens, Mary Ann C; Mahon, Pamela B; McCaul, Mary E; Wand, Gary S

    2016-04-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the

  18. Experimental hyperthyroidism and central mediators of stress axis and thyroid axis activity in common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Geven, Edwin J W; Verkaar, Folkert; Flik, Gert; Klaren, Peter H M

    2006-12-01

    The effect of experimental hyperthyroidism, realized by T(4) injection, on central mediators of the hypothalamo-pituitary-interrenal axis (HPI-axis) in common carp (Cyprinus carpio L.) was studied. Our results show that hyperthyroidism evokes a marked 3.2-fold reduction in basal plasma cortisol levels. Corticotropin-releasing hormone-binding protein (CRH-BP) mRNA levels in the hypothalamus, measured by real-time quantitative PCR, were significantly elevated by 40%, but CRH, urotensin-I, prepro-TRH, prohormone convertase-1 (PC1), and POMC mRNA levels were unchanged. In the pituitary pars distalis, PC1, CRH receptor-1, and POMC mRNA levels were unaffected, as was ACTH content. Plasma alpha-MSH concentrations were significantly elevated by 30% in hyperthyroid fish, and this was reflected in PC1 and POMC mRNA levels in pituitary pars intermedia that were increased 1.5- and 2.4-fold respectively. The alpha-MSH content of the pars intermedia was unchanged. Hyperthyroidism has profound effects on the basal levels of a central mediator, i.e., CRH-BP, of HPI-axis function in unstressed carp in vivo, and we conclude that HPI- and hypothalamo-pituitary-thyroid-axis functions are strongly interrelated. We suggest that the changes in plasma cortisol, thyroid hormone, and alpha-MSH levels reflect their concerted actions on energy metabolism.

  19. Urea and impairment of the Gut-Kidney axis in Chronic Kidney Disease.

    Science.gov (United States)

    Di Iorio, Biagio Raffaele; Marzocco, Stefania; Nardone, Luca; Sirico, Marilisa; De Simone, Emanuele; Di Natale, Gabriella; Di Micco, Lucia

    2017-12-05

    Gut microbiota can be considered a real organ coordinating health and wellness of our body. It is made of more than 100 trillions of microorganisms, thus about 3 times higher than the number of human body cells and more than 150 times than human genes containing 1000 different microbe species. It has been described a symbiotic relationship between gut and kidney, confirmed by several observations. This is a bi-directional relation with a mutual influence, even when kidney disease occurs, and consequent alterations of intestinal microbiota and production of uremic toxins, that in turn worsens kidney disease and its progression. Our review analyzes the components of gut-kidney axis and relative clinical consequences. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

  20. The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

    Science.gov (United States)

    McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

    2017-07-07

    The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Development of triple axis neutron spectrometer (Paper No. 24)

    International Nuclear Information System (INIS)

    Pal, B.C.; Wadhwa, N.R.; Goveas, S.H.

    1987-02-01

    The triple axis neutron spectrometers are the basic instruments intended for use with neutron beams from reactors. Various types of spectrometers, each devoted to different kinds of measurement can be designed and manufactured, once a prototype having all the attributes of a versatile instrument is designed and developed. With the view to achieving self reliance in this field, Central Workshops of Bhabha Atomic Research Centre (BARC), Bombay designed and developed a prototype of triple axis spectrometer meeting the specifications prepared by Nuclear Physics Division of BARC . This spectrometer, with a moving wedge system was successfully manufactured and installed at 'DHRUVA'. Another version of this spectrometer, called the 'Polarised Neutron Spectrometer' was also built and exported to South Korea and installed at Korea Advanced Energy Research Institute, Seoul. This paper deals with basic concept, development of design, engineering of mechanical assemblies, the manufacturing approach and problems encountered during manufacture. (author). 3 figs

  2. Self-assembly of orthogonal three-axis sensors

    International Nuclear Information System (INIS)

    Cho, J. H.; Hu, S.; Gracias, D. H.

    2008-01-01

    Conventional planar microfabrication is widely utilized to construct sensors for the measurement of physical or chemical properties. However, in these devices, the information component measured is typically restricted to only one vectorial axis. Here, we describe a self-assembling strategy that can be utilized to construct three dimensional (3D) cubic devices that facilitate measurement along three axes. This 3D measurement is achieved by arranging sensing elements orthogonally; any sensing element that can be lithographically patterned can be utilized. The 3D arrangement of sensors allows for the measurement of angular and orientation parameters. As an example, we describe a three-axis cantilever based sensor and demonstrate measurement of an evaporated analyte using resonant frequency shifts of cantilevers in each of the x, y, and z axes

  3. Dynamic Compensation for Two-Axis Robot Wrist Force Sensors

    Directory of Open Access Journals (Sweden)

    Junqing Ma

    2013-01-01

    Full Text Available To improve the dynamic characteristic of two-axis force sensors, a dynamic compensation method is proposed. The two-axis force sensor system is assumed to be a first-order system. The operation frequency of the system is expanded by a digital filter with backward difference network. To filter high-frequency noises, a low-pass filter is added after the dynamic compensation network. To avoid overcompensation, parameters of the proposed dynamic compensation method are defined by trial and error. Step response methods are utilized in dynamic calibration experiments. Compared to experiment data without compensation, the response time of the dynamic compensated data is reduced by 30%~40%. Experiments results demonstrate the effectiveness of our method.

  4. Efficiency of the DOMUS 750 vertical-axis wind turbine

    Science.gov (United States)

    Hallock, Kyle; Rasch, Tyler; Ju, Guoqiang; Alonso-Marroquin, Fernando

    2017-06-01

    The aim of this paper is to present some preliminary results on the efficiency of a wind turbine for an off-grid housing unit. To generate power, the unit uses a photovoltaic solar array and a vertical-axis wind turbine (VAWT). The existing VAWT was analysed to improve efficiency and increase power generation. There were found to be two main sources of inefficiency: 1. the 750W DC epicyclic generator performed poorly in low winds, and 2. the turbine blades wobbled, allowing for energy loss due to off-axis rotation. A 12V DC permanent magnet alternator was chosen that met the power requirements of the housing unit and would generate power at lower wind speeds. A support bracket was designed to prevent the turbine blades from wobbling.

  5. Design optimization and analysis of vertical axis wind turbine blade

    International Nuclear Information System (INIS)

    Jarral, A.; Ali, M.; Sahir, M.H.

    2013-01-01

    Wind energy is clean and renwable source of energy and is also the world's fastest growing energy resource. Keeping in view power shortages and growing cost of energy, the low cost wind energy has become a primary solution. It is imperative that economies and individuals begin to conserve energy and focus on the production of energy from renewable sources. Present study describes a wind turbine blade designed with enhanced aerodynamic properties. Vertical axis turbine is chosen because of its easy installment, less noisy and having environmental friendly characteristics. Vertical axis wind turbines are thought to be ideal for installations where wind conditions are not consistent. The presented turbine blade is best suitable for roadsides where the rated speed due to vehicles is most /sup -1/ often 8 ms .To get an optimal shape design symmetrical profile NACA0025 has been considered which is then analyzed for stability and aerodynamic characteristics at optimal conditions using analysis tools ANSYS and CFD tools. (author)

  6. A new vertical axis wind turbine design for urban areas

    Science.gov (United States)

    Frunzulica, Florin; Cismilianu, Alexandru; Boros, Alexandru; Dumitrache, Alexandru; Suatean, Bogdan

    2016-06-01

    In this paper we aim at developing the model of a Vertical Axis Wind Turbine (VAWT) with the short-term goal of physically realising this turbine to operate at a maximmum power of 5 kW. The turbine is designed for household users in the urban or rural areas and remote or isolated residential areas (hardly accsessible). The proposed model has a biplane configuration on each arm of the VAWT (3 × 2 = 6 blades), allowing for increased performance of the turbine at TSR between 2 and 2.5 (urban area operation) compared to the classic vertical axis turbines. Results that validate the proposed configuration as well as passive control methods to increase the performance of the classic VAWTs are presented.

  7. Tuning the DARHT Axis-II linear induction accelerator focusing

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, Carl A. [Los Alamos National Laboratory

    2012-04-24

    Flash radiography of large hydrodynamic experiments driven by high explosives is a well-known diagnostic technique in use at many laboratories, and the Dual-Axis Radiography for Hydrodynamic Testing (DARHT) facility at Los Alamos produces flash radiographs of large hydrodynamic experiments. Two linear induction accelerators (LIAs) make the bremsstrahlung radiographic source spots for orthogonal views of each test. The 2-kA, 20-MeV Axis-I LIA creates a single 60-ns radiography pulse. The 1.7-kA, 16.5-MeV Axis-II LIA creates up to four radiography pulses by kicking them out of a longer pulse that has a 1.6-{mu}s flattop. The Axis-II injector, LIA, kicker, and downstream transport (DST) to the bremsstrahlung converter are described. Adjusting the magnetic focusing and steering elements to optimize the electron-beam transport through an LIA is often called 'tuning.' As in all high-current LIAs, the focusing field is designed to be as close to that of the ideal continuous solenoid as physically possible. In ideal continuous solenoidal transport a smoothly varying beam size can easily be found for which radial forces balance, and the beam is said to be 'matched' to the focusing field. A 'mismatched' beam exhibits unwanted oscillations in size, which are a source of free energy that contributes to emittance growth. This is undesirable, because in the absence of beam-target effects, the radiographic spot size is proportional to the emittance. Tuning the Axis-II LIA is done in two steps. First, the solenoidal focusing elements are set to values designed to provide a matched beam with little or no envelope oscillations, and little or no beam-breakup (BBU) instability growth. Then, steering elements are adjusted to minimize the motion of the centroid of a well-centered beam at the LIA exit. This article only describes the design of the tune for the focusing solenoids. The DARHT Axis-II LIA was required to be re-tuned after installing an

  8. Ground Vibration Attenuation Measurement using Triaxial and Single Axis Accelerometers

    Science.gov (United States)

    Mohammad, A. H.; Yusoff, N. A.; Madun, A.; Tajudin, S. A. A.; Zahari, M. N. H.; Chik, T. N. T.; Rahman, N. A.; Annuar, Y. M. N.

