Sample records for 5-hydroxytryptamine modulates migration

  1. 5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo.

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    Tobias Müller

    Full Text Available Beside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT, commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs. In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR(1 and 5-HTR(2 receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR(3, 5-HTR(4 and 5-HTR(7 receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders.

  2. 5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials


    Pithadia, Anand B.; Jain, Sunita M.


    5-hydroxytryptamine (5-HT) has become one of the most investigated and complex biogenic amines. The main receptors and their subtypes, e.g., 5-HTI (5-HT1A, 5-HT1B, 5-HTID, 5-HTIE and 5-HT1F), 5-HT2 (5-HT2A, 5-HT2B and 5-HT2C), 5-HT3, 5-HT4, 5-HT5 (5-HT5A, 5-HT5B), 5-HT6 and 5-HT7 have been identified. Specific drugs which are capable of either selectively stimulating or inhibiting these receptor subtypes are being designed. This has generated therapeutic potentials of 5-HT receptor modulators...

  3. Designing modulators of 5-hydroxytryptamine signaling to treat abuse disorders

    NARCIS (Netherlands)

    Wiel, S.M. van de; Verheij, M.M.M.; Homberg, J.R.


    INTRODUCTION: There are currently no treatments approved by the FDA to effectively treat cocaine dependence. Research of recent years has gradually revealed the importance of 5-hydroxytryptamine (5-HT) in the reinforcing and rewarding effects of cocaine and the potential for relapse. Brain-derived n

  4. Modulation by thyroid hormones of rat parotid amylase secretion stimulated by 5-hydroxytryptamine. (United States)

    Ostuni, Mariano Aníbal; Houssay, Alberto Bernardo; Tumilasci, Omar René


    The effects of 5-hydroxytryptamine (5-HT) upon amylase secretion by rat parotid glands were studied in three groups of animals: (a) intact control rats (euthyroid rats); (b) hypothyroid rats obtained by surgical thyroidectomy 2 wk before the experiments; and (c) hyperthyroid rats obtained by the administration of sodium l-triiodothyronine for 2 wk before the experiments. Hyperthyroid rats showed significantly higher baseline amylase release than control rats. When the glands were stimulated with 5-HT (30 micro m), amylase release was significantly lower in the hypothyroid group and higher in the hyperthyroid rats than in control group. Addition of cholinergic, adrenergic or substance P antagonists did not modify 5-HT-stimulated amylase activity. The effects of 5-HT were partly but significantly blocked by the addition of 10 micro m methysergide (HT1/2/7 receptor blocker) in the three groups of rats. In contrast, 10 micro m ketanserine (HT2A receptor blocker) partly blocked the response to 5-HT only in the hyperthyroid animals. It was concluded that 5-HT induces amylase secretion by rat parotid glands through specific serotoninergic receptors, and that thyroid status modulates the 5-HT effect.

  5. Chronotropic action of 5-hydroxytryptamine (5-HT) on colonic migrating motor complexes (CMMCs) in the isolated mouse colon. (United States)

    Fida, R; Bywater, R A; Lyster, D J; Taylor, G S


    The effects of 5-hydroxytryptamine (5-HT) and related drugs on colonic migrating motor complexes (CMMCs) were evaluated in isolated colons from the heterozygotes of pie-bald lethal mice. 5-HT produced a dose-related increase in the frequency of CMMCs without any change in the amplitude or duration of the CMMC contractions themselves. The 5-HT(2) agonist, alpha-methyl 5-HT, (100 nM-1 microM) increased the frequency of CMMCs whilst the 5-HT(3) agonist, 2-methyl 5-HT, did so at 10 microM. The 5-HT(4) agonist, 5-methoxy dimethyl tryptamine oxalate did not alter the frequency of CMMCs in the concentration range 1 nM-10 microM. The 5-HT(3) receptor antagonist, ondansetron, increased the interval between CMMCs in the concentration range 100 nM-1 microM, whilst the 5-HT(1) receptor antagonist, methiothepin, the 5-HT(2) receptor antagonist, cyproheptadine and the 5-HT(4) receptor antagonist, SDZ 205 557, had no significant effects on the interval between CMMCs in the concentration range 1 nM-10 microM. The effects of 5-HT did not appear to be altered by the presence of ondansetron (1 microM) or cyproheptadine (1 microM). However, in the presence of ondansetron (1 microM), the further addition of cyproheptadine (1 microM) effectively abolished CMMCs. Furthermore, in the combined presence of these antagonists the effects of 5-HT were severely diminished. It is suggested that the frequency of CMMCs may be under the influence of endogenously released 5-HT in this preparation

  6. 5-Hydroxytryptamine 1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception. (United States)

    Biagioni, Audrey Franceschi; de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; da Silva, Juliana Almeida; dos Anjos-Garcia, Tayllon; Roncon, Camila Marroni; Corrado, Alexandre Pinto; Zangrossi, Hélio; Coimbra, Norberto Cysne


    The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT1A receptor-labelled neurons in the MH. Moreover, the effects of pre-treatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABAA receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT1A receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5-HT1A DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH.

  7. Ovarian hormone modulates 5-hydroxytryptamine 3 receptors mRNA expression in rat colon with restraint stress-induced bowel dysfunction

    Institute of Scientific and Technical Information of China (English)

    Tian-Jin Li; Bao-Ping Yu; Wei-Guo Dong; He-Sheng Luo; Long Xu; Mu-Qi Li


    AIM: To examine the effects of ovarian hormone on the expression of 5-hydroxytryptamine 3 receptors (5-HT3R)in rat colon of restraint stress-induced bowel dysfunction.METHODS: Twenty-four female Sprague-Dawley rats were randomly dMded into three groups of 8 each: sham operation,ovariectomy (OVX) and ovariectomy with estrogen (E2) andprogesterone (P) replacement therapy (OVX+E2+P). The rats were subjected to 1-h restraint stress 4 wk after operation. The changes of defecation were monitored by collection of fecal pellets. The gonadal steroids were measured in duplicate by radioimmunoassay (RTA). The expression of 5-HT3R mRNA in the colon was studied by RT-PCR. RESULTS: Compared with sham group and OVX+E2+P group, OVX group showed increase in fecal pellets and decrease in the time of vitreous pellets excretion (P<0.01).Serum levels of E2 and P were suppressed in OVX group and restored following treatment with ovarian steroids (P<0.01), and the levels of 5-HT3R mRNA in the colon of ovariectomized rats were significantly increased, the expression of 5-HT3R mRNA was significantly decreased in hormone replacement therapy group (P<0.01).CONCLUSION: Ovarian hormone plays a role in the regulation of 5-HT3R expressions in restraint stress-induced bowel dysfunction of rats. The interactions between ovarian steroids and gastrointestinal tract may have major pathophysiologicalimplications in 5-HT-related disorders, such as irritable bowel syndrome (IBS).

  8. 5-hydroxytryptamine-mediated apnea caused by the habenular nucleus

    Institute of Scientific and Technical Information of China (English)

    Min Wang; Weihong Lin; Jinghua Wang; Min Huang; Chunyong Wang; Mingxian Li; Shao Wang


    5-hydroxytryptamine contributes to the control of activities of the dilator muscle in the upper respiratory tract, and is derived from the raphe nuclei, in which the habenular nucleus exerts a sustained inhibitory effect. In the present study, respiratory motion curve of the genioglossus muscle and peripheral 5-hydroxytryptamine changes were observed following L-glutamate stimulation of the habenular nucleus of adult Wistar rats. Results showed that the rats had apnea and decreased plasma 5-hydroxytryptamine content after the neurons in habenular nucleus were excited. Genioglossus muscle electromyogram amplitude and integral were significantly reduced. The genioglossus myoelectric activity and respiratory motion curve were similar to obstructive sleep apnea syndrome, thus confirming that the habenular nucleus is the key nucleus involved in the pathogenesis of obstructive sleep apnea syndrome, and is the primary regulated center in the raphe nuclei. Stimulation of the habenular nucleus may suppress 5-hydroxytryptamine release and result in apnea, which is similar to obstructive sleep apnea syndrome.

  9. 5-hydroxytryptamine release into human jejunum by cholera toxin.


    Bearcroft, C P; Perrett, D.; Farthing, M J


    BACKGROUND: Cholera toxin produces intestinal secretion by activation of the adenylate cyclase complex. However animal studies have shown 5-hydroxytryptamine may be released after exposure to cholera toxin, and thereby contribute to the secretory state. AIM: To determine whether cholera toxin releases 5-hydroxytryptamine in human jejunum. SUBJECTS: Seven male subjects were given a subclinical dose of cholera toxin in a paired, controlled, randomised, double blind study. METHODS: A closed 10 c...

  10. 5-Hydroxytryptamine3 receptor antagonists and cardiac side effects

    DEFF Research Database (Denmark)

    Brygger, Louise; Herrstedt, Jørn


    INTRODUCTION: 5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients. AREAS COVERED: The purpose of this article is to outline the risk of cardiac adverse events...

  11. Age-dependent effects of the 5-hydroxytryptamine-2a-receptor polymorphism (His452Tyr) on human memory. (United States)

    Papassotiropoulos, Andreas; Henke, Katharina; Aerni, Amanda; Coluccia, Daniel; Garcia, Esmeralda; Wollmer, Marc A; Huynh, Kim-Dung; Monsch, Andreas U; Stähelin, Hannes B; Hock, Christoph; Nitsch, Roger M; de Quervain, Dominique J-F


    A polymorphism (His452Tyr) of the 5-hydroxytryptamine (5-HT)2a receptor is associated with episodic memory in healthy young humans. Because 5-HT2a-receptor density decreases with increasing age, we tested whether the 5-HT2a receptor genotype effect on memory is influenced by age. We investigated the association of the His452Tyr genotype with memory performance in 622 healthy study participants aged from 18 to 90 years. In young to middle-aged participants, age significantly influenced genotype effects on episodic memory: the His452Tyr genotype exerted a significant influence on memory only in young participants. In the group of elderly cognitively healthy participants, the His452Tyr genotype did not affect memory performance. We conclude that age strongly modulates the effect of the 5-HT2a receptor polymorphism at residue 452 on episodic memory.

  12. Release of ( sup 14 C)5-hydroxytryptamine from human platelets by red wine

    Energy Technology Data Exchange (ETDEWEB)

    Jarman, J.; Glover, V.; Sandler, M. (Queen Charlotte' s and Chelsea Hospital, London (England))


    Red wine, at a final dilution of 1/50, caused released of ({sup 14}C)5-hydroxytryptamine (5-HT) from preloaded platelets, an effect which was not observed with any white wines or beers tested. Since 5-HT, is probably released from body stores during migraine attacks and red wine is known to provoke migraine episodes in susceptible individuals, release of 5-HT, possibly from central stores, could represent a plausible mechanism for its mode of action.

  13. The distribution of 5-hydroxytryptamine in the gastrointestinal tract of reptiles, birds and a prototherian mammal. An immunohistochemical study. (United States)

    Adamson, S; Campbell, G


    The distribution of 5-hydroxytryptamine in the gut of several species of birds and reptiles, and of a prototherian mammal, the platypus, was studied using a monoclonal antibody. 5-Hydroxytryptamine-like immunoreactivity was found in enterochromaffin cells and, in birds, in thrombocytes. Immunoreactivity was not found in enteric neurons fixed immediately after dissection. A detailed study was made on one avian species, the budgerigar. Following incubation of intestine in physiological solution, immunoreactivity was found in nerve fibres in the gut wall that was more marked after incubation with the monoamine oxidase inhibitor pargyline. These fibres took up exogenous 5-hydroxytryptamine. Similar fibres were found in the intestinal nerves and in perivascular plexuses on mesenteric arteries. Both the uptake of 5-hydroxytryptamine and the appearance of neuronal immunoreactivity after incubation were inhibited by the amine uptake inhibitors desmethylimipramine or fluoxetine. Fibres taking up 5-hydroxytryptamine were damaged by pretreatment with 6-hydroxydopamine. It was concluded that the fibres showing immunoreactivity after incubation were adrenergic fibres that had taken up 5-hydroxytryptamine released in vitro from enterochromaffin cells or thrombocytes. These, and more limited observations made on the other species, suggest that birds, reptiles and prototherian mammals lack enteric neurons that use 5-hydroxytryptamine as a transmitter substance.

  14. Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a "brake" on neuronal excitability in ischemic stroke

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    Pallab Bhattacharya


    Full Text Available Our previous studies indicated an increase in extracellular γ-aminobutyric acid (GABA in rodent′s ischemic brain after Piroxicam administration, leading to alleviation of glutamate mediated excitotoxicity through activation of type A GABA receptor (GABAA. This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a significant decrease in extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

  15. A comparison of the effects of two putative 5-hydroxytryptamine renal prodrugs in normal man.


    LI KAM WA, T. C.; Freestone, S.; Samson, R. R.; JOHNSTON, N. R.; Lee, M.R.


    1. The effects of 1 h intravenous infusions of equimolar amounts of two putative 5-hydroxytryptamine (5-HT) renal prodrugs, 5-hydroxy-L-tryptophan (5-HTP, 10 micrograms kg-1 min-1) and gamma-L-glutamyl-5-hydroxy-L-tryptophan (glu-5-HTP, 16.6 micrograms kg-1 min-1) were examined in five healthy male volunteers in a randomised, placebo-controlled, cross-over study. 2. Both compounds increased urinary excretion of 5-HT and there was greater extra-renal formation of 5-HT following 5-HTP administr...

  16. 5-羟色胺与骨质疏松症%5-hydroxytryptamine and osteoporosis

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    康庐琛; 邓伟民


    5-Hydroxytryptamine ( 5-HT ) is a kind of indole amine compounds. According to different locations of synthesis 5-HT can be classified as peripheral 5-HT and central 5-HT, which can regulate the bone mass through two different and contrary pathways. 5-HT related system has showed tremendous potency in new treatment target, improving osteoporosis, and affecting bone metabolism. 5-HT receptor blockers and SERT antagonists are expected to be new drugs for the treatment of osteoporosis. This paper reviews the research progress of peripheral 5-HT and osteoporosis.%5 羟色胺( 5-Hydroxytryptamine,5-HT) 是一种吲哚胺类化合物.根据其合成部位的不同,而分为外周性5-HT和中枢性5-HT,可以通过两种截然不同的、相反的途径调节骨量.5-HT 相关系统已经展现出其作为新的治疗靶点和改善OP、影响骨代谢的巨大潜力,5-HT受体阻断剂、SERT 拮抗剂等有望成为新的一类有效治疗骨质疏松症的良药.本文就外周性5-HT与骨质疏松症的研究进展作一综述.

  17. Effects of 5-hydroxytryptamine and 5-hydroxytryptamine 2A/2C agonist on the genioglossus activity and sleep apnea in rats

    Institute of Scientific and Technical Information of China (English)

    ZHONG Yi-jue; ZHANG Cheng; WANG Guang-fa


    Background 5-hydroxytryptamine (5-HT) is a common neurotransmitter in the brain which plays an important role in the pathogenesis of sleep apnea.Dysfunction of 5-HT and 5-HT2 receptors may lead to the collapse of the upper airway and the instability of respiratory control, which in turn produce apnea.Genioglossus (GG) is one of the most important oropharyngeal muscles maintaining the upper airway open.The present study aimed to investigate the effects of 5-HT and 5-HT2 receptor on GG activity and the sleep apnea in Sprague-Dawley (SD) rats.Methods Microinjection probes were placed within the fourth ventricle of sixteen SD rats.After recovery for a week, the electromyogram (EMG) of GG was recorded in the anesthetized and vagotomized rats.The changes of GG activity before and after the microinjection of 5-HT or 5-HT2A/2c agonist -2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI)were observed.Probes were also laid in another eight SD rats.Electroencephalogram (EEG), EMG of neck muscle and respiration were recorded at the same time a week later.The effects of DOI on the occurrence of sleep apnea were explored.Results Both 5-HT and DOI significantly enhanced the activity of GG just 3 minutes after the completion of injection.The effect of 5-HT disappeared quickly and the effect of DOI lasted for more than 27 minutes.DOI also significantly decreased the post-sigh apnea index in non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep and decreased the spontaneous apnea index only in NREM sleep (P <0.05, respectively).Conclusion 5-HT and 5-HT2A/2c system correlated closely with the pathogenesis of the sleep apnea syndrome and 5-HT receptors may become the target of the drug treatment.

  18. Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats (United States)

    Liu, Chunyan; Wang, Yangang


    In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive

  19. 5-Hydroxytryptamine2A/2C receptors of nucleus raphe magnus and gigantocellularis/paragigantocellularis pars α reticular nuclei modulate the unconditioned fear-induced antinociception evoked by electrical stimulation of deep layers of the superior colliculus and dorsal periaqueductal grey matter. (United States)

    de Oliveira, Ricardo; de Oliveira, Rithiele Cristina; Falconi-Sobrinho, Luiz Luciano; da Silva Soares, Raimundo; Coimbra, Norberto Cysne


    The electrical stimulation of the dorsolateral columns of the periaquedutal grey matter (dlPAG) or deep layers of the superior colliculus (dlSC) evokes defensive behaviours followed by an antinociceptive response. Monoaminergic brainstem reticular nuclei are suggested to comprise the endogenous pain modulatory system. The aim of the present work was to investigate the role played by 5-HT2 subfamily of serotonergic receptors of the nucleus raphe magnus (NRM) and the gigantocellularis/paragigantocellularis pars α reticular nuclei (Gi/PGiα) in the elaboration of instinctive fear-induced antinociception elicited by electrical stimulation of dlPAG or of dlSC. The nociceptive thresholds were measured by the tail-flick test in Wistar rats. The 5-HT2A/2C-serotonergic receptors antagonist ritanserin was microinjected at different concentrations (0.05, 0.5 and 5.0μg/0.2μL) either in Gi/PGiα or in NRM. The blockade of 5-HT2 receptors in both Gi/PGiα and NRM decreased the innate fear-induced antinociception elicited by electrical stimulation of the dlSC or the dlPAG. These findings indicate that serotonin is involved in the hypo-algesia induced by unconditioned fear-induced behavioural responses and the 5-HT2A/2C-serotonergic receptor subfamily in neurons situated in the Gi/PGiα complex and NRM are critically recruited in pain modulation during the panic-like emotional behaviour.

  20. Autoradiographic localization of 5-hydroxytryptamine and noradrenaline in the central nervous system of Lithobius forficatus L. (Myriapoda; Chilopoda)

    NARCIS (Netherlands)

    Descamps, Michel; Joly, Robert; Jamault-Navarro, Catherine


    Using the ability of selective uptake by the neurons of their own secreted amines, two 3H labeled neurotransmitters were used: 5-hydroxytryptamine (5 HT, serotonin) and noradrenaline (NA). Autoradiographic study was conducted on semithin and on ultrathin sections. In the brain, 3H-5 HT labeling is o

  1. 5-Hydroxytryptamine Induces Electrogenic Secretion in the Duodenum of Gerbil (Gerbillus cheesmani

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    Fawzia Y. Al-Balool


    Full Text Available The effect of serosally added 5-hydroxytryptamine (5-HT 100 µ­M on the short circuit-current (Isc across duodenum taken from fed, starved (4 days, water ad lib and undernourished (50% control food intake for 21 days gerbils (Gerbillus cheesmani were investigated. The effect of the neurotoxin, tetrodotoxin (TTX 10 µM and atropine (100 µ­M on the maximum increase in Isc induced by 5-HT were also studied. The 5-HT-induced Isc were higher in unstripped than in the stripped sheets in the three feeding conditions. TTX reduced the maximum increase in Isc induced by 5-HT across stripped and unstripped sheets taken from fed, starved and undernourished gerbils. Atropine decreased the 5-HT-induced Isc of stripped sheets in the three feeding conditions and it also decreased the 5-HT-induced Isc in unstripped sheets in fed duodenum. Therefore, the duodenal response to 5-HT occur partly by activation of a nonneural pathway and partly by activating electrogenic ion transport via muscarinic neural mechanism. It also showed that the 5-HT-induced Isc was chloride-dependent in fed duodenum and were chloride and bicarbonate dependent in the duodenum taken from starved and undernourished gerbil The results also showed that the increase in 5-HT-induced Isc as a results of starvation and undernourishment were TTX-sensitive and both chloride and bicarbonate dependent.

  2. Methotrexate causes a change in intestinal 5-hydroxytryptamine metabolism in rats. (United States)

    Takano, Yuho; Machida, Takuji; Obara, Yusuke; Hirano, Megumi; Kudo, Sae; Takagi, Minako; Hamaue, Naoya; Iizuka, Kenji; Hirafuji, Masahiko


    The effects of methotrexate on 5-hydroxytryptamine (5-HT) metabolism in the intestinal tissue of rats were investigated during the delayed phase after a single administration. Rats were i.p. injected with methotrexate or with saline as a control, and kaolin and food intakes were measured by an automatic monitoring apparatus. At 96 h after administration, dissected-out ileal tissue was frozen rapidly in liquid nitrogen for further analysis or fixed for immunohistochemical staining. Methotrexate at a dose of 50 mg/kg caused a time-dependent increase in kaolin intake lasting up to 72 h after administration, which returned to the control level at 96 h after administration. This dose of methotrexate caused a gradual decrease in body weight, food intake, and water intake lasting up to 72 h, which approached the control level at 96 h. Methotrexate caused pathologic changes, including a moderate inflammatory response in the ileal tissue and an increase in the number of L-tryptophan hydroxylase (TPH)-expressing cells in the ileal mucosa. Methotrexate also caused a significant increase in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content and in TPH1 mRNA expression in the ileal tissues. It had no significant effects on mRNA expression of serotonin transporter, COX-1, or COX-2 or on myeloperoxidase activity. This study demonstrated, for the first time, that methotrexate caused a change in the ileal 5-HT metabolism associated with hyperplasia of mucosal enterochromaffin cells.

  3. Vasoconstrictor responses to 5-hydroxytryptamine in the autoperfused hindquarters of spontaneously hypertensive rats. (United States)

    Calama, E; Morán, A; Ortiz de Urbina, A V; Martín, M L; San Román, L


    In this work we studied the responses and receptors involved in the effects of intra-arterial 5-hydroxytryptamine (5-HT) in the in situ autoperfused hindquarters of spontaneously hypertensive rats (SHR). Intra-arterial administration of the highest doses (50-1,000 ng/kg) produced a vasoconstrictor effect that was inhibited by ritanserin (a selective 5-HT2 receptor antagonist), SB 206553 (a selective 5-HT(2B/2C) receptor antagonist) and spiperone (a nonspecific 5-HT(1/2A) receptor antagonist), and was mimicked by alpha-methyl-5-HT (a selective 5-HT2 receptor agonist) and m-CPP (a selective 5-HT2C receptor agonist), but not by the intra-arterial administration of BW 723C86, a selective 5HT2B receptor agonist. SB 206553 and spiperone inhibited alpha-methyl-5HT-induced vasoconstriction in the hindquarters of SHR. Our data suggest that the vasoconstrictor response induced by 5-HT in the autoperfused hindquarters of SHR is mainly mediated by the activation of 5-HT2A and 5-HT2C receptors.

  4. Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat (United States)

    Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.


    The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

  5. Role of 5-hydroxytryptamine in mediating adenosine-induced airway contraction. (United States)

    Matera, M G; De Santis, D; D'Agostino, B; Pallotta, M; Vacca, C; Cazzola, M; Rossi, F


    We have investigated the role of 5-hydroxytryptamine (5-HT) on adenosine-induced guinea-pig trachea contraction. R-N6-phenylisopropyladenosine (R-PIA), an A1 receptor subtype agonist, induced a concentration-dependent contraction of tracheal rings. The pD2 values were 7.43 +/- 0.26. A 30-min pretreatment with 1,3-dipropyl-8-amino-4-clorophenylxantine (PACPX), a selective A1 receptor antagonist, shifted to the right the R-PIA concentration effect curves. Ketanserin (1 microM), a 5-HT2 receptor antagonist, also caused a rightward shift of the R-PIA concentration-effect curves. The changes for the pD2 values comparing the controls and the tissues incubated with ketanserin were statistically significant (P diphenydramine (1 microM), nor indomethacin (5 microM) showed any effects. The challenge of R-PIA (1 microM) with said substances induced a release of 5-HT (4.8 +/- 0.20 fmol/ml) from guinea-pig trachea in presence or in absence of epithelium; in the same experimental conditions, this effect did not occur in the controls. Our data support the hypothesis that 5-HT plays a role in adenosine-induced airway contraction.

  6. Nelotanserin, a novel selective human 5-hydroxytryptamine2A inverse agonist for the treatment of insomnia. (United States)

    Al-Shamma, Hussien A; Anderson, Christen; Chuang, Emil; Luthringer, Remy; Grottick, Andrew J; Hauser, Erin; Morgan, Michael; Shanahan, William; Teegarden, Bradley R; Thomsen, William J; Behan, Dominic


    5-Hydroxytryptamine (5-HT)(2A) receptor inverse agonists are promising therapeutic agents for the treatment of sleep maintenance insomnias. Among these agents is nelotanserin, a potent, selective 5-HT(2A) inverse agonist. Both radioligand binding and functional inositol phosphate accumulation assays suggest that nelotanserin has low nanomolar potency on the 5-HT(2A) receptor with at least 30- and 5000-fold selectivity compared with 5-HT(2C) and 5-HT(2B) receptors, respectively. Nelotanserin dosed orally prevented (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 5-HT(2A) agonist)-induced hypolocomotion, increased sleep consolidation, and increased total nonrapid eye movement sleep time and deep sleep, the latter marked by increases in electroencephalogram (EEG) delta power. These effects on rat sleep were maintained after repeated subchronic dosing. In healthy human volunteers, nelotanserin was rapidly absorbed after oral administration and achieved maximum concentrations 1 h later. EEG effects occurred within 2 to 4 h after dosing, and were consistent with vigilance-lowering. A dose response of nelotanserin was assessed in a postnap insomnia model in healthy subjects. All doses (up to 40 mg) of nelotanserin significantly improved measures of sleep consolidation, including decreases in the number of stage shifts, number of awakenings after sleep onset, microarousal index, and number of sleep bouts, concomitant with increases in sleep bout duration. Nelotanserin did not affect total sleep time, or sleep onset latency. Furthermore, subjective pharmacodynamic effects observed the morning after dosing were minimal and had no functional consequences on psychomotor skills or memory. These studies point to an efficacy and safety profile for nelotanserin that might be ideally suited for the treatment of sleep maintenance insomnias.

  7. Effect of 5-hydroxytryptamine on neurogenic vasoconstriction in the isolated, autoperfused hindquarters of the rat. (United States)

    Calama, E; Ortíz de Urbina, A V; Morán, A; Martín, M L; San Román, L


    1. In the present study, we analysed the effect of different doses of 5-hydroxytryptamine (5-HT; intravenous infusions of 0.001-40 microg/kg per min) in the autoperfused hindquarters of the rat subjected to electrical stimulation (frequencies of 0.5-20 Hz) of the lumbar chains, investigating the relationship between the adrenergic and serotonergic systems in this vascular bed. 2. Because we observed that 5-HT inhibited the increases in perfusion pressure induced by electrical stimulation of the lumbar chains, we used different agonists and antagonists to analyse the mechanism of action of 5-HT. 3. The effect of 5-HT was inhibited by methiothepin (a non-specific 5-HT receptor antagonist), but not by ritanserin (a selective 5-HT2 receptor antagonist). The effects of 5-HT were mimicked by 5-carboxamidotryptamine (a 5-HT1 receptor agonist) and L-694 247 (a selective 5-HT1D receptor agonist), but not by 8-hydroxy-2-dipropylaminotetralin (a 5-HT1A receptor agonist), CGS-12066B (a 5-HT1B receptor agonist), alpha-methyl-5-HT (a 5-HT2 receptor agonist), 1-(3-chlorophenyl) piperazine (a 5-HT2C receptor agonist) or 1-phenylbiguanide (a 5-HT3 receptor agonist). The selective 5-HT1D/1B receptor antagonist BRL 15572 inhibited the effect of the agonist L-694 247. 4. Our data suggest that 5-HT inhibits the increases in perfusion pressure induced by the electrical stimulation of the lumbar chains, acting on presynaptic 5-HT1D receptors and decreasing the release of noradrenaline from the sympathetic nerves in the hindquarter vascular bed of the rat.

  8. Upregulation of 5-hydroxytryptamine receptor signaling in coronary arteries after organ culture.

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    Chun-Yu Deng

    Full Text Available BACKGROUND: 5-Hydroxytryptamine (5-HT is a powerful constrictor of coronary arteries and is considered to be involved in the pathophysiological mechanisms of coronary-artery spasm. However, the mechanism of enhancement of coronary-artery constriction to 5-HT during the development of coronary artery disease remains to be elucidated. Organ culture of intact blood-vessel segments has been suggested as a model for the phenotypic changes of smooth muscle cells in cardiovascular disease. METHODOLOGY/PRINCIPAL FINDINGS: We wished to characterize 5-HT receptor-induced vasoconstriction and quantify expression of 5-HT receptor signaling in cultured rat coronary arteries. Cumulative application of 5-HT produced a concentration-dependent vasoconstriction in fresh and 24 h-cultured rat coronary arteries without endothelia. 5-HT induced greater constriction in cultured coronary arteries than in fresh coronary arteries. U46619- and CaCl2-induced constriction in the two groups was comparable. 5-HT stimulates the 5-HT2A receptor and cascade of phospholipase C to induce coronary vasoconstriction. Calcium influx through L-type calcium channels and non-L-type calcium channels contributed to the coronary-artery constrictions induced by 5-HT. The contractions mediated by non-L-type calcium channels were significantly enhanced in cultured coronary arteries compared with fresh coronary arteries. The vasoconstriction induced by thapsigargin was also augmented in cultured coronary arteries. The decrease in Orai1 expression significantly inhibited 5-HT-evoked entry of Ca2+ in coronary artery cells. Expression of the 5-HT2A receptor, Orai1 and STIM1 were augmented in cultured coronary arteries compared with fresh coronary arteries. CONCLUSIONS: An increased contraction in response to 5-HT was mediated by the upregulation of 5-HT2A receptors and downstream signaling in cultured coronary arteries.

  9. Increased responsiveness to 5-hydroxytryptamine after antigenic challenge is inhibited by nifedipine and niflumic acid in rat trachea in vitro. (United States)

    Moura, Carlos Tiago Martins; Bezerra, Fernanda Carvalho; de Moraes, Isabelle Maciel; Magalhães, Pedro Jorge Caldas; Capaz, Francisco Ruy


    Antigenic challenge often induces hyperreactivity in asthmatic airway, although the precise mechanism(s) underlying this increased responsiveness is not entirely known. Tracheae obtained from ovalbumin (OVA)-sensitized saline- or OVA-challenged rats were placed in 10 mL bath chambers for isometric recording of 5-hydroxytryptamine (5-HT)-induced contractions. 5-Hydroxytryptamine induced a stronger contraction compared with control in antigen-challenged trachea under normal or Ca2+-free conditions. In tracheae pretreated with the L-type Ca2+ channel blocker nifedipine (10(-6) mol/L) or the Ca2+-activated Cl- channel blocker niflumic acid (10(-4) mol/L), this hyperresponsiveness was not developed in either normal or Ca2+-free medium. The increased contractile response to 5-HT in allergic rat isolated trachea may be related to a greater ionic (Ca2+ and Cl-) channel involvement.

  10. Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a “brake” on neuronal excitability in ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Pallab Bhattacharya; Anand Kumar Pandey; Sudip Paul; Ranjana Patnaik


    Our previous studies indicated an increase in extracellularγ-aminobutyric acid (GABA) in rodent’s ischemic brain after Piroxicam administration, leading to alleviation of glutamate me-diated excitotoxicity through activation of type A GABA receptor (GABAA). This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a signiifcant decrease in ex-tracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hy-droxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

  11. Associations of the 5-hydroxytryptamine (Serotonin) Receptor 1B Gene (HTR1B) with Alcohol, Cocaine, and Heroin Abuse


    Cao, Jian; LaRocque, Emily; Li, Dawei


    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To ...

  12. Chemistry and biology of the compounds that modulate cell migration. (United States)

    Tashiro, Etsu; Imoto, Masaya


    Cell migration is a fundamental step for embryonic development, wound repair, immune responses, and tumor cell invasion and metastasis. Extensive studies have attempted to reveal the molecular mechanisms behind cell migration; however, they remain largely unclear. Bioactive compounds that modulate cell migration show promise as not only extremely powerful tools for studying the mechanisms behind cell migration but also as drug seeds for chemotherapy against tumor metastasis. Therefore, we have screened cell migration inhibitors and analyzed their mechanisms for the inhibition of cell migration. In this mini-review, we introduce our chemical and biological studies of three cell migration inhibitors: moverastin, UTKO1, and BU-4664L.

  13. Two cases of mild serotonin toxicity via 5-hydroxytryptamine 1A receptor stimulation

    Directory of Open Access Journals (Sweden)

    Nakayama H


    Full Text Available Hiroto Nakayama,1,* Sumiyo Umeda,2,* Masashi Nibuya,3 Takeshi Terao,4 Koichi Nisijima,5 Soichiro Nomura3 1Yamaguchi Prefecture Mental Health Medical Center, Yamaguchi, Japan; 2Department of Psychiatry, NTT West Osaka Hospital, Osaka, Japan; 3Department of Psychiatry, National Defense Medical College, Saitama, Japan; 4Department of Neuropsychiatry, Oita University Faculty of Medicine, Oita, Japan; 5Department of Psychiatry, Jichi University School of Medicine, Tochigi, Japan  *These authors contributed equally to this work Abstract: We propose the possibility of 5-hydroxytryptamine (5-HT1A receptor involvement in mild serotonin toxicity. A 64-year-old woman who experienced hallucinations was treated with perospirone (8 mg/day. She also complained of depressed mood and was prescribed paroxetine (10 mg/day. She exhibited finger tremors, sweating, coarse shivering, hyperactive knee jerks, vomiting, diarrhea, tachycardia, and psychomotor agitation. After the discontinuation of paroxetine and perospirone, the symptoms disappeared. Another 81-year-old woman, who experienced delusions, was treated with perospirone (8 mg/day. Depressive symptoms appeared and paroxetine (10 mg/day was added. She exhibited tachycardia, finger tremors, anxiety, agitation, and hyperactive knee jerks. The symptoms disappeared after the cessation of paroxetine and perospirone. Recently, the effectiveness of coadministrating 5-HT1A agonistic psychotropics with selective serotonin reuptake inhibitors (SSRIs has been reported, and SSRIs with 5-HT1A agonistic activity have been newly approved in the treatment of depression. Perospirone is a serotonin–dopamine antagonist and agonistic on the 5-HT1A receptors. Animal studies have indicated that mild serotonin excess induces low body temperature through 5-HT1A, whereas severe serotonin excess induces high body temperature through 5-HT2A activation. Therefore, it could be hypothesized that mild serotonin excess induces side effects

  14. Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist. (United States)

    Zhang, Minli; Zhou, Diansong; Wang, Yi; Maier, Donna L; Widzowski, Daniel V; Sobotka-Briner, Cynthia D; Brockel, Becky J; Potts, William M; Shenvi, Ashok B; Bernstein, Peter R; Pierson, M Edward


    The preclinical pharmacology and pharmacokinetic properties of (2R)-6-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)chromane-2-carboxamide (AZD3783), a potent 5-hydroxytryptamine 1B (5-HT(1B)) receptor antagonist, were characterized as part of translational pharmacokinetic/pharmacodynamic hypothesis testing in human clinical trials. The affinity of AZD3783 to the 5-HT(1B) receptor was measured in vitro by using membrane preparations containing recombinant human or guinea pig 5-HT(1B) receptors and in native guinea pig brain tissue. In vivo antagonist potency of AZD3783 for the 5HT(1B) receptor was investigated by measuring the blockade of 5-HT(1B) agonist-induced guinea pig hypothermia. The anxiolytic-like potency was assessed using the suppression of separation-induced vocalization in guinea pig pups. The affinity of AZD3783 for human and guinea pig 5-HT(1B) receptor (K(i), 12.5 and 11.1 nM, respectively) was similar to unbound plasma EC(50) values for guinea pig receptor occupancy (11 nM) and reduction of agonist-induced hypothermia (18 nM) in guinea pig. Active doses of AZD3783 in the hypothermia assay were similar to doses that reduced separation-induced vocalization in guinea pig pups. AZD3783 demonstrated favorable pharmacokinetic properties. The predicted pharmacokinetic parameters (total plasma clearance, 6.5 ml/min/kg; steady-state volume of distribution, 6.4 l/kg) were within 2-fold of the values observed in healthy male volunteers after a single 20-mg oral dose. This investigation presents a direct link between AZD3783 in vitro affinity and in vivo receptor occupancy to preclinical disease model efficacy. Together with predicted human pharmacokinetic properties, we have provided a model for the quantitative translational pharmacology of AZD3783 that increases confidence in the optimal human receptor occupancy required for antidepressant and anxiolytic effects in patients.