    2018-04-01

    Peak Particle Velocity is one of the important term to show the level of the vibration amplitude especially traveling wave by distance. Vibration measurement using triaxial accelerometer is needed to obtain accurate value of PPV however limited by the size and the available channel of the data acquisition module for detailed measurement. In this paper, an attempt to estimate accurate PPV has been made by using only a triaxial accelerometer together with multiple single axis accelerometer for the ground vibration measurement. A field test was conducted on soft ground using nine single axis accelerometers and a triaxial accelerometer installed at nine receiver location R1 to R9. Based from the obtained result, the method shows convincing similarity between actual PPV with the calculated PPV with error ratio 0.97. With the design method, vibration measurement equipment size can be reduced with fewer channel required.

  9. Vertical-axis turbine/propeller for ship propulsion

    Energy Technology Data Exchange (ETDEWEB)

    Barkla, H.M.

    1984-01-01

    There are so many variables in the design and operating conditions of a vertical-axis turbine/propeller for the propulsion of a ship by wind that a preliminary study is offered, based on two simplified models. Study of a linear motion of blades in air and water shows optimum conditions for blade-speed and blade-incidence. Analysis of the second, cyclical model is simplified by the assumption of constant angles of incidence. While the logical superiority of the vertical-axis system, with its low transmission loss, may not alone give it the advantage over all other systems in upwind and downwind sailing, there are indications that in the beam wind it is in a class of its own; the Voith-Schneider-Type propeller then produces a thrust with a major component to windward, so that the combined unit leaves little or no athwartships force.

  10. APS-U LATTICE DESIGN FOR OFF-AXIS ACCUMULATION

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yipeng; Borland, M.; Lindberg, R.; Sajaev, V.

    2017-06-25

    A 67-pm hybrid-seven-bend achromat (H7BA) lattice is being proposed for a future Advanced Photon Source (APS) multi-bend-achromat (MBA) upgrade project. This lattice design pushes for smaller emittance and requires use of a swap-out (on-axis) injection scheme due to limited dynamic acceptance. Alternate lattice design work has also been performed for the APS upgrade to achieve better beam dynamics performance than the nominal APS MBA lattice, in order to allow off-axis accumulation. Two such alternate H7BA lattice designs, which target a still-low emittance of 90 pm, are discussed in detail in this paper. Although the single-particle-dynamics performance is good, simulations of collective effects indicate that surprising difficulty would be expected accumulating high single-bunch charge in this lattice. The brightness of the 90-pm lattice is also a factor of two lower than the 67-pm H7BA lattice.

  11. Axis-switching of a micro-jet

    Science.gov (United States)

    Cabaleiro, Juan Martin; Aider, Jean-Luc

    2014-03-01

    In this study, it is shown that free microjets can undergo complex transitions similar to large-scale free jets despite relatively low Reynolds numbers. Using an original experimental method allowing for the 3D reconstruction of the instantaneous spatial organization of the microjet, the axis-switching of a micro-jet is observed for the first time. This is the first experimental evidence of such complex phenomena for free micro-jets. Combining these experimental results with Direct Numerical Simulations it is shown that the mechanism responsible for the axis-switching is the deformation of a micro-vortex ring due to induction by the corner vortices, as it occurs in large scale non-circular jets.

  12. Averaging scheme for atomic resolution off-axis electron holograms.

    Science.gov (United States)

    Niermann, T; Lehmann, M

    2014-08-01

    All micrographs are limited by shot-noise, which is intrinsic to the detection process of electrons. For beam insensitive specimen this limitation can in principle easily be circumvented by prolonged exposure times. However, in the high-resolution regime several instrumental instabilities limit the applicable exposure time. Particularly in the case of off-axis holography the holograms are highly sensitive to the position and voltage of the electron-optical biprism. We present a novel reconstruction algorithm to average series of off-axis holograms while compensating for specimen drift, biprism drift, drift of biprism voltage, and drift of defocus, which all might cause problematic changes from exposure to exposure. We show an application of the algorithm utilizing also the possibilities of double biprism holography, which results in a high quality exit-wave reconstruction with 75 pm resolution at a very high signal-to-noise ratio. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Development of a Single-Axis Edge Detection System

    Energy Technology Data Exchange (ETDEWEB)

    Hanshaw, R.A.

    2000-02-18

    A SIP (Societe Genevoise d'Instruments de Physique) Trioptic coordinate measuring machine was modified for calibration of high quality single-axis glass standards to an uncertainty of {+-}0.000020 inch. The modification was accomplished through the addition of a frame grabber board, vision software, a high-resolution camera, stepper motors, a two-axis motor controller, and an HP-IB interface card. An existing temperature system (hygrometer, barometer, laser interferometer system, and optics) was retained as part of the system. An existing Hewlett Packard computer was replaced with a personal computer to accommodate the frame grabber board. Each component was integrated into the existing system using Visual Basic. The system was automated for unattended measurements by creating a machine programming language, which is recognized within the main program.

  14. Targeting the gut-liver axis in cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn S; Havelund, Troels; Krag, Aleksander

    2013-01-01

    The gut-liver axis in cirrhosis and portal hypertension is gaining increasing attention as a key pathophysiological mechanism responsible for progression of liver failure and development of complications such as spontaneous infections and hepatocellular carcinoma. Antibiotics and non-selective β......-blockers (NSBB) intercept this axis and each drug has proven efficacy in clinical trials. A synergistic effect is a hitherto unproven possibility. There is an increasing body of evidence supporting improved outcome with expanded use of NSBB and antibiotic therapy beyond current indications. This review addresses...... the issue of pharmacological treatment of cirrhosis and portal hypertension with antibiotics and NSBB. We discuss their mechanism of action and suggest that combining the two treatment modalities could potentially reduce the risk of complications....

  15. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, Ronnie [Univ. of Rochester, NY (United States)

    1977-01-01

    Plasma corticosterone and ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, under a variety of experimental conditions, to obtain more information on the postnatal development of the rat hypothalamo-adrenal (HHA) axis. The results indicate that: (1) there is a diminution followed by an increase in responsiveness of the adrenal gland, but the pituitary response to direct hormonal stimulation is unchanged during the first three postnatal weeks; (2) continued stimulation of the adrenal by ACTH or of the central nervous system (CNS) or hypothalamus by corticosterone is necessary during early postnatal development to allow normal maturation of the HHA axis; and (3) feedback inhibition is operative by birth, at least to a moderate degree. Taken together, the studies suggest that both the adrenal and pituitary glands are potentially functional at birth, but that the hypothalamic and CNS mediators of the stress response are not mature until at least the second or third postnatal week. (ERB)

  16. Application of one-axis sun tracking system

    Energy Technology Data Exchange (ETDEWEB)

    Sefa, Ibrahim; Demirtas, Mehmet; Colak, Ilhami [Gazi University, Faculty of Technical Education, Department of Electrical Education, GEMEC-Gazi Electric Machines and Control Group, Ankara (Turkey)

    2009-11-15

    This paper introduces design and application of a novel one-axis sun tracking system which follows the position of the sun and allows investigating effects of one-axis tracking system on the solar energy in Turkey. The tracking system includes a serial communication interface based on RS 485 to monitor whole processes on a computer screen and to plot data as graphic. In addition, system parameters such as the current, the voltage and the panel position have been observed by means of a microcontroller. The energy collected is measured and compared with a fixed solar system for the same solar panel. The results show that the solar energy collected on the tracking system is considerably much efficient than the fixed system. The tracking system developed in this study provides easy installation, simple mechanism and less maintenance. (author)

  17. Summary of tower designs for large horizontal axis wind turbines

    Science.gov (United States)

    Frederick, G. R.; Savino, J. M.

    1986-01-01

    Towers for large horizontal axis wind turbines, machines with a rotor axis height above 30 meters and rated at more than 500 kW, have varied in configuration, materials of construction, type of construction, height, and stiffness. For example, the U.S. large HAWTs have utilized steel truss type towers and free-standing steel cylindrical towers. In Europe, the trend has been to use only free-standing and guyed cylindrical towers, but both steel and reinforced concrete have been used as materials of construction. These variations in materials of construction and type of construction reflect different engineering approaches to the design of cost effective towers for large HAWTs. Tower designs are the NASA/DOE Mod-5B presently being fabricated. Design goals and requirements that influence tower configuration, height and materials are discussed. In particular, experiences with United States large wind turbine towers are elucidated. Finally, current trends in tower designs for large HAWTs are highlighted.

  18. Application of one-axis sun tracking system

    International Nuclear Information System (INIS)

    Sefa, Ibrahim; Demirtas, Mehmet; Colak, Ilhami

    2009-01-01

    This paper introduces design and application of a novel one-axis sun tracking system which follows the position of the sun and allows investigating effects of one-axis tracking system on the solar energy in Turkey. The tracking system includes a serial communication interface based on RS 485 to monitor whole processes on a computer screen and to plot data as graphic. In addition, system parameters such as the current, the voltage and the panel position have been observed by means of a microcontroller. The energy collected is measured and compared with a fixed solar system for the same solar panel. The results show that the solar energy collected on the tracking system is considerably much efficient than the fixed system. The tracking system developed in this study provides easy installation, simple mechanism and less maintenance.

  19. Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis

    Directory of Open Access Journals (Sweden)

    Ran Huo

    2017-11-01

    Full Text Available Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on behavior, we examined behavioral changes associated with hormones and hormone receptors in the hypothalamic-pituitary-adrenal (HPA axis under stress. We tested germ-free (GF mice and specific pathogen-free (SPF mice, divided into four groups. A chronic restraint stress (CRS protocol was utilized to induce external pressure in two stress groups by restraining mice in a conical centrifuge tube for 4 h per day for 21 days. After CRS, Initially, GF restraint-stressed mice explored more time than SPF restraint-stressed mice in the center and total distance of the OFT. Moreover, the CRH, ACTH, CORT, and ALD levels in HPA axis of GF restraint-stressed mice exhibited a significantly greater increase than those of SPF restraint-stressed mice. Finally, the Crhr1 mRNA levels of GF CRS mice were increased compared with SPF CRS mice. However, the Nr3c2 mRNA levels of GF CRS mice were decreased compared with SPF CRS mice. All results revealed that SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress. Moreover, we also found that GF mice exhibited significant differences in, hormones, and hormone receptors compared with SPF mice. In conclusion, Imbalances of the HPA axis caused by intestinal microbes could affect the neuroendocrine system in the brain, resulting in an anxiety-like behavioral phenotype. This study suggested that intervention into intestinal microflora may provide a new approach for treating stress-related diseases.

  20. Central regulation of the hypothalamo-pituitary-thyroid (HPT) axis: focus on clinical aspects.

    Science.gov (United States)

    Fliers, E; Boelen, A; van Trotsenburg, A S P

    2014-01-01

    The hypothalamus is the most prominent brain region involved in setpoint regulation of the thyroid axis. It generates the diurnal thyroid-stimulating hormone (TSH) rhythm, and it plays a central role in the adaptation of the thyroid axis to environmental factors such as caloric deprivation or infection. Many studies, including studies in human post-mortem tissue samples, have confirmed a key role for the thyrotropin-releasing hormone (TRH) neuron in the hypothalamic paraventricular nucleus (PVN) in thyroid axis regulation. In addition to their negative feedback action on TRH neurons in the hypothalamus, intrahypothalamic thyroid hormones can also modulate metabolism in adipose tissue and the liver via the autonomic nervous system. Congenital or acquired dysfunction of the hypothalamus or pituitary gland may result in central hypothyroidism (CeH). In the Netherlands, the prevalence of permanent congenital CeH as detected by neonatal screening is approximately 1 in 18000. In most neonates congenital CeH is accompanied by additional anterior pituitary hormone deficiencies, and many show clear morphological abnormalities such as a small anterior gland, a thin or absent pituitary stalk, or an ectopic posterior pituitary gland. Recently, a mutation in the immunoglobulin superfamily member 1 (IGSF1) gene was reported as a novel cause of X-linked, apparently isolated CeH occurring in neonates, children and adults. In adults, the most frequent cause of acquired CeH is a pituitary macroadenoma, usually accompanied by other pituitary hormone deficiencies. Central hyperthyroidism is a rare disorder, especially in children. In adults, it is mostly caused by a TSH-secreting pituitary adenoma. © 2014 Elsevier B.V. All rights reserved.

  1. Device for passive flow control around vertical axis marine turbine

    Science.gov (United States)

    Coşoiu, C. I.; Georgescu, A. M.; Degeratu, M.; Haşegan, L.; Hlevca, D.

    2012-11-01

    The power supplied by a turbine with the rotor placed in a free stream flow may be increased by augmenting the velocity in the rotor area. The energy of the free flow is dispersed and it may be concentrated by placing a profiled structure around the bare turbine in order to concentrate more energy in the rotor zone. At the Aerodynamic and Wind Engineering Laboratory (LAIV) of the Technical University of Civil Engineering of Bucharest (UTCB) it was developed a concentrating housing to be used for hydro or aeolian horizontal axis wind turbines, in order to increase the available energy in the active section of turbine rotor. The shape of the concentrating housing results by superposing several aero/hydro dynamic effects, the most important being the one generated by the passive flow control devices that were included in the housing structure. Those concentrating housings may be also adapted for hydro or aeolian turbines with vertical axis. The present paper details the numerical research effectuated at the LAIV to determine the performances of a vertical axis marine turbine equipped with such a concentrating device, in order to increase the energy quantity extracted from the main flow. The turbine is a Darrieus type one with three vertical straight blades, symmetric with respect to the axis of rotation, generated using a NACA4518 airfoil. The global performances of the turbine equipped with the concentrating housing were compared to the same characteristics of the bare turbine. In order to validate the numerical approach used in this paper, test cases from the literature resulting from experimental and numerical simulations for similar situations, were used.

  2. Device for passive flow control around vertical axis marine turbine

    International Nuclear Information System (INIS)

    Coşoiu, C I; Georgescu, A M; Degeratu, M; Haşegan, L; Hlevca, D

    2012-01-01

    The power supplied by a turbine with the rotor placed in a free stream flow may be increased by augmenting the velocity in the rotor area. The energy of the free flow is dispersed and it may be concentrated by placing a profiled structure around the bare turbine in order to concentrate more energy in the rotor zone. At the Aerodynamic and Wind Engineering Laboratory (LAIV) of the Technical University of Civil Engineering of Bucharest (UTCB) it was developed a concentrating housing to be used for hydro or aeolian horizontal axis wind turbines, in order to increase the available energy in the active section of turbine rotor. The shape of the concentrating housing results by superposing several aero/hydro dynamic effects, the most important being the one generated by the passive flow control devices that were included in the housing structure. Those concentrating housings may be also adapted for hydro or aeolian turbines with vertical axis. The present paper details the numerical research effectuated at the LAIV to determine the performances of a vertical axis marine turbine equipped with such a concentrating device, in order to increase the energy quantity extracted from the main flow. The turbine is a Darrieus type one with three vertical straight blades, symmetric with respect to the axis of rotation, generated using a NACA4518 airfoil. The global performances of the turbine equipped with the concentrating housing were compared to the same characteristics of the bare turbine. In order to validate the numerical approach used in this paper, test cases from the literature resulting from experimental and numerical simulations for similar situations, were used.

  3. Small-Scale vertical axis wind turbine design

    OpenAIRE

    Castillo Tudela, Javier

    2011-01-01

    The thesis focuses on the design of a small vertical axis wind turbine rotor with solid wood as a construction material. The aerodynamic analysis is performed implementing a momentum based model on a mathematical computer program. A three bladed wind turbine is proposed as candidate for further prototype testing after evaluating the effect of several parameters in turbine efficiency, torque and acceleration. The results obtained indicate that wood is a suitable material for rotor cons...

  4. 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...

  5. Classification of threespine stickleback along the benthic-limnetic axis

    OpenAIRE

    Willacker, James J.; von Hippel, Frank A.; Wilton, Peter R.; Walton, Kelly M.

    2010-01-01

    Many species of fish display morphological divergence between individuals feeding on macroinvertebrates associated with littoral habitats (benthic morphotypes) and individuals feeding on zooplankton in the limnetic zone (limnetic morphotypes). Threespine stickleback (Gasterosteus aculeatus L.) have diverged along the benthic-limnetic axis into allopatric morphotypes in thousands of populations and into sympatric species pairs in several lakes. However, only a few well known populations have b...

  6. From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis

    Directory of Open Access Journals (Sweden)

    Jakob Triebel

    2017-12-01

    Full Text Available The prolactin/vasoinhibin axis defines an endocrine system, in which prolactin (PRL and vasoinhibins regulate blood vessel growth and function, the secretion of other hormones, inflammatory and immune processes, coagulation, and behavior. The core element of the PRL/vasoinhibin axis is the generation of vasoinhibins, which consists in the proteolytic cleavage of their precursor molecule PRL. Vasoinhibins can interact with multiple different partners to mediate their effects in various tissues and anatomical compartments, indicating their pleiotropic nature. Based on accumulating knowledge about the PRL/vasoinhibin axis, two clinical trials were initiated, in which vasoinhibin levels are the target of therapeutic interventions. One trial investigates the effect of levosulpiride, a selective dopamine D2-receptor antagonist, on retinal alterations in patients with diabetic macular edema and retinopathy. The rationale of this trial is that the levosulpiride-induced hyperprolactinemia resulting in increased retinal vasoinhibins could lead to beneficiary outcomes in terms of a vasoinhibin-mediated antagonization of diabetes-induced retinal alterations. Another trial investigated the effect of bromocriptine, a dopamine D2-receptor agonist, for the treatment of peripartum cardiomyopathy. The rationale of treatment with bromocriptine is the inhibition of vasoinhibin generation by substrate depletion to prevent detrimental effects on the myocardial microvascularization. The trial demonstrated that bromocriptine treatment was associated with a high rate of left ventricular recovery and low morbidity and mortality. Therapeutic interventions into the PRL/vasoinhibin axis bear the risk of side effects in the areas of blood coagulation, blood pressure, and alterations of the mental state.

  7. Roll-Axis Hydrofluidic Stability Augmentation System Development

    Science.gov (United States)

    1975-09-01

    lifi .1035 SW 30 left for znro time delay - r Ight for other. 17 Preceding page Hank Recordings of the simulated aircraft performance to...DESIGN The analytical effort defined the gains and shaping networks required for the roll-axis damper system for the OH-58A helicopter, and the...Shaping Networks Usually a combination of resistors and capacitors (bellows) is designed to provide the following functions: a) b) 3.1.4 1 Lag

  8. Three-axis orthogonal transceiver coil for eddy current sounding

    Science.gov (United States)

    Sukhanov, D.; Zavyalova, K.; Goncharik, M.

    2017-08-01

    We propose the new structure of three-axis transceiver magnetic-induction coil for eddy current probing. Due to the orientation of the coils, the direct signal from the transmitting coil to the receiving coil is minimized, which provided a high dynamic range. Sensitivity in all directions is provided by combining coils of different orientations. Numerical simulation and experimental studies of such a system have been carried out and confirmed the applicability of the proposed method and the mathematical model.

  9. Inelastic scattering using the three-axis spectrometer technique

    International Nuclear Information System (INIS)

    Currat, R.

    1999-01-01

    The three-axis technique is a basic neutron scattering technique for inelastic work on single-crystal specimens. There is, at the moment, a fair degree of complementarity between TAS instruments on steady-state sources and TOF instruments on steady-state or pulsed sources. The technique is described, the issue of TAS versus TOF method is discussed, and investigations relating to the resolution functions are presented. (K.A.)

  10. Estimation of power in low velocity vertical axis wind turbine

    Science.gov (United States)

    Sampath, S. S.; Shetty, Sawan; Chithirai Pon Selvan, M.