  15. Association between 5-hydroxytryptamine transporter gene-linked polymorphic region and smoking behavior in Chinese males

    Institute of Scientific and Technical Information of China (English)

    CHU Shui-lian; XIAO Dan; WANG Chen; JING Hang


    Background Tobacco use is the major risk factor for numerous health problems. However, only 5% of smokers can successfully quit without therapy owing to the highly addictive properties of nicotine. The serotoninergic system may be involved in smoking behavior because nicotine increases brain serotonin secretion, nicotine withdrawal decreases serotonin levels, and a selective serotonin reuptake inhibitor antagonizes the response to nicotine withdrawal. Serotonin transporter (5-HTT) is the most important protein, as it adjusts the serotonin concentration in the synaptic cleft. There is a polymorphism in the upstream regulatory region of the 5-HTT gene, named 5-hydroxytryptamine transporter gene-Iinked poyymorphic region (5-HTTLPR). Compared with the L allele, the S allele of the polymorphism is associated with decreased transcription efficiency of the 5-HTT gene. In this study, we investigated the relationship between this gene polymorphism and smoking behavior in Chinese males.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find 5-HTTLPR gene polymorphisms in 144 smokers and 135 age-matched healthy non-smokers. A questionnaire was completed in all recruited subjects.Results The proportion of L/L (15.3% vs 5.2%) and S/L (50.0% vs 33.3%) genotypes was significantly higher in the smokers than that in the non-smokers (χ2=21.9; P <0.01). The odds ratio (OR) adjusted by age, education, effects of family members and friends who smoke, and alcohol intake was 2.9 (95%CI 1.78-4.80). In smokers, the number of cigarettes/day (L/L vs S/L vs S/S: 28+12 vs 20±8 vs 16±6, χ2=18.5, P <0.01), smoking index (L/L vs S/L vs S/S.. 561±446vs 393±341 vs 237+901, χ2=12.5, P <0.01) and score on the Fagerstrom test for nicotine dependence (FTND) (L/L vs S/L vs S/S. 7.8±1.6 vs 6.2±9.5 vs 3.5±9.1, χ2=48.3, P <0.01) were significantly higher in smokers with an L/L or S/L genotype than that in the smokers with the S/S genotype

  16. 5-hydroxytryptamine (5-HT) reduces total peripheral resistance during chronic infusion: direct arterial mesenteric relaxation is not involved


    Davis, Robert Patrick; Pattison, Jill; Janice M Thompson; Tiniakov, Ruslan; Scrogin, Karie E.; Watts, Stephanie W.


    Serotonin (5-hydroxytryptamine; 5-HT) delivered over 1 week results in a sustained fall in blood pressure in the sham and deoxycorticosterone acetate (DOCA)-salt rat. We hypothesized 5-HT lowers blood pressure through direct receptor-mediated vascular relaxation. In vivo, 5-HT reduced mean arterial pressure (MAP), increased heart rate, stroke volume, cardiac index, and reduced total peripheral resistance during a 1 week infusion of 5-HT (25 µg/kg/min) in the normotensive Sprague Dawley rat. T...

  17. 5-Hydroxytryptamine 2C receptors tonically augment synaptic currents in the nucleus tractus solitarii


    Austgen, James R.; Dantzler, Heather A.; Barger, Brenna K.; Kline, David D.


    The nucleus tractus solitarii (nTS) is the primary termination and integration point for visceral afferents in the brain stem. Afferent glutamate release and its efficacy on postsynaptic activity within this nucleus are modulated by additional neuromodulators and transmitters, including serotonin (5-HT) acting through its receptors. The 5-HT2 receptors in the medulla modulate the cardiorespiratory system and autonomic reflexes, but the distribution of the 5-HT2C receptor and the role of these...

  18. Ag ion irradiated based sensor for the electrochemical determination of epinephrine and 5-hydroxytryptamine in human biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, Rajendra N., E-mail: [Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247667 (India); Agrawal, Bharati [Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247667 (India)


    Highlights: Black-Right-Pointing-Pointer Ag ions irradiation enhances the electrocatalytic activity of carbon nano tubes. Black-Right-Pointing-Pointer The low fluence of irradiation caused the ordering of carbon nano tubes. Black-Right-Pointing-Pointer Simultaneous determination of epinephrine and 5-hydroxytryptamine has been carried out. Black-Right-Pointing-Pointer The determination of the neurotransmitters in human blood and urine is reported. - Abstract: A promising and highly sensitive voltammetric method has been developed for the first time for the determination of epinephrine (EP) and 5-hydroxytryptamine (5-HT) using 120 MeV Ag ion irradiated multi-walled carbon nano tube (MWCNT) based sensor. The MWCNT were irradiated at various fluences of 1e12, 3e12 and 1e13 ions cm{sup -2} using palletron accelerator. The simultaneous determination of EP and 5-HT has been carried out in phosphate buffer solution of pH 7.20 using square wave voltammetry and cyclic voltammetry. Experimental results suggested that irradiation of MWCNT by Ag ions enhanced the electrocatalytic activity due to increase in effective surface area and insertion of Ag ions, leading to a remarkable enhancement in peak currents and shift of peak potentials to less positive values as compared to the unirradiated MWCNT (pristine). The developed sensor exhibited a linear relationship between peak current and concentration of EP and 5-HT in the range 0.1-105 {mu}M with detection limit (3{sigma}/b) of 2 nM and 0.75 nM, respectively. The practical utility of irradiation based MWCNT sensor has been demonstrated for the determination of EP and 5-HT in human urine and blood samples.

  19. Effects of 5-hydroxytryptamine, dopamine, and acetylcholine on accumulation of cyclic AMP and cyclic GMP in the anterior byssus retractor muscle of Mytilus edulis L. (Mollusca). (United States)

    Köhler, G; Lindl, T


    We investigated in vitro accumulation of adenosine 3',5'-monophosphate (induced by 5-hydroxytryptamine and dopamine) and of guanosine 3',5'-monophosphate (induced by acetylcholine) in the anterior byssus retractor muscle of Mytilus. The response to 5-hydroxytryptamine exceeded that induced by equimolar concentrations of dopamine. 1-methyl lysergic acid, a 5-hydroxytryptamine-blocking agent, diminished the 5-hydroxytryptamine-induced increase of cyclic AMP level. This parallels the effect of this amine on the contracted muscle. Acetylcholine, which causes a tonic contraction of the muscle, increased intracellular levels of cyclic GMP in a dose-dependent (max. 45-fold at 10(-4) M ACh) manner. The time course of the rise in cyclic GMP level was rapid and transient (peak concentration of cyclic GMP at 2 min). Mytolon was the most effective of all cholinergic blockers tested. It was concluded that cyclic nucleotides may play a role in the modulatory process of the transmitters. A direct relation to the relaxation-contraction process could not be established.

  20. Comparative effects of niflumic acid and nifedipine on 5-hydroxytryptamine- and acetylcholine-induced contraction of the rat trachea. (United States)

    Teixeira, M C; Coelho, R R; Leal-Cardoso, J H; Criddle, D N


    The effects of niflumic acid, an inhibitor of Ca(2+)-activated Cl(-) (Cl((Ca))) channels, were compared with those of the voltage-dependent Ca(2+) channel (VDCC) blocker nifedipine on 5-hydroxytryptamine (5-HT)- and acetylcholine-induced contractions of the rat isolated trachea. Niflumic acid (3-100 microM) induced a concentration-dependent inhibition of 5-HT (10 microM)-induced contractions, with a reduction to 37.0+/-9.5% of the control at the highest concentration. One micromolar nifedipine, which completely blocked 60 mM KCl-induced contractions, reduced the response to 5-HT similarly to 39.2+/-11.5% of the control. The inhibition of the 5-HT response was not significantly different from that produced by the combined presence of nifedipine (1 microM) and niflumic acid (100 microM), suggesting that their effects were not additive. In contrast, neither niflumic acid (3-100 microM) nor nifedipine (1 microM) inhibited acetylcholine-induced contractions. The contraction to 5-HT (10 microM) in Cl(-)-free solution was decreased by more than approximately 85% of the control, whilst that of acetylcholine was reduced only by approximately 36%. Our data show that niflumic acid exerts selective inhibitory effects on 5-HT-induced contraction, and suggest that activation of Cl((Ca)) channels may be a mechanism whereby 5-HT (but not acetylcholine) induces Ca(2+) entry via VDCCs to elicit contraction.

  1. Identification of 5-Hydroxytryptamine-Producing Cells by Detection of Fluorescence in Paraffin-Embedded Tissue Sections (United States)

    Kaneko, Y.; Onda, N.; Watanabe, Y.; Shibutani, M.


    5-Hydroxytryptamine (5-HT) produced by enterochromaffin (EC) cells is an important enteric mucosal signaling ligand and has been implicated in several gastrointestinal diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. The present study reports a new, simple and rapid visualization method of 5-HT-producing EC cells utilizing detection of fluorescence in paraffin-embedded tissue sections after formalin fixation. In human samples, there was a high incidence of fluorescence+ cells in the 5-HT+ cells in the pyloric, small intestinal and colonic glands, while co-localization was lacking between fluorescence+ and gastrin+ cells in the pyloric and small intestinal glands. Fluorescence+ EC cells were detected in the colon of mice and rats. Fluorescence+ cells were also observed in 5-HT+ β cells in the pancreatic islets of Langerhans in pregnant mice, while non-pregnant mouse pancreatic islet cells showed no 5-HT immunoreactivity or fluorescence. These results suggest that fluorescence+ cells are identical to 5-HT+ cells, and the source of fluorescence may be 5-HT itself or molecules related to its synthesis or degradation. This fluorescence signal detection method may be applicable for monitoring of inflammatory status of inflammatory bowel diseases in both the experimental and clinical settings. PMID:27734992

  2. Identification of 5-hydroxytryptamine-producing cells by detection of fluorescence in paraffin-embedded tissue sections

    Directory of Open Access Journals (Sweden)

    Y. Kaneko


    Full Text Available 5-Hydroxytryptamine (5-HT produced by enterochromaffin (EC cells is an important enteric mucosal signaling ligand and has been implicated in several gastrointestinal diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. The present study reports a new, simple and rapid visualization method of 5-HT-producing EC cells utilizing detection of autofluorescence in paraffin-embedded tissue sections after formalin fixation. In human samples, there was a high incidence of autofluorescence+ cells in the 5-HT+ cells in the pyloric, small intestinal and colonic glands, while co-localization was lacking between autofluorescence+ and gastrin+ cells in the pyloric and small intestinal glands. Autofluorescence+ EC cells were detected in the colon of mice and rats. Autofluorescence+ cells were also observed in 5-HT+ β cells in the pancreatic islets of Langerhans in pregnant mice, while non-pregnant mouse pancreatic islet cells showed no 5-HT immunoreactivity or autofluorescence. These results suggest that autofluorescence+ cells are identical to 5-HT+ cells, and the source of autofluorescence may be 5-HT itself or molecules related to its synthesis or degradation. This autofluorescence signal detection method may be applicable for monitoring of inflammatory status of inflammatory bowel diseases in both the experimental and clinical settings.

  3. Maternal ethanol administration inhibits 5-hydroxytryptamine synthesis and tryptophan hydroxylase expression in the dorsal raphe of rat offspring. (United States)

    Kim, Eun-Kyung; Lee, Myoung-Hwa; Kim, Hong; Sim, Young-Je; Shin, Mal-Soon; Lee, Sam-Jun; Yang, Hye-Young; Chang, Hyun-Kyung; Lee, Taeck-Hyun; Jang, Mi-Hyeon; Shin, Min-Chul; Lee, Hee-Hyuk; Kim, Chang-Ju


    Maternal ethanol consumption during pregnancy has a detrimental effect on the central nervous system (CNS) development of fetus. 5-Hydroxytryptamine (5-HT) is an important neurotransmitter and/or neuromodulator in the mammalian CNS. Tryptophan hydroxylase (TPH) is the rate limiting enzyme of 5-HT synthesis. Ethanol is known to induce neuropsychiatric disorders by alteration of the central serotonergic system. In the present study, the effects of maternal ethanol intake on the 5-HT synthesis and the TPH expression in the dorsal raphe of rat offspring were investigated. The present results show that the synthesis of 5-HT and the expression of TPH in the dorsal raphe of rat offspring were suppressed by maternal ethanol intake and that the suppressive effect of alcohol was more potent in the 5 weeks old rat pups compared to the 3 weeks old rat pups. Based on the present study, it can be suggested that the pathogenesis of ethanol-induced neuropsychological disorders involves ethanol-induced suppression on the 5-HT synthesis and the TPH expression in the dorsal raphe of offspring.

  4. Synergistic effect of 5-hydroxytryptamine 3 and neurokinin 1 receptor antagonism in rodent models of somatic and visceral pain. (United States)

    Greenwood-Van Meerveld, Beverley; Mohammadi, Ehsan; Tyler, Karl; Pietra, Claudio; Bee, Lucy A; Dickenson, Anthony


    Synergistic activity has been observed between serotonergic 5-hydroxytryptamine 3 (5-HT3) and tachykinergic neurokinin 1 (NK1) receptor-mediated responses. This study investigated the efficacy of a 5-HT3 antagonist, palonosetron, and a NK1 antagonist, netupitant, alone or in combination in rodent models of somatic and visceral colonic hypersensitivity. In a rat model of experimental neuropathic pain, somatic hypersensitivity was quantified by the number of ipsilateral paw withdrawals to a von Frey filament (6g). Electrophysiologic responses were recorded in the dorsal horn neurons after mechanical or thermal stimuli. Acute colonic hypersensitivity was induced experimentally in rats by infusing dilute acetic acid (0.6%) directly into the colon. Colonic sensitivity was assessed by a visceromotor behavioral response quantified as the number of abdominal contractions in response to graded isobaric pressures (0-60 mm Hg) of colorectal distension. Palonosetron or netupitant was administered alone or in combination via oral gavage. When dosed alone, both significantly reduced somatic sensitivity, decreased the evoked response of spinal dorsal horn neurons to mechanical or thermal stimulation, and caused significant (P somatic and visceral sensitivity and decreased the evoked response of spinal dorsal horn neurons to mechanical or thermal stimulation. In summary, the combination of palonosetron with a NK1 receptor antagonist showed synergistic analgesic activity in rodent models of somatic and visceral hypersensitivity, and may prove to be a useful therapeutic approach to treat pain associated with irritable bowel syndrome.

  5. Action of angiotensin II, 5-hydroxytryptamine and adenosine triphosphate on ionic currents in single ear artery cells of the rabbit. (United States)

    Hughes, A D; Bolton, T B


    1. Angiotensin II, 5-hydroxytryptamine (5-HT) and adenosine triphosphate (ATP) evoked a transient inward current in isolated single car artery cells of rabbit held at -60 mV by whole cell voltage clamp in physiological saline using a KCL-containing pipette solution. Under these conditions agonist did not activate a calcium-dependent potassium current. 2. Responses to each agonist were transient and desensitized rapidly. Inward current at -60 mV holding potential was not abolished by blockade of voltage-dependent calcium channels or by buffering intracellular calcium with BAPTA, a calcium chelator, or following depletion of intracellular calcium stores with ryanodine. 3. The shape of the current-voltage relationships and the reversal potentials of the current induced by angiotensin II, 5-HT and ATP were similar under a variety of ionic conditions. Agonist-induced current was unaffected by replacing intracellular chloride with citrate ions or by replacing intracellular sodium with caesium or extracellular sodium with barium or calcium. Replacement of extracellular sodium with Tris shifted the reversal potential in all cases by around 30 mV negatively. 4. These data suggest that angiotensin II, 5-HT and ATP activate similar cationic conductances which are relatively non-selective allowing mono- and divalent cations to cross the smooth muscle cell membrane. These channels may allow the influx of calcium under physiological conditions.

  6. A noncanonical release of GABA and glutamate modulates neuronal migration. (United States)

    Manent, Jean-Bernard; Demarque, Michaël; Jorquera, Isabel; Pellegrino, Christophe; Ben-Ari, Yehezkel; Aniksztejn, Laurent; Represa, Alfonso


    Immature neurons express GABA and glutamate receptors before synapse formation, and both transmitters are released at an early developmental stage. We have now tested the hypothesis that the ongoing release of GABA and glutamate modulates neuronal migration. Using 5-bromo-2'-deoxyuridine labeling and cocultures of hippocampal slices obtained from naive and green fluorescent protein-transgenic mice, we report that migration is severely affected by GABA(A) or NMDA receptor antagonist treatments. These effects were also present in munc18-1 knock-out slices in which soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent vesicular secretion of transmitters has been deleted. GABA(A) antagonists were more efficient than NMDA antagonists to reduce cell migration, in keeping with the earlier maturation of GABAergic mechanisms. We conclude that GABA and, to a lesser degree, glutamate released in a SNARE-independent mechanism exert a paracrine action on neuronal migration.

  7. 5-hydroxytryptamine (5-HT) reduces total peripheral resistance during chronic infusion: direct arterial mesenteric relaxation is not involved. (United States)

    Davis, Robert Patrick; Pattison, Jill; Thompson, Janice M; Tiniakov, Ruslan; Scrogin, Karie E; Watts, Stephanie W


    Serotonin (5-hydroxytryptamine; 5-HT) delivered over 1 week results in a sustained fall in blood pressure in the sham and deoxycorticosterone acetate (DOCA)-salt rat. We hypothesized 5-HT lowers blood pressure through direct receptor-mediated vascular relaxation. In vivo, 5-HT reduced mean arterial pressure (MAP), increased heart rate, stroke volume, cardiac index, and reduced total peripheral resistance during a 1 week infusion of 5-HT (25 µg/kg/min) in the normotensive Sprague Dawley rat. The mesenteric vasculature was chosen as an ideal candidate for the site of 5-HT receptor mediated vascular relaxation given the high percentage of cardiac output the site receives. Real-time RT-PCR demonstrated that mRNA transcripts for the 5-HT2B, 5-HT1B, and 5-HT7 receptors are present in sham and DOCA-salt superior mesenteric arteries. Immunohistochemistry and Western blot validated the presence of the 5-HT2B, 5- HT1B and 5-HT7 receptor protein in sham and DOCA-salt superior mesenteric artery. Isometric contractile force was measured in endothelium-intact superior mesenteric artery and mesenteric resistance arteries in which the contractile 5- HT2A receptor was antagonized. Maximum concentrations of BW-723C86 (5- HT2B agonist), CP 93129 (5-HT1B agonist) or LP-44 (5-HT7 agonist) did not relax the superior mesenteric artery from DOCA-salt rats vs. vehicle. Additionally, 5-HT (10-9 M to 10-5 M) did not cause relaxation in either contracted mesenteric resistance arteries or superior mesenteric arteries from normotensive Sprague- Dawley rats. Thus, although 5-HT receptors known to mediate vascular relaxation are present in the superior mesenteric artery, they are not functional, and are therefore not likely involved in a 5-HT-induced fall in total peripheral resistance and MAP.

  8. Changes in 5-hydroxytryptamine and cortisol plasma levels in menopausal women after inhalation of clary sage oil. (United States)

    Lee, Kyung-Bok; Cho, Eun; Kang, Young-Sook


    The purpose of this study was to examine the antidepressant-like effects of clary sage oil on human beings by comparing the neurotransmitter level change in plasma. The voluntary participants were 22 menopausal women in 50's. Subjects were classified into normal and depression tendency groups using each of Korean version of Beck Depression Inventory-I (KBDI-I), KBDI-II, and Korean version of Self-rating Depression Scale. Then, the changes in neurotransmitter concentrations were compared between two groups. After inhalation of clary sage oil, cortisol levels were significantly decreased while 5-hydroxytryptamine (5-HT) concentration was significantly increased. Thyroid stimulating hormone was also reduced in all groups but not statistically significantly. The different change rate of 5-HT concentration between normal and depression tendency groups was variable according to the depression measurement inventory. When using KBDI-I and KBDI-II, 5-HT increased by 341% and 828% for the normal group and 484% and 257% for the depression tendency group, respectively. The change rate of cortisol was greater in depression tendency groups compared with normal groups, and this difference was statistically significant when using KBDI-II (31% vs. 16% reduction) and Self-rating Depression Scale inventory (36% vs. 8.3% reduction). Among three inventories, only KBDI-II differentiated normal and depression tendency groups with significantly different cortisol level. Finally, clary sage oil has antidepressant-like effect, and KBDI-II inventory may be the most sensitive and valid tool in screening for depression status or severity.

  9. Corticotropin-releasing factor increases GABA synaptic activity and induces inward current in 5-hydroxytryptamine dorsal raphe neurons. (United States)

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


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

  10. Reduced sensitivity to both positive and negative reinforcement in mice over-expressing the 5-hydroxytryptamine transporter. (United States)

    Line, Samantha J; Barkus, Chris; Rawlings, Nancy; Jennings, Katie; McHugh, Stephen; Sharp, Trevor; Bannerman, David M


    The 5-hydroxytryptamine (5-HT) transporter (5-HTT) is believed to play a key role in both normal and pathological psychological states. Much previous data suggest that the s allele of the polymorphic regulatory region of the 5-HTT gene promoter is associated with reduced 5-HTT expression and vulnerability to psychiatric disorders, including anxiety and depression. In comparison, the l allele, which increases 5-HTT expression, is generally considered protective. However, recent data link this allele to both abnormal 5-HT signalling and psychopathic traits. Here, we studied the processing of aversive and rewarding cues in transgenic mice that over-express the 5-HTT (5-HTTOE mice). Compared with wild-type mice, 5-HTTOE mice froze less in response to both a tone that had previously been paired with footshock, and the conditioning context. In addition, on a decision-making T-maze task, 5-HTTOE mice displayed reduced preference for a larger, delayed reward and increased preference for a smaller, immediate reward, suggesting increased impulsiveness compared with wild-type mice. However, further inspection of the data revealed that 5-HTTOE mice displayed a relative insensitivity to reward magnitude, irrespective of delay. In contrast, 5-HTTOE mice appeared normal on tests of spatial working and reference memory, which required an absolute choice between options associated with either reward or no reward. Overall, the present findings suggest that 5-HTT over-expression results in a reduced sensitivity to both positive and negative reinforcers. Thus, these data show that increased 5-HTT expression has some maladaptive effects, supporting recent suggestions that l allele homozygosity may be a potential risk factor for disabling psychiatric traits.

  11. 5-羟色胺转运体与糖尿病%5-Hydroxytryptamine transporter and diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    秦永章; 胡敬; 荣海钦


    5-Hydroxytryptamine (5-HT) plays an important role in maintaining the glucose homeostasis. Studies show that intracellular 5-HT of β-cells can promote insulin releasing, while the 5-HT transporter (SERT)which extensively resides in cell membrane and nerve synapse can reuptake 5-HT by a mechanism of terminating its action to regulate the physiological function of 5-HT. Recent studies suggest a possible relationship between SERT,its gene polymorphism and diabetes mellitus. So the research of SERT and diabetes mellitus can yield novel insights into the connection of nervous system and glycometaholism, and explore new target of diabetic therapy.%5-羟色胺(5-HT)在维持葡萄糖内环境稳态中起重要作用,研究显示存在于β细胞内的5-HT可以促进胰岛素释放,而广泛存在于细胞膜和神经突触上的5-HT转运体(SERT)蛋白可以重摄取5-HT,通过转运灭活机制调控5-HT使生理功能.近来研究发现SERT蛋白及其基因多态性与糖尿病的发生、发展存在一定关联性.因此对SERT与糖尿病的研究有助于揭示神经系统与糖代谢的联系,为治疗糖尿病寻找新的靶点.

  12. Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse. (United States)

    Cao, Jian; LaRocque, Emily; Li, Dawei


    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To clarify the roles of commonly reported single nucleotide polymorphisms (SNPs) of the HTR1B gene underlying alcohol and drug dependence (abuse), we performed a meta-analysis based on the available genotype data from individual candidate gene-based association studies. Evidence of association was found between the functional SNP -161A>T (rs130058) and alcohol, cocaine, and heroin dependence (e.g., P = 0.03 and odds ratio (OR) = 1.2 (1.02, 1.42) in the combined European, Asian, African, and Hispanic populations). SNP -261T>G (rs11568817) also showed evidence of association but with different directions in Europeans and non-Europeans (e.g., P = 0.0018 with OR = 1.42 (1.14, 1.76) and P = 0.01 with ORs = 0.5 (0.3, 0.85), respectively). This meta-analysis supports the associations of HTR1B -261T>G and -161A>T with alcohol and drug abuse and further investigations are warranted in larger samples.

  13. 5-Hydroxytryptamine-induced vasodilator responses in the hindquarters of the anaesthetized rat, involve beta2-adrenoceptors. (United States)

    Calama, E; García, M; Jarque, M J; Morán, A; Martín, M L; San Román, L


    These studies were conducted to examine the role of the vasoactive mediators nitric oxide (NO) and adrenaline (epinephrine) in the serotonin (5-hydroxytryptamine; 5-HT)-induced vasodilator response in the hindquarter vascular bed of anaesthetized rats. Intra-arterial administration of doses of 5-HT in the range 0.12-25 ng kg(-1) produced a dose-independent vasodilator effect in the hindquarters. The selective 5-HT(1D/1B) receptor agonist, L-694,247 at intra-arterial doses of 0.0012-1000 ng kg(-1), as well as adrenaline (at doses of 0.05-50 ng kg(-1) i.a.), mimicked the dose-independent vasodilator effect induced by intra-arterial administration of 5-HT. Intravenous pre-treatment with the selective beta2-receptor antagonist ICI 118,551 (0.5 mg kg(-1)) blocked the vasodilator effect of 5-HT, adrenaline and L-694,247. Additionally, the inhibitor of NO synthase NG-nitro-L-arginine (L-NAME) (at a dose of 10 mg kg(-1) i.v.) blocked the vasodilator action of acetylcholine 300-3000 ng kg(-1)) but did not modify 5-HT-induced vasodilatation. The vasodilator effect produced by intra-arterial administration of 5-HT in the hindquarters was significantly inhibited both 30 min after denervation of the lumbar sympathetic chains and 1 h after bilateral adrenalectomy. Our data suggest that in the in-situ autoperfused hindquarters of the rat 5-HT-induced vasodilatation is mediated by a local 5-HT(1D) or 5-HT(1D/1B) activation, which in turn mediates the adrenal release of adrenaline, which then produces beta2-activation and vasodilatation.

  14. Effects of inorganic cations on K+-, 5-hydroxytryptamine- and noradrenaline-induced contractions of the isolated rat jugular vein and aorta

    NARCIS (Netherlands)

    Gouw, M.A.M.; Wilffert, B.; Van Zwieten, P.A.


    We investigated the inhibitory effects of 1 mM of the inorganic cations, La3+, Cd2+, Mn2+, Ni2+and Co2+on contractions induced by K+(100 mM) and 5-hydroxytryptamine (5-HT, 10-5M) in the isolated rat jugular vein and on contractions induced by K+(100 mM), 5-HT (10-5) and noradrenaline (NA, 10-5M) in

  15. Changes of Plasma Concentration of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in climacteric women with hot flushes

    Institute of Scientific and Technical Information of China (English)

    Chen Ya-qiong; Wu Wei-guang


    Objective: To investigate the relationship between the changes of serotonin metabolism and the hot flushes in climacteric women.Methods.Ninety eight climacteric women, aged 40-60, were enrolled and divided into 4 groups: Group A: 20 cases of early menopausal transition.Group B: 26 cases of late menopausal transition, with skip of periods 3-12 months.Group C: 28 cases of early postmenopause (1-3 yrs).Group D: 24 cases of late postmenopause(>3-6 yrs).Twelve normal women of reproductive age (24±3yrs) were served as young controls.Fifty two postmenopausal women were subdivided into 3 groups according to the presence or the absence of hot flushes: (1) postmenopausal controls without hot flushz 17 cases, (2) mild hot flushes group: 20 eases,fewer≤5 times/d, (3) severe hot flushes group: 15 cases, more than 5 times/d.Plasma concentrations of tryptophan (TP), 5-hydroxytryptophane (5-HTP), 5-hydroxytryptamine (5-HT or serotonin), 5-hydroxyindoleacetic acid (5-HIAA) and luteinizing hormone (LH) were measured in all participants by high pressure liquid chromatography-fluorescence spectrophotometer (HPLC-FS).The relationship between serotonin metabolic parameters and menopause, hot flushes were analysed.Results: (1) Mean 5-HT and 5-HIAA concentrations in plasma were significantly higher in climacteric women than those in young controls, especially in Group B.Mean 5-HTP and 5-HT levels were higher and 5-HIAA lower in Group D as compared with those of young controls.(2) Plasma 5-HT levels was positively correlated to luteinizing hormone concentration in postmenopansal women (P<0.01).(3) In the mild hot flushes group, only plasma 5-HTP levels were significantly higher than that in the non-hot flushes group.In severe hot flushes group,plasma 5-HT and 5-HTP contents were significantly higher and 5-HIAA/5-HT ratio lower than those in the non-hotflushes groups.Conclusion: The results suggest that the catabolic disorder of serotonin maybe involve in the underling mechanism of

  16. Vasodilator and vasoconstrictor responses induced by 5-hydroxytryptamine in the in situ blood autoperfused hindquarters of the anaesthetized rat. (United States)

    Calama, E; Fernández, M M; Morán, A; Martín, M L; San Román, L


    In the present study we attempted to characterise the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT, serotonin) in in situ autoperfused rat hindquarters. Intra-arterial administration of the lowest doses of 5-HT used (0.12-12.5 ng/kg) induced vasodilator responses, whereas the highest doses (25-1000 ng/kg) produced vasoconstriction. The vasodilator effect was inhibited by methiothepin (a non-specific 5-HT(1,2,5,6,7) receptor antagonist) and by a 5-HT(1D/1B) receptor antagonist, i.e., 3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanolol (BRL 15572), but not by ritanserin (a selective 5-HT(2) receptor antagonist), 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f] indole (SB 206553, a selective 5-HT(2B/2C) receptor antagonist) or mesulergine (a non-specific serotonergic antagonist that shows affinity to the 5-HT(7) receptor). This vasodilator effect was mimicked by administration of a selective 5-HT(1) receptor agonist - 5-carboxamidotryptamine (5-CT) - and by 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-1 H-indol-3-yl]ethanamine (L-694,247, a selective 5-HT(1D/1B) receptor agonist). Methiothepin, but not mesulergine, inhibited 5-CT-induced vasodilatation and the selective 5-HT(1D/1B) receptor antagonist (BRL 15572) inhibited the vasodilator action induced by L-694,247. The vasoconstrictor effect of 5-HT was significantly decreased by methiothepin, ritanserin and SB 206553, and was mimicked by alpha-methyl-5-HT (a selective 5-HT(2) receptor agonist) but not by administration of BW 723C86, a selective 5HT(2B) receptor agonist. Ritanserin, SB 206553 and spiperone (a non-specific 5-HT(1/2A) receptor antagonist) inhibited the alpha-methyl-5HT-induced vasoconstriction.Our data suggest that the vasodilator response induced by 5-HT in autoperfused rat hindquarters is mainly mediated by 5-HT(1D/1B) receptors, whereas the vasoconstrictor effect is mainly due to the activation of 5-HT(2A) receptors.

  17. Orbitofrontal cortex action of 5-hydroxytryptamine and its receptor in an acute forced swimming stress-induced depression model

    Institute of Scientific and Technical Information of China (English)

    Huipeng Li; Fengli An; Shucheng An


    BACKGROUND: The orbitofrontal cortex (OFC) is a brain region closely associated with emotion.5-hydroxytryptamine (5-HT) has been shown to be involved in human depression.OBJECTIVE: To investigate OFC actions and mechanisms of 5-HT and 5-HT1A receptor (5-HT1AR)in stress-induced depression.DESIGN, TIME AND SEI-rlNG: A randomized, controlled, animal experiment was performed at Laboratory of Neurobiology, College of Life Science, Shaanxi Normal University between May 2006 and March 2008.MATERIALS: 5-HT, p-chlorophenylalanine (PCPA, an inhibitor to tryptophan hydroxylase) andspiperone (5-HT1AR antagonist) were provided by Sigma, USA; rabbit anti-rat 5-HT1AR antibody was provided by Tlanjin Haoyang Biological Manufacture.METHODS: A total of 40 male Sprague Dawley rats, aged 3 months, were randomly divided into five groups: control, model, 5-HT, spiperone+5-HT, and PCPA, with 8 rats in each group. Except for control group, rats in the other four groups were used to establish depression models by forced swimming for 15 minutes. At 30 minutes before forced swimming test, 0.5μL of 5-HT (12.5μg/pL),PCPA (20μg/μL), spiperone (1.3 μg/μL)+5-HT (12.5μg/μL, 10 minutes later), and saline were respectively injected into the OFC of 5-HT, PCPA, spiperone+5-HT, and model groups, respectively.The control group received a saline microinjection into the OFC.MAIN OUTCOME MEASURES: Forced swimming and open field tests were employed to measure animal behaviors, and immunohistochemistry was used to analyze 5-HT1AR expression in the OFC,cingulate cortex, and piriform cortex.RESULTS: (1) Compared with the model group, 5-HT microinjection into the OFC prominently reduced immobility time in the forced swimming test and rearing in open field test (P0.05). Furthermore, following PCPA microinjection into the OFC (PCPA + forced swimming stress),immobility time in forced swimming test increased dramatically (P<0.01), locomotion and rearing inopen field test declined (P<0.05 and P<0

  18. The depolarizing action of 5-hydroxytryptamine on rabbit vagal afferent and sympathetic neurones in vitro and its selective blockade by ICS 205-930.



    Depolarizing responses to 5-hydroxytryptamine (5-HT) were recorded from rabbit nodose (NG) and superior cervical (SCG) ganglia using the sucrose-gap technique. The antagonist potency and selectivity of ICS 205-930 ([3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester) were investigated. In NG, 5-HT (5 to 80 nmol) evoked depolarizations of graded amplitude. The ED50 was 18.2 (10.9-30.5) nmol (geometric mean, 95% confidence limits). Responses were blocked surmountably by ICS 205-930, 10(-11) an...

  19. Evaluation of S-[[sup 11]C]citalopram as a radioligand for in vivo labelling of 5-hydroxytryptamine uptake sites

    Energy Technology Data Exchange (ETDEWEB)

    Hume, S.P.; Lammertsma, A.A.; Bench, C.J.; Pike, V.W.; Pascali, C.; Cremer, J.E. (Hammersmith Hospital, London (United Kingdom). M.R.C. Cyclotron Unit); Dolan, R.J. (Royal Free Hospital, London (United Kingdom))


    The biologically active S-enantiomer of [N-methyl-[sup 11]C]citalopram was evaluated as a radioligand for in vivo labelling of the 5-hydroxytryptamine uptake site in brain, using ex vivo tissue counting in rats and positron emission tomography in man. In rats, the maximal signal for total versus non-specific binding was approx. 2 at 60-120 min after radioligand injection. Subsequent studies in man failed to identify a specific signal over a 90 min scanning period, due to prolonged retention of non-specific label. (author).

  20. Does pharmacogenomics account for variability in control of acute chemotherapy-induced nausea and vomiting with 5-hydroxytryptamine type 3 receptor antagonists? (United States)

    Trammel, Morgan; Roederer, Mary; Patel, Jai; McLeod, Howard


    Chemotherapy-induced nausea and vomiting is one of the most concerning adverse drug effects from cytotoxic chemotherapy. Despite appropriate use of antiemetic guidelines, 20-30 % of patients experience breakthrough nausea and vomiting secondary to chemotherapy. To assess the variability of 5-hydroxytryptamine type 3 receptor antagonist efficacy caused by genetic variation, a review of the available literature was conducted. From the literature, three sources of pharmacogenomic variability were identified: polymorphisms associated with 5-hydroxytryptamine type 3 receptor subunits, drug metabolism via cytochromes P450, and drug transport in the body. Testing for receptor subunit polymorphisms is not applicable to a clinical setting at this time; however, cytochrome P450 2D6 testing is FDA-approved and widely accessible. Cytochrome P450 2D6 ultrarapid metabolizers and poor metabolizers displayed altered antiemetic efficacy when compared with intermediate metabolizers and extensive metabolizers. We postulate that testing for cytochrome P450 2D6 phenotypes may be the most accessible way to provide individualized antiemetic therapy in the future.

  1. Prophylaxis of Radiation-Induced Nausea and Vomiting Using 5-Hydroxytryptamine-3 Serotonin Receptor Antagonists: A Systematic Review of Randomized Trials

    Energy Technology Data Exchange (ETDEWEB)

    Salvo, Nadia; Doble, Brett [Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario (Canada); Khan, Luluel [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Amirthevasar, Gayathri [Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario (Canada); Dennis, Kristopher [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Pasetka, Mark; DeAngelis, Carlo [Department of Oncology Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Tsao, May [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Chow, Edward, E-mail: [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)


    Purpose: To systematically review the effectiveness and safety of 5-hydroxytryptamine-3 receptor antagonists (5-HT3 RAs) compared with other antiemetic medication or placebo for prophylaxis of radiation-induced nausea and vomiting. Methods and Materials: We searched the following electronic databases: MEDLINE, Embase, the Cochrane Central Register of Controlled Clinical Trials, and Web of Science. We also hand-searched reference lists of included studies. Randomized, controlled trials that compared a 5-HT3 RA with another antiemetic medication or placebo for preventing radiation-induced nausea and vomiting were included. We excluded studies recruiting patients receiving concomitant chemotherapy. When appropriate, meta-analysis was conducted using Review Manager (v5) software. Relative risks were calculated using inverse variance as the statistical method under a random-effects model. We assessed the quality of evidence by outcome using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Eligibility screening of 47 articles resulted in 9 included in the review. The overall methodologic quality was moderate. Meta-analysis of 5-HT3 RAs vs. placebo showed significant benefit for 5-HT3 RAs (relative risk [RR] 0.70; 95% confidence interval [CI] 0.57-0.86 for emesis; RR 0.84, 95% CI 0.73-0.96 for nausea). Meta-analysis comparing 5-HT3 RAs vs. metoclopramide showed a significant benefit of the 5-HT3 RAs for emetic control (RR 0.27, 95% CI 0.15-0.47). Conclusion: 5-Hydroxytryptamine-3 RAs are superior to placebo and other antiemetics for prevention of emesis, but little benefit was identified for nausea prevention. 5-Hydroxytryptamine-3 RAs are suggested for prevention of emesis. Limited evidence was found regarding delayed emesis, adverse events, quality of life, or need for rescue medication. Future randomized, controlled trials should evaluate different 5-HT3 antiemetics and new agents with novel mechanisms of action such at the NK

  2. Comparison of the performance of different DFT methods in the calculations of the molecular structure and vibration spectra of serotonin (5-hydroxytryptamine, 5-HT) (United States)

    Yang, Yue; Gao, Hongwei


    Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter which plays an important role in treating acute or clinical stress. The comparative performance of different density functional theory (DFT) methods at various basis sets in predicting the molecular structure and vibration spectra of serotonin was reported. The calculation results of different methods including mPW1PW91, HCTH, SVWN, PBEPBE, B3PW91 and B3LYP with various basis sets including LANL2DZ, SDD, LANL2MB, 6-31G, 6-311++G and 6-311+G* were compared with the experimental data. It is remarkable that the SVWN/6-311++G and SVWN/6-311+G* levels afford the best quality to predict the structure of serotonin. The results also indicate that PBEPBE/LANL2DZ level show better performance in the vibration spectra prediction of serotonin than other DFT methods.