    2015-06-01

    The present work involves in the construction of a vertical axis wind turbine and the determination of power. Various different types of turbine blades are considered and the optimum blade is selected. Mechanical components of the entire setup are built to obtain maximum rotation per minute. The mechanical energy is converted into the electrical energy by coupling coaxially between the shaft and the generator. This setup produces sufficient power for consumption of household purposes which is economic and easily available.

  11. MARRT: Medial Axis biased rapidly-exploring random trees

    KAUST Repository

    Denny, Jory

    2014-05-01

    © 2014 IEEE. Motion planning is a difficult and widely studied problem in robotics. Current research aims not only to find feasible paths, but to ensure paths have certain properties, e.g., shortest or safest paths. This is difficult for current state-of-the-art sampling-based techniques as they typically focus on simply finding any path. Despite this difficulty, sampling-based techniques have shown great success in planning for a wide range of applications. Among such planners, Rapidly-Exploring Random Trees (RRTs) search the planning space by biasing exploration toward unexplored regions. This paper introduces a novel RRT variant, Medial Axis RRT (MARRT), which biases tree exploration to the medial axis of free space by pushing all configurations from expansion steps towards the medial axis. We prove that this biasing increases the tree\\'s clearance from obstacles. Improving obstacle clearance is useful where path safety is important, e.g., path planning for robots performing tasks in close proximity to the elderly. Finally, we experimentally analyze MARRT, emphasizing its ability to effectively map difficult passages while increasing obstacle clearance, and compare it to contemporary RRT techniques.

  12. A New, Adaptable, Optical High-Resolution 3-Axis Sensor

    Directory of Open Access Journals (Sweden)

    Niels Buchhold

    2017-01-01

    Full Text Available This article presents a new optical, multi-functional, high-resolution 3-axis sensor which serves to navigate and can, for example, replace standard joysticks in medical devices such as electric wheelchairs, surgical robots or medical diagnosis devices. A light source, e.g., a laser diode, is affixed to a movable axis and projects a random geometric shape on an image sensor (CMOS or CCD. The downstream microcontroller’s software identifies the geometric shape’s center, distortion and size, and then calculates x, y, and z coordinates, which can be processed in attached devices. Depending on the image sensor in use (e.g., 6.41 megapixels, the 3-axis sensor features a resolution of 1544 digits from right to left and 1038 digits up and down. Through interpolation, these values rise by a factor of 100. A unique feature is the exact reproducibility (deflection to coordinates and its precise ability to return to its neutral position. Moreover, optical signal processing provides a high level of protection against electromagnetic and radio frequency interference. The sensor is adaptive and adjustable to fit a user’s range of motion (stroke and force. This recommendation aims to optimize sensor systems such as joysticks in medical devices in terms of safety, ease of use, and adaptability.

  13. Blade pitch optimization methods for vertical-axis wind turbines

    Science.gov (United States)

    Kozak, Peter

    Vertical-axis wind turbines (VAWTs) offer an inherently simpler design than horizontal-axis machines, while their lower blade speed mitigates safety and noise concerns, potentially allowing for installation closer to populated and ecologically sensitive areas. While VAWTs do offer significant operational advantages, development has been hampered by the difficulty of modeling the aerodynamics involved, further complicated by their rotating geometry. This thesis presents results from a simulation of a baseline VAWT computed using Star-CCM+, a commercial finite-volume (FVM) code. VAWT aerodynamics are shown to be dominated at low tip-speed ratios by dynamic stall phenomena and at high tip-speed ratios by wake-blade interactions. Several optimization techniques have been developed for the adjustment of blade pitch based on finite-volume simulations and streamtube models. The effectiveness of the optimization procedure is evaluated and the basic architecture for a feedback control system is proposed. Implementation of variable blade pitch is shown to increase a baseline turbine's power output between 40%-100%, depending on the optimization technique, improving the turbine's competitiveness when compared with a commercially-available horizontal-axis turbine.

  14. A procedure for denoising dual-axis swallowing accelerometry signals

    International Nuclear Information System (INIS)

    Sejdić, Ervin; Chau, Tom; Steele, Catriona M

    2010-01-01

    Dual-axis swallowing accelerometry is an emerging tool for the assessment of dysphagia (swallowing difficulties). These signals however can be very noisy as a result of physiological and motion artifacts. In this note, we propose a novel scheme for denoising those signals, i.e. a computationally efficient search for the optimal denoising threshold within a reduced wavelet subspace. To determine a viable subspace, the algorithm relies on the minimum value of the estimated upper bound for the reconstruction error. A numerical analysis of the proposed scheme using synthetic test signals demonstrated that the proposed scheme is computationally more efficient than minimum noiseless description length (MNDL)-based denoising. It also yields smaller reconstruction errors than MNDL, SURE and Donoho denoising methods. When applied to dual-axis swallowing accelerometry signals, the proposed scheme exhibits improved performance for dry, wet and wet chin tuck swallows. These results are important for the further development of medical devices based on dual-axis swallowing accelerometry signals. (note)

  15. l=1 helical axis heliotron device in Kyoto university

    International Nuclear Information System (INIS)

    Nagasaki, K.; Sano, F.; Mizuuchi, T.; Hanatani, K.; Okada, H.; Obiki, T.

    1999-01-01

    Helical systems are an attractive candidate for magnetic fusion reactor. Recently, there has been great progress in theoretical research of three dimensional magnetic field structures, resulting in several kinds of confinement optimization being proposed for toroidal magnetic confinement system. For example, some sophisticated ideas have appeared on stage such as quasi-helical symmetry and quasi-isodynamic system. To find experimentally which way is the best Optimisation, a new helical axis heliotron device, so called 'Heliotron J', is under construction in the Institute of Advanced Energy, Kyoto University, Japan. In this conference, the basic concept and the present status will be presented. In the conventional plane axis helical system, it was difficult to have both good particle confinement and good MHD stability simultaneously. The goal of Heliotron J project is to clarify their compatibility in the spatial axis toroidal device. The best way for Optimising the helical magnetic field configuration will be explored by investigating the plasma response to the change in the field components. The main subjects for plasma experiment are: demonstration of the existence of good magnetic flux surfaces, reduction of neoclassical transport in collisionless regime, MHD Stabilisation in high β plasma, controllability of bootstrap current, good confinement of high energy particles

  16. Three-Axis Attitude Estimation Using Rate-Integrating Gyroscopes

    Science.gov (United States)

    Crassidis, John L.; Markley, F. Landis

    2016-01-01

    Traditionally, attitude estimation has been performed using a combination of external attitude sensors and internal three-axis gyroscopes. There are many studies of three-axis attitude estimation using gyros that read angular rates. Rate-integrating gyros measure integrated rates or angular displacements, but three-axis attitude estimation using these types of gyros has not been as fully investigated. This paper derives a Kalman filtering framework for attitude estimation using attitude sensors coupled with rate- integrating gyroscopes. In order to account for correlations introduced by using these gyros, the state vector must be augmented, compared with filters using traditional gyros that read angular rates. Two filters are derived in this paper. The first uses an augmented state-vector form that estimates attitude, gyro biases, and gyro angular displacements. The second ignores correlations, leading to a filter that estimates attitude and gyro biases only. Simulation comparisons are shown for both filters. The work presented in this paper focuses only on attitude estimation using rate-integrating gyros, but it can easily be extended to other applications such as inertial navigation, which estimates attitude and position.

  17. The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure: Sleep and the HPA Axis in Obesity

    OpenAIRE

    Lucassen, Eliane A.; Cizza, Giovanni

    2012-01-01

    Obesity, exposure to stress and inadequate sleep are prevalent phenomena in modern society. In this review we focus on their relationships and critically evaluate causality. In obese individuals, one of the main stress systems, the hypothalamic-pituitary-adrenal axis, is altered, and concentrations of cortisol are elevated in adipose tissue due to elevated local activity of 11β-hydroxysteroid dehydrogenase (HSD) type 1. Short sleep and decreased sleep quality are also associated with obesity....

  18. Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis: Incorporating Protein Synthesis in Improving Predictability of Responses to Endocrine Active Chemicals

    Science.gov (United States)

    There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minno...

  19. Computational Modeling of Hypothalamic-Pituitary-Gonadal Axis to Predict Adaptive Responses in Female Fathead Minnows Exposed to an Aromatase Inhibitor

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose response and time-course...

  20. Differences in IGF-axis protein expression and survival among multiethnic breast cancer patients

    International Nuclear Information System (INIS)

    Hernandez, Brenda Y; Wilkens, Lynne R; Le Marchand, Loïc; Horio, David; Chong, Clayton D; Loo, Lenora W M

    2015-01-01

    There is limited knowledge about the biological basis of racial/ethnic disparities in breast cancer outcomes. Aberrations in IGF signaling induced by obesity and other factors may contribute to these disparities. This study examines the expression profiles of the insulin-like growth factor (IGF)-axis proteins and the association with breast cancer survival across a multiethnic population. We examined the expression profiles of the IGF1, IGF1R, IGFBP2 (IGF-binding proteins), and IGFBP3 proteins in breast tumor tissue and their relationships with all-cause and breast cancer-specific survival up to 17 years postdiagnosis in a multiethnic series of 358 patients in Hawaii, USA. Native Hawaiians, Caucasians, and Japanese were compared. Covariates included demographic and clinical factors and ER/PR/HER2 (estrogen receptor/progesterone receptor/human epidermal growth factor receptor-2) status. In Native Hawaiian patients, IGFBP2 and IGFBP3 expression were each independently associated with overall and breast cancer mortality (IGFB2: HR mort = 10.96, 95% CI: 2.18–55.19 and HR mort = 35.75, 95% CI: 3.64–350.95, respectively; IGFBP3: HR mort = 5.16, 95% CI: 1.27–20.94 and HR mort = 8.60, 95% CI: 1.84–40.15, respectively). IGF1R expression was also positively associated with all-cause mortality in Native Hawaiians. No association of IGF-axis protein expression and survival was observed in Japanese or Caucasian patients. The interaction of race/ethnicity and IGFBP3 expression on mortality risk was significant. IGF-axis proteins may have variable influence on breast cancer progression across different racial/ethnic groups. Expression of binding proteins and receptors in breast tumors may influence survival in breast cancer patients by inducing aberrations in IGF signaling and/or through IGF-independent mechanisms. Additional studies to evaluate the role of the IGF-axis in breast cancer are critical to improve targeted breast cancer treatment strategies

  1. Design of an off-axis visual display based on a free-form projection screen to realize stereo vision

    Science.gov (United States)

    Zhao, Yuanming; Cui, Qingfeng; Piao, Mingxu; Zhao, Lidong

    2017-10-01

    A free-form projection screen is designed for an off-axis visual display, which shows great potential in applications such as flight training for providing both accommodation and convergence cues for pilots. The method based on point cloud is proposed for the design of the free-form surface, and the design of the point cloud is controlled by a program written in the macro-language. In the visual display based on the free-form projection screen, when the error of the screen along Z-axis is 1 mm, the error of visual distance at each filed is less than 1%. And the resolution of the design for full field is better than 1‧, which meet the requirement of resolution for human eyes.