  3. Effect on the uptake kinetics of serotonin (5-hydroxytryptamine) in platelets from workers with long-term exposure to organic solvents. A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Beving, H.; Kristensson, J.; Malmgren, R.; Olsson, P.; Unge, G.


    Six workers from a paint industry were examined concerning the concentration of solvents in the breathing zone, the platelet count and kinetic uptake of serotonin (5-hydroxytryptamine (5-HT)), the serum concentration of calcium, potassium and sodium, and pH. The degree of exposure was found to be moderate. The results showed a decrease in platelet count in whole blood and platelet-rich plasma. The maximum uptake rate for serotonin in platelets (Vmax) was significantly increased compared to that of nonexposed subjects. No changes in the ionic concentration and pH of serum were observed. One worker was reexamined after a six-week period of nonexposure. Though the measured platelet variables were still aberrant, the values approached normal.

  4. Modulation of epithelial tissue and cell migration by microgrooves.

    NARCIS (Netherlands)

    Dalton, B.A.; Walboomers, X.F.; Dziegielewski, M.; Evans, M.D.; Taylor, S.; Jansen, J.A.; Steele, J.G.


    We used a polystyrene substratum to study the response of migrating epithelium to 1- or 5-microm depth microgrooves with groove/ridge widths of 1, 2, 5, or 10 microm. The migration of a tissue sheet was enhanced along the microgrooves, while migration across the microgrooves was inhibited. Changing

  5. mRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene-related peptide in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, Dipak V; Ploug, Kenneth B; Hay-Schmidt, Anders;


    Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT(1) receptor that mediate the antimigraine effect have still to be identified. This study investigated the mRNA expres......Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT(1) receptor that mediate the antimigraine effect have still to be identified. This study investigated the m...

  6. 5-Hydroxytryptamine1A receptor-activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation. (United States)

    Johnston, April; McBain, Chris J; Fisahn, André


    Rhythmic cortical neuronal oscillations in the gamma frequency band (30-80 Hz, gamma oscillations) have been associated with cognitive processes such as sensory perception and integration, attention, learning, and memory. Gamma oscillations are disrupted in disorders for which cognitive deficits are hallmark symptoms such as schizophrenia and Alzheimer's disease.In vitro, various neurotransmitters have been found to modulate gamma oscillations. Serotonin(5-HT) has long been known to be important for both behavioural and cognitive functions such as learning and memory. Multiple 5-HT receptor subtypes are expressed in the CA3 region of the hippocampus and high doses of 5-HT reduce the power of induced gamma oscillations.Hypothesizing that 5-HT may have cell- and receptor subtype-specific modulatory effects, we investigated the receptor subtypes, cell types and cellular mechanisms engaged by 5-HT in the modulation of gamma oscillations in mice and rats. We found that 5-HT decreases the power of kainate-induced hippocampal gamma oscillations in both species via the 5-HT1A receptor subtype. Whole-cell patch clamp recordings demonstrated that this decrease was caused by a hyperpolarization of CA3 pyramidal cells and a reduction of their firing frequency, but not by alteration of inhibitory neurotransmission. Finally, our results show that the effect on pyramidal cells is mediated via the G protein-coupled receptor inwardly rectifying potassium channel Kir3.Our findings suggest this novel cellular mechanism as a potential target for therapies that are aimed at alleviating cognitive decline by helping the brain to maintain or re-establish normal gamma oscillation levels in neuropsychiatric and neurodegenerative disorders.

  7. A phase 1 randomized study evaluating the effect of omeprazole on the pharmacokinetics of a novel 5-hydroxytryptamine receptor 4 agonist, revexepride (SSP-002358, in healthy adults

    Directory of Open Access Journals (Sweden)

    Pierce D


    Full Text Available David Pierce,1 Mary Corcoran,2 Maria Velinova,3 Stuart Hossack,4 Mieke Hoppenbrouwers,5 Patrick Martin,21Shire, Basingstoke, UK; 2Shire, Wayne, PA, USA; 3PRA International, Zuidlaren, the Netherlands; 4Covance, Leeds, UK; 5Shire-Movetis NV, Turnhout, BelgiumBackground: About 30% of patients with gastroesophageal reflux disease continue to experience symptoms despite treatment with proton pump inhibitors. The 5-hydroxytryptamine 4 receptor agonist revexepride (SSP-002358 is a novel prokinetic that stimulates gastrointestinal motility, which has been suggested as a continued cause of symptoms in these patients. The aim of this study was to assess whether revexepride pharmacokinetics were affected by co-administration of omeprazole, in preparation for a proof-of-concept evaluation of revexepride added to proton pump inhibitor treatment.Methods: In this phase 1, open-label, randomized, two-period crossover study, healthy adults aged 18–55 years were given a single dose of revexepride 1 mg or revexepride 1 mg + omeprazole 40 mg. Pharmacokinetic parameters were assessed for up to 48 hours after administration of the investigational product. Adverse events, clinical chemistry and hematology parameters, electrocardiograms, and vital signs were monitored.Results: In total, 42 participants were enrolled and 40 completed the study. The median age was 24 years (18–54 years, 55% were women and 93% were white. The pharmacokinetic parameters of revexepride were similar without or with omeprazole co-administration. The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞ was 23.3 ng · h/mL (standard deviation [SD]: 6.33 ng · h/mL versus 24.6 ng · h/mL (SD: 6.31 ng · h/mL, and maximum plasma concentrations (Cmax were 3.89 ng/mL (SD: 1.30 ng/mL and 4.12 ng/mL (SD: 1.29 ng/mL in participants without and with omeprazole, respectively. For AUC0–∞ and Cmax, the 90% confidence intervals for the ratios of geometric least

  8. Regulator of calcineurin 1 modulates cancer cell migration in vitro


    Espinosa, Allan V.; Shinohara, Motoo; Porchia,Leonardo M; Chung, Yun Jae; McCarty, Samantha; Saji, Motoyasu; Ringel, Matthew D.


    Metastasis suppressors and other regulators of cell motility play an important role in tumor invasion and metastases. We previously identified that activation of the G protein coupled receptor 54 (GPR54) by the metastasis suppressor metastin inhibits cell migration in association with overexpression of Regulator of calcineurin 1 (RCAN1), an endogenous regulator of calcineurin. Calcineurin inhibitors also blocked cell migration in vitro and RCAN1 protein levels were reduced in nodal metastases...

  9. Altered responsiveness to substance P and 5-hydroxytryptamine in cat dorsal horn neurons after 5-HT depletion with p-chlorophenylalanine. (United States)

    Jeftinija, S; Raspantini, C; Randić, M; Yaksh, T L; Go, V L; Larson, A A


    The responsiveness of functionally identified cat spinal dorsal horn neurons to iontophoretically applied substance P (SP) and 5-hydroxytryptamine (5-HT) has been investigated by means of extracellular recording after 5-HT depletion with p-chlorophenylalanine (p-CPA). In addition, the spinal levels of 5-HT, SP, cholecystokinin octapeptide, neurotensin, and vasoactive intestinal polypeptide have been measured in intact and p-CPA-pretreated cats. In the present study we have demonstrated an altered responsiveness of dorsal horn neurons to locally applied SP and 5-HT. We found in p-CPA-pretreated cats that the proportion of neurons responding with excitation to SP and 5-HT was significantly increased. At the same time, depression induced by 5-HT in the dorsal horn cells was virtually absent in p-CPA-pretreated animals. Our finding that spinal level of 5-HT was significantly decreased in p-CPA-treated animals is consistent with previous studies. No convincing alteration in the spinal levels of 4 analyzed peptides was found in p-CPA-treated animals. The present study has shown that pharmacological depletion of 5-HT has two major effects: (1) it increases significantly the proportion of dorsal horn neurons excited by SP and 5-HT; and (2) it is ineffective in inducing 5-HT supersensitivity. Further work is needed to explain mechanisms involved in these effects.

  10. 5-Hydroxytryptamine 6 receptor (5-HT(6)) receptor and apolipoprotein E (ApoE) polymorphisms in patients with Alzheimer's disease in the Basque Country. (United States)

    Alvarez-Alvarez, Maite; Galdos, Luis; Fernández-Martínez, Manuel; Gómez-Busto, Fernando; García-Centeno, Victoria; Arias-Arias, Caridad; Sánchez-Salazar, Carmen; Rodríguez-Martínez, Ana Belén; Zarranz, Juan José; de Pancorbo, Marian M


    Although there is considerable evidence implicating apolipoprotein E (ApoE) epsilon4 in the development of the Alzheimer's disease (AD), additional factors are also known to be involved. Thus, an association has been described between C267T polymorphism of the 5-hydroxytryptamine 6 receptor (5-HT(6)) receptor gene and AD. This case-control study analyzes the ApoE and 5-HT(6) receptor polymorphisms in 173 cases and 102 age and sex matched controls from Araba and Bizkaia (The Basque Country, Spain). The analysis of ApoE showed the frequencies of epsilon4 allele to be significantly higher in AD patients (0.292) than in the controls (0.083). When 5-HT(6) receptor polymorphism was analyzed, a greater frequency of 267C allele was observed in AD patients than in controls, though the difference was not statistically significant. Likewise regarding ApoE epsilon4 status, no statistically significant difference was observed. In conclusion, the association of ApoE epsilon4 to AD in a sample of patients from the Basque Country is confirmed, though the association to C267T polymorphism of the 5-HT(6) receptor has not been observed.


    Institute of Scientific and Technical Information of China (English)

    Cao Yongxiao(曹永孝); He Langchong(贺浪冲); Xu Cangbao(徐仓宝); EDVINSSON Lars


    Objective To compare the vasoconstrictive effects of 9 mediators on fresh and incubated mesenteric arteries of rats. Methods The superior mesenteric artery of rat was removed and the endothelium was denuded. The vessels were cut into 1 mm long cylindrical segments and subjected to organ culture for 24 hours. Fresh or incubated segments were immersed into tissue baths and the concentration-response curves were obtained by cumulative administration of the vasoconstrictors. Results In fresh mesenteric artery, endothelin-1 (ET-1), 5-hydroxytryptamine (5-HT), noradrenaline (NA), 5-carboxamidotryptamine (5-CT), and angiotensinⅡ (AngⅡ) induced potent and sustained constrictions in a concentration-dependent manner. The contraction induced by sarafotoxin 6c (S6c) was weak, while bradykinin (BK), des-Arg-bradykinin (DA-BK), and human urotensinⅡ (hUT-II) showed no detectable contraction. The concentraion-response curves in order of slopes was ET-1, NA, 5-HT, 5-CT, and AngⅡ. The order of the maximum contractions was ET-1>NA=5-HT=5-CT>AngⅡ>S6c. After organ culture, the concentration-response curves induced by S6c, NA, and 5-HT were significantly increased, while that induced by AngⅡ was decreased as comparing to fresh arteries. BK contracted the artery only weakly. Conclusion Organ culture changed the phenotypes towards an increased efficacy of NA, 5-HT, S6c, and a reduced efficacy of AngⅡ, which is in accordance with the results of pharmacological characterization in some human vascular disease.

  12. PRX-08066, a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats. (United States)

    Porvasnik, Stacy L; Germain, Sean; Embury, Jennifer; Gannon, Kimberley S; Jacques, Vincent; Murray, Justin; Byrne, Barry J; Shacham, Sharon; Al-Mousily, Faris


    Pulmonary arterial hypertension (PAH) is a life-threatening disease that results in right ventricular failure. 5-((4-(6-Chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile monofumarate (PRX-08066) is a selective 5-hydroxytryptamine receptor 2B (5-HT2BR) antagonist that causes selective vasodilation of pulmonary arteries. In the current study, the effects of PRX-08066 were assessed by using the monocrotaline (MCT)-induced PAH rat model. Male rats received 40 mg/kg MCT or phosphate-buffered saline and were treated orally twice a day with vehicle or 50 or 100 mg/kg PRX-08066 for 5 weeks. Pulmonary and cardiac functions were evaluated by hemodynamics, heart weight, magnetic resonance imaging (MRI), pulmonary artery (PA) morphology, and histology. Cardiac MRI demonstrated that PRX-08066 (100 mg/kg) significantly (P PRX-08066 significantly reduced peak PA pressure at 50 and 100 mg/kg (P PRX-08066 therapy also significantly reduced right ventricle (RV)/body weight and RV/left ventricle + septum (P PRX-08066 (P PRX-08066 significantly attenuated the elevation in PA pressure and RV hypertrophy and maintained cardiac function. Pulmonary vascular remodeling was also diminished compared with MCT control rats. PRX-08066 prevents the severity of PAH in the MCT rat model.

  13. Neurotensin is a Versatile Modulator of In Vitro Human Pancreatic Ductal Adenocarcinoma Cell (PDAC Migration

    Directory of Open Access Journals (Sweden)

    Tatjana Mijatovic


    Full Text Available Background: While the neurotensin (NT roles in pancreatic cancer growth are well documented, its effects on pancreatic cancer cell migration have not been described. Methods: The NT-induced effects on the migration process of human pancreatic ductal adenocarcinoma cells (PDACs were characterized by means of various assays including computer-assisted video-microscopy, fluorescence microscopy, ELISA-based, small GTPase pull-down and phosphorylation assays. Results: The NT-induced modifications on in vitro PDACs migration largely depended on the extra-cellular matrix environment and cell propensity to migrate collectively or individually. While NT significantly reduced the level of migration of collectively migrating PDACs on vitronectin, it significantly increased the level of individually migrating PDACs. These effects were mainly mediated through the sortilin/NTR3 receptor. Neurotensin both induced altered expression of αV and β5 integrin subunits in PDACs cultured on vitronectin resulting in modified adhesion abilities, and caused modifications to the organization of the actin cytoskeleton through the NT-mediated activation of small Rho GTPases. While the NT effects on individually migrating PDACs were mediated at least through the EGFR/ERK signaling pathways, those on collectively migrating PDACs appeared highly dependent on the PI 3-kinase pathway. Conclusion: This study strongly suggests the involvement of neurotensin in the modulation of human PDAC migration.

  14. Comparative studies of huperzine A,donepezil,and rivastigmine on brain acetylcholine,dopamine,norepinephrine,and 5-hydroxytryptamine levels in freely-moving rats

    Institute of Scientific and Technical Information of China (English)

    Yan-qi LIANG; Xi-can TANG


    Aim: To assess the effects of cholinesterase inhibitors huperzine A, donepezil and rivastigmine on cerebral neurotransmitters in the cortex and hippocampus in freely-moving rats. Methods: Double-probe cerebral microdialysis and HPLC with electrochemical detection were used to detect neurotransmitters. Results: Our results showed that huperzine A (0.25, 0.5, and 0.75 μmol/kg, po) dose-depen-dently elevated extracellular acetylcholine (Ach) levels in the medial prefrontal cortex (Mpfc) and hippocampus. Oral administration of donepezil (5.4 μmol/kg) or rivastigmine (1 μmol/kg) also elicited significant increases in Ach in the Mpfc and hippocampus. The time course of cortical acetylcholinesterase (AChE) inhibition with the 3 inhibitors mirrored the increases of Ach at the same dose. The marked elevation of Ach after oral administration of huperzine A (0.5 μmol/kg) and donepezil (5.4 μmol/kg) was associated with a significantly increased release of dopamine (DA) in the Mpfc or hippocampus. None of the 3 inhibitors affected norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels in the Mpfc and hippocampus. The effects of huperzine A and rivastigmine did not depend on the route of administration, but donepezil was less efficacious by the oral route than by ip injection. The ability of huperzine A to increase Ach levels was unchanged when tests were performed after multiple oral administration of the drug at 0.5 μmol/kg, once per day for 30 d. Conclusion: The present findings showed that, in molar terms, huperzine A had similar potency on increasing Mpfc Ach and DA levels as compared to the 11- and 2-fold dosages of donepezil and rivastigmine, respectively, and had longer lasting effects after oral dosing.

  15. 5-Hydroxytryptamine (serotonin)2A receptors in rat anterior cingulate cortex mediate the discriminative stimulus properties of d-lysergic acid diethylamide. (United States)

    Gresch, Paul J; Barrett, Robert J; Sanders-Bush, Elaine; Smith, Randy L


    d-Lysergic acid diethylamide (LSD), an indoleamine hallucinogen, produces profound alterations in mood, thought, and perception in humans. The brain site(s) that mediates the effects of LSD is currently unknown. In this study, we combine the drug discrimination paradigm with intracerebral microinjections to investigate the anatomical localization of the discriminative stimulus of LSD in rats. Based on our previous findings, we targeted the anterior cingulate cortex (ACC) to test its involvement in mediating the discriminative stimulus properties of LSD. Rats were trained to discriminate systemically administered LSD (0.085 mg/kg s.c.) from saline. Following acquisition of the discrimination, bilateral cannulae were implanted into the ACC (AP, +1.2 mm; ML, +/-1.0 mm; DV, -2.0 mm relative to bregma). Rats were tested for their ability to discriminate varying doses of locally infused LSD (0.1875, 0.375, and 0.75 microg/side) or artificial cerebrospinal fluid (n = 3-7). LSD locally infused into ACC dose-dependently substituted for systemically administered LSD, with 0.75 microg/side LSD substituting completely (89% correct). Systemic administration of the selective 5-hydroxytryptamine (serotonin) (5-HT)(2A) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907; 0.4 mg/kg) blocked the discriminative cue of LSD (0.375 microg/side) infused into ACC (from 68 to 16% drug lever responding). Furthermore, M100907 (0.5 microg/microl/side) locally infused into ACC completely blocked the stimulus effects of systemic LSD (0.04 mg/kg; from 80 to 12% on the LSD lever). Taken together, these data indicate that 5-HT(2A) receptors in the ACC are a primary target mediating the discriminative stimulus properties of LSD.

  16. The depolarizing action of 5-hydroxytryptamine on rabbit vagal primary afferent and sympathetic neurones and its selective blockade by MDL 72222. (United States)

    Azami, J; Fozard, J R; Round, A A; Wallis, D I


    MDL 72222 (1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5-dichlorobenzoate) is a novel compound with potent and selective blocking actions at certain excitatory 5-hydroxytryptamine (5-HT) receptors on mammalian peripheral neurones. In the present study, the sucrose-gap technique has been used to record depolarizing responses to 5-HT from the cells of the rabbit nodose and superior cervical ganglia and to investigate the potency and selectivity of MDL 72222 as an antagonist of these responses. On nodose ganglia, responses to 5-HT were inhibited surmountably by MDL 72222 at concentrations up to 100 nmol/l. The threshold for antagonism was 2-10 nmol/l and the apparent pA2 value (Schild 1947) was 7.7 +/- 0.2, n = 10. Blockade was selective since responses to GABA and noradrenaline were unaffected by MDL 72222, 100 nmol/l. With concentrations of MDL 72222 higher than 100 nmol/l, antagonism was concentration-related but not in a manner consistent with simple competitive antagonism and even a concentration of 1 mumol/l failed to abolish the response to 5-HT. The results from the superior cervical ganglion were essentially similar to those obtained from the nodose ganglion. The threshold concentration of MDL 72222 for inhibition of 5-HT was 1-10 nmol/l and blockade was selective in that depolarizing responses to dimethylphenyl-piperazinium (DMPP) was unaffected by a concentration of MDL 72222 of 1 mumol/l. The data provide direct evidence that MDL 72222 is a potent and selective antagonist of the receptors for 5-HT which mediate depolarizing responses in vagal primary afferent cell bodies and in sympathetic ganglion cells.

  17. The depolarizing action of 5-hydroxytryptamine on rabbit vagal afferent and sympathetic neurones in vitro and its selective blockade by ICS 205-930. (United States)

    Round, A; Wallis, D I


    Depolarizing responses to 5-hydroxytryptamine (5-HT) were recorded from rabbit nodose (NG) and superior cervical (SCG) ganglia using the sucrose-gap technique. The antagonist potency and selectivity of ICS 205-930 ([3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester) were investigated. In NG, 5-HT (5 to 80 nmol) evoked depolarizations of graded amplitude. The ED50 was 18.2 (10.9-30.5) nmol (geometric mean, 95% confidence limits). Responses were blocked surmountably by ICS 205-930, 10(-11) and 10(-10) M, the threshold for blockade being below 10(-11) M. Parallel, rightward shifts in dose-response curves were seen with these concentrations of antagonist, but at higher concentrations (10(-9) and 10(-8) M) there was a further rightward shift with reduction in slope and maximum of the curves. In SCG, where 5-HT (20 to 320 nmol) evoked depolarizations of graded amplitude and the ED50 was 55.8 (22.3-139.6) nmol (geometric mean, 95% confidence limits), ICS 205-930 had a similar inhibitory effect to that observed in NG. The apparent pA2 values for the surmountable blockade produced by ICS 205-930 at concentrations of 10(-11) and 10(-10) M were 10.2 +/- 0.2 for NG and 10.4 +/- 0.1 for SCG (means +/- s.e. mean). ICS 205-930 was selective in its action since it had no effect on dimethylphenylpiperazinium (DMPP) responses in either ganglion or on GABA responses in NG. This study provides quantitative evidence on the blocking action of ICS 205-930 at neuronal 5-HT receptors using a technique that allows the depolarizing responses evoked by the amine to be directly recorded.

  18. 5-Hydroxytryptamine-induced proliferation of pulmonary artery smooth muscle cells are extracellular signal-regulated kinase pathway depen-dent

    Institute of Scientific and Technical Information of China (English)

    Dan SONG; Huai-liang WANG; Shuang WANG; Xin-hua ZHANG


    Aim:To investigate the effect of 5-hydroxytryptamine transporter (5-HTT) inhibitor fluoxetine and antisense oligodeoxynucleotide (ODN) to extracelluar signal regulated kinases (ERKs) on pulmonary arterial smooth muscle cells (PASMCs) proliferation induced by 5-HT. Methods: Liposomal transfection was used to introduce ODNs to ERK1/2 into cultured rat PASMCs and the transfection effi ciency was measured by observing the uptake of the fluorecein isothiocynate (FITC)-labeled antisense ODN in PASMCs. The effects of 5-HTT selective inhibi tor fluoxetine and ODNs on the proliferation of PASMCs were evaluated by cell number counting and cell cycle analysis, and measured by microculture tetrazo lium (MTT) assay and flow cytometry (FCM), respectively. Results: Liposomes mediated the transfection of ODNs into PASMCs with high efficiency. MTT assay showed fluoxetine (10 μmol/L, 1 μmol/L, and 100 nmol/L) concentration dependently inhibited the proliferation of PASMCs induced by 5-HT (1 μmol/L) in vitro. The proliferation rate of PASMCs by 5-HT was significantly inhibited by pretreatment with ERK1/2 antisense ODN (0.2 μmol/L) from 251%± 18% to 86%±5% (P<0.01). Flow cytometric analysis of cell cycle distribution showed that the increase of 5-HT induced S phase fraction (SPF) and proliferation index (PI) were significantly inhibited by fluoxetine (1 μmol/L) or antisense ODN with SPF from 36%±4% to 26%±3% and 24%±4%, and PI from 34%±2% to 29%±2% and 24%±2%,respectively. Conclusion: 5-HTT mediates the mitogenic effect of 5-HT on PASMCs and the proliferation of PASMCs induced by 5-HT is dependent on ERKs signal pathway.

  19. Advances in 5-hydroxytryptamine and its receptors in insects%昆虫5-羟色胺及其受体的研究进展

    Institute of Scientific and Technical Information of China (English)

    齐易香; 吴顺凡; 黄佳; 叶恭银



  20. Selective recognition of 5-hydroxytryptamine and dopamine on a multi-walled carbon nanotube-chitosan hybrid film-modified microelectrode array. (United States)

    Xu, Huiren; Wang, Li; Luo, Jinping; Song, Yilin; Liu, Juntao; Zhang, Song; Cai, Xinxia


    It is difficult to determine dopamine (DA) and 5-hydroxytryptamine (5-HT) accurately because of the interference of ascorbic acid (AA) in vitro, which has a high concentration and can be oxidized at a potential close to DA and 5-HT at a conventional electrode, combined with the overlapping voltammetric signal of DA and 5-HT at a bare electrode. Herein, chitosan (CS) was used as a stabilizing matrix by electrochemical reaction, and multi-walled carbon nanotubes (MWCNTs) were modified onto the microelectrode array (MEA). The CS-MWCNT hybrid film-modified MEA was quite effective at simultaneously recognizing these species in a mixture and resolved the overlapping anodic peaks of AA, DA and 5-HT into three well-defined oxidation peaks in differential pulse voltammetry (DPV) at -80 mV, 105 mV and 300 mV (versus Ag|AgCl), respectively. The linear responses were obtained in the range of 5 × 10(-6) M to 2 × 10(-4) M for DA (r = 0.996) and in the range of 1 × 10(-5) M to 3 × 10(-4) M for 5-HT (r = 0.999) using the DPV under the presence of a single substance. While DA coexisted with 5-HT in the interference of 3 × 10(-4) M AA, the linear responses were obtained in the range of 1 × 10(-5) M to 3 × 10(-4) M for selective molecular recognition of DA (r = 0.997) and 5-HT (r = 0.997) using the DPV. Therefore, this proposed MEA was successfully used for selective molecular recognition and determination of DA and 5-HT using the DPV, which has a potential application for real-time determination in vitro experiments.

  1. Selective Recognition of 5-Hydroxytryptamine and Dopamine on a Multi-Walled Carbon Nanotube-Chitosan Hybrid Film-Modified Microelectrode Array

    Directory of Open Access Journals (Sweden)

    Huiren Xu


    Full Text Available It is difficult to determine dopamine (DA and 5-hydroxytryptamine (5-HT accurately because of the interference of ascorbic acid (AA in vitro, which has a high concentration and can be oxidized at a potential close to DA and 5-HT at a conventional electrode, combined with the overlapping voltammetric signal of DA and 5-HT at a bare electrode. Herein, chitosan (CS was used as a stabilizing matrix by electrochemical reaction, and multi-walled carbon nanotubes (MWCNTs were modified onto the microelectrode array (MEA. The CS-MWCNT hybrid film-modified MEA was quite effective at simultaneously recognizing these species in a mixture and resolved the overlapping anodic peaks of AA, DA and 5-HT into three well-defined oxidation peaks in differential pulse voltammetry (DPV at −80 mV, 105 mV and 300 mV (versus Ag|AgCl, respectively. The linear responses were obtained in the range of 5 × 10−6 M to 2 × 10−4 M for DA (r = 0.996 and in the range of 1 × 10−5 M to 3 × 10−4 M for 5-HT (r = 0.999 using the DPV under the presence of a single substance. While DA coexisted with 5-HT in the interference of 3 × 10−4 M AA, the linear responses were obtained in the range of 1 × 10−5 M to 3 × 10−4 M for selective molecular recognition of DA (r = 0.997 and 5-HT (r = 0.997 using the DPV. Therefore, this proposed MEA was successfully used for selective molecular recognition and determination of DA and 5-HT using the DPV, which has a potential application for real-time determination in vitro experiments.

  2. Association between variants of 5-hydroxytryptamine receptor 3C (HTR3C) and chemotherapy-induced symptoms in women receiving adjuvant treatment for breast cancer. (United States)

    Pud, Dorit; Har-Zahav, Gil; Laitman, Yael; Rubinek, Tami; Yeheskel, Adva; Ben-Ami, Sarah; Kaufman, Bella; Friedman, Eitan; Symon, Zvi; Wolf, Ido


    Administration of chemotherapy is associated with a wide array of symptoms affecting quality of life. Genetic risk factors for severity of chemotherapy-induced symptoms have not been determined. The present study aimed to explore the associations between polymorphisms in candidate genes and chemotherapy-induced symptoms. Women treated with at least two cycles of adjuvant doxorubicin and cyclophosphamide, with or without paclitaxel for early breast cancer (n = 105) completed the memorial symptom assessment scale and provided blood for genotyping. DNA was extracted from peripheral blood leukocytes and assayed for single nucleotide polymorphisms (SNPs) in GTP cyclohydrolase 1 (GCH1, rs10483639, rs3783641, and rs8007267), catecholamine-o-methyltransferase (COMT, rs4818), and 5-hydroxytryptamine (serotonin) receptor 3C (HTR3C, rs6766410, and rs6807362). Genotyping of HTR3C revealed a significant association between the presence of rs6766410 and rs6807362 SNPs (K163 and G405 variants) and increased severity of symptoms (p = 0.0001 and p = 0.007, respectively). Multiple regressions revealed that rs6766410 and rs6807362, but not age or stage at diagnosis, predicted severity of symptoms (p = 0.001 and p = 0.006, respectively) and explained 12 % of the variance in each regression model. No association was found between the genetic variants of CGH1 or COMT and symptom score. Our study indicates, for the first time, an association between variants of HTR3C and severity of chemotherapy-induced symptoms. Analyzing these genetic variants may identify patients at increased risk for the development of chemotherapy-induced symptoms and targeting the serotonin pathway may serve as a novel treatment strategy for these patients.

  3. Translational evaluation of JNJ-18038683, a 5-hydroxytryptamine type 7 receptor antagonist, on rapid eye movement sleep and in major depressive disorder. (United States)

    Bonaventure, Pascal; Dugovic, Christine; Kramer, Michelle; De Boer, Peter; Singh, Jaskaran; Wilson, Sue; Bertelsen, Kirk; Di, Jianing; Shelton, Jonathan; Aluisio, Leah; Dvorak, Lisa; Fraser, Ian; Lord, Brian; Nepomuceno, Diane; Ahnaou, Abdellah; Drinkenburg, Wilhelmus; Chai, Wenying; Dvorak, Curt; Sands, Steve; Carruthers, Nicholas; Lovenberg, Timothy W


    In rodents 5-hydroxytryptamine type 7 (5-HT(7)) receptor blockade has been shown to be effective in models of depression and to increase the latency to rapid eye movement (REM) sleep and decrease REM duration. In the clinic, the REM sleep reduction observed with many antidepressants may serve as a biomarker. We report here the preclinical and clinical evaluation of a 5-HT(7) receptor antagonist, (3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydro-1-(phenylmethyl)pyrazolo[3,4-d]azepine 2-hydroxy-1,2,3-propanetricarboxylate) (JNJ-18038683). In rodents, JNJ-18038683 increased the latency to REM sleep and decreased REM duration, and this effect was maintained after repeated administration for 7 days. The compound was effective in the mouse tail suspension test. JNJ-18038683 enhanced serotonin transmission, antidepressant-like behavior, and REM sleep suppression induced by citalopram in rodents. In healthy human volunteers JNJ-18038683 prolonged REM latency and reduced REM sleep duration, demonstrating that the effect of 5-HT(7) blockade on REM sleep translated from rodents to humans. Like in rats, JNJ-18038683 enhanced REM sleep suppression induced by citalopram in humans, although a drug-drug interaction could not be ruled out. In a double-blind, active, and placebo-controlled clinical trial in 225 patients suffering from major depressive disorder, neither treatment with pharmacologically active doses of JNJ-18038683 or escitalopram separated from placebo, indicating a failed study lacking assay sensitivity. Post hoc analyses using an enrichment window strategy, where all the efficacy data from sites with an implausible high placebo response [placebo group Montgomery-Åsberg Depression Rating Scale (MADRS) = 28) are removed, there was a clinically meaningful difference between JNJ-18038683 and placebo. Further clinical studies are required to characterize the potential antidepressant efficacy of JNJ-18038683.

  4. The 5-hydroxytryptamine4 receptor agonists prucalopride and PRX-03140 increase acetylcholine and histamine levels in the rat prefrontal cortex and the power of stimulated hippocampal θ oscillations. (United States)

    Johnson, David E; Drummond, Elena; Grimwood, Sarah; Sawant-Basak, Aarti; Miller, Emily; Tseng, Elaine; McDowell, Laura L; Vanase-Frawley, Michelle A; Fisher, Katherine E; Rubitski, David M; Stutzman-Engwall, Kim J; Nelson, Robin T; Horner, Weldon E; Gorczyca, Roxanne R; Hajos, Mihaly; Siok, Chester J


    5-Hydroxytryptamine (5-HT)(4) receptor agonists reportedly stimulate brain acetylcholine (ACh) release, a property that might provide a new pharmacological approach for treating cognitive deficits associated with Alzheimer's disease. The purpose of this study was to compare the binding affinities, functional activities, and effects on neuropharmacological responses associated with cognition of two highly selective 5-HT(4) receptor agonists, prucalopride and 6,7-dihydro-4-hydroxy-7-isopropyl-6-oxo-N-[3-(piperidin-1-yl)propyl]thieno[2,3-b]pyridine-5-carboxamide (PRX-03140). In vitro, prucalopride and PRX-03140 bound to native rat brain 5-HT(4) receptors with K(i) values of 30 nM and 110 nM, respectively, and increased cAMP production in human embryonic kidney-293 cells expressing recombinant rat 5-HT(4) receptors. In vivo receptor occupancy studies established that prucalopride and PRX-03140 were able to penetrate the brain and bound to 5-HT(4) receptors in rat brain, achieving 50% receptor occupancy at free brain exposures of 330 nM and 130 nM, respectively. Rat microdialysis studies revealed that prucalopride maximally increased ACh and histamine levels in the prefrontal cortex at 5 and 10 mg/kg, whereas PRX-03140 significantly increased cortical histamine levels at 50 mg/kg, failing to affect ACh release at doses lower than 150 mg/kg. In combination studies, donepezil-induced increases in cortical ACh levels were potentiated by prucalopride and PRX-03140. Electrophysiological studies in rats demonstrated that both compounds increased the power of brainstem-stimulated hippocampal θ oscillations at 5.6 mg/kg. These findings show for the first time that the 5-HT(4) receptor agonists prucalopride and PRX-03140 can increase cortical ACh and histamine levels, augment donepezil-induced ACh increases, and increase stimulated-hippocampal θ power, all neuropharmacological parameters consistent with potential positive effects on cognitive processes.

  5. NHERF-1: Modulator of Glioblastoma Cell Migration and Invasion

    Directory of Open Access Journals (Sweden)

    Kerri L. Kislin


    Full Text Available The invasive nature of malignant gliomas is a clinical problem rendering tumors incurable by conventional treatment modalities such as surgery, ionizing radiation, and temozolomide. Na+/H+ exchanger regulatory factor 1 (NHERF-1 is a multifunctional adaptor protein, recruiting cytoplasmic signaling proteins and membrane receptors/transporters into functional complexes. This study revealed that NHERF-1 expression is increased in highly invasive cells that reside in the rim of glioblastoma multiforme (GBM tumors and that NHERF-1 sustains glioma migration and invasion. Gene expression profiles were evaluated from laser capture-microdissected human GBM cells isolated from patient tumor cores and corresponding invaded white matter regions. The role of NHERF-1 in the migration and dispersion of GBM cell lines was examined by reducing its expression with small-interfering RNA followed by radial migration, three-dimensional collagen dispersion, immunofluorescence, and survival assays. The in situ expression of NHERF-1 protein was restricted to glioma cells and the vascular endothelium, with minimal to no detection in adjacent normal brain tissue. Depletion of NHERF-1 arrested migration and dispersion of glioma cell lines and caused an increase in cell-cell cohesiveness. Glioblastoma multiforme cells with depleted NHERF-1 evidenced a marked decrease in stress fibers, a larger cell size, and a more rounded shape with fewer cellular processes. When NHERF-1 expression was reduced, glioma cells became sensitized to temozolomide treatment resulting in increased apoptosis. Taken together, these results provide the first evidence for NHERF-1 as a participant in the highly invasive phenotype of malignant gliomas and implicate NHERF-1 as a possible therapeutic target for treatment of GBM.

  6. Inhibitory action of niflumic acid on noradrenaline- and 5-hydroxytryptamine-induced pressor responses in the isolated mesenteric vascular bed of the rat. (United States)

    Criddle, D N; de Moura, R S; Greenwood, I A; Large, W A


    1. The effects of niflumic acid, an inhibitor of calcium-activated chloride currents, were compared with the actions of the calcium channel blocker nifedipine on noradrenaline- and 5-hydroxytryptamine (5-HT)-induced pressor responses of the rat perfused isolated mesenteric vascular bed. 2. Bolus injections of noradrenaline (1 and 10 nmol) increased the perfusion pressure in a dose-dependent manner. Nifedipine (1 microM) inhibited the increase in pressure produced by 1 nmol noradrenaline by 31 +/- 5%. Niflumic acid (10 and 30 microM) also inhibited the noradrenaline-induced increase in perfusion pressure and 30 microM niflumic acid reduced the pressor response to 1 nmol noradrenaline by 34 +/- 6%. 3. The increases in perfusion elicited by 5-HT (0.3 and 3 nmol) were reduced by niflumic acid (10 and 30 microM) in a concentration-dependent manner and 30 microM niflumic acid inhibited responses to 0.3 and 3 nmol 5-HT by, respectively, 49 +/- 8% and 50 +/- 7%. Nifedipine (1 microM) decreased the pressor response to 3 nmol 5-HT by 44 +/- 9%. 4. In the presence of a combination of 30 microM niflumic acid and 1 microM nifedipine the inhibition of the pressor effects of noradrenaline (10 nmol) and 5-HT (3 nmol) was not significantly greater than with niflumic acid (30 microM) alone. Thus the effects of niflumic acid and nifedipine were not additive. 5. In Ca-free conditions the transient contractions induced by 5-HT (3 nmol) were not reduced by 30 microM niflumic acid, suggesting that this agent does not inhibit calcium release from the intracellular store or the binding of 5-HT to its receptor. 6. Niflumic acid 30 microM did not inhibit the pressor responses induced by KCl (20 and 60 mumol) which were markedly reduced by 1 microM nifedipine. In addition, 1 microM levcromakalim decreased pressor responses produced by 20 mumol KCl. These data suggest that niflumic acid does not block directly calcium channels or activate potassium channels. 7. It is concluded that niflumic

  7. 5-Hydroxytryptamine(1F) receptors do not participate in vasoconstriction: lack of vasoconstriction to LY344864, a selective serotonin(1F) receptor agonist in rabbit saphenous vein. (United States)

    Cohen, M L; Schenck, K


    Recently, several novel approaches to the treatment of migraine have been advanced, including selective 5-hydroxytryptamine (or serotonin) 1B/1D (5-HT(1B/1D)) receptor agonists such as sumatriptan and 5-HT(1F) receptor agonists such as LY344864. Many 5-HT(1B/1D) receptor agonists have been identified based on their ability to produce cerebral vascular contraction, whereas LY344864 was identified as an inhibitor of trigeminal nerve-mediated dural extravasation. In our study, several triptan derivatives were compared with LY344864 for their ability to contract the rabbit saphenous vein, a tissue used in the preclinical identification of sumatriptan-related agonists. Sumatriptan, zolmitriptan, rizatriptan, and naratriptan all contracted the rabbit saphenous vein from baseline tone, whereas LY344864 in concentrations up to 10(-4) M did not contract the rabbit saphenous vein. Furthermore, vascular contractions to sumatriptan were markedly augmented in the presence of prostaglandin F(2alpha) (PGF(2alpha)). However, even in the presence of PGF(2alpha) (3 x 10(-7) M), LY344864 did not contract the rabbit saphenous vein in concentrations well in excess of its 5-HT(1F) receptor affinity (pK(i) = 8.2). Only when concentrations exceeded those likely to activate 5-HT(1B) and 5-HT(1D) receptors (>10(-5) M) did modest contractile responses occur in the presence of PGF(2alpha). Use of these serotonergic agonists revealed a significant correlation between the contractile potency in the rabbit saphenous vein and the affinities of these agonists at 5-HT(1B) and 5-HT(1D) receptors, although contractile agonist potencies were not quantitatively similar to 5-HT(1B) or 5-HT(1D) receptor affinities. In contrast, no significant correlation existed between the contractile potencies of these serotonergic agonists in the rabbit saphenous vein and their affinity at 5-HT(1F) receptors. These data support the contention that activation of 5-HT(1F) receptors will not result in vascular

  8. A meta-analysis of the effects of the 5-hydroxytryptamine transporter gene-linked promoter region polymorphism on susceptibility to lifelong premature ejaculation.

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    Lijie Zhu

    Full Text Available OBJECTIVE: Premature ejaculation (PE has been reported as the most common male sexual dysfunction with global prevalence rates estimated at approximately 30%. The neurobiogenesis of ejaculation is very complex and involves the serotoninergic (5-hydroxytryptamine, 5-HT system. Recently, genetic polymorphisms located on SLC6A4 gene codifying for 5-HT transporter (5-HTT, the major regulator of serotonic neurotransmission, have been linked with the pathogenesis and risk of PE. Apparently studies of this type of polymorphism in PE have show conflicting results. METHODS: A meta-analysis was performed that are available in relation with 5-HTT gene-linked promoter region (5-HTTLPR polymorphism and the risk of lifelong PE (LPE in men to clarify this relationship. We searched Pubmed and Embase (last search updated on Aug 2012 using 'premature ejaculation', 'polymorphism or variant', 'genotype', 'ejaculatory function', and 'rapid ejaculation' as keywords and reference lists of studies corresponded to the inclusion criteria for meta-analysis. These studies involved the total number of 481 LPE men and 466 health control men subjects. Odds ratio (OR and 95% confidence intervals (CIs were used to evaluate this relationship. RESULTS: In the overall analysis, significant associations between LPE risk and 5-HTTLPR polymorphism were found (L-allele vs. S-allele OR = 0.86, 95% CI = 0.79-0.95, P = 0.002; LL vs. SS: OR = 0.80, 95% CI = 0.68-0.95, P = 0.009; LS vs. SS: OR = 0.85, 95% CI = 0.76-0.97, P = 0.012 and LL+LS vs. SS: OR = 0.88, 95% CI = 0.81-0.95, P = 0.002. Moreover, in subgroup analysis based on ethnicity, similar significant associations were detected. The Egger's test did not reveal presence of a publication bias. CONCLUSIONS: Our investigations demonstrate that 5-HTTLPR (L>S polymorphism might protect men against LPE risk. Further studies based on larger sample size and gene-environment interactions should

  9. Diabetes-induced changes in the 5-hydroxytryptamine inhibitory receptors involved in the pressor effect elicited by sympathetic stimulation in the pithed rat. (United States)

    García, Mónica; Morán, Asunción; Calama, Elena; Martín, Maria Luisa; Barthelmebs, Mariette; Román, Luis San


    1. We investigated the effect of alloxan-induced diabetes on the inhibitory mechanisms of 5-hydroxytryptamine (5-HT) in the pressor responses induced by stimulation of sympathetic vasopressor outflow in pithed rats, and analysed the type and/or subtype of 5-HT receptors involved. 2. Diabetes was induced in male Wistar rats by a single s.c. injection of alloxan, then 4 weeks later, they were anaesthetized, pretreated with atropine and pithed. Electrical stimulation of the sympathetic outflow from the spinal cord (0.1, 0.5, 1 and 5 Hz) resulted in frequency-dependent increases in blood pressure. 3. Intravenous infusions of 5-HT (1-80 microg kg(-1) min(-1)) reduced the pressor effects obtained by electrical stimulation. The 5-HT(1) receptor agonist 5-carboxamidotryptamine, 5-CT (5 microg kg(-1) min(-1)), caused an inhibition of the pressor response, whereas the selective 5-HT(2) receptor agonist, alpha-methyl-5-HT (5 microg kg(-1) min(-1)) and the selective 5-HT(3) receptor agonist, 1-phenylbiguanide (40 microg kg(-1) min(-1)), did not modify the sympathetic pressor responses. 5-HT had no effect on exogenous noradrenaline (NA)-induced pressor responses. 4. The inhibition of electrically induced pressor responses by 5-HT (10 microg kg(-1) min(-1)) was unable to be elicited after i.v. treatment with methiothepin (100 microg kg(-1)) because of the marked inhibition produced by methiothepin alone. The 5-HT-induced inhibition was blocked after i.v. administration of WAY-100,635 (100 microg kg(-1)) and not affected by ritanserin (1 mg kg(-1)), MDL 72222 (2 mg kg(-1)). 5. The selective 5-HT(1A) receptor agonist, 8-hydroxydipropylaminotretalin hydrobromide (8-OH-DPAT) (5-20 microg kg(-1) min(-1)) but neither the rodent 5-HT(1B) receptor agonist, CGS-12066B (5 microg kg(-1) min(-1)), nor the selective nonrodent 5-HT(1B) and 5-HT(1D) receptor agonist, L-694,247 (5 and 40 microg kg(-1) min(-1)), inhibited the electrically induced pressor response. The selective 5-HT(1A) receptor

  10. Migration

    NARCIS (Netherlands)

    Gienapp, P.; Candolin, Ulrika; Wong, Bob


    This chapter examines how human-induced environmental changes affect migration. It explores how such changes affect conditions along the migration route, as well as the cues that are used in the timing of migration such as the celestial bodies and the planet's magnetic field. It emphasizes the effec

  11. Screening and target identification of bioactive compounds that modulate cell migration and autophagy. (United States)

    Tashiro, Etsu; Imoto, Masaya


    Cell migration is a fundamental step for embryonic development, wound repair, immune responses, and tumor cell invasion and metastasis. It is well known that protrusive structures, namely filopodia and lamellipodia, can be observed at the leading edge of migrating cells. The formation of these structures is necessary for cell migration; however, the molecular mechanisms behind the formation of these structures remain largely unclear. Therefore, bioactive compounds that modulate protrusive structures are extremely powerful tools for studying the mechanisms behind the formation of these structures and subsequent cell migration. Therefore, we have screened for bioactive compounds that inhibit the formation of filopodia, lamellipodia, or cell migration from natural products, and attempted to identify the target molecules of our isolated compounds. Additionally, autophagy is a bulk, non-specific protein degradation system that is involved in the pathogenesis of cancer and neurodegenerative disorders. Recent extensive studies have revealed the molecular mechanisms of autophagy, however, they also remain largely unclear. Thus, we also have screened for bioactive compounds that modulate autophagy, and identified the target molecules. In the present article, we introduce the phenotypic screening system and target identification of four bioactive compounds.

  12. The highly selective 5-hydroxytryptamine (5-HT)2A receptor antagonist, EMD 281014, significantly increases swimming and decreases immobility in male congenital learned helpless rats in the forced swim test. (United States)

    Patel, Jignesh G; Bartoszyk, Gerd D; Edwards, Emmeline; Ashby, Charles R


    We examined the effect of the highly selective 5-hydroxytryptamine (5-HT)(2A) receptor antagonist 7-[4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl]-1H-indole-3-carbonitrile HCl (EMD 281014) in congenital learned helpless male rats in the forced swim test. The administration of EMD-281014 (0.3-30 mg/kg i.p.) to congenital learned helpless rats dose-dependently and significantly (at 10 and 30 mg/kg) decreased immobility and increased swimming compared to vehicle-treated animals. Thus, EMD 281014 produces effects in the forced swim test resembling those of antidepressants.

  13. Improvement in neurological outcome and abolition of cerebrovascular endothelin B and 5-hydroxytryptamine 1B receptor upregulation through mitogen-activated protein kinase kinase 1/2 inhibition after subarachnoid hemorrhage in rats

    DEFF Research Database (Denmark)

    Larsen, Carl Christian; Povlsen, Gro Klitgaard; Rasmussen, Marianne Nelly Paola;


    )) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors has been demonstrated in cerebral artery smooth muscles in the delayed ischemic phase after experimental SAH, and intracellular signaling via the mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase 1/2 pathway has been shown......Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) remains a major cause of death and disability. It has been hypothesized that cerebrovascular upregulation of vasoconstrictor receptors is a key step in the development of delayed cerebral ischemia. Upregulation of endothelin-B (ET(B...

  14. Enhanced particle filtration in straight microchannels using shear-modulated inertial migration (United States)

    Bhagat, Ali Asgar S.; Kuntaegowdanahalli, Sathyakumar S.; Papautsky, Ian


    In this work, we introduce a novel method for enhanced particle filtration using shear-modulated inertial migration in straight microchannels. Depending on their size, inertial lift causes particles to migrate toward microchannel walls. Using microchannels with high aspect ratio cross sections, the fluidic shear can be modulated, resulting in preferential equilibration of particles along the longer microchannel walls. Due to large lift forces generated in these high aspect ratio channels, complete particle filtration can be achieved in short distances even at low flow rates (Re<50). Based on this principle, we use a straight microfluidic channel with a rectangular cross section to passively and continuously filter 1.9 μm polystyrene particles. Overall, the proposed technique is versatile and can be easily integrated with on-chip microfluidic systems for filtration of a wide range of particle sizes, from micro- to nanoparticles.

  15. Kaempferol inhibits vascular smooth muscle cell migration by modulating BMP-mediated miR-21 expression. (United States)

    Kim, Kwangho; Kim, Sunghwan; Moh, Sang Hyun; Kang, Hara


    Bioflavonoids are known to induce cardioprotective effects by inhibiting vascular smooth muscle cell (VSMC) proliferation and migration. Kaempferol has been shown to inhibit VSMC proliferation. However, little is known about the effect of kaempferol on VSMC migration and the underlying molecular mechanisms. Our studies provide the first evidence that kaempferol inhibits VSMC migration by modulating the BMP4 signaling pathway and microRNA expression levels. Kaempferol activates the BMP signaling pathway, induces miR-21 expression and downregulates DOCK4, 5, and 7, leading to inhibition of cell migration. Moreover, kaempferol antagonizes the PDGF-mediated pro-migratory effect. Therefore, our study uncovers a novel regulatory mechanism of VSMC migration by kaempferol and suggests that miRNA modulation by kaempferol is a potential therapy for cardiovascular diseases.

  16. Evidence for a model of agonist-induced activation of 5-hydroxytryptamine 2A serotonin receptors that involves the disruption of a strong ionic interaction between helices 3 and 6. (United States)

    Shapiro, David A; Kristiansen, Kurt; Weiner, David M; Kroeze, Wesley K; Roth, Bryan L


    5-Hydroxytryptamine 2A (5-HT2A) receptors are essential for the actions of serotonin (5-hydroxytryptamine (5-HT)) on physiological processes as diverse as vascular smooth muscle contraction, platelet aggregation, perception, and emotion. In this study, we investigated the molecular mechanism(s) by which 5-HT activates 5-HT2A receptors using a combination of approaches including site-directed mutagenesis, molecular modeling, and pharmacological analysis using the sensitive, cell-based functional assay R-SAT. Alanine-scanning mutagenesis of residues close to the intracellular end of H6 of the 5-HT2A receptor implicated glutamate Glu-318(6.30) in receptor activation, as also predicted by a newly constructed molecular model of the 5-HT2A receptor, which was based on the x-ray structure of bovine rhodopsin. Close examination of the molecular model suggested that Glu-318(6.30) could form a strong ionic interaction with Arg-173(3.50) of the highly conserved "(D/E)RY motif" located at the interface between the third transmembrane segment and the second intracellular loop (i2). A direct prediction of this hypothesis, that disrupting this ionic interaction by an E318(6.30)R mutation would lead to a highly constitutively active receptor with enhanced affinity for agonist, was confirmed using R-SAT. Taken together, these results predict that the disruption of a strong ionic interaction between transmembrane helices 3 and 6 of 5-HT2A receptors is essential for agonist-induced receptor activation and, as recently predicted by ourselves (B. L. Roth and D. A. Shapiro (2001) Expert Opin. Ther. Targets 5, 685-695) and others, that this may represent a general mechanism of activation for many, but not all, G-protein-coupled receptors.

  17. LIM and SH3 protein-1 modulates CXCR2-mediated cell migration.

    Directory of Open Access Journals (Sweden)

    Dayanidhi Raman

    Full Text Available BACKGROUND: The chemokine receptor CXCR2 plays a pivotal role in migration of neutrophils, macrophages and endothelial cells, modulating several biological responses such as angiogenesis, wound healing and acute inflammation. CXCR2 is also involved in pathogenesis of chronic inflammation, sepsis and atherosclerosis. The ability of CXCR2 to associate with a variety of proteins dynamically is responsible for its effects on directed cell migration or chemotaxis. The dynamic network of such CXCR2 binding proteins is termed as "CXCR2 chemosynapse". Proteomic analysis of proteins that co-immunoprecipitated with CXCR2 in neutrophil-like dHL-60 cells revealed a novel protein, LIM and SH3 protein 1 (LASP-1, binds CXCR2 under both basal and ligand activated conditions. LASP-1 is an actin binding cytoskeletal protein, involved in the cell migration. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that CXCR2 and LASP-1 co-immunoprecipitate and co-localize at the leading edge of migrating cells. The LIM domain of LASP-1 directly binds to the carboxy-terminal domain (CTD of CXCR2. Moreover, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and CXCR4. Using a site-directed and deletion mutagenesis approach, Iso323-Leu324 of the conserved LKIL motif on CXCR2-CTD was identified as the binding site for LASP-1. Interruption of the interaction between CXCR2-CTD and LIM domain of LASP-1 by dominant negative and knock down approaches inhibited CXCR2-mediated chemotaxis. Analysis for the mechanism for inhibition of CXCR2-mediated chemotaxis indicated that LASP-1/CXCR2 interaction is essential for cell motility and focal adhesion turnover involving activation of Src, paxillin, PAK1, p130CAS and ERK1/2. CONCLUSIONS/SIGNIFICANCE: We demonstrate here for the first time that LASP-1 is a key component of the "CXCR2 chemosynapse" and LASP-1 interaction with CXCR2 is critical for CXCR2-mediated chemotaxis. Furthermore, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and

  18. Curcumin is a potent modulator of microglial gene expression and migration

    Directory of Open Access Journals (Sweden)

    Aslanidis Alexander


    Signal transducer and activator of transcription 1 was reduced in LPS-triggered microglia. These transcriptional changes in curcumin-treated LPS-primed microglia also lead to decreased neurotoxicity with reduced apoptosis of 661W photoreceptor cultures. Conclusions Collectively, our results suggest that curcumin is a potent modulator of the microglial transcriptome. Curcumin attenuates microglial migration and triggers a phenotype with anti-inflammatory and neuroprotective properties. Thus, curcumin could be a nutraceutical compound to develop immuno-modulatory and neuroprotective therapies for the treatment of various neurodegenerative disorders.

  19. Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Jahn, Franziska, E-mail: [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Riesner, Anica [Department of Gastroenterology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jahn, Patrick [Nursing Research Unit, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Sieker, Frank; Vordermark, Dirk [Department of Radiation Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jordan, Karin [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany)


    Purpose: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy–induced nausea and vomiting. Patients and Methods: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period. Results: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). Conclusion: This is the first study of an NK1-RA–containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

  20. Adding 5-hydroxytryptamine receptor type 3 antagonists may reduce drug-induced nausea in poor insight obsessive-compulsive patients taking off-label doses of selective serotonin reuptake inhibitors: a 52-week follow-up case report

    Directory of Open Access Journals (Sweden)

    Martino Matteo


    Full Text Available Abstract Poor-insight obsessive-compulsive disorder (PI-OCD is a severe form of OCD where the 'typically obsessive' features of intrusive, 'egodystonic' feelings and thoughts are absent. PI-OCD is difficult to treat, often requiring very high doses of serotonergic drugs as well as antipsychotic augmentation. When this occurs, unpleasant side effects as nausea are common, eventually further reducing compliance to medication and increasing the need for pharmacological alternatives. We present the case of a PI-OCD patient who developed severe nausea after response to off-label doses of the selective serotonin reuptake inhibitor (SSRI, fluoxetine. Drug choices are discussed, providing pharmacodynamic rationales and hypotheses along with reports of rating scale scores, administered within a follow-up period of 52 weeks. A slight reduction of fluoxetine dose, augmentation with mirtazapine and a switch from amisulpride to olanzapine led to resolution of nausea while preserving the anti-OCD therapeutic effect. Mirtazapine and olanzapine have already been suggested for OCD treatment, although a lack of evidence exists about their role in the course of PI-OCD. Both mirtazapine and olanzapine also act as 5-hydroxytryptamine receptor type 3 (5-HT3 blockers, making them preferred choices especially in cases of drug-induced nausea.

  1. Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice. (United States)

    Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul


    Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords.NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a

  2. Effect of basic fibroblast growth factor on the proliferation, migration and phenotypic modulation of airway smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    ZOU Hui; NIE Xiu-hong; ZHANG Yi; HU Mu; ZHANG Yu Alex


    Background Proliferation,cell migration and phenotypic modulation of airway smooth muscle cells(ASMCs)are important features of airway remodelling in asthma.The precise cellular and molecular mechanisms that regulate ASMCs proliferation,migration and phenotypic modulation in the lung remain unknown.Basic fibroblast growth factor(bFGF),a highly specific chemotactic and mitogenic factor for many cell types,appears to be involved in the development of airway remodelling.Our study assessed whether bFGF directly stimulates the proliferation,migration and phenotypic modulation of ASMCs.Methods Confluent and growth arrested human ASMCs were treated with human recombinant FGF.Proliferation was measured by BrdU incorporation and cell counting.Migration was examined using Boyden chamber apparatus.Expressions of smooth muscle(sm)-α-actin and sm-myosin heavy chain(MHC)isoform 1 were determined by RT-PCR and Western blot analysis.Results It was found that hrbFGF(10 ng/ml),when added to ASMCs,induced a significant increase in BrdU uptake and cell number by ASMCS as compared to controls and a significant increase in ASMCs migration with respect to controls.The mRNA and protein expressions of sm-α-actin and sm-MHC in ASMCs that were stimulated with hrbFGF decreased with respect to controls.Conclusion It appears that bFGF can directly stimulate proliferation and migration of ASMCs.however,the expressions of cells'contractive phenotype decreased.

  3. Nuclear receptors Nur77 and Nurr1 modulate mesenchymal stromal cell migration

    NARCIS (Netherlands)

    Maijenburg, M.W.; Gilissen, C.; Melief, S.M.; Kleijer, M.; Weijer, K.; Ten Brinke, A.; Roelofs, H.; Tiel, C.M. van; Veltman, J.A.; Vries, C.J. de; Schoot, C.E. van der; Voermans, C.


    Detailed understanding of mesenchymal stromal cells (MSC) migration is imperative for future cellular therapies. To identify genes involved in the process of MSC migration, we generated gene expression profiles of migrating and nonmigrating fetal bone marrow MSC (FBMSC). Only 12 genes showed differe

  4. Effects of 5-hydroxytryptamine (serotonin) and forskolin on intracellular free calcium in isolated and fura-2 loaded smooth-muscle cells from the anterior byssus retractor (catch) muscle of Mytilus edulis. (United States)

    Ishii, N; Simpson, A W; Ashley, C C


    Effects of 5-hydroxytryptamine (5-HT) and forskolin on intracellular free calcium concentration [( Ca2+]i) were studied in suspensions of fura-2 loaded smooth-muscle cells from the anterior byssus retractor 'catch' muscle of Mytilus edulis. The successive addition of 5 mM carbachol (CCh) and 100 mM KCl to the suspension evoked a transient elevation of [Ca2+]i from the resting value of 124 +/- 2.7 nM (mean +/- SE, n = 18) to 300-400 nM, which was associated with contraction. The change in [Ca2+]i induced CCh was concentration-dependent with the EC50 of 10(-5) M. The resting [Ca2+]i was unaffected by 10 microM 5-HT. The change in [Ca2+]i induced by 5 mM CCh was suppressed by 5-HT from 167 +/- 14.0 (n = 11) to 124 +/- 14.9 (n = 8) nM whereas that induced by 100 mM KCl was enhanced from 321 +/- 31.9 to 405 +/- 17.6 nM (n = 8). 5-HT applied during the decaying phase of the CCh response caused a rapid decline in [Ca2+]i. In both the responses to CCh and KCl, the falling phase was accelerated by 5-HT. 10 microM forskolin, a potent activator of adenylate cyclase, mimicked the effects of 5-HT as did a membrane-permeant cyclic AMP analogue, 8-parachlorophenylthio cyclic AMP (cpt-cAMP). Application of 100 microM cpt-cAMP partially suppressed the Ca2+i response to CCh and enhanced that to KCl. D-Tubocurarine (500 microM) added during the decaying phase of the response induced by 100 microM CCh, caused a rapid decline in [Ca2+]i similar to that caused by both 5-HT and forskolin.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Chronic treatment with escitalopram but not R-citalopram translocates Galpha(s) from lipid raft domains and potentiates adenylyl cyclase: a 5-hydroxytryptamine transporter-independent action of this antidepressant compound. (United States)

    Zhang, Lanqiu; Rasenick, Mark M


    Chronic antidepressant treatment has been shown to increase adenylyl cyclase activity, in part, due to translocation of Galpha(s) from lipid rafts to a nonraft fraction of the plasma membrane where they engage in a more facile stimulation of adenylyl cyclase. This effect holds for multiple classes of antidepressants, and for serotonin uptake inhibitors, it occurs in the absence of the serotonin transporter. In the present study, we examined the change in the amount of Galpha(s) in lipid raft and whole cell lysate after exposing C6 cells to escitalopram. The results showed that chronic (but not acute) escitalopram decreased the content of Galpha(s) in lipid rafts, whereas there was no change in overall Galpha(s) content. These effects were drug dose- and exposure time-dependent. Although R-citalopram has been reported to antagonize some effects of escitalopram, this compound was without effect on Galpha(s) localization in lipid rafts, and R-citalopram did not inhibit these actions of escitalopram. Escitalopram treatment increased cAMP accumulation, and this seemed due to increased coupling between Galpha(s) and adenylyl cyclase. Thus, escitalopram is potent, rapid and efficacious in translocating Galpha(s) from lipid rafts, and this effect seems to occur independently of 5-hydroxytryptamine transporters. Our results suggest that, although antidepressants display distinct affinities for well identified targets (e.g., monoamine transporters), several presynaptic and postsynaptic molecules are probably modified during chronic antidepressant treatment, and these additional targets may be required for clinical efficacy of these drugs.

  6. A space oddity: geographic and specific modulation of migration in Eudyptes penguins.

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Thiebot

    Full Text Available Post-breeding migration in land-based marine animals is thought to offset seasonal deterioration in foraging or other important environmental conditions at the breeding site. However the inter-breeding distribution of such animals may reflect not only their optimal habitat, but more subtle influences on an individual's migration path, including such factors as the intrinsic influence of each locality's paleoenvironment, thereby influencing animals' wintering distribution. In this study we investigated the influence of the regional marine environment on the migration patterns of a poorly known, but important seabird group. We studied the inter-breeding migration patterns in three species of Eudyptes penguins (E. chrysolophus, E. filholi and E. moseleyi, the main marine prey consumers amongst the World's seabirds. Using ultra-miniaturized logging devices (light-based geolocators and satellite tags, we tracked 87 migrating individuals originating from 4 sites in the southern Indian Ocean (Marion, Crozet, Kerguelen and Amsterdam Islands and modelled their wintering habitat using the MADIFA niche modelling technique. For each site, sympatric species followed a similar compass bearing during migration with consistent species-specific latitudinal shifts. Within each species, individuals breeding on different islands showed contrasting migration patterns but similar winter habitat preferences driven by sea-surface temperatures. Our results show that inter-breeding migration patterns in sibling penguin species depend primarily on the site of origin and secondly on the species. Such site-specific migration bearings, together with similar wintering habitat used by parapatrics, support the hypothesis that migration behaviour is affected by the intrinsic characteristics of each site. The paleo-oceanographic conditions (primarily, sea-surface temperatures when the populations first colonized each of these sites may have been an important determinant of

  7. Focal adhesion kinase modulates radial glia-dependent neuronal migration through connexin-26. (United States)

    Valiente, Manuel; Ciceri, Gabriele; Rico, Beatriz; Marín, Oscar


    Focal adhesion kinase (FAK) is an intracellular kinase and scaffold protein that regulates migration in many different cellular contexts but whose function in neuronal migration remains controversial. Here, we have analyzed the function of FAK in two populations of neurons with very distinct migratory behaviors: cortical interneurons, which migrate tangentially and independently of radial glia; and pyramidal cells, which undergo glial-dependent migration. We found that FAK is dispensable for glial-independent migration but is cell-autonomously required for the normal interaction of pyramidal cells with radial glial fibers. Loss of FAK function disrupts the normal morphology of migrating pyramidal cells, delays migration, and increases the tangential dispersion of neurons arising from the same radial unit. FAK mediates this process by regulating the assembly of Connexin-26 contact points in the membrane of migrating pyramidal cells. These results indicate that FAK plays a fundamental role in the dynamic regulation of Gap-mediated adhesions during glial-guided neuronal migration in the mouse.

  8. Migration of Sn and Pb from Solder Ribbon onto Ag Fingers in Field-Aged Silicon Photovoltaic Modules

    Directory of Open Access Journals (Sweden)

    Wonwook Oh


    Full Text Available We investigated the migration of Sn and Pb onto the Ag fingers of crystalline Si solar cells in photovoltaic modules aged in field for 6 years. Layers of Sn and Pb were found on the Ag fingers down to the edge of the solar cells. This phenomenon is not observed in a standard acceleration test condition for PV modules. In contrast to the acceleration test conditions, field aging subjects the PV modules to solar irradiation and moisture condensation at the interface between the solar cells and the encapsulant. The solder ribbon releases Sn and Pb via repeated galvanic corrosion and the Sn and Pb precipitate on Ag fingers due to the light-induced plating under solar irradiation.

  9. The Alteration of 5-Hydroxytryptamine Content in the Patients with Irritable Bowel Syndrome%肠易激综合征患者5-羟色胺含量的变化

    Institute of Scientific and Technical Information of China (English)

    张川; 李定国; 王彝康; 陆汉明


    Objective To study the relationship between 5-hydroxytryptamine (5-HT) and the patients with irritable bowel syndrome (IBS). Methods The contents of free tryptophan (TP), to- tal TP, 5-HT in serum and 5-HT in sigrnoid colon mucosa specimens were detected by spectrofluo- rophotometry and high-performance liquid chromatograph (HPLC) with thin-layer electrochemical (EC) detection method in patients with irritable bowel syndrome (IBS) and healthy volunteers. Results The concentrations of 5-HT in the serum of diarrhea-predominant IBS, the contents of 5- HT in both diarrhea-predominant IBS and constipation-predominant IBS in sigmoid colon mucosa were significantly higher; the concentrations of free and total TP were similar to those of the control group. Conclusion The results suggest that higher level of 5-HT may be involved in the pathogenic mecha- nism. The results also suggest that the increased content of 5-HT in the patients with IBS is not related to total and free TP in serum.%目的探讨5-羟色胺(5-HT)与肠易激综合征(irritable bowel syndrome,IBS)发病的关系。方法应用荧光分光光度法测定IBS患者和对照组血清5HT、游离色氨酸(TP)和总TP含量。应用高效液相色谱仪测定乙状结肠粘膜中2-HT的含量。结果与对照组比较,腹泻型血清5-HT浓度(496.27±128.22ng/ml)显著升高(P<0.05)。两种类型乙状结肠粘膜5-HT含量(1877 67±655.00ng/g,1899.55±817.89ng/g)均显著高于对照组(1202.69±512.69ng/g)(P<0.05)。结论5-HT浓度升高可能与IBS发病有关;IBS患者5-HT含量升高与血清中总TP或游离TP浓度无关。

  10. 5-羟色胺对大鼠膀胱传入神经活动的影响%Effect of 5-hydroxytryptamine on activity of bladder afferent nerves in rats

    Institute of Scientific and Technical Information of China (English)

    孙俏; 孙碧英; 罗萍; 王莹萍; 董莉; 戎伟芳


    Objective To investigate the effect of 5-hydroxytryptamine (5-HT) on the spontaneous and mechanosensitive activity of bladder afferent nerves. Methods The effects of intravesical instillation of different concentrations of 5-HT on the spontaneous and distension-induced pelvic afferent nerve activity were observed in the isolated rat bladder/pelvic nerve preparations. Results At rest, with the bladder empty, there was little background activity ( < 10 imp/s) in the pelvic nerve branch innervating the bladder. During ramp distension, the afferent nerve activity increased progressively as the intravesical pressure rose. Intraluminal instillation of 0. 1 mL 5-HT (1 to 30 |xmol/L) caused an increase of the ongoing afferent discharge and potentiated the low threshold (0 — 15 mmHg) mechanosensory responses in a concentration-dependent manner. Conclusion 5-HT directly activates low threshold bladder afferent fibers in the pelvic nerve, and can potentiate their mechanosensitivity.%目的 观察5-羟色胺(5-HT)对膀胱传入神经自发放电活动和机械敏感性的影响.方法 采用离体大鼠膀胱—盆神经标本,观察膀胱腔内给予不同浓度5-HT后,盆神经自发放电频率及充胀膀胱引起的放电活动的变化.结果 膀胱未充胀时,盆神经仅有少量自发放电活动(< 10 imp/s);充胀时,盆神经放电频率随膀胱内压力递增而升高;膀胱腔内给予5-HT(1~ 30μmol/L,0.1 mL)后,盆神经自发放电频率呈剂量依赖性增加,对0~ 15 mmHg范围(低压区)充胀刺激的反应增强.结论 5-HT能直接激活膀胱低阈值传入神经,并增强其对机械刺激的反应.

  11. CD69 modulates sphingosine-1-phosphate-induced migration of skin dendritic cells


    Lamana, Amalia; Martin, Pilar; de la Fuente, Hortensia; Martinez-Muñoz, Laura; Cruz-Adalia, Aranzazu; Ramirez-Huesca, Marta; Escribano, Cristina; Gollmer, Kathrin; Mellado, Mario; Stein, Jens V.; Rodriguez-Fernandez, Jose Luis; Sanchez-Madrid, Francisco; del Hoyo, Gloria Martinez


    In this study, we have investigated the role of CD69, an early inducible leukocyte activation receptor, in murine dendritic cell (DC) differentiation, maturation, and migration. Skin DCs and DC subsets present in mouse lymphoid organs express CD69 in response to maturation stimuli. Using a contact sensitization model, we show that skin DCs migrated more efficiently to draining lymph nodes (LNs) in the absence of CD69. This was confirmed by subcutaneous transfer of CD69–/– DCs, which presented...

  12. The ectonucleotidase cd39/ENTPDase1 modulates purinergic-mediated microglial migration. (United States)

    Färber, Katrin; Markworth, Sören; Pannasch, Ulrike; Nolte, Christiane; Prinz, Vincent; Kronenberg, Golo; Gertz, Karen; Endres, Matthias; Bechmann, Ingo; Enjyoji, Keiichi; Robson, Simon C; Kettenmann, Helmut


    Microglia is activated by brain injury. They migrate in response to ATP and although adenosine alone has no effect on wild type microglial migration, we show that inhibition of adenosine receptors impedes ATP triggered migration. CD39 is the dominant cellular ectonucleotidase that degrades nucleotides to nucleosides, including adenosine. Importantly, ATP fails to stimulate P2 receptor mediated migration in cd39(-/-) microglia. However, the effects of ATP on migration in cd39(-/-) microglia can be restored by co-stimulation with adenosine or by addition of a soluble ectonucleotidase. We also tested the impact of cd39-deletion in a model of ischemia, in an entorhinal cortex lesion and in the facial nucleus after facial nerve lesion. The accumulation of microglia at the pathological sites was markedly decreased in cd39(-/-) animals. We conclude that the co-stimulation of purinergic and adenosine receptors is a requirement for microglial migration and that the expression of cd39 controls the ATP/adenosine balance.

  13. Transforming growth factor-β1 induces intestinal myofibroblast differentiation and modulates their migration

    Institute of Scientific and Technical Information of China (English)

    Julia Brenmoehl; Sandra Nicole Miller; Claudia Hofmann; Daniela Vogl; Werner Falk; Jürgen Scholmerich; Gerhard Rogler


    AIM:To investigate the effects of transforming growth factor β1 (TGF-β1) on the differentiation of colonic lamina propria fibroblasts (CLPF) into myofibroblasts in vitro. METHODS:Primary CLPF cultures were incubated with TGF-β1 and analyzed for production of α-smooth muscle actin (α-SMA), fibronectin (FN) and FN isoforms. Migration assays were performed in a modified 48-well Boyden chamber. Levels of total and phosphorylated focal adhesion kinase (FAK) in CLPF were analyzed after induction of migration. RESULTS:Incubation of CLPF with TGF-β1 for 2 d did not change α-SMA levels, while TGF-β1 treatment for 6 d significantly increased α-SMA production. Short term incubation (6 h) with TGF-β1 enhanced CLPF migration, while long term treatment (6 d) of CLPF with TGF-β1 reduced migration to 15%-37% compared to untreated cells. FN and FN isoform mRNA expression were increased after short term incubation with TGF-β1 (2 d) in contrast to long term incubation with TGF-β1 for 6 d. After induction of migration, TGF-β1-preincubated CLPF showed higher amounts of FN and its isoforms and lower levels of total and phosphorylated FAK than untreated cells. CONCLUSION:Long term incubation of CLPF with TGF-β1 induced differentiation into myofibroblasts with enhanced α-SMA, reduced migratory potential and FAK phosphorylation, and increased FN production. In contrast, short term contact (6 h) of fibroblasts with TGF-β1 induced a dose-dependent increase of cell migration and FAK phosphorylation without induction of α-SMA production.