  2. Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine.

    Science.gov (United States)

    Khalsa, Jag; Duffy, Linda C; Riscuta, Gabriela; Starke-Reed, Pamela; Hubbard, Van S

    2017-03-01

    Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. The gut microbiome, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease. Gut bacterial communities directly metabolize certain drugs, reducing their bioavailability and influencing individual variation in drug response. In addition, some microbiome-produced compounds may affect drug pharmacokinetics and pharmacodynamics via altered expression of metabolizing enzymes and drug transporters or genes coding for drug target proteins, drug response phenotypes, and disease states. Molecular-based high-throughput technologies are providing novel insight about host-gut microbiome interactions, homeostasis, and xenobiotic effects associated with wide variation in efficacy or toxicity in humans. It is envisioned that future approaches to treating and preventing liver disease will benefit from in-depth studies of the liver-microbiome axis. Thus, the microbiome shares a fundamental role in human physiology with various organ systems, and its importance must be considered in the rapid evolution of precision medicine. A new emerging perspective of understanding the effect of the gut microbiome on human response to drugs would be indispensable for developing efficacious, safe, and cost-effective precision therapies. © 2017, The American College of Clinical Pharmacology.

  3. Automated Slicing for a Multi-Axis Metal Deposition System (Preprint)

    Science.gov (United States)

    2006-09-01

    experimented with different materials like H13 tool steel to build the part. Following the same slicing and scanning toolpath result, there is a geometric...and analysis tool -centroidal axis. Similar to medial axis, it contains geometry and topological information but is significantly computationally...geometry reasoning and analysis tool -centroidal axis. Similar to medial axis, it contains geometry and topological information but is significantly

  4. FAMILY HISTORY STUDY OF THE FAMILIAL COAGGREGATION OF BORDERLINE PERSONALITY DISORDER WITH AXIS I AND NON-BORDERLINE DRAMATIC CLUSTER AXIS II DISORDERS

    OpenAIRE

    Zanarini, Mary C.; Barison, Leah K.; Frankenburg, Frances R.; Reich, D. Bradford; Hudson, James I.

    2009-01-01

    The purpose of this study was to assess the familial coaggregation of borderline personality disorder (BPD) with a full array of axis I disorders and four axis II disorders (antisocial personality disorder, histrionic personality disorder, narcissistic personality disorder, and sadistic personality disorder) in the first-degree relatives of borderline probands and axis II comparison subjects. Four hundred and forty-five inpatients were interviewed about familial psychopathology using the Revi...

  5. Adversity-driven changes in hypothalamic-pituitary-adrenal axis functioning during adolescence

    NARCIS (Netherlands)

    Laceulle, O.M.; Nederhof, Esther; van Aken, M.A.G.; Ormel, Johan

    2017-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during

  6. Adolescent Survivors of Hurricane Katrina: A Pilot Study of Hypothalamic-Pituitary-Adrenal Axis Functioning

    Science.gov (United States)

    Pfefferbaum, Betty; Tucker, Phebe; Nitiéma, Pascal

    2015-01-01

    Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina…

  7. Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis in patients with recently diagnosed rheumatoid arthritis

    NARCIS (Netherlands)

    Dekkers, J. C.; Geenen, R.; Godaert, G. L.; Glaudemans, K. A.; Lafeber, F. P.; van Doornen, L. J.; Bijlsma, J. W.

    2001-01-01

    There is evidence that the hypothalamic pituitary adrenal (HPA) axis is subresponsive in patients with rheumatoid arthritis (RA). We assessed HPA axis responses to experimental stressors mimicking daily life challenges in patients with RA to determine whether HPA axis activity is associated with Th1

  8. Multiscale mathematical modeling of the hypothalamo-pituitary-gonadal axis.

    Science.gov (United States)

    Clément, Frédérique

    2016-07-01

    Although the fields of systems and integrative biology are in full expansion, few teams are involved worldwide into the study of reproductive function from the mathematical modeling viewpoint. This may be due to the fact that the reproductive function is not compulsory for individual organism survival, even if it is for species survival. Alternatively, the complexity of reproductive physiology may be discouraging. Indeed, the hypothalamo-pituitary-gonadal (HPG) axis involves not only several organs and tissues but also intricate time (from the neuronal millisecond timescale to circannual rhythmicity) and space (from molecules to organs) scales. Yet, mathematical modeling, and especially multiscale modeling, can renew our approaches of the molecular, cellular, and physiological processes underlying the control of reproductive functions. In turn, the remarkable dynamic features exhibited by the HPG axis raise intriguing and challenging questions to modelers and applied mathematicians. In this article, we draw a panoramic review of some mathematical models designed in the framework of the female HPG, with a special focus on the gonadal and central control of follicular development. On the gonadal side, the modeling of follicular development calls to the generic formalism of structured cell populations, that allows one to make mechanistic links between the control of cell fate (proliferation, differentiation, or apoptosis) and that of the follicle fate (ovulation or degeneration) or to investigate how the functional interactions between the oocyte and its surrounding cells shape the follicle morphogenesis. On the central, mainly hypothalamic side, models based on dynamical systems with multiple timescales allow one to represent within a single framework both the pulsatile and surge patterns of the neurohormone GnRH. Beyond their interest in basic research investigations, mathematical models can also be at the source of useful tools to study the encoding and decoding of

  9. Optical diffraction tomography: accuracy of an off-axis reconstruction

    Science.gov (United States)

    Kostencka, Julianna; Kozacki, Tomasz

    2014-05-01

    Optical diffraction tomography is an increasingly popular method that allows for reconstruction of three-dimensional refractive index distribution of semi-transparent samples using multiple measurements of an optical field transmitted through the sample for various illumination directions. The process of assembly of the angular measurements is usually performed with one of two methods: filtered backprojection (FBPJ) or filtered backpropagation (FBPP) tomographic reconstruction algorithm. The former approach, although conceptually very simple, provides an accurate reconstruction for the object regions located close to the plane of focus. However, since FBPJ ignores diffraction, its use for spatially extended structures is arguable. According to the theory of scattering, more precise restoration of a 3D structure shall be achieved with the FBPP algorithm, which unlike the former approach incorporates diffraction. It is believed that with this method one is allowed to obtain a high accuracy reconstruction in a large measurement volume exceeding depth of focus of an imaging system. However, some studies have suggested that a considerable improvement of the FBPP results can be achieved with prior propagation of the transmitted fields back to the centre of the object. This, supposedly, enables reduction of errors due to approximated diffraction formulas used in FBPP. In our view this finding casts doubt on quality of the FBPP reconstruction in the regions far from the rotation axis. The objective of this paper is to investigate limitation of the FBPP algorithm in terms of an off-axis reconstruction and compare its performance with the FBPJ approach. Moreover, in this work we propose some modifications to the FBPP algorithm that allow for more precise restoration of a sample structure in off-axis locations. The research is based on extensive numerical simulations supported with wave-propagation method.

  10. Gaussian tunneling model of c-axis twist Josephson junctions

    International Nuclear Information System (INIS)

    Bille, A.; Klemm, R.A.; Scharnberg, K.

    2001-01-01

    We calculate the critical current density J c J ((var p hi) 0 ) for Josephson tunneling between identical high-temperature superconductors twisted an angle (var p hi) 0 about the c axis. Regardless of the shape of the two-dimensional Fermi surface and for very general tunneling matrix elements, an order parameter (OP) with general d-wave symmetry leads to J c J (π/4)=0. This general result is inconsistent with the data of Li et al. [Phys. Rev. Lett. 83, 4160 (1999)] on Bi 2 Sr 2 CaCu 2 O 8+δ (Bi2212), which showed J c J to be independent of (var p hi) 0 . If the momentum parallel to the barrier is conserved in the tunneling process, J c J should vary substantially with the twist angle (var p hi) 0 when the tight-binding Fermi surface appropriate for Bi2212 is taken into account, even if the OP is completely isotropic. We quantify the degree of momentum nonconservation necessary to render J c J ((var p hi) 0 ) constant within experimental error for a variety of pair states by interpolating between the coherent and incoherent limits using five specific models to describe the momentum dependence of the tunneling matrix element squared. From the data of Li et al., we conclude that the c-axis tunneling in Bi2212 must be very nearly incoherent, and that the OP must have a nonvanishing Fermi-surface average for T c . We further show that the apparent conventional sum-rule violation observed by Basov et al. [Science 283, 49 (1999)] can be consistent with such strongly incoherent c-axis tunneling.