  14. Annexin A6 and Late Endosomal Cholesterol Modulate Integrin Recycling and Cell Migration* (United States)

    García-Melero, Ana; Reverter, Meritxell; Hoque, Monira; Meneses-Salas, Elsa; Koese, Meryem; Conway, James R. W.; Johnsen, Camilla H.; Alvarez-Guaita, Anna; Morales-Paytuvi, Frederic; Elmaghrabi, Yasmin A.; Pol, Albert; Tebar, Francesc; Murray, Rachael Z.; Timpson, Paul; Enrich, Carlos; Grewal, Thomas; Rentero, Carles


    Annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner. Earlier studies implicated annexin A6 (AnxA6) to inhibit secretion and participate in the organization of the extracellular matrix. We recently showed that elevated AnxA6 levels significantly reduced secretion of the extracellular matrix protein fibronectin (FN). Because FN is directly linked to the ability of cells to migrate, this prompted us to investigate the role of AnxA6 in cell migration. Up-regulation of AnxA6 in several cell models was associated with reduced cell migration in wound healing, individual cell tracking and three-dimensional migration/invasion assays. The reduced ability of AnxA6-expressing cells to migrate was associated with decreased cell surface expression of αVβ3 and α5β1 integrins, both FN receptors. Mechanistically, we found that elevated AnxA6 levels interfered with syntaxin-6 (Stx6)-dependent recycling of integrins to the cell surface. AnxA6 overexpression caused mislocalization and accumulation of Stx6 and integrins in recycling endosomes, whereas siRNA-mediated AnxA6 knockdown did not modify the trafficking of integrins. Given our recent findings that inhibition of cholesterol export from late endosomes (LEs) inhibits Stx6-dependent integrin recycling and that elevated AnxA6 levels cause LE cholesterol accumulation, we propose that AnxA6 and blockage of LE cholesterol transport are critical for endosomal function required for Stx6-mediated recycling of integrins in cell migration. PMID:26578516

  15. Fucoidan modulates cytokine production and migration of THP‑1‑derived macrophages via colony‑stimulating factor‑1. (United States)

    Li, Peng; Wang, Huayang; Shao, Qianqian; Kong, Beihua; Qu, Xun


    Fucoidan is known for its various biological activities, including immunomodulatory effects on immune cells. However, the effect of fucoidan on the functions of macrophages remains to be elucidated. The present study examined the effects of fucoidan on cytokine production and migration of THP‑1‑derived macrophages and its potential mechanisms. Fucoidan was added during the differentiation process of THP‑1‑derived macrophages along with lipopolysaccharide and interferon‑γ for 42 h, and then macrophages were harvested for functional assays. Fucoidan altered the morphology of THP‑1‑derived macrophages, and also attenuated their migration activity and pro‑inflammatory cytokine production. Additionally, THP‑1‑derived macrophages intensively produced colony‑stimulating factor‑1 (CSF‑1), which was significantly decreased by fucoidan. CSF‑1 neutralizing antibody attenuated the basic production level of pro‑inflammatory cytokines in macrophages. Furthermore, when recombinant human CSF‑1 was added along with fucoidan, the attenuating effects of fucoidan on migration and cytokine production were significantly reversed. In conclusion, the present study suggests that macrophages appear to be a potential target in the immunomodulatory action of fucoidan, and CSF‑1 may be involved in this modulation.

  16. Expresion of 5 - Hydroxytryptamine 4 Receptor in Congenital Hirschsprung's Disease and Hirschsprung's Allied Disease%5-羟色胺4受体在先天性巨结肠和同源病中的表达

    Institute of Scientific and Technical Information of China (English)

    朱旭; 魏明发; 卞红强; 段栩飞


    目的 探讨5-羟色胺4(5-HT4)受体在先天性巨结肠(HD)和先天性巨结肠同源病(HAD)中的表达,并研究能否将此检测应用于HD和HAD的术前鉴别诊断.方法 共收集HD标本25例(HD组)、HAD标本20例(HAD组)和正常结肠标本15例(正常对照组).应用免疫组织化学SP法染色,分析5-HT4受体表达的部位及肠管不同部位5-HT4受体表达水平强度的差异.采用t检验比较其表达是否存在差异性.结果 HD组5-HT4受体阳性指数在远端黏膜层较近端表达下降,肌间神经丛无表达;HAD组远端5 -HT4受体阳性指数在黏膜层和肌间神经丛中均显著低于近端.与正常对照组比较,HD组和HAD组5-HT4受体阳性指数在黏膜及肌间神经从表达均下降.结论 5 -HT4受体在HD及HAD中的表达水平可作为术前鉴别诊断的参考指标之一,也为临床治疗提供新的参考指标.%Objective To explore the role of 5 - hydroxytryptamine 4(5 - HT4) receptor in the pathogenesis of Hirschsprung disease (HD)and Hirschsprung's allied disorder (HAD) .and to research whether the study could be used for preoperative diagnosis of HD and HAD. Methods Twenty -five cases of HD specimens( HD group) .20 cases of HAD specimens( HAD group) and 15 normal colon specimens (normal control group) were collected. SP irnmunorustochemical staining was used to analyze 5 - HT4 receptor sites and the differences of 5 - HT4 receptor sites expression levels in different parts of intestines. T - test was adopted to compare the expression differences. Results In HD group, 5 - HT4 receptors in the distal end of mucosa decreased compared with the proximal end, while 5 - HT4 receptors were not expressed in the mye-nteric plexus of the proximal end. In HAD group, the number of 5 - HT4 receptors also decreased in the distal mucosa and myenteric plexus. Compared with the normal control group ,5 - HT4 receptor expression decreased in HD group and HAD group. Conclusion 5 - HT4 receptors in HD/HAD can


    Derkach, K V; Moyseuk, I V; Shpakova, E A; Sphakov, A O


    The activity of the hypothalamic-pituitary-thyroid (HPT) axis is controlled by the brain neurotransmitter systems, including the melanocortin signaling system. Pharmacological inhibition of type 4 melanocortin receptor (M4R) leads to disruption of the functioning of HPT axis and to reduction of the level of thyroid hormones. At the same time, the data on how prolonged inhibition of M4R affects this axis and on its role in regulation of M3R are absent. The relationship between the thyroid status and the activity of 1B-subtype 5-hydroxytryptamine receptor (5-HT1BR) is scarcely explored. The aim of this work to study the effects of chronic inhibition of M3R, M4R and 5-HT1BR induced by immunization of rats with BSA-conjugated peptide derived from the extracellular regions of these receptors on the thyroid status and the activity of thyroid stimulating hormone (TSH)-sensitive adenylyl cyclase signaling system (ACSS) in the thyroid glarid (TG) of the immunized animals. In rats immunized with the peptides K-[TSLHL WNRSSHGLHG11-25]-A of M4R, A[PTNPYCICTTAH269-280]-A of M3R and. [QAKAEE-EVSEC(Acm)-VVNTDH189-205]-A of 5-HT1BR levels of thyroid hormones such as fT4, tT4 and tT3 were significantly reduced. In rats immunized with M4R and M3R peptides, an increase of TSH was detected whereas in the animals immunized with 5-HT1BR peptide the level of TSH, on the contrary, was reduced. In the TG of rats immunized with M4R and M3R peptides, the stimulatory effects of hormones (TSH, PA-CAP-3 8) and GppNHp on adenylyl cyclase activity were attenuated, and the changes were most pronounced in the case M4R peptide immunization. After immunization with 5-HT1BR peptide the stimulatory effects of TSH, PACAP-38 and GppNHp were retained. Thus, the main cause of thyroid hormones deficit in rats immunized with M4R and M3R peptides was the decreased sensitivity of ACSS thyrocytes to TSH, whereas in rats iimunized with 5-HT1BR peptide the deficit of thyroid hormones was associated with decreased

  18. 5-Hydroxytryptamine catabolic changes of rats by short-term exposure to nonylphenol%壬基酚对大鼠5-羟色胺分解代谢通路的影响

    Institute of Scientific and Technical Information of China (English)

    赖玉婷; 欧阳俊彦; 郭佑廷; 杨童旺; 林媛; 吕宝怡; 柳春红


    Effects of nonylphenol (NP) on monoamine oxidase (MAO) activity and 5-hydroxytryptamine (5-HT) level of rats were investigated. The toxic mechanisms of NP on catabolism of 5-HT were also analyzed. 24 male SD rats were randomly divided into 4groups, namely NP low-dose group 30mg/(kg·bw), NP medium-dose group 90mg/(kg·bw), NP high-dose group 270mg/(kg·bw) and control group (equal volume of the solvent). NP in corn oil was administrated orally to rats once every other day for 28days, and rats in control group was only given corn oil. The increment of rat body weight in NP high-dose group was lower than that of control group (P<0.01). From the third week of exposure, significant differences were found for the food utilization rates, the liver, kidney and testis coefficients between treatment groups and control group (P<0.05, P<0.01, P<0.01, P<0.05). Compared with control group, significantly lower MAO activities of plasma and liver homogenate and higher 5-HT levels were observed in treatment groups (P<0.01, P<0.05, P<0.01). NP exposure has a dose-dependent effect on MAO activity and 5-HT level of rats, suggesting that NP may affect the metabolic network of 5-HT by inhibiting its catabolism.%为探讨壬基酚对5-羟色胺(5-HT)代谢网络分解代谢通路的毒性作用机制,将24只SD雄性大鼠分为阴性对照组和壬基酚低、中、高剂量组[30,90,270mg/(kg·bw)],隔日玉米油灌胃染毒28d后检测大鼠血浆及肝匀浆中单胺氧化酶(MAO)活性和血浆中5-HT含量,并称量肝、肾和睾丸重量.结果显示,壬基酚暴露高剂量组大鼠体质量增量极显著低于对照组(P<0.01);染毒至第3周起,各组大鼠平均食物利用率有统计学意义(P<0.05);与对照组相比,高剂量组肝脏、肾脏脏器系数均有统计学意义(P<0.01),中、高剂量组睾丸脏器系数均有统计学意义(P<0.05);中、高剂量组血浆MAO酶活性极显著低于对照组(P<0.01),中、高剂量组肝匀浆MAO酶

  19. CalpB modulates border cell migration in Drosophila egg chambers

    Directory of Open Access Journals (Sweden)

    Kókai Endre


    Full Text Available Abstract Background Calpains are calcium regulated intracellular cysteine proteases implicated in a variety of physiological functions and pathological conditions. The Drosophila melanogaster genome contains only two genes, CalpA and CalpB coding for canonical, active calpain enzymes. The movement of the border cells in Drosophila egg chambers is a well characterized model of the eukaryotic cell migration. Using this genetically pliable model we can investigate the physiological role of calpains in cell motility. Results We demonstrate at the whole organism level that CalpB is implicated in cell migration, while the structurally related CalpA paralog can not fulfill the same function. The downregulation of the CalpB gene by mutations or RNA interference results in a delayed migration of the border cells in Drosophila egg chambers. This phenotype is significantly enhanced when the focal adhesion complex genes encoding for α-PS2 integrin ( if, β-PS integrin ( mys and talin ( rhea are silenced. The reduction of CalpB activity diminishes the release of integrins from the rear end of the border cells. The delayed migration and the reduced integrin release phenotypes can be suppressed by expressing wild-type talin-head in the border cells but not talin-headR367A, a mutant form which is not able to bind β-PS integrin. CalpB can cleave talin in vitro, and the two proteins coimmunoprecipitate from Drosophila extracts. Conclusions The physiological function of CalpB in border cell motility has been demonstrated in vivo. The genetic interaction between the CalpB and the if, mys, as well as rhea genes, the involvement of active talin head-domains in the process, and the fact that CalpB and talin interact with each other collectively suggest that the limited proteolytic cleavage of talin is one of the possible mechanisms through which CalpB regulates cell migration.

  20. Selection in spatial stochastic models of cancer: Migration as a key modulator of fitness

    Directory of Open Access Journals (Sweden)

    Stupack Dwayne


    Full Text Available Abstract Background We study the selection dynamics in a heterogeneous spatial colony of cells. We use two spatial generalizations of the Moran process, which include cell divisions, death and migration. In the first model, migration is included explicitly as movement to a proximal location. In the second, migration is implicit, through the varied ability of cell types to place their offspring a distance away, in response to another cell's death. Results In both models, we find that migration has a direct positive impact on the ability of a single mutant cell to invade a pre-existing colony. Thus, a decrease in the growth potential can be compensated by an increase in cell migration. We further find that the neutral ridges (the set of all types with the invasion probability equal to that of the host cells remain invariant under the increase of system size (for large system sizes, thus making the invasion probability a universal characteristic of the cells selection status. We find that repeated instances of large scale cell-death, such as might arise during therapeutic intervention or host response, strongly select for the migratory phenotype. Conclusions These models can help explain the many examples in the biological literature, where genes involved in cell's migratory and invasive machinery are also associated with increased cellular fitness, even though there is no known direct effect of these genes on the cellular reproduction. The models can also help to explain how chemotherapy may provide a selection mechanism for highly invasive phenotypes. Reviewers This article was reviewed by Marek Kimmel and Glenn Webb.

  1. LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts. (United States)

    Zhang, Hui; Sweezey, Neil B; Kaplan, Feige


    Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development.

  2. Navigator-3, a modulator of cell migration, may act as a suppressor of breast cancer progression (United States)

    Cohen-Dvashi, Hadas; Ben-Chetrit, Nir; Russell, Roslin; Carvalho, Silvia; Lauriola, Mattia; Nisani, Sophia; Mancini, Maicol; Nataraj, Nishanth; Kedmi, Merav; Roth, Lee; Köstler, Wolfgang; Zeisel, Amit; Yitzhaky, Assif; Zylberg, Jacques; Tarcic, Gabi; Eilam, Raya; Wigelman, Yoav; Will, Rainer; Lavi, Sara; Porat, Ziv; Wiemann, Stefan; Ricardo, Sara; Schmitt, Fernando; Caldas, Carlos; Yarden, Yosef


    Dissemination of primary tumor cells depends on migratory and invasive attributes. Here, we identify Navigator-3 (NAV3), a gene frequently mutated or deleted in human tumors, as a regulator of epithelial migration and invasion. Following induction by growth factors, NAV3 localizes to the plus ends of microtubules and enhances their polarized growth. Accordingly, NAV3 depletion trimmed microtubule growth, prolonged growth factor signaling, prevented apoptosis and enhanced random cell migration. Mathematical modeling suggested that NAV3-depleted cells acquire an advantage in terms of the way they explore their environment. In animal models, silencing NAV3 increased metastasis, whereas ectopic expression of the wild-type form, unlike expression of two, relatively unstable oncogenic mutants from human tumors, inhibited metastasis. Congruently, analyses of > 2,500 breast and lung cancer patients associated low NAV3 with shorter survival. We propose that NAV3 inhibits breast cancer progression by regulating microtubule dynamics, biasing directionally persistent rather than random migration, and inhibiting locomotion of initiated cells. PMID:25678558

  3. The Exposure of Breast Cancer Cells to Fulvestrant and Tamoxifen Modulates Cell Migration Differently

    Directory of Open Access Journals (Sweden)

    Dionysia Lymperatou


    Full Text Available There is no doubt that there are increased benefits of hormonal therapy to breast cancer patients; however, current evidence suggests that estrogen receptor (ER blockage using antiestrogens is associated with a small induction of invasiveness in vitro. The mechanism by which epithelial tumor cells escape from the primary tumor and colonize to a distant site is not entirely understood. This study investigates the effect of two selective antagonists of the ER, Fulvestrant (Fulv and Tamoxifen (Tam, on the invasive ability of breast cancer cells. We found that 17β-estradiol (E2 demonstrated a protective role regarding cell migration and invasion. Fulv did not alter this effect while Tam stimulated active cell migration according to an increase in Snail and a decrease in E-cadherin protein expression. Furthermore, both tested agents increased expression of matrix metalloproteinases (MMPs and enhanced invasive potential of breast cancer cells. These changes were in line with focal adhesion kinase (FAK rearrangement. Our data indicate that the anti-estrogens counteracted the protective role of E2 concerning migration and invasion since their effect was not limited to antiproliferative events. Although Fulv caused a less aggressive result compared to Tam, the benefits of hormonal therapy concerning invasion and metastasis yet remain to be investigated.

  4. Melanoma Cell Adhesion and Migration Is Modulated by the Uronyl 2-O Sulfotransferase (United States)

    Nikolovska, Katerina; Spillmann, Dorothe; Haier, Jörg; Ladányi, Andrea; Stock, Christian; Seidler, Daniela G.


    Although the vast majority of melanomas are characterized by a high metastatic potential, if detected early, melanoma can have a good prognostic outcome. However, once metastasised, the prognosis is bleak. We showed previously that uronyl-2-O sulfotransferase (Ust) and 2-O sulfation of chondroitin/dermatan sulfate (CS/DS) are involved in cell migration. To demonstrate an impact of 2-O sulfation in metastasis we knocked-down Ust in mouse melanoma cells. This significantly reduced the amount of Ust protein and enzyme activity. Furthermore, in vitro cell motility and adhesion were significantly reduced correlating with the decrease of cellular Ust protein. Single cell migration of B16VshUst(16) cells showed a decreased cell movement phenotype. The adhesion of B16V cells to fibronectin depended on α5β1 but not αvβ3 integrin. Inhibition of glycosaminoglycan sulfation or blocking fibroblast growth factor receptor (FgfR) reduced α5 integrin in B16V cell lines. Interestingly, FgfR1 expression and activation was reduced in Ust knock-down cells. In vivo, pulmonary metastasis of B16VshUst cells was prevented due to a reduction of α5 integrin. As a proof of concept UST knock-down in human melanoma cells also showed a reduction in ITGa5 and adhesion. This is the first study showing that Ust, and consequently 2-O sulfation of the low affinity receptor for FgfR CS/DS, reduces Itga5 and leads to an impaired adhesion and migration of melanoma cells. PMID:28107390

  5. Circadian Clock Genes Modulate Human Bone Marrow Mesenchymal Stem Cell Differentiation, Migration and Cell Cycle. (United States)

    Boucher, Helene; Vanneaux, Valerie; Domet, Thomas; Parouchev, Alexandre; Larghero, Jerome


    Many of the components that regulate the circadian clock have been identified in organisms and humans. The influence of circadian rhythm (CR) on the regulation of stem cells biology began to be evaluated. However, little is known on the role of CR on human mesenchymal stem cell (hMSCs) properties. The objective of this study was to investigate the influence of CR on the differentiation capacities of bone marrow hMSCs, as well as the regulation of cell cycle and migration capabilities. To that, we used both a chemical approach with a GSK-3β specific inhibitor (2'E,3'Z-6-bromoindirubin-3'-oxime, BIO) and a knockdown of CLOCK and PER2, two of the main genes involved in CR regulation. In these experimental conditions, a dramatic inhibition of adipocyte differentiation was observed, while osteoblastic differentiation capacities were not modified. In addition, cell migration was decreased in PER2-/- cells. Lastly, downregulation of circadian clock genes induced a modification of the hMSCs cell cycle phase distribution, which was shown to be related to a change of the cyclin expression profile. Taken together, these data showed that CR plays a role in the regulation of hMSCs differentiation and division, and likely represent key factor in maintaining hMSCs properties.

  6. Research of linkage disequilibrium between suicide attempts and 5-hydroxytryptamine transporter gene%自杀未遂与5-羟色胺转运体基因的连锁不平衡研究

    Institute of Scientific and Technical Information of China (English)

    高新学; 艾明; 陈建梅; 黎雪梅; 甘窈; 况利


    目的 探讨自杀未遂与5-羟色胺转运体(5-HTT)基因之间的分子遗传学关系.方法 以重庆地区汉族人群中自杀未遂核心家系作为研究对象,采集86个核心家系的258个家系成员的肘静脉血,将其分为患者组与父母组.应用聚合酶链反应(PCR)和限制性片段长度多态性方法,研究5-HTT基因启动子区多态性(5-HTTLPR)、5-HTT基因第二内含子多态性(5-HTTVNTR)与自杀未遂之间的分子遗传学关系,并进行基于单体型的单体型相对风险(HHRR)分析及连锁不平衡(TDT)分析.结果 父母组和患者组的5-HTTLPR、5-HTTVNTR基因型及等位基因频率的总体分布比较差异均无统计学意义(P>0.05).HHRR分析结果显示患者组与虚拟对照组的5-HTTLPR、5-HTTVNTR基因频率差异均无统计学意义(P>0.05).多等位基因TDT统计分析显示86个核心家系分别有54及89个杂合子父母纳入5-HTTLPR、5-HTTVNTR的统计,5-HTTLPR、5-HTTVNTR与自杀未遂间不存在连锁不平衡(P>0.05).在5-HTT基因的2个多态性位点组合成的4种单体型中进行单体型分析,组间差异均无统计学意义(P>0.05),提示自杀未遂患者与这2个位点形成的单体型不存在传递上的偏倚.结论 5-HTT基因不是自杀未遂的主要遗传基因.%Objective To discuss the molecular genetics correlation between suicide attempts and 5 hydroxytryptamine trans porter(5-HTT) gene. Methods Nuclear family with suicide attempts of Han nationality in Chongqing area was served as research object. Cubital venous blood were collected from 258 members in 86 nuclear families,and they were divided into patient group and parents goup. Polymerase chain reaction(PCR) and restriction fragment length polymorphism method were employed to study the molecular genetics correlation between serotonin-transporter linked polymorphic region(5 HTTLPR) or serotonin transporter gene2 VNTR polymorphism(5-HTTVNTR) and suicide attempts,and haplotype-based haplotype

  7. The Pseudomonas aeruginosa N-acylhomoserine lactone quorum sensing molecules target IQGAP1 and modulate epithelial cell migration.

    Directory of Open Access Journals (Sweden)

    Thommie Karlsson

    Full Text Available Quorum sensing (QS signaling allows bacteria to control gene expression once a critical population density is achieved. The Gram-negative human pathogen Pseudomonas aeruginosa uses N-acylhomoserine lactones (AHL as QS signals, which coordinate the production of virulence factors and biofilms. These bacterial signals can also modulate human cell behavior. Little is known about the mechanisms of the action of AHL on their eukaryotic targets. Here, we found that N-3-oxo-dodecanoyl-L-homoserine lactone 3O-C(12-HSL modulates human intestinal epithelial Caco-2 cell migration in a dose- and time-dependent manner. Using new 3O-C(12-HSL biotin and fluorescently-tagged probes for LC-MS/MS and confocal imaging, respectively, we demonstrated for the first time that 3O-C(12-HSL interacts and co-localizes with the IQ-motif-containing GTPase-activating protein IQGAP1 in Caco-2 cells. The interaction between IQGAP1 and 3O-C(12-HSL was further confirmed by pull-down assay using a GST-tagged protein with subsequent Western blot of IQGAP1 and by identifying 3O-C(12-HSL with a sensor bioassay. Moreover, 3O-C(12-HSL induced changes in the phosphorylation status of Rac1 and Cdc42 and the localization of IQGAP1 as evidenced by confocal and STED microscopy and Western blots. Our findings suggest that the IQGAP1 is a novel partner for P. aeruginosa 3O-C(12-HSL and likely the integrator of Rac1 and Cdc42- dependent altered cell migration. We propose that the targeting of IQGAP1 by 3O-C(12-HSL can trigger essential changes in the cytoskeleton network and be an essential component in bacterial--human cell communication.


    Directory of Open Access Journals (Sweden)

    Mohale Deepak S.


    Full Text Available Anxiety can be a core symptom of various mental/ behavioral disorders such as major depressive disorders, obsessive-compulsive disorders, panic disorder, adaptive disorder, post-traumatic stress disorder, social withdrawal disorder, and various phobias. The neuroanatomic circuits that support fear and anxiety behavior are modulated by a variety of neurochemicals, these include the peptidergic neurotransmitters, Corticotrophin releasing factor (CRF, neuropeptide Y (NPY, and substance P, the monoaminergic transmitters, Norepinephrine (NE, serotonin (5-hydroxytryptamine or 5-HT, and dopamine (DA, and the amino acid transmitters, Gamma Aminobuteric Acid (GABA and glutamate and many more. These neurochemical systems subserve important adaptive functions in preparing the organism for responding to threat or stress, by increasing vigilance, modulating memory, mobilizing energy stores, and elevating cardiovascular function. Nevertheless, these biological responses to threat and stress can become maladaptive if they are chronically or inappropriately activated.

  9. SPAG9 is involved in hepatocarcinoma cell migration and invasion via modulation of ELK1 expression

    Directory of Open Access Journals (Sweden)

    Yan QY


    Full Text Available Qiuyue Yan,1,2 Guohua Lou,3 Ying Qian,1 Bo Qin,1 Xiuping Xu,1,2 Yanan Wang,1,2 Yanning Liu,3 Xuejun Dong1 1Shaoxing People’s Hospital, Shaoxing Hospital Zhejiang University, Shaoxing, Zhejiang, 2The Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Background: Sperm-associated antigen 9 (SPAG9 is upregulated in several malignancies and its overexpression is positively correlated with cancer cell malignancies. However, the specific biological roles of SPAG9 in hepatocellular carcinoma (HCC are less understood. Methods: We analyzed SPAG9 and ETS-like gene 1, tyrosine kinase (ELK1 expression in 50 paired HCC specimens and adjacent noncancerous liver specimens using immunohistochemistry. SPAG9 small interfering RNA (siRNA was used to knockdown SPAG9 expression in HCCLM3 and HuH7 cell lines. We used plasmids to upregulate ELK1 expression and siRNA to downregulate ELK1 expression in HuH7 cells. Quantitative real-time polymerase chain reaction and Western blot were used to evaluate the expression of SPAG9 and ELK1 at the mRNA and protein level, respectively. Wound healing, matrigel migration, and invasion analyses were performed to determine the effect of SPAG9 and ELK1 on HCC metastasis. Results: SPAG9 and ELK1 were overexpressed in HCC tissue specimens and their expressions were higher in HCCLM3 and HuH7 cells compared to the low-metastatic HepG2 cells. Overexpression of SPAG9 was positively associated with tumor-node-metastasis staging (P=0.032, metastasis parameters (P=0.018 of HCC patients, and ELK1 expression (r=0.422, P<0.001 in HCC tissue specimens. In addition

  10. Opposite modulation of cell migration by distinct subregions of urokinase connecting peptide. (United States)

    Franco, Paola; Carotenuto, Alfonso; Marcozzi, Cristina; Votta, Giuseppina; Sarno, Ciro; Iaccarino, Ingram; Brancaccio, Diego; De Vincenzo, Anna; Novellino, Ettore; Grieco, Paolo; Stoppelli, Maria Patrizia


    Functional analysis of isolated protein domains may uncover cryptic activities otherwise missed. The serine protease urokinase (uPA) has a clear-cut motogen activity that is catalytically independent and resides in its amino-terminal growth factor domain (GFD, residues 1-49) and connecting peptide region (CP, residues 132-158). To functionally dissect the CP region, we analysed the biological activity of two synthetic peptides corresponding to the N-terminal [uPA-(135-143), residues 135-143] and C-terminal [uPA-(144-158), residues 144-158] CP subregions. Most of the chemotactic activity of connecting peptide-derived peptide (CPp, [uPA-(135-158)]) for embryonic kidney HEK293/uPAR-25 cells is retained by uPA-(144-158) at nanomolar concentrations. In contrast, uPA-(135-143) inhibits basal, CPp -, vitronectin- and fibronectin-induced cell migration. Radioreceptor binding assays on intact HEK293 cells revealed that uPA-(135-143) and uPA-(144-158) are both able to compete with [(125)I]-CPp, albeit with different binding affinities. The consequences of phospho-mimicking, S138E substitution, were studied using [138E]uPA-(135-158) and [138E]uPA-(135-143) peptides. Unlike CPp, [138E]uPA-(135-158) and [138E]uPA-(135-143) exhibit remarkable inhibitory properties. Finally, analysis of the conformational preferences of the peptides allowed to identify secondary structure elements exclusively characterising the stimulatory CPp and uPA-(144-158) versus the inhibitory uPA-(135-143), [138E]uPA-(135-158) and [138E]uPA-(135-143) peptides. In conclusion, these data shed light on the cryptic activities of uPA connecting peptide, revealing the occurrence of two adjacent regions, both competing for binding to cell surface but conveying opposite signalling on cell migration.

  11. Migrating Motor Complex in Colectomized Ileo Stoma Patients

    DEFF Research Database (Denmark)

    Hansen, Mark B; Wallin, Lene; Husebye, Einar


    muscarinic receptors. We aimed to evaluate the effect of 5-hydroxytryptamine (5-HT), ondansetron and atropine on fasting and stimulated antro-duodeno-jejunal migrating motor complex (MMC) in colectomized patients with ileo stoma compared with healthy subjects. Manometric recordings were obtained in a blinded......, age- and gender-matched design. The effects of either standard meal or intravenous 5-HT (10 nmol/kg/min.) treatment with pre-treatment of saline (placebo) or ondansetron (250 µg/kg) or atropine (10 µg/kg) were compared. Adverse effects, blood pressure, heart rate and electrocardiographic data were...... also evaluated. 5-HT increased the frequency (threefold) and migration velocity (twofold) of MMC phase III in both experimental groups. Ondansetron reduced 5-HT-induced frequency of MMC phase III in patients (p Atropine reduced 5-HT-induced frequency of MMC phase...

  12. Nonlinear instability in flagellar dynamics: a novel modulation mechanism in sperm migration?

    KAUST Repository

    Gadelha, H.


    Throughout biology, cells and organisms use flagella and cilia to propel fluid and achieve motility. The beating of these organelles, and the corresponding ability to sense, respond to and modulate this beat is central to many processes in health and disease. While the mechanics of flagellum-fluid interaction has been the subject of extensive mathematical studies, these models have been restricted to being geometrically linear or weakly nonlinear, despite the high curvatures observed physiologically. We study the effect of geometrical nonlinearity, focusing on the spermatozoon flagellum. For a wide range of physiologically relevant parameters, the nonlinear model predicts that flagellar compression by the internal forces initiates an effective buckling behaviour, leading to a symmetry-breaking bifurcation that causes profound and complicated changes in the waveform and swimming trajectory, as well as the breakdown of the linear theory. The emergent waveform also induces curved swimming in an otherwise symmetric system, with the swimming trajectory being sensitive to head shape-no signalling or asymmetric forces are required. We conclude that nonlinear models are essential in understanding the flagellar waveform in migratory human sperm; these models will also be invaluable in understanding motile flagella and cilia in other systems.

  13. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2. (United States)

    Kozlova, Nina; Jensen, Jan K; Chi, Tabughang Franklin; Samoylenko, Anatoly; Kietzmann, Thomas


    Plasminogen activator inhibitor-1 (PAI-1) is the major and most specific acting urokinase (uPA) and tissue plasminogen activator (tPA) inhibitor. Apart from its function in the fibrinolytic system, PAI-1 was also found to contribute to processes like tissue remodelling, angiogenesis, and tumour progression. However, the role of PAI-1 in those processes remains largely controversial with respect to the influence of PAI-1 on cell signalling pathways. Although PAI-1 does not possess its own cellular receptor, it can be bound to low-density lipoprotein receptor-related protein 1 (LRP1) which was proposed to modulate the β-catenin pathway. Therefore, we used wild-type mouse embryonic fibroblasts (MEFs), and MEFs deficient of LRP1 to study PAI-1 as modulator of the β-catenin pathway. We found that PAI-1 influences MEF proliferation and motility in a LRP1-dependent manner and that β-catenin is important for that response. In addition, expression of β-catenin and β-catenin-dependent transcriptional activity were induced by PAI-1 in wild type MEFs, but not in LRP1-deficient cells. Moreover, PAI-1-induced ERK1/2 activation was more prominent in the LRP1-deficient cells and interestingly knockdown of β-catenin abolished this effect. Together, the data of the current study show that PAI-1 can promote cell migration via LRP1-dependent activation of the β-catenin and ERK1/2 MAPK pathway which may be important in stage-specific treatment of human diseases associated with high PAI-1 levels.

  14. Differential modulation of IL-1-induced endothelial adhesion molecules and transendothelial migration of granulocytes by G-CSF. (United States)

    Eissner, G; Lindner, H; Reisbach, G; Klauke, I; Holler, E


    Granulocyte colony stimulating factor (G-CSF) is widely used for mobilization of haemopoietic stem cells into the peripheral blood. However, little is known about the mechanisms involved in mobilization and the immune modulatory effects of this growth factor. In this report we show that G-CSF down-regulated intercellular adhesion molecule 1 (ICAM-1) induced by Interleukin-1 (IL-1) on human endothelial cells. Interestingly, the G-CSF-mediated down-modulation of IL-1-induced ICAM-1 appeared to be biphasic. In pharmacological concentrations (> 300 ng/ml), and in dose ranges of plasma G-CSF levels above that of nonfebrile healthy individuals (30 pg/ml), a significant decrease in surface ICAM-1 could be observed. This could be explained, at least in part, by an increased autocrine G-CSF production by endothelial cells in response to IL-1 and exogenous G-CSF. In contrast to ICAM-1, IL-1-triggered VCAM-1 expression was superinduced by G-CSF with the optimal concentration of 30 pg/ml. To evaluate the functional significance of these findings, 51Cr adhesion assays with peripheral blood mononuclear cells (PBMC) or granulocytes known to lack the VCAM-1 counter-receptor very late antigen 4 (VLA-4) and IL-1-stimulated endothelial cells, in the presence or absence of G-CSF, were performed. G-CSF could not inhibit the IL-1-induced adhesion of PBMC to endothelial cells, which may be due to the differential adhesion molecule modulation. In contrast, granulocyte adhesion induced by IL-1 could effectively be blocked by co-incubation with G-CSF. Finally, G-CSF also inhibited transendothelial migration of granulocytes through IL-1-activated endothelial cells in a concentration-dependent manner.

  15. Peripheral 5-HT 1A and 5-HT 7 Serotonergic Receptors Modulate Parasympathetic Neurotransmission in Long-Term Diabetic Rats


    Beatriz Restrepo; María Luisa Martín; Luis San Román; Asunción Morán


    We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT1/7 agonist. The enhancement of the bradycardia at l...

  16. Effect of gold migration on the morphology of germanium nanowires grown by a two-step growth method with temperature modulation (United States)

    Xu, Zhengyu; Usami, Koichi; Simanullang, Marolop; Noguchi, Tomohiro; Kawano, Yukio; Oda, Shunri


    Germanium nanowires (Ge NWs) grown at high temperatures (HTs) are investigated because of the demand for impurity doping. However, gold agglomeration, which occurs at HTs, results in undesired moundlike structures. A two-step growth technique with temperature modulation from low temperatures (LTs) to HTs was adopted to prevent gold agglomeration, thus revealing high-yield HT Ge NWs on top of LT Ge NWs. These Ge NWs can be classified into two groups on the basis of their shape. The timing of gold migration plays a crucial role in determining the shape of these NWs. Fat core-shell-like Ge NWs, where gold migration occurs as temperature increases, are due to the enhanced radial growth at HTs generated from the migrated gold nanoparticles on the NW sidewalls. However, for thin NWs, because Au seeds were stabilized on top of NWs until synthesis ended, the axial growth of Ge NWs continued at HTs.

  17. Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway (United States)

    Simon, Sylvia; Schell, Ursula; Heuer, Natalie; Hager, Dominik; Albers, Michael F.; Matthias, Jan; Fahrnbauer, Felix; Trauner, Dirk; Eichinger, Ludwig; Hedberg, Christian; Hilbi, Hubert


    Small molecule signaling promotes the communication between bacteria as well as between bacteria and eukaryotes. The opportunistic pathogenic bacterium Legionella pneumophila employs LAI-1 (3-hydroxypentadecane-4-one) for bacterial cell-cell communication. LAI-1 is produced and detected by the Lqs (Legionella quorum sensing) system, which regulates a variety of processes including natural competence for DNA uptake and pathogen-host cell interactions. In this study, we analyze the role of LAI-1 in inter-kingdom signaling. L. pneumophila lacking the autoinducer synthase LqsA no longer impeded the migration of infected cells, and the defect was complemented by plasmid-borne lqsA. Synthetic LAI-1 dose-dependently inhibited cell migration, without affecting bacterial uptake or cytotoxicity. The forward migration index but not the velocity of LAI-1-treated cells was reduced, and the cell cytoskeleton appeared destabilized. LAI-1-dependent inhibition of cell migration involved the scaffold protein IQGAP1, the small GTPase Cdc42 as well as the Cdc42-specific guanine nucleotide exchange factor ARHGEF9, but not other modulators of Cdc42, or RhoA, Rac1 or Ran GTPase. Upon treatment with LAI-1, Cdc42 was inactivated and IQGAP1 redistributed to the cell cortex regardless of whether Cdc42 was present or not. Furthermore, LAI-1 reversed the inhibition of cell migration by L. pneumophila, suggesting that the compound and the bacteria antagonistically target host signaling pathway(s). Collectively, the results indicate that the L. pneumophila quorum sensing compound LAI-1 modulates migration of eukaryotic cells through a signaling pathway involving IQGAP1, Cdc42 and ARHGEF9. PMID:26633832

  18. Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway.