  11. H I Kinematics along the Minor Axis of M82

    Science.gov (United States)

    Martini, Paul; Leroy, Adam K.; Mangum, Jeffrey G.; Bolatto, Alberto; Keating, Katie M.; Sandstrom, Karin; Walter, Fabian

    2018-03-01

    M82 is one of the best-studied starburst galaxies in the local universe, and is consequently a benchmark for studying star formation feedback at both low and high redshift. We present new VLA H I observations that reveal the cold gas kinematics along the minor axis in unprecedented detail. This includes the detection of H I up to 10 kpc along the minor axis toward the south and beyond 5 kpc to the north. A surprising aspect of these observations is that the line-of-sight H I velocity decreases substantially from about 120 to 50 {km} {{{s}}}-1 from 1.5 to 10 kpc off the midplane. The velocity profile is not consistent with the H I gas cooling from the hot wind. We demonstrate that the velocity decrease is substantially greater than the deceleration expected from gravitational forces alone. If the H I consists of a continuous population of cold clouds, some additional drag force must be present, and the magnitude of the drag force places a joint constraint on the ratio of the ambient medium to the typical cloud size and density. We also show that the H I kinematics are inconsistent with a simple conical outflow centered on the nucleus, but instead require the more widespread launch of the H I over the ∼1 kpc extent of the starburst region. Regardless of the launch mechanism for the H I gas, the observed velocity decrease along the minor axis is sufficiently great that the H I may not escape the halo of M82. The inferred H I outflow rate at 10 kpc off the midplane is much less than 1 {M}ȯ yr‑1.

  12. Active optics: off axis aspherics generation for high contrast imaging

    Science.gov (United States)

    Hugot, E.; Laslandes, M.; Ferrari, M.; Vives, S.; Moindrot, S.; El Hadi, K.; Dohlen, K.

    2017-11-01

    Active Optics methods, based on elasticity theory, allow the aspherisation of optical surfaces by stress polishing but also active aspherisation in situ. Researches in this field will impact the final performance and the final cost of any telescope or instrument. The stress polishing method is well suited for the superpolishing of aspheric components for astronomy. Its principle relies on spherical polishing with a full-sized tool of a warped substrate, which becomes aspherical once unwarped. The main advantage of this technique is the very high optical quality obtained either on form or on high spatial frequency errors. Furthermore, the roughness can be decreased down to a few angstroms, thanks the classical polishing with a large pitch tool, providing a substantial gain on the final scientific performance, for instance on the contrast on coronagraphic images, but also on the polishing time and cost. Stress polishing is based on elasticity theory, and requires an optimised deformation system able to provide the right aspherical form on the optical surface during polishing. The optical quality of the deformation is validated using extensive Finite Element Analysis, allowing an estimation of residuals and an optimisation of the warping harness. We describe here the work realised on stress polishing of toric mirrors for VLT-SPHERE and then our actual work on off axis aspherics (OAA) for the ASPIICS-Proba3 mission for solar coronagraphy. The ASPIICS optical design made by Vives et al is a three mirrors anastigmat including a concave off axis hyperboloid and a convex off axis parabola (OAP). We are developing a prototype in order to demonstrate the feasibility of this type of surface, using a multi-mode warping harness (Lemaitre et al). Furthermore, we present our work on variable OAP, meaning the possibility to adjust the shape of a simple OAP in situ with a minimal number of actuators, typically one actuator per optical mode (Focus, Coma and Astigmatism

  13. Serdemetan antagonizes the Mdm2-HIF1α axis leading to decreased levels of glycolytic enzymes.

    Directory of Open Access Journals (Sweden)

    Jason A Lehman

    Full Text Available Serdemetan (JNJ-26854165, an antagonist to Mdm2, was anticipated to promote the activation of p53. While regulation of p53 by Mdm2 is important, Mdm2 also regulates numerous proteins involved in diverse cellular functions. We investigated if Serdemetan would alter the Mdm2-HIF1α axis and affect cell survival in human glioblastoma cells independently of p53. Treatment of cells with Serdemetan under hypoxia resulted in a decrease in HIF1α levels. HIF1α downstream targets, VEGF and the glycolytic enzymes (enolase, phosphoglycerate kinase1/2, and glucose transporter 1, were all decreased in response to Serdemetan. The involvement of Mdm2 in regulating gene expression of glycolytic enzymes raises the possibility of side effects associated with therapeutically targeting Mdm2.

  14. An Ad-Hoc Adaptive Pilot Model for Pitch Axis Gross Acquisition Tasks

    Science.gov (United States)

    Hanson, Curtis E.

    2012-01-01

    An ad-hoc algorithm is presented for real-time adaptation of the well-known crossover pilot model and applied to pitch axis gross acquisition tasks in a generic fighter aircraft. Off-line tuning of the crossover model to human pilot data gathered in a fixed-based high fidelity simulation is first accomplished for a series of changes in aircraft dynamics to provide expected values for model parameters. It is shown that in most cases, for this application, the traditional crossover model can be reduced to a gain and a time delay. The ad-hoc adaptive pilot gain algorithm is shown to have desirable convergence properties for most types of changes in aircraft dynamics.

  15. Development of 6-axis portable manipulator which traces over 3-dimensional curved surface for ultrasonic inspection

    International Nuclear Information System (INIS)

    Hayashi, Tetsuji; Tsuzuki, Satoshi; Tsunewaki, Hiroshi.

    1993-01-01

    A 6-axis portable manipulator, weighing 120 N (12.3 kg) which traces over a 3-dimensional curved surface for ultrasonic testing has been developed. The manipulator body is made of carbon-fiber-reinforced plastic and magnesium alloy. A feature of the system is that deviation of the manipulator from its nominal path caused by arm bending due to its own weight can be corrected. The deviation is calculated by premeasuring spring coefficients and hysteresis characteristics of the arm structure. In a mock-up calibration performance test the accuracy was shown to be as high as that of a human inspector. The manipulator can be installed within 3 minutes by a single person. Joint angles are calculated with a direct memory access (DMA) handler using a poling method. Signals are transmitted to servo-controllers through an optical fiber of 2.5 Mbps. (author)

  16. Interactions between the thyroid hormones and the hormones of the growth hormone axis.

    Science.gov (United States)

    Laron, Zvi

    2003-12-01

    The normal secretion and action of the thyroid hormones and the hormones of the GH/IGF-I (growth hormone/ insulin-like growth factor I) axis are interdependent. Their interactions often differ in man from animal studies in rodents and sheep. Thus neonates with congenital hypothyroidism are of normal length in humans but IUGR (intrauterine growth retardation) in sheep. Postnatally normal GH/IGF-I secretion and action depends on an euthyroid state. Present knowledge on the interactions between the two axes is reviewed in states of hypo- and hyperthyroidism, states of GH/IGF-I deprivation and hypersecretion, as well as the relationship between IGF-I and thyroid cancer. Emphasis is given to data in children and aspects of linear growth and skeletal maturation.

  17. Electric power from vertical-axis wind turbines

    Science.gov (United States)

    Touryan, K. J.; Strickland, J. H.; Berg, D. E.

    1987-12-01

    Significant advancements have occurred in vertical axis wind turbine (VAWT) technology for electrical power generation over the last decade; in particular, well-proven aerodynamic and structural analysis codes have been developed for Darrieus-principle wind turbines. Machines of this type have been built by at least three companies, and about 550 units of various designs are currently in service in California wind farms. Attention is presently given to the aerodynamic characteristics, structural dynamics, systems engineering, and energy market-penetration aspects of VAWTs.

  18. A 34-meter VAWT (Vertical Axis Wind Turbine) point design

    Science.gov (United States)

    Ashwill, T. D.; Berg, D. E.; Dodd, H. M.; Rumsey, M. A.; Sutherland, H. J.; Veers, P. S.

    The Wind Energy Division at Sandia National Laboratories recently completed a point design based on the 34-m Vertical Axis Wind Turbine (VAWT) Test Bed. The 34-m Test Bed research machine incorporates several innovations that improve Darrieus technology, including increased energy production, over previous machines. The point design differs minimally from the Test Bed; but by removing research-related items, its estimated cost is substantially reduced. The point design is a first step towards a Test-Bed-based commercial machine that would be competitive with conventional sources of power in the mid-1990s.

  19. Spatial structure of extensive air showers near the axis

    Energy Technology Data Exchange (ETDEWEB)

    Alekseev, E N; Gal' perin, M D; Glemba, P Ya [AN SSSR, Moscow. Inst. Yadernykh Issledovanij; Moskovskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Yadernoj Fiziki; Consiglio Nazionale delle Ricerche, Turin (Italy). Lab. di Cosmo-Geofisica)

    1978-07-01

    The spatial structure of the extensive air showers has been investigated. The tests have been staged on the 400 scintillation counter installation. It has been shown, that spatial distribution of the extensive air showers in the vicinity of the axis does not vary in case of the Nsub(e) electron number showers in the 10/sup 5/-10/sup 6/ range. The share of the showers having a clear-cut multicore structure is approximately 3% with Nsub(e) >= 2x10/sup 5/.

  20. Vertical axis wind turbine drive train transient dynamics

    Science.gov (United States)

    Clauss, D. B.; Carne, T. G.

    1982-01-01

    Start up of a vertical axis wind turbine causes transient torque oscillations in the drive train with peak torques which may be over two and one half times the rated torque of the turbine. A computer code, based on a lumped parameter model of the drive train, was developed and tested for the low cost 17 meter turbine; the results show excellent agreement with field data. The code was used to predict the effect of a slip clutch on transient torque oscillations. It was demonstrated that a slip clutch located between the motor and brake can reduce peak torques by thirty eight percent.

  1. Dynamic Analysis of Darrieus Vertical Axis Wind Turbine Rotors

    Science.gov (United States)

    Lobitz, D. W.

    1981-01-01

    The dynamic response characteristics of the vertical axis wind turbine (VAWT) rotor are important factors governing the safety and fatigue life of VAWT systems. The principal problems are the determination of critical rotor speeds (resonances) and the assessment of forced vibration response amplitudes. The solution to these problems is complicated by centrifugal and Coriolis effects which can have substantial influence on rotor resonant frequencies and mode shapes. The primary tools now in use for rotor analysis are described and discussed. These tools include a lumped spring mass model (VAWTDYN) and also finite-element based approaches. The accuracy and completeness of current capabilities are also discussed.

  2. Experimental characterization of vertical-axis wind turbine noise.

    Science.gov (United States)

    Pearson, C E; Graham, W R

    2015-01-01

    Vertical-axis wind turbines are wind-energy generators suitable for use in urban environments. Their associated noise thus needs to be characterized and understood. As a first step, this work investigates the relative importance of harmonic and broadband contributions via model-scale wind-tunnel experiments. Cross-spectra from a pair of flush-mounted wall microphones exhibit both components, but further analysis shows that the broadband dominates at frequencies corresponding to the audible range in full-scale operation. This observation has detrimental implications for noise-prediction reliability and hence also for acoustic design optimization.

  3. Endothelial Activation: The Ang/Tie Axis in Sepsis

    Directory of Open Access Journals (Sweden)

    Aleksandra Leligdowicz

    2018-04-01

    Full Text Available Sepsis, a dysregulated host response to infection that causes life-threatening organ dysfunction, is a highly heterogeneous syndrome with no specific treatment. Although sepsis can be caused by a wide variety of pathogenic organisms, endothelial dysfunction leading to vascular leak is a common mechanism of injury that contributes to the morbidity and mortality associated with the syndrome. Perturbations to the angiopoietin (Ang/Tie2 axis cause endothelial cell activation and contribute to the pathogenesis of sepsis. In this review, we summarize how the Ang/Tie2 pathway is implicated in sepsis and describe its prognostic as well as therapeutic utility in life-threatening infections.

  4. Brake lock mechanism for the two axis pointing system

    Science.gov (United States)

    Posey, Alan; Clark, Mike; Mignosa, Larry

    1991-01-01

    Six months prior to shipment of the Broadband X-ray Telescope to the Kennedy Space Center for flight aboard the Space Shuttle Columbia, a major system failure occurred. During modal survey testing of the telescope's gimbal pointing system, the roll axis brake unexpectedly released. Low level vibration and static preloads present during the modal survey were within the expected flight environment. Brake release during shuttle liftoff or ascent was an unacceptable risk to mission success; thus, a Brake Lock Mechanism (BLM) was developed.

  5. Instability of nuclear wobbling motion and tilted axis rotation

    International Nuclear Information System (INIS)

    Matsuzaki, Masayuki; Ohtsubo, Shin-Ichi

    2004-01-01

    We study a possible correspondence between the softening of the wobbling mode and the 'phase transition' of the one-dimensionally rotating mean field to a three-dimensionally rotating one by comparing the properties of the wobbling mode obtained by the one-dimensional cranking model + random phase approximation with the total Routhian surface obtained by the three-dimensional tilted-axis cranking model. The potential surface for the observed wobbling mode excited on the triaxial superdeformed states in 163 Lu is also analyzed

  6. Design of tracking photovoltaic systems with a single vertical axis

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzo, E. [Ciudad Universitaria, Madrid (Spain). Instituto de Energeia Solar; Perez, M. [Pol Industrial La Nava, Naavarrsa (Spain). Alternativas Energeticas Solares; Ezpeleta, A. [Energia Hidroelectrica Navarra, Pamplona (Spain); Acedo, J. [Ingeteam SA, Pamplona (Spain)

    2002-07-01

    Solar tracking is used in large grid-connected photovoltaic plants to maximise solar radiation collection and, hence, to reduce the cost of delivered electricity. In particular, single vertical axis tracking, also called azimuth tracking, allows for energy gains up to 40%, compared with optimally tilted fully static arrays. This paper examines the theoretical aspects associated with the design of azimuth tracking, taking into account shadowing between different trackers and back-tracking features. Then, the practical design of the trackers installed at the 1.4 MW Tudela PV plant is presented and discussed. Finally, this tracking alternative is compared with the more conventional fully stationary approach. (author)

  7. Synchrotron X-ray diffraction using triple-axis spectrometry

    International Nuclear Information System (INIS)

    Als-Nielsen, J.

    1980-12-01

    High resolution X-ray diffraction studies of (i) monolayers of the noble gases Kr and Ar physiosorbed on graphite (ii) smectic A fluctuations in the nematic and the smectic A phases of liquid crystals are described. The apparatus used is a triple axis spectrometer situated at the storage ring DORIS at Hasylab, DESY, Hamburg. A monochromatic, well collimated beam is extracted from the synchrotron radiation spectrum by Bragg reflection from perfect Si or Ge crystals. The direction of the beam scattered from the sample is determined by Bragg reflection from a perfect Si or Ge crystal. High intensities even with resolution extending beyond the wavelength of visible light can be obtained. (Auth.)

  8. Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms

    Energy Technology Data Exchange (ETDEWEB)

    Broström, Julia M. [Division of Occupational and Environmental Medicine, Lund University, SE 221 85 Lund (Sweden); Ye, Zhi-wei [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm (Sweden); Axmon, Anna; Littorin, Margareta; Tinnerberg, Håkan; Lindh, Christian H. [Division of Occupational and Environmental Medicine, Lund University, SE 221 85 Lund (Sweden); Zheng, Huiyuan; Ghalali, Aram; Stenius, Ulla [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm (Sweden); Jönsson, Bo A.G. [Division of Occupational and Environmental Medicine, Lund University, SE 221 85 Lund (Sweden); Högberg, Johan, E-mail: johan.hogberg@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm (Sweden)

    2015-09-15

    Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to < 5 ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10 min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose–response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting “sneezing”, the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity. - Highlights: • Human epithelial cells release autotaxin in response to 1 nM toluene diisocyanate (TDI). • The release involves P2X4 and P2X7 receptors and is modulated by ATP and MCP-1. • Lysophosphatidic acid (LPA) was measured in workers exposed to < 5 ppb TDI. • LPA in plasma correlated to TDI exposure

  9. On the spin-axis dynamics of a Moonless Earth

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gongjie; Batygin, Konstantin, E-mail: gli@cfa.harvard.edu [Harvard-Smithsonian Center for Astrophysics, The Institute for Theory and Computation, 60 Garden Street, Cambridge, MA 02138 (United States)

    2014-07-20

    The variation of a planet's obliquity is influenced by the existence of satellites with a high mass ratio. For instance, Earth's obliquity is stabilized by the Moon and would undergo chaotic variations in the Moon's absence. In turn, such variations can lead to large-scale changes in the atmospheric circulation, rendering spin-axis dynamics a central issue for understanding climate. The relevant quantity for dynamically forced climate change is the rate of chaotic diffusion. Accordingly, here we re-examine the spin-axis evolution of a Moonless Earth within the context of a simplified perturbative framework. We present analytical estimates of the characteristic Lyapunov coefficient as well as the chaotic diffusion rate and demonstrate that even in absence of the Moon, the stochastic change in Earth's obliquity is sufficiently slow to not preclude long-term habitability. Our calculations are consistent with published numerical experiments and illustrate the putative system's underlying dynamical structure in a simple and intuitive manner.

  10. Wake structure of a single vertical axis wind turbine

    International Nuclear Information System (INIS)

    Posa, Antonio; Parker, Colin M.; Leftwich, Megan C.; Balaras, Elias

    2016-01-01

    Highlights: • The wake structure of an isolated Vertical Axis Wind Turbine is studied by both Particle Imaging Velocimetry and Large Eddy Simulation. • The wake structure is investigated for two values of tip speed ratio, TSR_1=1.35 and TSR_2=2.21. • A displacement of the momentum deficit towards the windward side is verified in the wake. • Higher turbulence and coherence is observed on the leeward side of the wake, due to the upwind stall of the blades. • Coherence in the wake core, associated to the downwind stall, decays quickly downstream. - Abstract: The wake structure behind a vertical axis wind turbine (VAWT) is both measured in a wind tunnel using particle imaging velocimetry (PIV) and computed with large-eddy simulation (LES). Geometric and dynamic conditions are closely matched to typical applications of VAWTs (Re_D ∼ 1.8 × 10"5). The experiments and computations were highly coordinated with continuous two-way feedback to produce the most insightful results. Good qualitative agreement is seen between the computational and experimental results. The dependence of the wake structure on the tip speed ratio, TSR, is investigated, showing higher asymmetry and larger vortices at the lower rotational speed, due to stronger dynamic stall phenomena. Instantaneous, ensemble-averaged and phase-averaged fields are discussed, as well as the dynamics of coherent structures in the rotor region and downstream wake.

  11. Computational analysis of vertical axis wind turbine arrays

    Science.gov (United States)

    Bremseth, J.; Duraisamy, K.

    2016-10-01

    Canonical problems involving single, pairs, and arrays of vertical axis wind turbines (VAWTs) are investigated numerically with the objective of understanding the underlying flow structures and their implications on energy production. Experimental studies by Dabiri (J Renew Sustain Energy 3, 2011) suggest that VAWTs demand less stringent spacing requirements than their horizontal axis counterparts and additional benefits may be obtained by optimizing the placement and rotational direction of VAWTs. The flowfield of pairs of co-/counter-rotating VAWTs shows some similarities with pairs of cylinders in terms of wake structure and vortex shedding. When multiple VAWTs are placed in a column, the extent of the wake is seen to spread further downstream, irrespective of the direction of rotation of individual turbines. However, the aerodynamic interference between turbines gives rise to regions of excess momentum between the turbines which lead to significant power augmentations. Studies of VAWTs arranged in multiple columns show that the downstream columns can actually be more efficient than the leading column, a proposition that could lead to radical improvements in wind farm productivity.