    Directory of Open Access Journals (Sweden)

    Sylvia Simon


    Full Text Available Small molecule signaling promotes the communication between bacteria as well as between bacteria and eukaryotes. The opportunistic pathogenic bacterium Legionella pneumophila employs LAI-1 (3-hydroxypentadecane-4-one for bacterial cell-cell communication. LAI-1 is produced and detected by the Lqs (Legionella quorum sensing system, which regulates a variety of processes including natural competence for DNA uptake and pathogen-host cell interactions. In this study, we analyze the role of LAI-1 in inter-kingdom signaling. L. pneumophila lacking the autoinducer synthase LqsA no longer impeded the migration of infected cells, and the defect was complemented by plasmid-borne lqsA. Synthetic LAI-1 dose-dependently inhibited cell migration, without affecting bacterial uptake or cytotoxicity. The forward migration index but not the velocity of LAI-1-treated cells was reduced, and the cell cytoskeleton appeared destabilized. LAI-1-dependent inhibition of cell migration involved the scaffold protein IQGAP1, the small GTPase Cdc42 as well as the Cdc42-specific guanine nucleotide exchange factor ARHGEF9, but not other modulators of Cdc42, or RhoA, Rac1 or Ran GTPase. Upon treatment with LAI-1, Cdc42 was inactivated and IQGAP1 redistributed to the cell cortex regardless of whether Cdc42 was present or not. Furthermore, LAI-1 reversed the inhibition of cell migration by L. pneumophila, suggesting that the compound and the bacteria antagonistically target host signaling pathway(s. Collectively, the results indicate that the L. pneumophila quorum sensing compound LAI-1 modulates migration of eukaryotic cells through a signaling pathway involving IQGAP1, Cdc42 and ARHGEF9.

  19. 精神分裂症患者5-羟色胺2A受体基因T102C基因型频率的地区差异%Regional differences of genotype frequency of 5-hydroxytryptamine 2A receptor gene T102C of schizophrenics patients

    Institute of Scientific and Technical Information of China (English)

    汪广剑; 王云征; 仲爱芳; 张理义; 王焕林; 赵汉清; 余海鹰; 瞿发林; 苏宗荣; 胡传荣


    背景:由于分子遗传学技术的发展,关于精神疾病与分子遗传的研究日趋增多,但结论不尽一致,对5-羟色胺2A受体基因T102C基因型频率分布是否有地区、种族差异尚需要更多证实.目的:分析精神分裂症患者5-羟色胺2A受体基因T102C基因型频率在地理上的分布设计:以精神分裂症患者为脱察对象的抽样调查.单位:常州和平医院精神科.对象:实验于 1999-01/2003-08在解放军第102医院完成.选取符合中国精神疾病分类和诊断标准第三版关于精神分裂症诊断标准的患者177例,来自不同省区汉族军人,年龄18~45岁,病程1个月~20年.方法:采集117例精神分裂症患者的血样进行聚合酶链反应检测,并比较不同省区区正常对照人群5-羟色胺2A受体基因型频率的分布有何差异.应用常规苯酚氯仿法抽提DNA,目的DNA的聚合酶链反应扩增及电泳检测,5-羟色胺2A受体基因T102C基因片断扩增的引物序列:5'-TCT GCT ACA AGT TCT GGC TT-3'.5'-CTG CAG CTY TTT CTC TAGGG-3';采用50 μL反应体系,DNA 0.5 μg,引物50 pmol,TagDNA酶2U加dNTP至终浓度200μmol/L.主要观察指标:精神分裂症患者DNA电泳检测及5-羟色胺2A受体基因型频率分布.结果:5-羟色胺2A受体各基因型频率分布为:A1A1,0.07~0.33;A1A2,0.50~0.72;A2A2,0.17~0.29.基因型频率在不同地区的相关分析:A1A1,x2=4.44,P=0.617 1,P>0.05;A1A2,x2=1.14,P=0.942 2,P>0.05;A2A2,x2=0.93,P=0.985 7,P>0.05.结论:117例精神分裂症患者5-羟色胺2A受体基因T102C基因型频率的地理分布比较均一.%BACKGROUND:Now researches on psychiatric disease and molecular heredity are becoming more and more gradually because of the development of molecular genetics,but conclusions are controversial,and for the time being there are no reports about whether there are regional differences and ethnical differences in the distribution of genotype frequency of 5-hydroxytryptamine 2A receptor gene T

  20. Sphingosine-1-phosphate/S1P receptors signaling modulates cell migration in human bone marrow-derived mesenchymal stem cells. (United States)

    Kong, Yaxian; Wang, Hong; Lin, Tao; Wang, Shuling


    The recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to damaged tissues and sites of inflammation is an essential step for clinical therapy. However, the signals regulating the motility of these cells are still not fully understood. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is known to have a variety of biological effects on various cells. Here, we investigated the roles of S1P and S1P receptors (S1PRs) in migration of human BMSCs. We found that S1P exerted a powerful migratory action on human BMSCs. Moreover, by employing RNA interference technology and pharmacological tools, we demonstrated that S1PR1 and S1PR3 are responsible for S1P-induced migration of human BMSCs. In contrast, S1PR2 mediates the inhibition of migration. Additionally, we explored the downstream signaling pathway of the S1P/S1PRs axis and found that activation of S1PR1 or S1PR3 increased migration of human BMSCs through a G i /extracellular regulated protein kinases 1/2- (ERK1/2-) dependent pathway, whereas activation of S1PR2 decreased migration through the Rho/Rho-associated protein kinase (ROCK) pathway. In conclusion, we reveal that the S1P/S1PRs signaling axis regulates the migration of human BMSCs via a dual-directional mechanism. Thus, selective modulation of S1PR's activity on human BMSCs may provide an effective approach to immunotherapy or tissue regeneration.

  1. Effect of Combined Acupuncture and Medicine on Striatal DA,NE and 5-hydroxytryptamine in a Mouse Model of Parkinson Disease%针药并用对帕金森病小鼠纹状体DA、NE和5-羟色胺的影响

    Institute of Scientific and Technical Information of China (English)

    陆征宇; 赵虹; 陈洁; 程波; 宗蕾


    Objective To investigate the effect of tremor and depression-relieving prescription plus acupuncture on striatal neurotransmitters DA, NE and 5-HT in a mouse model of Parkinson disease. Methods Twenty-eight adult male C57/BL mice were randomly allocated to four groups: normal, model, Western drug and combined acupuncture and medicine, 7 mice each. Striatal DA, NE and 5-hydroxytryptamine (5-HT) contents were measured by high efficiency liquid chromatography-electrochemical determination in every group of mice. Results Striatal DA, NE and 5-hydroxytryptamine (5-HT)contents were significantly lower in the model, Western drug and combined acupuncture and medicine groups of mice than in the normal group (P<0.01,P<0.05) and significantly higher in the Western drug and combined acupuncture and medicine groups of mice than in the model group (P<0.01, P<0.05). Conclusion Tremor and depression-relieving prescription combined with acupuncture can raise low striatal DA, NE and 5-HT levels.%目的:观察平颤解郁方配合针刺治疗对帕金森病模型小鼠纹状体DA、NE和5-HT等神经递质的影响.方法 :将成年C57/BL雄性小鼠28只随机分为正常组、模型组、西药组和针药组4组,每组7只.采用高效液相色谱-电化学检测法,测定各组小鼠纹状体DA、NE和5-羟色胺(5-HT)的含量.结果 :模型组、西药组和针药组小鼠纹状体DA、NE、5-HT含量均显著低于正常组(P<0.01,P<0.05),西药组和针药组小鼠纹状体DA、NE、5-HT含量显著高于模型组(P<0.01,P<0.05).结论 :平颤解郁方配合针刺治疗可提高纹状体下降的DA、NE、5-HT水平.

  2. IGD motifs, which are required for migration stimulatory activity of fibronectin type I modules, do not mediate binding in matrix assembly.

    Directory of Open Access Journals (Sweden)

    Lisa M Maurer

    Full Text Available Picomolar concentrations of proteins comprising only the N-terminal 70-kDa region (70K of fibronectin (FN stimulate cell migration into collagen gels. The Ile-Gly-Asp (IGD motifs in four of the nine FN type 1 (FNI modules in 70K are important for such migratory stimulating activity. The 70K region mediates binding of nanomolar concentrations of intact FN to cell-surface sites where FN is assembled. Using baculovirus, we expressed wildtype 70K and 70K with Ile-to-Ala mutations in (3FNI and (5FNI; (7FNI and (9FNI; or (3FNI, (5FNI, (7FNI, and (9FNI. Wildtype 70K and 70K with Ile-to-Ala mutations were equally active in binding to assembly sites of FN-null fibroblasts. This finding indicates that IGD motifs do not mediate the interaction between 70K and the cell-surface that is important for FN assembly. Further, FN fragment N-(3FNIII, which does not stimulate migration, binds to assembly sites on FN-null fibroblast. The Ile-to-Ala mutations had effects on the structure of FNI modules as evidenced by decreases in abilities of 70K with Ile-to-Ala mutations to bind to monoclonal antibody 5C3, which recognizes an epitope in (9FNI, or to bind to FUD, a polypeptide based on the F1 adhesin of Streptococcus pyogenes that interacts with 70K by the β-zipper mechanism. These results suggest that the picomolar interactions of 70K with cells that stimulate cell migration require different conformations of FNI modules than the nanomolar interactions required for assembly.

  3. Ganglioside GM2 mediates migration of tumor cells by interacting with integrin and modulating the downstream signaling pathway. (United States)

    Kundu, Manjari; Mahata, Barun; Banerjee, Avisek; Chakraborty, Sohini; Debnath, Shibjyoti; Ray, Sougata Sinha; Ghosh, Zhumur; Biswas, Kaushik


    The definitive role of ganglioside GM2 in mediating tumor-induced growth and progression is still unknown. Here we report a novel role of ganglioside GM2 in mediating tumor cell migration and uncovered its mechanism. Data shows differential expression levels of GM2-synthase as well as GM2 in different human cancer cells. siRNA mediated knockdown of GM2-synthase in CCF52, A549 and SK-RC-26B cells resulted in significant inhibition of tumor cell migration as well as invasion in vitro without affecting cellular proliferation. Over-expression of GM2-synthase in low-GM2 expressing SK-RC-45 cells resulted in a consequent increase in migration thus confirming the potential role GM2 and its downstream partners play in tumor cell migration and motility. Further, treatment of SK-RC-45 cells with exogenous GM2 resulted in a dramatic increase in migratory and invasive capacity with no change in proliferative capacity, thereby confirming the role of GM2 in tumorigenesis specifically by mediating tumor migration and invasion. Gene expression profiling of GM2-synthase silenced cells revealed altered expression of several genes involved in cell migration primarily those controlling the integrin mediated signaling. GM2-synthase knockdown resulted in decreased phosphorylation of FAK, Src as well as Erk, while over-expression and/or exogenous GM2 treatment caused increased FAK and Erk phosphorylation respectively. Again, GM2 mediated invasion and Erk phosphorylation is blocked in integrin knockdown SK-RC-45 cells, thus confirming that GM2 mediated migration and phosphorylation of Erk is integrin dependent. Finally, confocal microscopy suggested co-localization while co-immunoprecipitation and surface plasmon resonance (SPR) confirmed direct interaction of membrane bound ganglioside, GM2 with the integrin receptor.

  4. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2

    DEFF Research Database (Denmark)

    Kozlova, Nina; Jensen, Jan Kristian; Chi, Tabughang Franklin


    of β-catenin abolished this effect. Together, the data of the current study show that PAI-1 can promote cell migration via LRP1-dependent activation of the β-catenin and ERK1/2 MAPK pathway which may be important in stage-specific treatment of human diseases associated with high PAI-1 levels....

  5. In vitro Leishmania major promastigote-induced macrophage migration is modulated by sensory and autonomic neuropeptides

    DEFF Research Database (Denmark)

    Ahmed, A A; Wahbi, A; Nordlind, K


    Recruitment, migration and adherence of macrophages and their interaction with inoculated promastigotes are key steps in the initiation of the inflammatory process in cutaneous leishmaniasis. Parasite- and nervous system-derived factors might be involved in this process. In the present study...

  6. 5- Hydroxytryptamine- inhibiting property of Feverfew: role of parthenolide content

    Institute of Scientific and Technical Information of China (English)

    Aniruddha DATFA; S K SINGH; Amarjit SINGH; Shivani MITIRA


    AIM: To study the mechanism of antimigraine activity of Tanacetum parthenium (Feverfew), its extracts and parthenolide, a component of Feverfew, by observing their effect on 5-HT storage and release, and stimulation of 5-HT2B and 5-HT2A receptors. Also to standardize a dosage form of Feverfew with respect to its parthenolide content. METHODS: Isomeaic responses to 5-HT and an indirect acting serotonergic, d-fenfluramine, were obtained on rat fundus and ileum. In one set of experiments the effect of dichloromethane extract of Feveffew and parthenolide was observed on the above. The extract was then thermally degraded upto 10 %, 23 %, and 33 % with respect to its parthenolide content by keeping at 60 ℃ and 75 % relative humidity and the expe nments were reperepeated. In another set of experiments rats were fed with 20 rog/kg Feverfew powder (equivalent to a human dose of 500 pg parthenolide per day) for 30 d or were ip injected with parthenolide (23.4 μg/day) for 7 d. In the same set of experiments one group of rats were fed with 15 % and 77 % degraded Feverfew powder in the same dose as mentioned above. After 30 days the effects of the above were observed on 5-HT and d-fenfluramine. Feveffew was specially formulated and tested for stability under accelerated conditions. RESULTS: Parthenolide (1 × 10-5 mol/L) non-competitively antagonised the effects of d-fenfluramine but had nosignificant effect on 5-HT2B and 5-HT2A receptors in rat fundus and ileum at 30 ain which turned significant on increasing the incubation time to 1.5 h, in rat fundus. Parthenolide (5 × 10-5 mol/L) followed the same trend.. However, Feverfew extract (1 × 10-5 mol/L) potently and directly blocked 5-HT2B and 5-HT2A receptors and neuronally released 5-HT. At 5 × 10-5 mol/L the extract potently and irreversibly blocked the above. Both parthenolide and Feverfew extract showed a time-dependency in their action. The extract when degraded thermally upto 10 % could significantly block the 5-HT receptors and neuronal release of 5-HT, however, on further degradation it lost its inhibitory capacity markedly. Similar results were observed in rats fed orally with undegraded and degraded Feveffew powder and injected ip with parthenolide. Feverfew powder was more effective than any of its extracts or pure parthenolide. CONCLUSION: Feveffew powder is more potent than any of its extract or parthenolide alone in its antiserotonergic activity. Degraded Feverfew extracts show a marked decrease in their antiserotonergic activity. With thermally degraded Feveffew powder containing less contents of parthenolide no builtup antiserotonergic responses were observed after one month. This ascertains that Feverfew should be dispensed in a properly stabilized form wherein its partbenolide content is not degraded to less than 90 % of the original content.

  7. 5-Hydroxytryptamine 4 Receptor in the Endothelial Cells

    DEFF Research Database (Denmark)

    Profirovic, Jasmina; Vardya, Irina; Voyno-Yasenetskaya, Tatyana


    in the CNS, none of the studies showed its expression and function in the endothelial cells. In the present study, we provide evidence for the first time that 5-HT4 receptor is expressed in the human umbilical vein endothelial cells (HUVECs). We demonstrate the transcription of 5-HT4 mRNA in the HUVECs using...... reverse transcription polimerase chain reaction. Additionally, we show 5- HT4 receptor expression in HUVECs by immunoblotting and immunofluorescent analysis with 5-HT4 specific antibody. Importantly, we determine that overexpression of 5-HT4 receptor leads to a pronounced cell rounding and intercellular...... gap formation in HUVECs. We are currently investigating the mechanism underlying 5-HT4 receptor-induced actin cytoskeleton changes in the endothelial cells. These data suggest that by activating 5-HT4 receptor, serotonin could be involved in regulation of actin cytoskeleton dynamics in the endothelial...

  8. NDUFV2 regulates neuronal migration in the developing cerebral cortex through modulation of the multipolar-bipolar transition. (United States)

    Chen, Tianda; Wu, Qinwei; Zhang, Yang; Zhang, Dai


    Abnormalities during brain development are tightly linked several psychiatric disorders. Mutations in NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2) are responsible for schizophrenia, bipolar disorder and Parkinson׳s disease. However, the function of NDUFV2 during brain development remains unclear. Here we reported that ndufv2 is expressed in the developing cerebral cortex. In utero suppression of ndufv2 arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. ndufv2 inhibition did not affect radial glia scaffold, progenitor cells or neurons survival. However, the loss of ndufv2 impairs neuronal multipolar-bipolar transition in vivo and polarization in vitro. Moreover, ndufv2 affected actin cytoskeleton and tubulin stabilization in cortical neurons. Overall, our findings establish a new NDUFV2 dependent mechanism underlying neuronal migration and psychiatric disorders.

  9. Regulation of cell migration and invasion by specific modules of uPA: mechanistic insights and specific inhibitors. (United States)

    Carriero, Maria Vincenza; Franco, Paola; Votta, Giuseppina; Longanesi-Cattani, Immacolata; Vento, Maria Teresa; Masucci, Maria Teresa; Mancini, Alessandro; Caputi, Mario; Iaccarino, Ingram; Stoppelli, Maria Patrizia


    Urokinase (uPA) is a 411 residues serine protease originally identified for its ability to activate plasminogen and generate plasmin, a broad-spectrum matrix- and fibrin-degrading enzyme. Later, this protease has been shown to possess also a clear-cut ability to stimulate cell migration and survival in a catalytic-independent manner. This activity turned out to be exerted through the growth factor-like domain (GFD-like, residues 1-49) of the protease binding to a GPIanchored membrane receptor (uPAR), in complex with transmembrane receptors such as integrins, the epidermal growth factor and the formyl-peptide receptors. Direct binding of uPA to integrins through its kringle (residues 50-131) and connecting peptide (residues 132-158) regions results in enhanced migration. The dual function of uPA in promoting migration while reducing the physical resistance of extracellular matrix underlies its crucial role in the invasion of malignant tumours. Consolidated evidence emerging from animal models and clinical studies shows that the overexpression of uPA is a causal determinant to tumour metastasis and is associated to a poor prognosis. Therefore, pinpointing the molecular interactions and identifying novel agents to interfere with the diverse activities of uPA is a goal of basic and applied research. In this review, we discuss the general theme of cell migration and invasion. A description of the uPA structure-function relationship and the functional effects of isolated domains is presented. Current information on molecular agonistic as well as antagonistic compounds, including the compounds which have reached clinical trials, is provided.

  10. Meta analysis on the relationship between 5-hydroxytryptamine 2A receptor gene polymorphism T102C and schizophrenia%中国人群5-HT2A受体基因T102C与精神分裂症患者关联性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    黄月薪; 吴娴波; 吴晓翔


    目的 探讨5-羟色胺2A(5-hydroxytryptamine,5-HT2A)受体基因T102C多态性与精神分裂症患者相关性.方法 检索EMBASE、PubMed、CBM、CNKI、万方等数据库,收集在中国地区进行的与5-HT2A受体基因T102C多态性研究相关的文献,按照纳入与排除标准筛选整理相关数据后用Revman 5.0软件进行Meta分析,并进行文献发表偏倚检验.结果 检索到相关研究56篇,纳入符合标准的11篇文献,共收集4 728个研究个体,其中研究组例数2 135例,对照组人数2 593人.各研究均符合Hardy-Weinberg平衡(均P>0.05),Meta分析结果显示5-HT2A受体基因T102C多态性等位基因模型(Tvs C)、隐性基因模型(CC+CT) vs TT和共显性基因模型(TT vs CC和CT vs CC)三种基因模型差异无显著统计学意义(均P>0.05).显性基因模型(CT+TT) vs CC分析结果I2=45%有中度异质性,但采用亚组分析法去除Ni等的数据分析时I2=9%,Z=2.01,P<0.05.结论 5-HT2A受体基因T102C位点C等位基因为隐性基因,CC可能是治病因子,需待进一步循征研究提供证据.%Objective To assess the association of 5-hydroxytryptamine 2A (5-HT2A) receptor gene polymorphism with schizophrenia by Meta analysis.Methods Literatures on the relationship between 5-HT2A receptor gene polymorphism T102C and the Chinese schizophrenia in EMBASE,PubMed,CBM,CNKI and Wanfang Med Online were taken as research objects.Screening the relevant data according to the included and excluded standard,then,Software of RevMan 5.0 was employed to do Meta analysis.Meanwhile,we inspect the literatures publication bias.Results Twelve literatures were included,collecting 4 728 individuals,enrolling 2 135 for the schizophrenia group and 2 593 for the control group.The research conforms to Hardy Weinberg equilibrium (all P>0.05).The Meta analysis results showed that there was no significant association between 5-HT2A receptor gene polymorphism and schizophrenia including the allele model

  11. Synergism interaction between arachidonic acid by 5-hydroxytryptamine in human platelet aggregation is mediated through multiple signalling pathways%多种信号途径介导花生四烯酸与5-羟色胺在促人类血小板凝集中的协同作用

    Institute of Scientific and Technical Information of China (English)

    Sheikh Arshad SAEED; Huma RASHEED; Anwar-ul-Hassan GILANI


    AIM: To examine the signalling mechanisms involved in the synergistic interaction of 5-hydroxytryptamine (5-HT)and arachidonic acid (AA) in human platelet aggregation. METHODS: Blood was obtained from healthy human subjects, mixed with 3.8 % sodium citrate (9:1), and centrifuged to prepare platelet rich plasma (PRP). Aggregation was monitored using a Dual-channel Lumi-aggregometer. The agonist-induced influx of Ca2+ was measured using Fura-2 AM. TXA2 formation was studied using radiochemical method. RESULTS: Subthreshold concentration of 5-HT (2 μmol/L) potentiated the effect of low dose of AA (0.2 mmol/L) in human platelets. This synergistic effect was blocked by 5-HT2 receptor antagonist (methysergide IC50=5.2 nmol/L; cyproheptadine IC50=0.6 nmol/L), and thromboxane A2 receptor antagonist (SQ 29 548; IC50=30 nmol/L), showing that the effect is receptor-mediated.To examine the down-stream signalling pathways, we found that such an interaction was inhibited by calcium channel blockers (diltiazem; IC50=3 μmol/L and verapamil; IC50=5 μmol/L), phospholipase C (PLC) inhibitor (U73122;IC50=4 μmol/L), cyclooxygenase inhibitor, (indomethacin; IC50=0.2 μmol/L) and mitogen-activated protein (MAP)kinase inhibitor (PD98059; IC50=3 μmol/L). The effect was also inhibited by a specific tyrosine light chain kinase (TLCK) inhibitor, herbimycin A with IC50 value of 5 μmol/L. Pretreatment of platelet with 5-HT and AA induced rise in intracellular calcium and this effect was blocked by verapamil. CONCLUSION: The synergism between 5-HT and AA in platelet aggregation involves activation of PLC/Ca2+, COX, and MAP kinase pathways.

  12. MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2

    Directory of Open Access Journals (Sweden)

    Qin X


    Full Text Available Xian Qin,1 Yajun Wan,1 Saiying Wang,2 Min Xue1 1Department of Obstetrics and Gynecology, 2Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China Background: In this study, we intended to understand the regulatory mechanisms of microRNA-125a-5p (miR-125a-5p in human cervical carcinoma.Methods: The gene expressions of miR-125a-5p in seven cervical carcinoma cell lines and 12 human cervical carcinoma samples were evaluated by quantitative real-time reverse transcription polymerase chain reaction. Ca-Ski and HeLa cells were transduced with lentivirus carrying miR-125a-5p mimics, and the effects of lentivirus-induced miR-125a-5p upregulation on cervical carcinoma proliferation and migration were examined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and transwell assays, respectively. In additional, HeLa cells were inoculated into null mice to evaluate the effect of miR-125a-5p upregulation on in vivo cervical carcinoma growth. The direct regulation of miR-125a-5p on its target gene, ABL proto-oncogene 2 (ABL2, in cervical carcinoma was evaluated by quantitative real-time reverse transcription polymerase chain reaction, Western blotting and luciferase reporter assays, respectively. ABL2 was then downregulated by small interfering RNA to examine its effect on cervical carcinoma proliferation and migration.Results: miR-125a-5p was downregulated in both cervical carcinoma cell lines and human cervical carcinomas. In Ca-Ski and HeLa cells, lentivirus-mediated miR-125a-5p upregulation inhibited cancer proliferation and migration in vitro and cervical carcinoma transplantation in vivo. ABL2 was shown to be directly targeted by miR-125a-5p. In cervical carcinoma, ABL2 gene and protein levels were both downregulated by miR-125a-5p. Small interfering RNA-mediated ABL2 downregulation also had tumor-suppressive effects on cervical carcinoma proliferation and migration

  13. Parathyroid hormone-related protein (PTHrP) modulates adhesion, migration and invasion in bone tumor cells. (United States)

    Mak, Isabella W Y; Turcotte, Robert E; Ghert, Michelle


    Parathyroid-hormone-related protein (PTHrP) has been shown to be an important factor in osteolysis in the setting of metastatic carcinoma to the bone. However, PTHrP may also be central in the setting of primary bone tumors. Giant cell tumor of bone (GCT) is an aggressive osteolytic bone tumor characterized by osteoclast-like giant cells that are recruited by osteoblast-like stromal cells. The stromal cells of GCT are well established as the only neoplastic element of the tumor, and we have previously shown that PTHrP is highly expressed by these cells both in vitro and in vivo. We have also found that the stromal cells exposed to a monoclonal antibody to PTHrP exhibited rapid plate detachment and quickly died in vitro. Therefore, PTHrP may serve in an autocrine manner to increase cell proliferation and promote invasive properties in GCT. The purpose of this study was to use transcriptomic microarrays and functional assays to examine the effects of PTHrP neutralization on cell adhesion, migration and invasion. Microarray and proteomics data identified genes that were differentially expressed in GCT stromal cells under various PTHrP treatment conditions. Treatment of GCT stromal cells with anti-PTHrP antibodies showed a change in the expression of 13 genes from the integrin family relative to the IgG control. Neutralization of PTHrP reduced cell migration and invasion as evidenced by functional assays. Adhesion and anoikis assays demonstrated that although PTHrP neutralization inhibits cell adhesion properties, cell detachment related to PTHrP neutralization did not result in associated cell death, as expected in mesenchymal stromal cells. Based on the data presented herein, we conclude that PTHrP excreted by GCT stromal cells increases bone tumor cell local invasiveness and migration.

  14. Low-Molecular-Weight Fucoidan Induces Endothelial Cell Migration via the PI3K/AKT Pathway and Modulates the Transcription of Genes Involved in Angiogenesis

    Directory of Open Access Journals (Sweden)

    Claire Bouvard


    Full Text Available Low-molecular-weight fucoidan (LMWF is a sulfated polysaccharide extracted from brown seaweed that presents antithrombotic and pro-angiogenic properties. However, its mechanism of action is not well-characterized. Here, we studied the effects of LMWF on cell signaling and whole genome expression in human umbilical vein endothelial cells and endothelial colony forming cells. We observed that LMWF and vascular endothelial growth factor had synergistic effects on cell signaling, and more interestingly that LMWF by itself, in the absence of other growth factors, was able to trigger the activation of the PI3K/AKT pathway, which plays a crucial role in angiogenesis and vasculogenesis. We also observed that the effects of LMWF on cell migration were PI3K/AKT-dependent and that LMWF modulated the expression of genes involved at different levels of the neovessel formation process, such as cell migration and cytoskeleton organization, cell mobilization and homing. This provides a better understanding of LMWF’s mechanism of action and confirms that it could be an interesting therapeutic approach for vascular repair.

  15. Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Cheng Cui


    Full Text Available Planar cell polarity (PCP regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin

  16. BDNF-TrkB axis regulates migration of the lateral line primordium and modulates the maintenance of mechanoreceptor progenitors.

    Directory of Open Access Journals (Sweden)

    Eugene V Gasanov

    Full Text Available BDNF and its specialized receptor TrkB are expressed in the developing lateral line system of zebrafish, but their role in this organ is unknown. To tackle this problem in vivo, we used transgenic animals expressing fluorescent markers in different cell types of the lateral line and combined a BDNF gain-of-function approach by BDNF mRNA overexpression and by soaking embryos in a solution of BDNF, with a loss-of-function approach by injecting the antisence ntrk2b-morpholino and treating embryos with the specific Trk inhibitor K252a. Subsequent analysis demonstrated that the BDNF-TrkB axis regulates migration of the lateral line primordium. In particular, BDNF-TrkB influences the expression level of components of chemokine signaling including Cxcr4b, and the generation of progenitors of mechanoreceptors, at the level of expression of Atoh1a-Atp2b1a.

  17. 二十二碳-6烯酸对注意缺陷多动障碍患儿神经生化及行为影响的研究%Effect of correlation of DoCosahexaenoiC acid with attention deficit hyperactivity disorder and dopamine, 5-hydroxytryptamine,adrenocorticotropic hormone

    Institute of Scientific and Technical Information of China (English)

    雷晓梅; 杨玉凤; 吕晔; 刘灵


    [目的]探讨二十二碳6烯酸(DoCosahexaenoiC acid,DHA)对注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)患儿神经生化及行为影响,观察补充DHA对ADHD患儿症状行为的改变情况.[方法]通过对确诊的ADHD儿童补充DHA,检测其血清中多巴胺(dopamine,DA)、5-羟色胺(5-hydroxytryptamine,5-HT)以及促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)的水平在服用前后的变化,并分析这些变化对ADHD儿童行为改变的影响.[结果]①ADHD儿童血清DA、5-HT、ACTH含量在服用前后差异均有显著性(P<0.05).男童血清DA、ACTH水平,女童血清5-HT、ACTH水平,中学生血清DA、5-HT水平在服用前后差异也均有显著性.②服用后儿童行为问题检出率12.5%,低于服用前的37.9%(P<0.05).6~16岁ADHD男童Achenbach儿童行为量表(Child Be havior Checklist,CBCL)行为得分在补充DHA后有所改善(P<0.05).③DA水平与多动指数水平呈负相关(r=-0.300,P<0.05);5-HT水平与注意缺陷指数水平存在负相关(r=-0.434,P<0.05);ACTH水平与注意缺陷指数水平存在边缘正相关(r=0.236,P=0.047).[结论]DHA对ADHD患儿DA、5-HT及ACTH水平有一定调控作用,对改善其临床症状有一定疗效.

  18. 传统抗精神病药物所致迟发性运动障碍的药理遗传学初步研究%Pharmacogenetic assessment of antipsychotic-induced tardive dyskinesia: contribution of 5-hydroxytryptamine 2C receptor gene and of a combination of dopamine D3 variant allele (Gly) and MnSOD wild allele (Val)

    Institute of Scientific and Technical Information of China (English)

    张珺; 侯钢; 张晓斌; 姚辉; 沙维伟; 张心保


    目的进一步探讨多巴胺D2、D3受体(dopamine D2,D3 receptor, DRD2,DRD3)功能基因多态性与迟发性运动障碍(tardive dyskinesia, TD)的相关性及各候选基因,同时包括五羟色胺2C受体(5-hydroxytryptamine 2C receptor, HTR2C)和锰超氧化物歧化酶(manganese superoxide dismutase, MnSOD)基因的相互作用对TD发生的影响.方法使用异常不自主运动量表(abnormal involuntary movement scale, AIMS)评定精神分裂症(schizophrenia, SCH)患者有无TD及其严重程度,并采用简明精神病评定量表评定患者精神症状;应用聚合酶链反应-限制性片段长度多态性技术分析TD组和非TD组各候选基因等位基因和(或)基因型分布频率及其结合分布频率,并分析对AIMS总分值的影响.结果各候选基因在SCH患者组以及TD和非TD组基因型分布均符合Hardy-Weinberg平衡定律;TD组HTR2C基因-697C(突变型)等位基因频率高于非TD组,差异有显著性(P0.05);仅DRD3突变型(Gly)和MnSOD野生型(Val)结合分布频率高于其它结合型,差异有显著性(P0.05).结论 HTR2C基因启动区-697G→C单碱基置换可能是中国汉族男性SCH患者TD发生的易感因素;而SCH患者若同时携带DRD3基因9Gly突变型和MnSOD基因-9Val 野生型等位基因可能增加了TD的易感性.

  19. Difference of 5-hydroxytryptamine expression in intestine of each subgroup of irritable bowel syndrome and its pathological mechanism%肠易激综合征患者肠黏膜5-羟色胺的表达及意义

    Institute of Scientific and Technical Information of China (English)

    孔武明; 张艳鹤; 李光


    Objective To investigate the role of 5-hydroxytryptamine (5-HT)in patients with irritable bowel syndrome (IBS). Methods By immunohistochemieal assay, the 5-HT levels were detected in intestinal mucosa in control group, D-IBS ( diarrhea IBS) group and C-IBS (constipation IBS) group. Results The number of 5-HT positive cell at ileum, proximate colon, distal colon were significantly more than that of control group, and the number of 5-HT positive cell at ileum was even more than C-IBS group. The number of 5-HT positive cell at ileum, proximate colon, distal colon in C-IBS were higher that of control. Conclusions The enchanced 5-HT in intestine is related to the IBS pathological mechanism, while the occurrence of different IBS subgroups is probably related to the difference expression or distribution of receptors of 5-HT in center nerve systerm and gut.%目的 检测肠易激综合征(IBS)患者肠黏膜5-羟色胺(5-HT)表达的差异,探讨外周5-HT在IBS发病中的作用.方法 选择IBS腹泻型(D-IBS)21例、便秘型(C-IBS)22例患者及正常对照组19例,利用免疫组化方法检测各组回肠、近端结肠、远端结肠黏膜5-HT阳性细胞,计数阳性细胞数量并进行分析.结果 D-IBS组回肠、近端结肠、远端结肠5-HT阳性细胞数显著多于对照组(P<0.05),并且回肠黏膜阳性细胞数也多于C-IBS组(P<0.05),C-IBS组回肠、近端结肠、远端结肠阳性细胞显著多于对照组(P<0.05).结论 肠道5-HT的增加与IBS发病相关,IBS不同亚型发病机制可能与5-HT不同受体在中枢神经系统和消化道表达分布有一定关系.

  20. VEGFA upregulates FLJ10540 and modulates migration and invasion of lung cancer via PI3K/AKT pathway.

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    Chang-Han Chen

    Full Text Available BACKGROUND: Lung adenocarcinoma is the leading cause of cancer-related deaths among both men and women in the world. Despite recent advances in diagnosis and treatment, the mortality rates with an overall 5-year survival of only 15%. This high mortality is probably attributable to early metastasis. Although several well-known markers correlated with poor/metastasis prognosis in lung adenocarcinoma patients by immunohistochemistry was reported, the molecular mechanisms of lung adenocarcinoma development are still not clear. To explore novel molecular markers and their signaling pathways will be crucial for aiding in treatment of lung adenocarcinoma patients. METHODOLOGY/PRINCIPAL FINDINGS: To identify novel lung adenocarcinoma-associated /metastasis genes and to clarify the underlying molecular mechanisms of these targets in lung cancer progression, we created a bioinformatics scheme consisting of integrating three gene expression profile datasets, including pairwise lung adenocarcinoma, secondary metastatic tumors vs. benign tumors, and a series of invasive cell lines. Among the novel targets identified, FLJ10540 was overexpressed in lung cancer tissues and is associated with cell migration and invasion. Furthermore, we employed two co-expression strategies to identify in which pathway FLJ10540 was involved. Lung adenocarcinoma array profiles and tissue microarray IHC staining data showed that FLJ10540 and VEGF-A, as well as FLJ10540 and phospho-AKT exhibit positive correlations, respectively. Stimulation of lung cancer cells with VEGF-A results in an increase in FLJ10540 protein expression and enhances complex formation with PI3K. Treatment with VEGFR2 and PI3K inhibitors affects cell migration and invasion by activating the PI3K/AKT pathway. Moreover, knockdown of FLJ10540 destabilizes formation of the P110-alpha/P85-alpha-(PI3K complex, further supporting the participation of FLJ10540 in the VEGF-A/PI3K/AKT pathway. CONCLUSIONS

  1. Modulation of tumor cell stiffness and migration by type IV collagen through direct activation of integrin signaling pathway. (United States)

    Chen, Sheng-Yi; Lin, Jo-Shi; Yang, Bei-Chang


    Excessive collagen deposition plays a critical role in tumor progression and metastasis. To understand how type IV collagen affects mechanical stiffness and migration, low-collagen-IV-expressing transfectants of B16F10, U118MG, and Huh7 (denoted shCol cells) were established by the lentiviral-mediated delivery of small interfering RNA against type IV-α1 collagen (Col4A1). Although having similar growth rates, shCol cells showed a flatter morphology compared to that of the corresponding controls. Notably, knocking down the Col4A1 gene conferred the cells with higher levels of elasticity and lower motility. Exposure to blocking antibodies against human β1 integrin or α2β1 integrin or the pharmacological inhibition of Src and ERK activity by PP1 and U0126, respectively, effectively reduced cell motility and raised cell stiffness. Reduced Src and ERK activities in shCol cells indicate the involvement of a collagen IV/integrin signaling pathway. The forced expression of β1 integrin significantly stimulated Src and ERK phosphorylation, reduced cell stiffness, and accelerated cell motility. In an experimental metastasis assay using C57BL/6 mice, B16F10 shCol cells formed significantly fewer and smaller lung nodules, confirming the contribution of collagen to metastasis. In summary, the integrin signaling pathway activated in a tumor environment with collagen deposition is responsible for low cell elasticity and high metastatic ability.