  12. Application of Circulation Controlled Blades for Vertical Axis Wind Turbines

    Directory of Open Access Journals (Sweden)

    Velissarios Kourkoulis

    2013-07-01

    Full Text Available The blades of a vertical axis wind turbine (VAWT rotor see an inconsistent angle of attack through its rotation. Consequently, VAWT blades generally use symmetrical aerofoils with a lower lift-to-drag ratio than cambered aerofoils tailored to maximise horizontal axis wind turbine rotor performance. This paper considers the feasibility of circulation controlled (CC VAWT blades, using a tangential air jet to provide lift and therefore power augmentation. However CC blade sections require a higher trailing-edge thickness than conventional sections giving rise to additional base drag. The choice of design parameters is a compromise between lift augmentation, additional base drag as well as the power required to pump the air jet. Although CC technology has been investigated for many years, particularly for aerospace applications, few researchers have considered VAWT applications. This paper considers the feasibility of the technology, using Computational Fluid Dynamics to evaluate a baseline CC aerofoil with different trailing-edge ellipse shapes. Lift and drag increments due to CC are considered within a momentum based turbine model to determine net power production. The study found that for modest momentum coefficients significant net power augmentation can be achieved with a relatively simple aerofoil geometry if blowing is controlled through the blades rotation.

  13. RF generation in the DARHT Axis-II beam dump

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, Carl A. Jr. [Los Alamos National Laboratory

    2012-05-03

    We have occasionally observed radio-frequency (RF) electromagnetic signals in the downstream transport (DST) of the second axis linear induction accelerator (LIA) at the dual-axis radiographic hydrodynamic testing (DARHT) facility. We have identified and eliminated some of the sources by eliminating the offending cavities. However, we still observe strong RF in the range 1 GHz t0 2 GHz occurring late in the {approx}2-{micro}s pulse that can be excited or prevented by varying the downstream tune. The narrow frequency width (<0.5%) and near exponential growth at the dominant frequency is indicative of a beam-cavity interaction, and electro-magnetic simulations of cavity structure show a spectrum rich in resonances in the observed frequency range. However, the source of beam produced RF in the cavity resonance frequency range has not been identified, and it has been the subject of much speculation, ranging from beam-plasma or beam-ion instabilities to unstable cavity coupling.

  14. The methods of the LHC magnets' magnetic axis location measurement

    International Nuclear Information System (INIS)

    Bottura, L.; Buzio, M.; Deferne, G.; Sievers, P.; Smirnov, N.; Villar, F.P.; Walckiers, L.

    1999-01-01

    More than 8 thousands LHC magnets of various types will be extensively measured during series magnetic test at both room and superfluid helium temperature. The precise knowledge of the magnetic axis positioning is vital for the alignment of those magnets in the tunnel. The most efficient and cost effective method with rotating pick up coil is chosen currently as a baseline for series measurement. The position of the measuring coil axis herewith is measured with a dedicated optical system. The deflection of the light beam in the air due to temperature gradient either passing through the cold bore when the magnet excited for warm measurement or through the anti-cryostat during cold measurement can reach magnitudes significantly exceeding tolerance and therefore is a critical issue. We present studies of the light deflection in 10 m long dipole at warm and cold and propose means to reduce it. The result of the dipole centring powered in Quadrupole Configured Dipole (QCD) or 'ugly quad' configuration and correlation with centring based on high order harmonics are presented as well. (authors)

  15. Preferred axis of CMB parity asymmetry in the masked maps

    International Nuclear Information System (INIS)

    Cheng, Cheng; Zhao, Wen; Huang, Qing-Guo; Santos, Larissa

    2016-01-01

    Both WMAP and Planck data show a significant odd-multipole preference in the large scales of the cosmic microwave background (CMB) temperature anisotropies. If this pattern originates from cosmological effects, then it can be considered a crucial clue for a violation in the cosmological principle. By defining various direction dependent statistics in the full-sky Planck 2015 maps (see, for instance, Naselsky et al. (2012); W. Zhao (2014)), we found that the CMB parity asymmetry has a preferred direction, which is independent of the choices of the statistics. In particular, this preferred axis is strongly aligned with those in the CMB quadrupole and octopole, as well as that in the CMB kinematic dipole, which hints to their non-cosmological origin. In realistic observations, the foreground residuals are inevitable, and should be properly masked out in order to avoid possible misinterpretation of the results. In this paper, we extend our previous analyses to the masked Planck 2015 data. By defining a similar direction dependent statistic in the masked map, we find a preferred direction of the CMB parity asymmetry, in which the axis also coincides with that found in the full-sky analysis. Therefore, our conclusions on the CMB parity violation and its directional properties are confirmed.

  16. A cytokine axis regulates elastin formation and degradation

    Science.gov (United States)

    Sproul, Erin P.; Argraves, W. Scott

    2013-01-01

    Underlying the dynamic regulation of tropoelastin expression and elastin formation in development and disease are transcriptional and post-transcriptional mechanisms that have been the focus of much research. Of particular importance is the cytokine–governed elastin regulatory axis in which the pro-elastogenic activities of transforming growth factor β-1 (TGFβ1) and insulin-like growth factor-I (IGF-I) are opposed by anti-elastogenic activities of basic fibroblast growth factor (bFGF/FGF-2), heparin-binding epidermal growth factor-like growth factor (HB-EGF), EGF, PDGF-BB, TGFα, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and noncanonical TGFβ1 signaling. A key mechanistic feature of the regulatory axis is that cytokines influence elastin formation through effects on the cell cycle involving control of cyclin–cyclin dependent kinase complexes and activation of the Ras/MEK/ERK signaling pathway. In this article we provide an overview of the major cytokines/growth factors that modulate elastogenesis and describe the underlying molecular mechanisms for their action on elastin production. PMID:23160093

  17. PRIGo: a new multi-axis goniometer for macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Waltersperger, Sandro; Olieric, Vincent, E-mail: vincent.olieric@psi.ch; Pradervand, Claude [Paul Scherrer Institute, Villigen PSI (Switzerland); Glettig, Wayne [Centre Suisse d’Electronique et Microtechnique SA, Neuchâtel 2002 (Switzerland); Salathe, Marco; Fuchs, Martin R.; Curtin, Adrian; Wang, Xiaoqiang; Ebner, Simon; Panepucci, Ezequiel; Weinert, Tobias [Paul Scherrer Institute, Villigen PSI (Switzerland); Schulze-Briese, Clemens [Dectris Ltd, Baden 5400 (Switzerland); Wang, Meitian, E-mail: vincent.olieric@psi.ch [Paul Scherrer Institute, Villigen PSI (Switzerland)

    2015-05-09

    The design and performance of the new multi-axis goniometer PRIGo developed at the Swiss Light Source at Paul Scherrer Institute is described. The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high-precision goniometer providing an alternative to (mini-)kappa, traditional three-circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around ω and consists of four linear positioners working synchronously to achieve x, y, z translations and χ rotation (0–90°), followed by a ϕ stage (0–360°) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 µm, <7 µm and <10 µm for ω, χ and ϕ, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described.

  18. Classification of threespine stickleback along the benthic-limnetic axis.

    Science.gov (United States)

    Willacker, James J; von Hippel, Frank A; Wilton, Peter R; Walton, Kelly M

    2010-11-01

    Many species of fish display morphological divergence between individuals feeding on macroinvertebrates associated with littoral habitats (benthic morphotypes) and individuals feeding on zooplankton in the limnetic zone (limnetic morphotypes). Threespine stickleback (Gasterosteus aculeatus L.) have diverged along the benthic-limnetic axis into allopatric morphotypes in thousands of populations and into sympatric species pairs in several lakes. However, only a few well known populations have been studied because identifying additional populations as either benthic or limnetic requires detailed dietary or observational studies. Here we develop a Fisher's linear discriminant function based on the skull morphology of known benthic and limnetic stickleback populations from the Cook Inlet Basin of Alaska and test the feasibility of using this function to identify other morphologically divergent populations. Benthic and limnetic morphotypes were separable using this technique and of 45 populations classified, three were identified as morphologically extreme (two benthic and one limnetic), nine as moderately divergent (three benthic and six limnetic) and the remaining 33 populations as morphologically intermediate. Classification scores were found to correlate with eye size, the depth profile of lakes, and the presence of invasive northern pike (Esox lucius). This type of classification function provides a means of integrating the complex morphological differences between morphotypes into a single score that reflects the position of a population along the benthic-limnetic axis and can be used to relate that position to other aspects of stickleback biology.

  19. Pituitary-Adrenal Axis in Prader Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Olivia S. Edgar

    2016-01-01

    Full Text Available Purpose: Prader Willi syndrome (PWS is a rare genetic condition that has concurrent endocrinological insufficiencies. The presence of growth hormone deficiency has been well documented, but adrenal insufficiency (AI is not widely reported. A review was conducted to investigate its prevalence and relevance in PWS in both adults and children. Methodology: A literature review was performed with the search terms “Prader-Willi syndrome” and “adrenal insufficiency”. Results: The review found studies disagree on the prevalence and method of investigation of AI in PWS. Case studies demonstrate that patients with PWS are at risk of premature death, often secondary to respiratory infections. The possibility that this may be the result of the inability to mount an effective cortisol response has been studied, with some evidence confirming AI in PWS patients. Most reports agreed AI is present in PWS, however, Farholt et al. showed no HPA axis dysfunction in adults, suggesting that perhaps it is rare in adults, and children should be the focus of further studies. Conclusion: AI is present in some patients with PWS. Further research is required to ensure optimal treatment can be implemented and to prevent premature deaths related to adrenal insufficiency. Clinicians should have a low threshold for testing the adrenal axis and considering treatment for adrenal insufficiency in PWS patients.

  20. Optical Axis Identification Technique for Free Space Optics Transmission

    Directory of Open Access Journals (Sweden)

    Yuki Tashiro

    2017-07-01

    Full Text Available This paper describes optical axis adjustment technique for an active free space optics transmission system. This system precisely controls the direction of a collimated thin laser beam using a motor driven laser emitting mechanism and positioning photodiodes. Before beginning laser beam feedback control, it is required to guide the laser beam within the range of the positioning photodiodes for initial laser beam alignment. This paper proposes an arrival position presumption method of laser beam traveling along the long distance from transmitter. A positioning sensor containing several photodiodes measures laser luminescence distribution, and analytically calculates the optical axis of laser beam according to the modified Gaussian beam optics based on four or five distributed local intensity of laser luminescence. Experiments are conducted to evaluate the accuracy of the presumption, and results reveal that the method is effective in leading the laser beam onto a distant receiver.