  2. Unsaturated Fatty Acids Drive Disintegrin and Metalloproteinase (ADAM)-dependent Cell Adhesion, Proliferation, and Migration by Modulating Membrane Fluidity* (United States)

    Reiss, Karina; Cornelsen, Isabell; Husmann, Matthias; Gimpl, Gerald; Bhakdi, Sucharit


    The disintegrin-metalloproteinases ADAM10 and ADAM17 mediate the release of several cell signaling molecules and cell adhesion molecules such as vascular endothelial cadherin or L-selectin affecting endothelial permeability and leukocyte transmigration. Dysregulation of ADAM activity may contribute to the pathogenesis of vascular diseases, but the mechanisms underlying the control of ADAM functions are still incompletely understood. Atherosclerosis is characterized by lipid plaque formation and local accumulation of unsaturated free fatty acids (FFA). Here, we show that unsaturated FFA increase ADAM-mediated substrate cleavage. We demonstrate that these alterations are not due to genuine changes in enzyme activity, but correlate with changes in membrane fluidity as revealed by measurement of 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy and fluorescence recovery after photobleaching analyses. ELISA and immunoblot experiments conducted with granulocytes, endothelial cells, and keratinocytes revealed rapid increase of ectodomain shedding of ADAM10 and ADAM17 substrates upon membrane fluidization. Large amounts of unsaturated FFA may be liberated from cholesteryl esters in LDL that is entrapped in atherosclerotic lesions. Incubation of cells with thus modified LDL resulted in rapid cleavage of ADAM substrates with corresponding functional consequences on cell proliferation, cell migration, and endothelial permeability, events of high significance in atherogenesis. We propose that FFA represent critical regulators of ADAM function that may assume relevance in many biological settings through their influence on mobility of enzyme and substrate in lipid bilayers. PMID:21642425

  3. Unsaturated fatty acids drive disintegrin and metalloproteinase (ADAM)-dependent cell adhesion, proliferation, and migration by modulating membrane fluidity. (United States)

    Reiss, Karina; Cornelsen, Isabell; Husmann, Matthias; Gimpl, Gerald; Bhakdi, Sucharit


    The disintegrin-metalloproteinases ADAM10 and ADAM17 mediate the release of several cell signaling molecules and cell adhesion molecules such as vascular endothelial cadherin or L-selectin affecting endothelial permeability and leukocyte transmigration. Dysregulation of ADAM activity may contribute to the pathogenesis of vascular diseases, but the mechanisms underlying the control of ADAM functions are still incompletely understood. Atherosclerosis is characterized by lipid plaque formation and local accumulation of unsaturated free fatty acids (FFA). Here, we show that unsaturated FFA increase ADAM-mediated substrate cleavage. We demonstrate that these alterations are not due to genuine changes in enzyme activity, but correlate with changes in membrane fluidity as revealed by measurement of 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy and fluorescence recovery after photobleaching analyses. ELISA and immunoblot experiments conducted with granulocytes, endothelial cells, and keratinocytes revealed rapid increase of ectodomain shedding of ADAM10 and ADAM17 substrates upon membrane fluidization. Large amounts of unsaturated FFA may be liberated from cholesteryl esters in LDL that is entrapped in atherosclerotic lesions. Incubation of cells with thus modified LDL resulted in rapid cleavage of ADAM substrates with corresponding functional consequences on cell proliferation, cell migration, and endothelial permeability, events of high significance in atherogenesis. We propose that FFA represent critical regulators of ADAM function that may assume relevance in many biological settings through their influence on mobility of enzyme and substrate in lipid bilayers.

  4. Effects of Chinese herbal medicines for regulating liver qi on expression of 5-hydroxytryptamine 3B receptor in hypothalamic tissues of rats with anger emotion%调肝方药对愤怒和郁怒情绪模型大鼠下丘脑5-羟色胺3B受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    葛庆芳; 张惠云


    Objective: To explore the central mechanisms of anger emotion and the effects of Chinese herbal medicines for regulating liver qi on the anger emotion and the expression level of 5-hydroxytryptamine 3B receptor (5-HT3BR) in rat hypothalamus.Methods: Rat models of anger-in or anger-out emotions were prepared by the methods of resident intruder paradigm. There were five groups in this study: control, anger-in model, Jingqianshu Granule-treated anger-in, anger-out model and Jingqianping Granule-treated anger-out groups. The treatment groups were orally given Jingqianshu granules and Jingqianping granules respectively, and the model groups and the normal control group were given sterile water. Open-field test and sucrose preference test were used to evaluate behavioristics of the rats. Semi-quantitative reverse transcription-polymerase chain reaction and Western blot methods were used to detect the expression levels of 5-HT3BR mRNA and protein in the rat hypothalamus. Results; The expression of 5-HT3BR in hypothalamus of anger-in model rats increased obviously (P<0.01) and that of anger-out model rats decreased obviously (P<0.01) compared with the normal control group. Compared with the model group, the expressions of 5-HT3BR in the treatment groups were significantly improved (P<0.01) after treatment, and recovered to normal level.Conclusion: The anger-in stimulation obviously increases hypothalamic 5-HT3BR expression and the anger-out emotion can obviously reduce its expression. Chinese herbal medicines for regulating liver qi may treat anger emotion in rats by improving the hypothalamic 5-HT3BR protein and gene expression levels.%目的:观察大鼠下丘脑5-羟色胺3B受体(5-hydroxytryptamine 3B receptor,5-HT3BR)表达的变化,探讨大鼠下丘脑5-HT3BR在愤怒和郁怒反应情绪发生机制中的作用,研究中药复方经前平颗粒和经前舒颗粒改善愤怒和郁怒情绪的中枢作用靶点.方法:采用居住入侵结合社会隔离的方法

  5. Antioxidative Dietary Compounds Modulate Gene Expression Associated with Apoptosis, DNA Repair, Inhibition of Cell Proliferation and Migration

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    Likui Wang


    Full Text Available Many dietary compounds are known to have health benefits owing to their antioxidative and anti-inflammatory properties. To determine the molecular mechanism of these food-derived compounds, we analyzed their effect on various genes related to cell apoptosis, DNA damage and repair, oxidation and inflammation using in vitro cell culture assays. This review further tests the hypothesis proposed previously that downstream products of COX-2 (cyclooxygenase-2 called electrophilic oxo-derivatives induce antioxidant responsive elements (ARE, which leads to cell proliferation under antioxidative conditions. Our findings support this hypothesis and show that cell proliferation was inhibited when COX-2 was down-regulated by polyphenols and polysaccharides. Flattened macrophage morphology was also observed following the induction of cytokine production by polysaccharides extracted from viili, a traditional Nordic fermented dairy product. Coix lacryma-jobi (coix polysaccharides were found to reduce mitochondrial membrane potential and induce caspase-3- and 9-mediated apoptosis. In contrast, polyphenols from blueberries were involved in the ultraviolet-activated p53/Gadd45/MDM2 DNA repair system by restoring the cell membrane potential. Inhibition of hypoxia-inducible factor-1 by saponin extracts of ginsenoside (Ginsen and Gynostemma and inhibition of S100A4 by coix polysaccharides inhibited cancer cell migration and invasion. These observations suggest that antioxidants and changes in cell membrane potential are the major driving forces that transfer signals through the cell membrane into the cytosol and nucleus, triggering gene expression, changes in cell proliferation and the induction of apoptosis or DNA repair.

  6. BPAG1a and b associate with EB1 and EB3 and modulate vesicular transport, Golgi apparatus structure, and cell migration in C2.7 myoblasts.

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    Kseniia Poliakova

    Full Text Available BPAG1a and BPAG1b (BPAG1a/b constitute two major isoforms encoded by the dystonin (Dst gene and show homology with MACF1a and MACF1b. These proteins are members of the plakin family, giant multi-modular proteins able to connect the intermediate filament, microtubule and microfilament cytoskeletal networks with each other and to distinct cell membrane sites. They also serve as scaffolds for signaling proteins that modulate cytoskeletal dynamics. To gain better insights into the functions of BPAG1a/b, we further characterized their C-terminal region important for their interaction with microtubules and assessed the role of these isoforms in the cytoskeletal organization of C2.7 myoblast cells. Our results show that alternative splicing does not only occur at the 5' end of Dst and Macf1 pre-mRNAs, as previously reported, but also at their 3' end, resulting in expression of additional four mRNA variants of BPAG1 and MACF1. These isoform-specific C-tails were able to bundle microtubules and bound to both EB1 and EB3, two microtubule plus end proteins. In the C2.7 cell line, knockdown of BPAG1a/b had no major effect on the organization of the microtubule and microfilament networks, but negatively affected endocytosis and maintenance of the Golgi apparatus structure, which became dispersed. Finally, knockdown of BPAG1a/b caused a specific decrease in the directness of cell migration, but did not impair initial cell adhesion. These data provide novel insights into the complexity of alternative splicing of Dst pre-mRNAs and into the role of BPAG1a/b in vesicular transport, Golgi apparatus structure as well as in migration in C2.7 myoblasts.

  7. Paeonia lactiflora Extract Attenuating Cerebral Ischemia and Arterial Intimal Hyperplasia Is Mediated by Paeoniflorin via Modulation of VSMC Migration and Ras/MEK/ERK Signaling Pathway

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    Yuh-Fung Chen


    Full Text Available Paeonia lactiflora is a well-known traditional Chinese medicine. Paeoniflorin is an active component found in Paeonia lactiflora, which is used to treat smooth muscle spasms and pain and to protect the cardiovascular system. The objective of this study was to determine if Paeonia lactiflora would be protective in rodent models of cerebral ischemia and arterial intimal hyperplasia. Paeonia lactiflora extract (PLex and paeoniflorin (PF significantly attenuated cerebral infarction in ischemia/reperfusion injury rats and the severity of intimal hyperplasia in mice where the carotid artery was ligated. PLex and PF reduced PDGF-stimulated VSMC proliferation and migration in a dose-dependent manner by MTT, wound healing, and transwell assays. PF significantly reduced protein levels of Ras, MEK, p-MEK and p-ERK, but not MMP-2 and MMP-9. In summary, Paeonia lactiflora reduced cerebral ischemia and arterial intimal hyperplasia which were mainly made via the intermediary of PF. The protective effect of PF was related to the modulation of the Ras/MEK/ERK signaling pathway.

  8. Trafficking and cell migration. (United States)

    Ulrich, Florian; Heisenberg, Carl-Philipp


    The migration of single cells and epithelial sheets is of great importance for gastrulation and organ formation in developing embryos and, if misregulated, can have dire consequences e.g. during cancer metastasis. A keystone of cell migration is the regulation of adhesive contacts, which are dynamically assembled and disassembled via endocytosis. Here, we discuss some of the basic concepts about the function of endocytic trafficking during cell migration: transport of integrins from the cell rear to the leading edge in fibroblasts; confinement of signalling to the front of single cells by endocytic transport of growth factors; regulation of movement coherence in multicellular sheets by cadherin turnover; and shaping of extracellular chemokine gradients. Taken together, endocytosis enables migrating cells and tissues to dynamically modulate their adhesion and signalling, allowing them to efficiently migrate through their extracellular environment.

  9. 脑室内注射5-羟色胺受体激动剂对正常清醒大鼠排尿反射的影响%Effects of intracerebroventricular administration of 5-hydroxytryptamine receptor agonists on micturition reflex in normal conscious rats

    Institute of Scientific and Technical Information of China (English)

    程曙杰; 吴刚; 曹海兵; 谷宝军


    AIM To investigate the effects of intracerebroventricular administration of 5-hydroxytryptamine (5-HT) receptor agonists on micturition reflex in normal conscious rats.METHODS Thirty normal SD rats were randomized into 5 groups.A PE-50 catheter was placed into the dome of the bladder to record intravesical pressure.And a cerebroventricular cannula was inserted into the right ventricle for the injection of 5-HT, 8-hydroxy-N, N-dipropyl-2-aminotetralin (8-OH-DPAT, agonist at 5-HT1A receptor), 1-methyl-5-HT (agonist at 5-HT2 receptor), 2-methyl-5-HT (agonist at 5-HT3 receptor), and 1-( 4-amino-5-chloro2methoxyphenyl)-3-(1-n-butyl-4piperidinyl)-1-propanone hydrochloride (RS67506, agonist at 5-HT4 receptor).The dosage was 6, 18 or 60 nmol ·kg-1, respectively.Micturition pressure, bladder capacity,micturition volume and residual volume etc, before and after the administration were measured.RESULTS In the normal conscious rats, 6 nmol ·kg-1 5HT, 8-OH-DPAT, 1-methyl-5-HT, or RS67506 injected intracerebroventricularly promoted micturition reflex with decreased bladder capacity and residual volume; 18 nmol·kg-1 promoted micturition reflex more significantly.But there was no effect on cystometric parameters in the rats injected with 2-methyl-5-HT.CONCLUSION In normal conscious rats, 5-HT1A, 5-HT2, 5-HT4 receptor agonists can promote the micturition reflex in the level of superspinal central nervous system.%目的 探讨脑室内注射5-羟色胺(5-HT)受体激动剂对正常清醒大鼠排尿反射的影响.方法 SD大鼠30只随机分为5组,将PE-50聚乙烯导管分别插入大鼠膀胱顶部及右侧脑室进行膀胱测压与药物注入.在脑室内分别注入5-HT、5-HTlA受体激动剂8-OH-DPAT、5-HT2受体激动剂1-甲基-5-HT、5-HT3受体激动剂2-甲基-5-HT以及5-HT4受体激动剂RS67506,剂量分别为6、18或60 nmol·kg-1.记录给药前后的排尿压力、膀胱容量、排尿量以及残尿量等指数的变化.结果 6 nmol·kg-1剂量的5-HT、8

  10. Influence of Xiatian Capsule on Behavior and 5-hydroxytryptamine in Nitroglycerin Caused Migraine Model Rats%夏天胶囊对硝酸甘油偏头痛模型大鼠行为及5-羟色胺含量的影响

    Institute of Scientific and Technical Information of China (English)

    田涛; 王红宇


    目的:观察夏天胶囊对硝酸甘油(GTN)偏头痛模型大鼠行为及5-羟色胺(5-HT)含量的影响。方法将60只大鼠随机分为6组,正常组、模型组、氟桂利嗪(0.5 mg/kg)组及夏天胶囊高、中、低剂量(相当于生药20,10,5 g/kg)组,连续灌胃给药7 d,末次给药后除正常组外所有大鼠均皮下注射GTN(10 mg/kg)复制偏头痛模型。观察大鼠在注射GTN 2~4 h内挠头次数,采用高效液相色谱法测定大鼠脑组织和血清5-HT含量。结果高、中剂量夏天胶囊能明显减少大鼠的挠头次数( P<0.01和 P<0.05);夏天胶囊高、中剂量组脑组织的5-HT含量较模型组显著升高( P <0.01和 P <0.05),高剂量组血清的5-HT含量较模型组显著升高( P <0.05)。结论夏天胶囊能有效缓解偏头痛的临床症状,还可有效升高模型鼠脑组织和血清5-HT的含量。提示其能有效治疗偏头痛的作用机制可能与升高脑组织和血清中5-HT的含量有关。%Objective To observe the influence of Xiatian Capsule on the behavior and 5-hydroxytryptamine(5-HT)content in nitro-glycerin(GTN)caused migraine model rats. Methods 60 rats were randomly divided into 6 groups:normal group,model group and flu-narizine(0. 5 mg/kg)group,high,middle and low dose(20,10,5 g crude drugs/kg)Xiatian Capsule groups. Gavage administration lasted for continuous 7 d. After the last time of gavage administration,all the rats except for the normal group were subcutaneously injected by GTN(10 mg/kg)for duplicating the migraine model. The times for scratching head within 2~4 h after the injection of GTN were ob-served. The high performance liquid chromatography(HPLC)method was adopted to detect the content of brain tissue and serum 5-HT. Results The high and middle dose Xiatian Capsule groups could significantly reduce the times of scratching head( P < 0. 01,P < 0. 05);the brain tissues 5-HT content in the high and middle dose Xiatian

  11. 地西泮减弱5-羟色胺收缩老年大鼠离体胸主动脉的作用及其机制%Diazepam attenuates 5-hydroxytryptamine-induced contractions of thoracic aorta in elderly rats

    Institute of Scientific and Technical Information of China (English)

    高雪梅; 王微; 张轩萍; 范俊强; 张明升


    Objective To investigate the action of diazepam (DZP) on 5-hydroxytryptamine-induced contrac tions of thoracic aorta in elderly rats and probable mechanism that underlies this action. Methods Tonometry was used to determine the effects of DZP on 5-HT induced contractions in the thoracic aortic rings isolated from elderly rats. The influences of various drugs which include NG-nitro-L-arginine methyl ester (L-NAME, 10-4 mol/L), in domethacin (10-5 mol/L) and PK11195 (10-6 mol/L) on the effects of DZP were observed. Results ① (0.01~3)×10-5 mol/L 5-HT produced a concentration-dependent contraction in isolated thoracic aorta rings of elderly rats. The EC50 of 5-HT was ahout 3×10 mol/L. ② In the isolated thoracic aorta rings of elderly rats with intact endothelium, DZP (3× 10-6 mol/L) significantly attenuated the Emax of 5-HT induced vasoconstriction, compared with that of the rings not treated with DZP (P<0.01). There was no significant effect of DZP on rings with denuded endothelium (P>0.05). ③ The effects of DZP (3×10-6 mol/L) on the 5-HT induced vasoconstriction was suppressed by L-NAME, a nitric oxide syn thase inhibitor (P<0.01), but not by cyclooxygenase inhibitor indomethacin and PK11195. Conclusion 5-HT could produce concentration-dependent vasoconstriction in isolated thoracic aorta rings of elderly rats. DZP could attenuate the vasoconstriction effects of 5-HT in an endothelium-dependent manner. The underlying mechanisms may involve release of NO from endothelium, but not PCI2 and the peripheral benzodiazepine receptor.%目的 观察地西泮(DZP)对5-羟色胺(5-HT)诱导收缩的老年大鼠离体胸主动脉环的作用,并探讨其可能的机制.方法 采用离体血管张力记录法,观察5-HT 对老年大鼠离体胸主动脉环的作用及DZP的影响.结果 ①5-HT[(0.01~3)×10-5 mol/L]对老年大鼠离体胸主动脉环具有浓度依赖性的收缩作用,血管环收缩达最大收缩50%时的药物浓度(EC50)值约为3×10

  12. 多巴胺、5-羟色胺通路相关基因及家庭环境对创造力的影响及其作用机制%The Genetic Basis of Creativity in Dopamine and 5-hydroxytryptamine Pathway and the Moderating Effect of Family Environment

    Institute of Scientific and Technical Information of China (English)

    张景焕; 张木子; 张舜; 任菲菲


    Identification and exploration of the genetic basis of creativity as well as the possible mechanism through which they interact with environmental factors to contribute to creativity has been a leading issue in creativity research. The overarching goal of this project is to investigate the effect of about 700 SNPs on 32 genes in dopamine (DA) and 5-hydroxytryptamine (5-HT) pathway on creativity in the Han Chinese population, and to explore and characterize the interaction of the above genetic polymorphisms and family environmental factors in contributing to creativity. It is designed that one thousand university students participate in this project and three specific aims are expected: (1) To examine associations between creativity and genetic polymorphisms in DA and 5-HT pathways through three levels of association analysis (single gene association analysis, pathway-based association analysis and gene-gene interaction association analysis). (2) To examine the moderating effect of family environmental factors (including family’s socioeconomic status, family atmosphere and parenting style ) on the relationship between the above genetic polymorphisms and creativity. (3) To examine the common and differential mechanism of creative thinking and creative personality. It is expected that this project will advance our understanding of creativity from the perspective of the interactions between genetic and environmental factors, and will further help to construct a theoretical model based on analysis of creativity individual differences and also help to provide some useful insight into creativity assessing and cultivating.%创造力的遗传基础是近年来创造力研究领域的前沿和热点问题,但仍尚处于起步阶段,也未有研究系统探讨遗传与环境因素的交互作用对创造力的影响及其作用机制。本课题拟在中国汉族人群中考察多巴胺(DA)、5-羟色胺(5-HT)神经递质通路上的32个基因约700个多态性位点

  13. Return migration. (United States)

    Gmelch, G


    The author reviews the findings of the growing literature on return migration. Topics covered include typologies of return migrants, reasons for return, adaptation and readjustment of returnees, and the impact of return migration on the migrants' home societies. The focus of the study is on international return migration, migration to Northern Europe and northeastern North America, and return migration to the southern and eastern fringes of Europe and the Caribbean

  14. Bordetella adenylate cyclase toxin differentially modulates toll-like receptor-stimulated activation, migration and T cell stimulatory capacity of dendritic cells.

    Directory of Open Access Journals (Sweden)

    Irena Adkins

    Full Text Available Adenylate cyclase toxin (CyaA is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, we analyzed the modulatory effects of CyaA on adhesive, migratory and antigen presenting properties of Toll-like receptor (TLR-activated murine and human dendritic cells (DCs. cAMP signaling of CyaA enhanced TLR-induced dissolution of cell adhesive contacts and migration of DCs towards the lymph node-homing chemokines CCL19 and CCL21 in vitro. Moreover, we examined in detail the capacity of toxin-treated DCs to induce CD4(+ and CD8(+ T cell responses. Exposure to CyaA decreased the capacity of LPS-stimulated DCs to present soluble protein antigen to CD4+ T cells independently of modulation of co-stimulatory molecules and cytokine production, and enhanced their capacity to promote CD4(+CD25(+Foxp3(+ T regulatory cells in vitro. In addition, CyaA decreased the capacity of LPS-stimulated DCs to induce CD8(+ T cell proliferation and limited the induction of IFN-γ producing CD8(+ T cells while enhancing IL-10 and IL-17-production. These results indicate that through activation of cAMP signaling, the CyaA may be mobilizing DCs impaired in T cell stimulatory capacity and arrival of such DCs into draining lymph nodes may than contribute to delay and subversion of host immune responses during B. pertussis infection.

  15. Alternagin-C, a disintegrin-like protein from the venom of Bothrops alternatus, modulates a2ß1 integrin-mediated cell adhesion, migration and proliferation

    Directory of Open Access Journals (Sweden)

    Selistre-de-Araujo H.S.


    Full Text Available The alpha2ß1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Alternagin-C (ALT-C, a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, competitively interacts with the alpha2ß1 integrin, thereby inhibiting collagen binding. When immobilized in plate wells, ALT-C supports the adhesion of fibroblasts as well as of human vein endothelial cells (HUVEC and does not detach cells previously bound to collagen I. ALT-C is a strong inducer of HUVEC proliferation in vitro. Gene expression analysis was done using an Affimetrix HU-95A probe array with probe sets of ~10,000 human genes. In human fibroblasts growing on collagen-coated plates, ALT-C up-regulates the expression of several growth factors including vascular endothelial growth factor, as well as some cell cycle control genes. Up-regulation of the vascular endothelial growth factor gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates protein kinase B phosphorylation, a signaling event involved in endothelial cell survival and angiogenesis. In human neutrophils, ALT-C has a potent chemotactic effect modulated by the intracellular signaling cascade characteristic of integrin-activated pathways. Thus, ALT-C acts as a survival factor, promoting adhesion, migration and endothelial cell proliferation after binding to alpha2ß1 integrin on the cell surface. The biological activities of ALT-C may be helpful as a therapeutic strategy in tissue regeneration as well as in the design of new therapeutic agents targeting alpha2ß1 integrin.

  16. Effect of Acupuncture Combined with Antidepressant on Behavioral Changes, and mRNA Expression of 5-Hydroxytryptamine Receptors in Nucleus Raphes Dorsalis of Sleep Deprivation Depression Rats%针药结合对抑郁症睡眠障碍大鼠行为学与中缝背核5-羟色胺受体mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    俞裕天; 袁青; 陈津岩; 谢津津; 郎建英; 麦嘉玲; 曾晓林; 汪满霞; 薛尔平


    Objective To investigate the effect of acupuncture combined with antidepressant on behavioral changes and 5-hydroxytryptamine 1A and 2A receptor ( 5-HT1AR and 5-HT2AR) mRNA expression in nucleus raphes dorsalis (NRD) of sleep deprivation depression (SDD) rats. Methods Eight normal Sprague Dawley (SD) rats were caged together without any stimulus or treatment, serving as the normal group. Thirty-two SD rats were given solitary raise for 21 days, together with chronic unpredictable mild stress ( CUMS) and rapid eye movement ( REM) sleep deprivation to establish the model. Twenty-eight rats completed the modeling successfully, and were divided into model group, acupuncture group, medicine group, and combination group, 7 rats in each group. Rats in the model group were given modeling treatment but without any intervention. Rats in the acupuncture group were given acupuncture on acupoint Yintang, Shenting and bilateral Taichong, acupuncture stimulation lasting 15 s every 10 min and acupuncture retention for 20 min in each day. Rats in the medicine group were given gastric gavage of Zoloft solution (0.83 mg·kg-1·d-1) and Alprazolam solution (0.067 mg· kg-1·d-1) , and rats in the combination group were given both acupuncture and medicine intervention. The intervention for the three intervention groups lasted for 7 days. Results Compared with the normal group, body weight, Open-field scores and sucrose preference of the model rats were significantly decreased on modeling day 7, 14, 21 (P<0.05). On modeling day 28, body weight and Open-field scores of each intervention group were significantly increased compared with those of the model group (P<0.05), and Open-field scores of combination group differed from those of acupuncture group and medicine group ( P<0.05). Only sucrose preference of combination group was improved significantly compared with the model group (P<0.05). Compared with the model group, NRD 5-HT1AR mRNA expression level was increased in the combination

  17. Experimental study of 5-hydroxytryptamine 1A receptor agonist to improve the voiding dysfunction in diabetic rats%5-羟色胺1A受体激动剂改善糖尿病大鼠排尿功能障碍的实验研究

    Institute of Scientific and Technical Information of China (English)

    陈加生; 吴刚; 谷宝军


    目的 研究5-羟色胺1A(5-HT1A)受体激动剂对糖尿病大鼠排尿障碍的改善作用.方法 SD雌性大鼠14只,体质量250~ 275 g.采用随机数字表法随机分成2组:实验组7只腹腔注射链脲霉素65 mg/kg建立糖尿病大鼠模型,对照组7只.8周后乌拉坦1.3 g/kg麻醉下,2组大鼠颈静脉和膀胱内置管,连接压力感受器,记录排尿量、残余尿量、膀胱容量和尿道外括约肌的肌电活动.静脉注入5-HT1A受体激动剂8-羟基-丙胺-四氢萘(8-OH-DPAT,0.003~ 1.000 mg/kg),得到剂量-效应曲线后再给予5-HT1A受体抑制剂WAY-100635(0.300 mg/kg).观察比较2组大鼠用药前后尿动力学指标的变化. 结果 糖尿病大鼠膀胱容量、残余尿量高于对照组大鼠,排尿效率下降.随着8-OH-DPAT(0.003~ 1.000 mg/kg)剂量增加,糖尿病大鼠排尿量从(2.15±0.49) ml增至(2.85±0.21) ml,残余尿量从(3.40±0.74) ml降至(1.82±.0.48) ml,排尿效率从(39.0±9.3)%增至(61.6±6.9)%.对照组大鼠用药前后排尿情况变化差异无统计学意义(P>0.05).肌电图显示8-OH-DPAT能改善糖尿病大鼠受损的尿道外括约肌高频舒张收缩功能,对于对照组大鼠也有增强作用.而WAY-100635能逆转8-OH-DPAT的效应. 结论 糖尿病大鼠尿道外括约肌高频舒张收缩活动减弱,排尿效率下降.5-HT1A受体激动剂8-OH-DPAT可以部分恢复糖尿病大鼠尿道外括约肌协调性松弛,从而提高排尿效率,改善排尿障碍.%Objective To investigate the effect of 5-hydroxytryptamine 1A (5-HT1A) receptor agonists to improve micturition function in rats with diabetes mellitus (DM).Methods Fourteen female SD rats with the weight of 250 to 275 g were used.Seven rats were in the DM model group with intraperitoneal injection streptozotocin (STZ,65 mg/kg).Rats in the control group and DM group were anesthetized with urethane (1.3 g/kg) 8 weeks later.A polyethylene (PE)-50 catheter were placed in the left jugular vein for intravenous

  18. 母鼠妊娠前慢性不可预见性应激对胎鼠大脑5-羟色胺1A受体表达的影响%Effect of Pregestational Chronic Unpredictable Stress on Expression of 5-Hydroxytryptamine 1A Receptor of Brain in Fetal Rats

    Institute of Scientific and Technical Information of China (English)

    黄月君; 史雪川; 许宏武; 杨汉华; 陈思红; 陈晓东


    Objective To investigate the effect of chronic unpredictable stress(CUS) before pregnancy on serum cortisol(COR) level of maternal rats and the expression of 5 - hydroxytryptamine 1A(5 - HT1 A) of brain in fetal rats.Methods Adult female SD rats were divided randomly into 2 groups: control group (n = 8 )and C US model group( n = 12).All rats were tested in the open field test and sucrose intake test before and after CUS protocol.All maternal rats were sacrificed in embryonic day 20.Serum COR level of maternal rats was determined by using a standard radioimmunoassay kit.The expression levels of 5 - HT1A receptor mRNA in hippocampus, hypothalamus and prefrontal cortex of fetal rats were studied by reverse transcription polymerase chain reaction ( RT - PCR).Results 1.After CUS, the total distance, central distance and peripheral distance in the open field test and sucrose consumption in sucrose intake test of CUS group decreased compared with those before CUS and control group.2.CUS induced a significant increase in cortisol levels of the maternal rats( 190.2 ± 19.8 ) μg · L-1,compared with the control group[( 155.3 ± 14.4) μg · L-1].3.The body weight and brain weight between the fetal rats of 2 groups had no statistic significance.4.RT - PCR showed that the level of 5 - HT1 A receptor mRNA in the hippocampus of CUS group( 0.228 ± 0.132 ) less than in control group(0.286 ± 0.025 ), as well as in prefrontal cortex of CUS group(0.249 ± 0.027 )compared with control group (0.266 ±0.028 ) (Pa < 0.01 ), but it had no effect in hypothalamus( P > 0.05 ).Conclusion Progestational CUS reduced the expression of 5 - HT1 A receptor in corresponding brain of the fetus which related with COR.%目的 观察母鼠妊娠前接受慢性不可预见性应激(CUS)后皮质醇(COR)水平改变对胎鼠大脑不同区域5-羟色胺1A(5-HT1A)受体表达的影响.方法 SD成年健康雌性大鼠20只随机分为正常对照母鼠组(8只)和CUS母鼠组(12只).采用11种

  19. The expression and effect of 5-hydroxytryptamine 7 receptor in brain and intestine of rats with irritable bowel syndrome%肠易激综合征模型大鼠5-羟色胺7受体的表达及作用

    Institute of Scientific and Technical Information of China (English)

    邹百仓; 董蕾; 王深皓; 曹铭波; 王燕


    目的 观察5-羟色胺7受体在肠易激综合征(IBS)不同亚型模型大鼠大脑和消化道组织中表达和分布的差异,探讨其在IBS发病中的作用.方法 45只成年SD大鼠分均为对照组、腹泻型IBS(IBS-D)组和便秘型IBS(IB-C)组.乙酸加束缚应激法制备IBS-D模型,冰水灌胃法制备IBS-C模型.免疫组化法和实时定量PCR法检测各组大鼠大脑、空肠、回肠、近端结肠、远端结肠中5-HT7受体的分布及表达差异.放射免疫法测定以上各组织中环磷酸腺苷(cAMP)含量.结果 免疫组化结果 显示,IBS-C组和IBS-D组海马及下丘脑、IBS-C组回肠、近端结肠、远端结肠5-HT7受体表达强于对照组(P<0.05).实时定量PCR结果 显示,IBS-C和IBS-D组海马和下丘脑、IBS-C组回肠、近端结肠及远端结肠5-HT7受体mRNA明显高于对照组(P<0.05).IBS-C和IBS-D组海马和下丘脑、IBS-C组近端结肠和远端结肠cAMP含量显著高于对照组(P<0.05).结论 两组大鼠脑组织及IBS-C大鼠结肠5-HT7受体表达及cAMP水平明显增高,可能与IBS-C胃肠动力障碍和内脏感觉异常有关.%Objective To investigate the expression and distribution of 5-hydroxytryptamine 7(5-HT7)receptor in brain and intestine of rats with different subtype of irritable bowel syndrome(IBS).Methods Forty-five SD rats were divided into healthy contral.diarrhea-predominant(IBS-D)and consti pation-predominant(IBS-C)IBS groups.IBS-D and IBS-C models were established by either colonic instillation of acetic acid and restraint stress or stomach irrigation with cool water(0-4℃).The expression and distribution of 5-HT7 receptor at brain and intestine were determined by immunohistochemistry and real-time PCR.The tissue concentration of cyclic AMP(cAMP)was examined by radioimmunoassay.Results Immunohistochemistry study demonstrated that the staining of 5-HT7 receptor at hippocampus and hypothalamus were strong in IBS-C and IBS-D groups compared to control group(P<0

  20. Study of intervention effect and its mechanism of 5-hydroxytryptamine 1A receptor agonist 8-OH-DPAT on epileptic rats with depression%5-羟色胺1A受体激动剂8-OH-DPAT对癫痫合并抑郁大鼠的干预作用及其机制研究

    Institute of Scientific and Technical Information of China (English)

    李琼; 孙美珍; 杨萍


    目的 探讨5-羟色胺1A(5-HT1A)受体激动剂8-OH-DPAT对癫痫合并抑郁大鼠的干预作用及其机制.方法 成年级SD大鼠160只,随机选取8只为正常对照组,其余大鼠采用匹罗卡品诱导慢性癫痫大鼠模型.25 d后通过体质量与摄食量测量及旷场试验筛选出癫痫合并抑郁模型大鼠32只,随机分为模型组、卡马西平(CBZ)组、CBZ+ 8-OH-DPAT低剂量组(8-OH-DPAT低剂量组)及CBZ+ 8-OH-DPAT高剂量组(8-OH-DPAT高剂量组);分别给予CBZ 100 mg/kg、CBZ +8-OH-DPAT 0.1mg/(kg·d)、CBZ+ 8-OH-DPAT 1 mg/(kg·d).连续治疗7d后,进行癫痫发作的Racine分级、体质量、摄食量测量及旷场试验;采用荧光实时定量聚合酶链反应测定大鼠海马齿状回神经生长因子(NGF) mRNA表达,免疫组化染色观察苔藓纤维出芽(M FS).结果 治疗后,与正常对照组比较,模型组、CBZ组、8-OH-DPAT低、高剂量组的体质量与摄食量明显下降,海马NGF mRNA表达与Timm评分明显增高(均P<0.05).与模型组比较,CBZ组、8-OH-DPAT低、高剂量组的体质量、摄食量及旷场试验评分明显提高,Racine分级、海马NGF mRNA表达与Timm评分明显下降(均P<0.05);其中8-OH-DPAT高剂量组上述改变更明显(均P<0.05).结论 高剂量的5-HT1A受体激动剂8-OH-DPAT能抑制癫痫合并抑郁大鼠海马齿状回的MFS和神经生长因子的表达,促进海马神经重塑.这可能是5-HT1A受体激动剂抗癫痫、抗抑郁的分子机制之一.%Objective To study intervention effect and its mechanism of 5-hydroxytryptamine 1A (5-HT1A)receptor agonist 8-OH-DPAT on epileptic rats with depression.Methods Eight rats were randomly selected from 160 adult SD rats as normal control (NC) group,the other rats were induced epilepsy with pilocarpine.After 25 d,32 epileptic rats with depression were selected by the body weight and food intake measurements and open field test,and were randomly divided into model group,carbamazepine (CBZ) group

  1. Learning and cognitive flexibility: frontostriatal function and monoaminergic modulation. (United States)

    Kehagia, Angie A; Murray, Graham K; Robbins, Trevor W


    Learning in a constant environment, and adapting flexibly to a changing one, through changes in reinforcement contingencies or valence-free cues, depends on overlapping circuitry that interconnects the prefrontal cortex (PFC) with the striatum and is subject to several forms of neurochemical modulation. We present evidence from recent studies in animals employing electrophysiological, pharmacological and lesion techniques, and neuroimaging, neuropsychological and pharmacological investigations of healthy humans and clinical patients. Dopamine (DA) neurotransmission in the medial striatum and PFC is critical for basic reinforcement learning and the integration of negative feedback during reversal learning, whilst orbitofrontal 5-hydroxytryptamine (5-HT) likely mediates this type of low level flexibility, perhaps by reducing interference from salient stimuli. The role of prefrontal noradrenaline (NA) in higher order flexibility indexed through attentional set-shifting has recently received significant empirical support, and similar avenues appear promising in the field of task switching.

  2. MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells

    Directory of Open Access Journals (Sweden)

    Yamashita Shunichi


    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is often diagnosed at later stages until they are incurable. MicroRNA (miR is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC. Methods Total RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR. Results Based on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2

  3. 孤独症患儿血浆 5-羟色胺水平与出生季节和母亲孕期情绪的相关性%Correlation of plasma 5 hydroxytryptamine levels with season of birth and maternal mood during pregnancy in children with autism

    Institute of Scientific and Technical Information of China (English)

    张献共; 李思特; 李雪荣; 朱荣华; 罗学荣; 苏林雁; 陈劲梅; 颜家睦


    ACKGROUND:Autism is a kind of neurobiological disease.The increase of plasma concentration of 5 hydroxytryptamine(5 HT) is considered to be one of study results,which is the most definite and has the best repetition,for the biological investigation of autism. Whether the season of birth and maternal mood during pregnancy are correlated with the occurrence of autism? OBJECTIVE:To compare the differences of the plasma concentration of 5 HT,season of birth and the maternal mood during pregnancy between autistic and normal children,and probe into the cause of increased 5 HT in autism. DESIGN:An observational comparative study taking autistic and normal children as the subjects. SETTINGS:A clinical psychological department of a university hospital;Mental Health Institute of the Xiangya Second Hospital;A rehabilitation center for dumb children of city grade. PARTICIPANTS:Children in the autistic group(n=54),who were in accordance with the diagnostic criteria of autism in Diagnostic and Statistical Manual of Mental Disorders Fourth Edition(DSM IV) and had the total score of social adaptive ability scale(SAAS) over 40, were selected from the Outpatient Clinic for Children of the Mental Health Institute,Xiangya Second Hospital of Central South University and the training class of autism of Shenzhen Special Education School;Children in the normal control group,who had no obvious somatic and neurological diseases,and developing delay detected by physical,neurological and mental status examinations, rough detection of developing level,were selected from the primary school and kindergarten in Changsha and Shenzhen cities. INTERVENTIONS:The plasma level of 5 HT was examined, season of birth and maternal mood during pregnancy were investigated in autistic and normal children.The children with autism were accessed with SAAS. MAIN OUTCOME MEASURES:The plasma level of 5 HT,the season of birth and the maternal mood during pregnancy in both groups. RESULTS:The score of SAAS in

  4. 伴有对立违抗障碍注意缺陷多动障碍患儿智力和行为特征及与血清 5- 羟色胺水平的关系%Intellectual and behavioral characteristics and their relations with serum 5 hydroxytryptamine level in children with attention deficit hyperactivity disorder complicated by oppositional defiant disorder

    Institute of Scientific and Technical Information of China (English)

    高雪屏; 苏林雁; 谢光荣; 黄春香; 李雪荣


    BACKGROUND:Oppositional defiant disorder(ODD) often occurs as a comorbid condition of attention deficit hyperactivity disorder(ADHD),characterized by defiant behaviors.ADHD children with ODD have more extensive impairments than those with ADHD alone. Some studies suggest that decreased serum 5 hydroxytryptamine(5 HT) level is related to aggressive behavior in ADHD, but no relevant report is available in China. OBJECTIVE:To investigate the clinical features of ADHD with ODD,and their relations with serum 5 HT. DESIGN:A randomized case controlled study taking the ADHD children with or without ODD as the subjects for study. SETTING:Mental Health Institute of the Second Xiangya Hospital. PARTICIPANTS:Sixty one ADHD children(53 boys and 8 girls) aged 7 to 14 years visiting the Children's Clinic of Mental Health Institute of Central South University from June 2002 to May 2003 were recruited and divided into two groups based on the symptomatic criteria of ODD recommended by the Diagnostic and Statistical Manual of Mental Disorder(DSM Ⅳ ):ADHD group(n=33,without ODD) and ADHD+ ODD group(n=28). INTERVENTIONS:The parents of the enrolled children(n=61) were asked to complete the Achenbach child behavior checklist (CBCL),and the teachers(n=31) completed the teacher's report form (TRF).Two milliliters of fasting venous blood was drawn from these children and the serum separated by centrifugation for quantification of 5 HT using external standard method,and whole blood 5 HT was analyzed by LD 10AD high performance liquid chromatography(HPLC). MAIN OUTCOME MEASURES:Scores of CBCL,TRF and Chinese Wechsler Intelligence Scale for Children(C WISC) and serum 5 HT levels. RESULTS:In the ADHD+ ODD group,the scores of CBCL and TRF for externalizing, aggressive behaviors and total scores for behavioral problems rated by the parents and teachers were significantly higher than those of the ADHD group(t=2.28 to 3.76,P< 0.05 to 0.01);the former group also had significantly higher scores of

  5. The CLC-2 Chloride Channel Modulates ECM Synthesis, Differentiation, and Migration of Human Conjunctival Fibroblasts via the PI3K/Akt Signaling Pathway. (United States)

    Sun, Lixia; Dong, Yaru; Zhao, Jing; Yin, Yuan; Zheng, Yajuan


    Recent evidence suggests that chloride channels are critical for cell proliferation, migration, and differentiation. We examined the effects of transforming growth factor (TGF)-β1 on chloride channel expression and associations with human conjunctival fibroblast (HConF) biology. To investigate the potential role of chloride channel (CLC)-2 in migration, transition to myofibroblasts and extracellular matrix (ECM) synthesis of HconF, a small interfering RNA (siRNA) approach was applied. TGF-β1-induced migration and transition of fibroblasts to myofibroblasts characterized by α-smooth muscle actin (α-SMA) expression, supported by increased endogenous expression of CLC-2 protein and mRNA transcripts. ECM (collagen I and fibronectin) synthesis in HConF was enhanced by TGF-β1. CLC-2 siRNA treatment reduced TGF-β1-induced cell migration, transition of fibroblasts to myofibroblasts, and ECM synthesis of HConF. CLC-2 siRNA treatment in the presence of TGF-β1 inhibited phosphorylation of PI3K and Akt in HConF. These findings demonstrate that CLC-2 chloride channels are important for TGF-β1-induced migration, differentiation, and ECM synthesis via PI3K/Akt signaling in HConF.

  6. Lactate-modulated induction of THBS-1 activates transforming growth factor (TGF-beta2 and migration of glioma cells in vitro.

    Directory of Open Access Journals (Sweden)

    Corinna Seliger

    Full Text Available BACKGROUND: An important phenomenon observed in glioma metabolism is increased aerobic glycolysis in tumor cells, which is generally referred to as the Warburg effect. Transforming growth factor (TGF-beta2, which we previously showed to be induced by lactic acid, is a key pathophysiological factor in glioblastoma, leading to increased invasion and severe local immunosuppression after proteolytic cleavage from its latency associated peptide. In this study we tested the hypothesis, that lactate regulates TGF-beta2 expression and glioma cell migration via induction of Thrombospondin-1 (THBS-1, a TGF-beta activating protein. METHODS: Lactate levels were reduced by knockdown of LDH-A using specific small interfering RNA (siRNA and competitive inhibition of LDH-A by sodium oxamate. Knockdown of THBS-1 was performed using specific siRNA. Western Blot, qRT-PCR, and ELISA were used to investigate expression levels of LDH-A, LDH-B, TGF-beta2 and THBS-1. Migration of cells was examined by Spheroid, Scratch and Boyden Chamber assays. RESULTS: Knockdown of LDH-A with subsequent decrease of lactate concentration leads to reduced levels of THBS-1 and TGF-beta2 in glioma cells. Lactate addition increases THBS-1 protein, leading to increased activation of TGF-beta2. Inhibition of THBS-1 reduces TGF-beta2 protein and migration of glioma cells. Addition of synthetic THBS-1 can rescue reduced TGF-beta2 protein levels and glioma cell migration in siLDH-A treated cells. CONCLUSION: We define a regulatory cascade between lactate, THBS-1 and TGF-beta2, leading to enhanced migration of glioma cells. Our results demonstrate a specific interaction between tumor metabolism and migration and provide a better understanding of the mechanisms underlying glioma cell invasion.

  7. Distribution of a 69-kD laminin-binding protein in aortic and microvascular endothelial cells: modulation during cell attachment, spreading, and migration

    DEFF Research Database (Denmark)

    Yannariello-Brown, J; Wewer, U; Liotta, L;


    Affinity chromatography and immunolocalization techniques were used to investigate the mechanism(s) by which endothelial cells interact with the basement membrane component laminin. Bovine aortic endothelial cells (BAEC) membranes were solubilized and incubated with a laminin-Sepharose affinity...... column. SDS-PAGE analysis of the eluted proteins identified a 69-kD band as the major binding protein, along with minor components migrating at 125, 110, 92, 85, 75, 55, and 30 kD. Polyclonal antibodies directed against a peptide sequence of the 69-kD laminin-binding protein isolated from human tumor......, with a granular perinuclear distribution and in linear arrays throughout the cell. During migration a redistribution from diffuse to predominanately linear arrays that co-distributed with actin microfilaments was noted in double-label experiments. The 69-kD laminin-binding protein colocalized with actin filaments...

  8. MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer cells by modulating MAPK signaling, cell cycle regulators, and Ets-1-mediated MMP-2 expression. (United States)

    Shin, Seung-Shick; Park, Sung-Soo; Hwang, Byungdoo; Kim, Won Tae; Choi, Yung Hyun; Kim, Wun-Jae; Moon, Sung-Kwon


    Despite the clinical significance of tumorigenesis, little is known about the cellular signaling networks of microRNAs (miRs). Here we report a new finding that mir‑106a regulates the proliferation, migration, and invasion of bladder cancer cells. Basal expression levels of mir‑106a were significantly lower in bladder cancer cells than in normal urothelial cells. Overexpression of mir‑106a suppressed the proliferation of bladder cancer cell line EJ. Transient transfection of mir‑106a into EJ cells led to downregulation of ERK phosphorylation and upregulation of p38 and JNK phosphorylation over their levels in the control. Flow cytometry analysis revealed that mir‑106a-transfected cells accumulated in the G1-phase of the cell cycle, and cyclin D1 and CDK6 were significantly downregulated. This G1-phase cell cycle arrest was due in part to the upregulation of p21CIP1/WAF1. In addition, mir‑106a overexpression blocked the wound-healing migration and invasion of EJ cells. Furthermore, mir‑106a transfection resulted in decreased expression of MMP-2 and diminished binding activity of transcription factor Ets-1 in EJ cells. Collectively, we report the novel mir‑106a-mediated molecular signaling networks that regulate the proliferation, migration, and invasion of bladder cancer cells, suggesting that mir‑106a may be a therapeutic target for treating advanced bladder tumors.

  9. [Internal migration]. (United States)

    Borisovna, L


    Very few studies have been conducted that truly permit explanation of internal migration and it repercussions on social and economic structure. It is clear however that a profound knowledge of the determinants and consequences of internal migration will be required as a basis for economic policy decisions that advance the goal of improving the level of living of the population. the basic supposition of most studies of the relationship of population and development is that socioeconomic development conditions demographic dynamics. The process of development in Mexico, which can be characterized by great heterogeneity, consequently produces great regional disparities. At the national level various studies have estimated the volume of internal migration in Mexico, but they have usually been limited to interstate migration because the main source of data, the census, is classified by states. But given the great heterogeneity within states in all the elements related to internal migration, it is clear that studies of internal migration within states are also needed. Such studies are almost nonexistent because of their technical difficulty. National level studies show that interstate migration increased significantly between 1940-80. The proportion of Mexicans living outside their states of birth increased by 558% in those years, compared to the 342% increase in the total Mexican population. Although Puebla has a high rate of increase, migration has kept it below Mexico's national growth rate. Migration between Puebla and other states and within Puebla has led to an increasing unevenness of spatial distribution. Between 1970-80, 57 of Puebla's municipios had growth rates above the state average of 2.8%/year, 6 had growth rates equal to the average, and 129 had growth rates that were below the average but not negative. 25 states with negative growth rates that were considered strongly expulsive. In 1980, 51.7% of the population was concentrated in the 57 municipios

  10. High-throughput RNAi screening for novel modulators of vimentin expression identifies MTHFD2 as a regulator of breast cancer cell migration and invasion. (United States)

    Lehtinen, Laura; Ketola, Kirsi; Mäkelä, Rami; Mpindi, John-Patrick; Viitala, Miro; Kallioniemi, Olli; Iljin, Kristiina


    Vimentin is an intermediate filament protein, with a key role in the epithelial to mesenchymal transition as well as cell invasion, and it is often upregulated during cancer progression. However, relatively little is known about its regulation in cancer cells. Here, we performed an RNA interference screen followed by protein lysate microarray analysis in bone metastatic MDA-MB-231(SA) breast cancer cells to identify novel regulators of vimentin expression. Out of the 596 genes investigated, three novel vimentin regulators EPHB4, WIPF2 and MTHFD2 were identified. The reduced vimentin expression in response to EPHB4, WIPF2 and MTHFD2 silencing was observed at mRNA and protein levels. Bioinformatic analysis of gene expression data across cancers indicated overexpression of EPHB4 and MTHFD2 in breast cancer and high expression associated with poor clinical characteristics. Analysis of 96 cDNA samples derived from both normal and malignant human tissues suggested putative association with metastatic disease. MTHFD2 knockdown resulted in impaired cell migration and invasion into extracellular matrix as well as decreased the fraction of cells with a high CD44 expression, a marker of cancer stem cells. Furthermore, MTHFD2 expression was induced in response to TGF-β stimulation in breast cancer cells. Our results show that MTHFD2 is overexpressed in breast cancer, associates with poor clinical characteristics and promotes cellular features connected with metastatic disease, thus implicating MTHFD2 as a potential drug target to block breast cancer cell migration and invasion.

  11. Di-Ethylhexylphthalate (DEHP Modulates Cell Invasion, Migration and Anchorage Independent Growth through Targeting S100P in LN-229 Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Jennifer Nicole Sims


    Full Text Available Glioblastoma multiforme (GBM is the most aggressive brain cancer with a median survival of 1–2 years. The treatment of GBM includes surgical resection, radiation and chemotherapy, which minimally extends survival. This poor prognosis necessitates the identification of novel molecular targets associated with glioblastoma. S100P is associated with drug resistance, metastasis, and poor clinical outcomes in many malignancies. The functional role of S100P in glioblastoma has not been fully investigated. In this study, we examined the role of S100P mediating the effects of the environmental contaminant, DEHP, in glioblastoma cells (LN-229 by assessing cell proliferation, apoptosis, anchorage independent growth, cell migration and invasion following DEHP exposure. Silencing S100P and DEHP treatment inhibited LN-229 glioblastoma cell proliferation and induced apoptosis. Anchorage independent growth study revealed significantly decreased colony formation in shS100P cells. We also observed reduced cell migration in cells treated with DEHP following S100P knockdown. Similar results were observed in spheroid formation and expansion. This study is the first to demonstrate the effects of DEHP on glioblastoma cells, and implicates S100P as a potential therapeutic target that may be useful as a drug response biomarker.

  12. Novel migrating mouse neural crest cell assay system utilizing P0-Cre/EGFP fluorescent time-lapse imaging

    Directory of Open Access Journals (Sweden)

    Kawakami Minoru


    Full Text Available Abstract Background Neural crest cells (NCCs are embryonic, multipotent stem cells. Their long-range and precision-guided migration is one of their most striking characteristics. We previously reported that P0-Cre/CAG-CAT-lacZ double-transgenic mice showed significant lacZ expression in tissues derived from NCCs. Results In this study, by embedding a P0-Cre/CAG-CAT-EGFP embryo at E9.5 in collagen gel inside a culture glass slide, we were able to keep the embryo developing ex vivo for more than 24 hours; this development was with enough NCC fluorescent signal intensity to enable single-cell resolution analysis, with the accompanying NCC migration potential intact and with the appropriate NCC response to the extracellular signal maintained. By implantation of beads with absorbed platelet-derived growth factor-AA (PDGF-AA, we demonstrated that PDGF-AA acts as an NCC-attractant in embryos. We also performed assays with NCCs isolated from P0-Cre/CAG-CAT-EGFP embryos on culture plates. The neuromediator 5-hydroxytryptamine (5-HT has been known to regulate NCC migration. We newly demonstrated that dopamine, in addition to 5-HT, stimulated NCC migration in vitro. Two NCC populations, with different axial levels of origins, showed unique distribution patterns regarding migration velocity and different dose-response patterns to both 5-HT and dopamine. Conclusions Although avian species predominated over the other species in the NCC study, our novel system should enable us to use mice to assay many different aspects of NCCs in embryos or on culture plates, such as migration, division, differentiation, and apoptosis.

  13. Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE study.

    Directory of Open Access Journals (Sweden)

    Sara Hägg


    Full Text Available Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD. The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE study was to determine whether there are functionally associated genes (rather than individual genes important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue and atherosclerotic and unaffected arterial wall (n = 40/tissue isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes. In the second step (performed within tissue clusters, one atherosclerotic lesion (n = 49/48 and one visceral fat (n = 59 cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015. The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54 relating to carotid stenosis (P = 0.04, 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10(-27 and-30. Genes in the transendothelial migration of leukocytes (TEML pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module. In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004. The transcription co-factor LIM domain binding 2 (LDB2 was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2

  14. A preference for migration


    Stark, Oded


    At least to some extent migration behavior is the outcome of a preference for migration. The pattern of migration as an outcome of a preference for migration depends on two key factors: imitation technology and migration feasibility. We show that these factors jointly determine the outcome of a preference for migration and we provide examples that illustrate how the prevalence and transmission of a migration-forming preference yield distinct migration patterns. In particular, the imitation of...

  15. Modulatory Effect of 5-Hydroxytryptamine 2A Receptor on Discharge Activities of Inspiratory Neurons in the Medial Region of Nucleus Retrofacialis of Neonatal Rats in Vitro%5-羟色胺2A受体对新生大鼠离体延髓脑片吸气神经元放电的调制

    Institute of Scientific and Technical Information of China (English)

    千智斌; 姬明丽; 齐莹; 吴中海


    discharges of the inspiratory neurons and activities of the hypoglossal nerve rootlets were simultaneously recorded by using microelectrodes and suction electrodes, respectively. Roles of 5-HT2A receptors in modulation of the discharge activities of inspiratory neurons were investigated by administration of the 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodopbenyl)-2-aminopropane (DOI), and its specific antagonist ketanserine dissolved in modified Kreb's solution for perfused slices. Results In DOI group, the inspiratory time (TI) was (0.864±0.07)s, expiratory time (TE) was (10.78±1.06)s, respiratory cycle (RC) was (11.79±1.64)s, integral amplitude (IA) was (357.98±37.21)(μV·s) and the peak discharge frequency (PF) was (37.83±3.66)Hz. In control group, they were (0.68±0.06)s, (13.89±2.14)s, (14.77±1.92)s, (273.57±24.39)(μV·s), and (29.92±4.50)Hz, there were significant differences between the 2 groups (Pa<0.01). In ketanserine group, TI was (0.55±0.07)s, TE and RC were (18.43±3.28)s and (20.17+2.91)s respectively, IA and PF were (214.37±33.52)(μV·s) and (22.17±3.92)Hz, there were significant differences between ketanserine group and DOI, control group (Pa<0.01). Conclusion 5-HT2A receptors take part in modulate the discharge activities of inspiratory neurons in neonatal rat brainstem slices.

  16. Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) study

    KAUST Repository

    Hägg, Sara


    Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n =66/tissue) and atherosclerotic and unaffected arterial wall (n =40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n =15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n= 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n =49/48) and one visceral fat (n =59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P=0.008 and P=0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n =55/54) relating to carotid stenosis (P =0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n= 16/17, P<10 -27and-30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the Amodule was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the

  17. EU Migration Policy


    Kleinschmidt, Harald


    I shall confine myself in this paper to international migration as migration across international borders.I do so despite the fact that,still today,international migration accounts only for a small share of migration at large.Likewise,I shall deal widh voluntary migration and shall thus exclude,deportation ...

  18. Research on Protocol Migration

    Institute of Scientific and Technical Information of China (English)

    汪芸; 顾冠群; 等


    This paper elaborates the concept and model of protocol migration in network interconnection.Migration strategies and principles are discussed and several cases are studied in detail which show the basic procedure and techniques used in protocol migration.

  19. Migration of birds (United States)

    US Fish and Wildlife Service, Department of the Interior — This report covers the migration of birds. Topics covered include why birds migrate, when birds migrate, speed, altitude, courses, distance, major flyways and...

  20. Effect of domoic acid on metabolism of 5-hydroxytryptamine in rat brain. (United States)

    Arias, B; Arufe, M; Alfonso, M; Duran, R


    Domoic acid (Dom) is a neurotoxic secondary amino acid that interacts with the glutamate receptors, producing neurological problems. In the present work, we study the effects of Dom on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete rat brain regions. The effects of Dom on the brain metabolism of serotonin are also discussed in this paper. Dom stimulates the rat brain serotoninergic system, increasing differentially the synthesis and the catabolism of 5-HT and the elimination of 5-HIAA.

  1. An indirect action of dopamine on the rat fundus strip mediated by 5-hydroxytryptamine

    NARCIS (Netherlands)

    Sonneville, P.F.


    Dopamine in a concentration of 10−7 molar produces a contraction of the rat stomach fundus preparation. This effect is blocked by the 5-HT antagonist methysergide. Repeated exposure to dopamine results in tachyphylaxis, but the sensitivity to dopamine can be restored by incubating the tissue with 5-

  2. Molecular Cloning and Pharmacology of Porcine 5-Hydroxytryptamine Receptors Relevant to the Study of Antimigraine Drugs

    NARCIS (Netherlands)

    P.L. Bhalla (Pankaj)


    textabstractAt the beginning of last century, Brodie (1900) described in an extensive study that injection of blood serum causes vasoconstriction and a vagally-mediated reflex resulting in a reversible bradycardia, hypotension and arrest of the respiration, while injection of blood plasma was devoid

  3. Characterization of (/sup 3/H)5-hydroxytryptamine uptake within rat cerebrovascular tree

    Energy Technology Data Exchange (ETDEWEB)

    Amenta, F.; Rossi, M. de; Mione, M.C.; Geppetti, P.


    The in vitro uptake of tritiated serotonin ((/sup 3/H)5HT) was studied in a preparation of rat extracerebral arteries. The uptake of (/sup 3/H)5HT was time- and temperature-dependent and of high affinity; linear regression analysis gave a Ksub(m) value of 6.48 X 10/sup 7/ M for the specific uptake. Histoautoradiographic studies showed the highest density of silver grains at the level of the adventitial-medial border of the basilar artery. Fluoxetine inhibited the accumulation of silver grains within the adventitial-medial border in the blood vessel studied. The present data further support the view that a neuronal serotonergic system may play a role in the control of blood flow in the cerebrovascular tree.

  4. Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT4 receptor levels

    DEFF Research Database (Denmark)

    Jennings, Katie Ann; Licht, Cecilie Löe; Bruce, Aynsley


    +/+ mice in all brain regions. Compared to wild-type (WT) littermate controls, 5-HTT OE mice had increased 5-HT4 binding density across all brain regions, except amygdala (118-164% of WT) and this difference between genotypes was reduced by the 5-HTT inhibitor, fluoxetine (20 mg/kg twice daily, 3 d...

  5. The occurrence and distribution of 5-hydroxytryptamine in Hymenolepis diminuta and H. nana. (United States)

    Lee, M B; Bueding, E; Schiller, E L


    The presence of 5-HT in Hymenolepis diminuta and Hymenolepis nana was detected by 2 biochemical methods and as yellow fluorescence in a histochemical method. In H. diminuta, 5-HT was found in a concentration of about 1.2 micron/g; this amount did not vary significantly in worms aged 6 to 18 days or more or in various regions of the worm. In H. nana, 5-HT was found in a concentration of about 1.8 micron/g. It was histochemically localized in H. diminuta and H. nana in a pattern similar to that of acetylcholinesterase previously described in these 2 cestodes, and it may be the opposing neuro-transmitter to acetylcholine. The lack of 5-HT in the vestigial rostellum of H. diminuta may be correlated with loss of function of this organ.

  6. Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues. (United States)

    Kärkkäinen, J; Forsström, T; Tornaeus, J; Wähälä, K; Kiuru, P; Honkanen, A; Stenman, U H; Turpeinen, U; Hesso, A


    Bufotenine and N,N-dimethyltryptamine (DMT) are hallucinogenic dimethylated indolethylamines (DMIAs) formed from serotonin and tryptamine by the enzyme indolethylamine N-methyltransferase (INMT) ubiquitously present in non-neural tissues. In mammals, endogenous bufotenine and DMT have been identified only in human urine. The DMIAs bind effectively to 5HT receptors and their administration causes a variety of autonomic effects, which may reflect their actual physiological function. Endogenous levels of bufotenine and DMT in blood and a number of animal and human tissues were determined using highly sensitive and specific quantitative mass spectrometric techniques. A new finding was the detection of large amounts of bufotenine in stools, which may be an indication of its role in intestinal function. It is suggested that fecal and urinary bufotenine originate from epithelial cells of the intestine and the kidney, respectively, although the possibility of their synthesis by intestinal bacteria cannot be excluded. Only small amounts of the DMIAs were found in somatic or neural tissues and none in blood. This can be explained by rapid catabolism of the DMIAs by mitochondrial monoamino-oxidase or by the fact that the dimethylated products of serotonin and tryptamine are not formed in significant amounts in most mammalian tissues despite the widespread presence of INMT in tissues.

  7. Selective and functional 5-hydroxytryptamine4 receptor antagonism by SB 207266.


    Wardle, K.A.; Bingham, S; Ellis, E. S.; Gaster, L. M.; Rushant, B.; Smith, M. I.; Sanger, G J


    1. The pharmacology of a novel 5-HT4 receptor antagonist, SB 207266 has been evaluated in vitro in the guinea-pig distal colon longitudinal muscle myenteric plexus (LMMP) and in vivo in the dog Heidenhain pouch. 2. SB 207266 is a highly potent antagonist of 5-HT-evoked, cholinergically-mediated contractions in the guinea-pig distal colon. Low concentrations (0.1-10 nM) produced a parallel shift to the right of the concentration-effect curve (apparent pA2 10.6 +/- 0.1) with no significant effe...

  8. Internationalization and migration pressure. (United States)

    Kultalahti, O


    The author first develops the concept of migration pressure, which is defined as the growth in the number of people wishing to migrate and the barriers preventing them from so doing. Both macro- and micro-level factors affecting migration pressure are identified. Historical trends in migration pressure in Finland are then discussed. The author then applies this concept to the analysis of current Finnish migration trends. The primary focus is on international migration.

  9. Kirchhoff migration without phases (United States)

    Bardsley, Patrick; Guevara Vasquez, Fernando


    We present a simple, frequency domain, preprocessing step to Kirchhoff migration that allows the method to image scatterers when the wave field phase information is lost at the receivers, and only intensities are measured. The resulting imaging method does not require knowing the phases of the probing field or manipulating the phase of the wave field at the receivers. In a regime where the scattered field is small compared to the probing field, the problem of recovering the full-waveform scattered field from intensity data can be formulated as an embarrassingly simple least-squares problem. Although this only recovers the projection (on a known subspace) of the full-waveform scattered field, we show that, for high frequencies, this projection gives Kirchhoff images asymptotically identical to the images obtained with full waveform data. Our method can also be used when the source is modulated by a Gaussian process and autocorrelations are measured at an array of receivers.

  10. Kirchhoff migration without phases

    CERN Document Server

    Bardsley, Patrick


    We present a simple, frequency domain, preprocessing step to Kirchhoff migration that allows the method to image scatterers when the wave field phase information is lost at the receivers, and only intensities are measured. The resulting imaging method does not require knowing the phases of the probing field or manipulating the phase of the wave field at the receivers. In a regime where the scattered field is small compared to the probing field, the problem of recovering the full-waveform scattered field from intensity data can be formulated as an embarrassingly simple least-squares problem. Although this only recovers the projection (on a known subspace) of the full-waveform scattered field, we show that, for high frequencies, this projection gives Kirchhoff images asymptotically identical to the images obtained with full waveform data. Our method can also be used when the source is modulated by a Gaussian process and autocorrelations are measured at an array of receivers.

  11. Fertility, Migration, and Altruism



    Consider migration to a higher income region as a human capital investment in which parents bear migration costs and children share returns. Migrants from a population with heterogeneous intergenerational discount rates will be self-selected on intergenerational altruism. Thus, immigrants may be self-selected on fertility. Soviet Jews who migrate to Israel despite high migration costs have significantly more children than members of the same birth cohort who migrate later when costs are low. ...

  12. Governing Global Migration



    This study explores the global regulative function of migration politics. Its main aim is to rethink migration politics through an engagement with the Foucauldian governmentality perspective, which focuses on the relation between government and thought. A secondary aim is to use this perspective to explore the global description of migration and migration politics which is emerging with the currently evolving global governance of migration. Doing so, it wishes to contribute both to the study ...

  13. Return migration to Italy and labour migration. (United States)

    Calvaruso, C


    The problems caused by large-scale return migration to Italy in recent years are considered. The importance of the additional skills and capital acquired by these migrants while abroad is stressed. Extensive data on the volume of return migration in the 1970s are included.

  14. Population, migration and urbanization. (United States)


    Despite recent estimates that natural increase is becoming a more important component of urban growth than rural urban transfer (excess of inmigrants over outmigrants), the share of migration in the total population growth has been consistently increasing in both developed and developing countries. From a demographic perspective, the migration process involves 3 elements: an area of origin which the mover leaves and where he or she is considered an outmigrant; the destination or place of inmigration; and the period over which migration is measured. The 2 basic types of migration are internal and international. Internal migration consists of rural to urban migration, urban to urban migration, rural to rural migration, and urban to rural migration. Among these 4 types of migration various patterns or processes are followed. Migration may be direct when the migrant moves directly from the village to the city and stays there permanently. It can be circular migration, meaning that the migrant moves to the city when it is not planting season and returns to the village when he is needed on the farm. In stage migration the migrant makes a series of moves, each to a city closer to the largest or fastest growing city. Temporary migration may be 1 time or cyclical. The most dominant pattern of internal migration is rural urban. The contribution of migration to urbanization is evident. For example, the rapid urbanization and increase in urban growth from 1960-70 in the Republic of Korea can be attributed to net migration. In Asia the largest component of the population movement consists of individuals and groups moving from 1 rural location to another. Recently, because urban centers could no longer absorb the growing number of migrants from other places, there has been increased interest in the urban to rural population redistribution. This reverse migration also has come about due to slower rates of employment growth in the urban centers and improved economic opportunities

  15. More Myths of Migration. (United States)

    Basch, Linda; Lerner, Gail


    Challenges "myths" about women and migration, including (1) the causes of migration are economic, not racism; (2) migrant women receive support from feminist groups and trade unions; (3) transnational corporations are positive forces in developing nations; (4) migration today has little impact on family life; and (5) most migrants cluster in…

  16. Migration and Adult Education (United States)

    Gois, William


    The objective of this paper is to highlight the role of adult education as a tool in addressing labour migration issues, specifically those concerning the protection of migrant workers' rights and the transformation of the impact of migration into positive holistic developmental gains. The view of labour migration as a means to forge the economic…

  17. Migration and Literature

    DEFF Research Database (Denmark)

    Frank, Søren

    We live in an age of migration and more and more authors have migrant backgrounds. Migration and Literature offers a thorough and thought provoking examination of the thematic and formal role of migration in four contemporary and canonized novelists, Günter Grass, Milan Kundera, Salman Rushdie...

  18. Nuclear factor of activated T cells c1 mediates p21-activated kinase 1 activation in the modulation of chemokine-induced human aortic smooth muscle cell F-actin stress fiber formation, migration, and proliferation and injury-induced vascular wall remodeling. (United States)

    Kundumani-Sridharan, Venkatesh; Singh, Nikhlesh K; Kumar, Sanjay; Gadepalli, Ravisekhar; Rao, Gadiparthi N


    Recent literature suggests that cyclin-dependent kinases (CDKs) mediate cell migration. However, the mechanisms were not known. Therefore, the objective of this study is to test whether cyclin/CDKs activate Pak1, an effector of Rac1, whose involvement in the modulation of cell migration and proliferation is well established. Monocyte chemotactic protein 1 (MCP1) induced Pak1 phosphorylation/activation in human aortic smooth muscle cells (HASMCs) in a delayed time-dependent manner. MCP1 also stimulated F-actin stress fiber formation in a delayed manner in HASMCs, as well as the migration and proliferation of these cells. Inhibition of Pak1 suppressed MCP1-induced HASMC F-actin stress fiber formation, migration, and proliferation. MCP1 induced cyclin D1 expression as well as CDK6 and CDK4 activities, and these effects were dependent on activation of NFATc1. Depletion of NFATc1, cyclin D1, CDK6, or CDK4 levels attenuated MCP1-induced Pak1 phosphorylation/activation and resulted in decreased HASMC F-actin stress fiber formation, migration, and proliferation. CDK4, which appeared to be activated downstream of CDK6, formed a complex with Pak1 in response to MCP1. MCP1 also activated Rac1 in a time-dependent manner, and depletion/inhibition of its levels/activation abrogated MCP1-induced NFATc1-cyclin D1-CDK6-CDK4-Pak1 signaling and, thereby, decreased HASMC F-actin stress fiber formation, migration, and proliferation. In addition, smooth muscle-specific deletion of NFATc1 led to decreased cyclin D1 expression and CDK6, CDK4, and Pak1 activities, resulting in reduced neointima formation in response to injury. Thus, these observations reveal that Pak1 is a downstream effector of CDK4 and Rac1-dependent, NFATc1-mediated cyclin D1 expression and CDK6 activity mediate this effect. In addition, smooth muscle-specific deletion of NFATc1 prevented the capacity of vascular smooth muscle cells for MCP-1-induced activation of the cyclin D1-CDK6-CDK4-Pak1 signaling axis, affecting

  19. 5-HT7受体对肠道运动的调节作用%The role of 5-HT7 receptor in modulation of intestinal motility

    Institute of Scientific and Technical Information of China (English)

    邹百仓; 董蕾; 李红; 王燕; 赵刚


    Objective To observe the expression of 5-hydroxytryptamine (5-HT7) receptor in the intestinal tract of rat constipation and diarrhea models so as to probe the role of 5-HT7 receptor in modulation of intestinal motility. Methods Rat model of constipation was established by gastric irrigation with cool water. Rat model of diarrhea was established by restrain stress while the contorl rats were not intervened. After gastrointestinal transiting time and feces properties were surveyed, the expression of intestinal 5-HT7 receptor was investigater by immunohis-tochemistry and realtime quantitative PCR. Results The feces properties of constipation were less and drier than those of the controls, and the gastrointestinal transiting time in constipation was longer. The number of positive cells and mRNA expression of 5-HT7 receptor in the ileum and colon of the constipation rats were higher than those of the controls (P<0.01), and higher in the colon of the constipation rats than in the diarrhea group (P<0. 01). Conclusion 5-HT7 receptor plays a role in modulating gastrointestinal tract contractility and the colonic migrating motor complex (CMMC). The gastrointestinal dyskinesis in constipation rats may be associated with a higher expression of 5-HT7 receptor in the intestines.%目的 观察5羟色胺7(5-HT7)受体在便秘及腹泻模型大鼠肠道中的表达差异,探索其对肠道运动的调节作用.方法 用冰水灌胃法制备便秘大鼠模型,束缚刺激方法制备腹泻模型并设对照组.观察各组胃肠通过时间、粪便形状,用免疫组化及实时定量PCR法测定各组大鼠肠道组织中5-HT7受体阳性细胞数及基因表达差异.结果 便秘组大鼠粪便特征及胃肠通过时间显示胃肠运动迟缓特征;而腹泻组粪便特征及胃肠通过时间显示胃肠运动过速特征.便秘组回肠及结肠组织中5-HT7受体阳性细胞数及基因表达高于对照组(P<0.01),并且结肠组织中高于腹泻组(P<0.01).

  20. Iodine Migration and its Effect on Hysteresis in Perovskite Solar Cells. (United States)

    Li, Cheng; Tscheuschner, Steffen; Paulus, Fabian; Hopkinson, Paul E; Kießling, Johannes; Köhler, Anna; Vaynzof, Yana; Huettner, Sven


    The migration and accumulation of iodide ions create a modulation of the respective interfacial barriers causing the hysteresis in solar cells based on methylammonium lead iodide perovskites. Iodide ions are identified as the migrating species by measuring temperature dependent current-transients and photoelectron spectroscopy. The involved changes in the built-in potential due to ion migration are directly measured by electroabsorption spectroscopy.

  1. Pipoxolan ameliorates cerebral ischemia via inhibition of neuronal apoptosis and intimal hyperplasia through attenuation of VSMC migration and modulation of matrix metalloproteinase-2/9 and Ras/MEK/ERK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Yuh-Fung Chen

    Full Text Available Pipoxolan (PIPO has anti-spasmodic effects, and it is used clinically to relieve smooth muscle spasms. Cerebrovascular disease is one of the leading causes of disability and death worldwide. The main aim of this study was to investigate the effects of PIPO on cerebral ischemia and vascular smooth muscle cell (VSMC migration in vivo and in vitro. Cerebral infarction area, ratio of intima to media area (I/M ratio and PCNA antibody staining of the carotid artery in vivo were measured. Cell viability of A7r5 cells, PDGF-BB-stimulated cell migration, and potential mechanisms of PIPO were evaluated by wound healing, transwell and Western blotting. PIPO (10 and 30 mg/kg p.o. reduced: the cerebral infarction area; neurological deficit; TUNEL-positive cells; cleaved caspase 3-positive cells; intimal hyperplasia; and inhibited proliferating cell nuclear antigen (PCNA-positive cells in rodents. PIPO (5, 10 and 15 µM significantly inhibited PDGF-BB-stimulated VSMC migration and reduced Ras, MEK, and p-ERK levels. Moreover, PIPO decreased levels of matrix metalloproteinases -2 and -9 in PDGF-BB-stimulated A7r5 cells. In summary, PIPO is protective in models of ischemia/reperfusion-induced cerebral infarction, carotid artery ligation-induced intimal hyperplasia and VSMC migration both in vivo and in vitro. PIPO could be potentially efficacious in preventing cerebrovascular and vascular diseases.

  2. Malaysia and forced migration


    Arzura Idris


    This paper analyzes the phenomenon of “forced migration” in Malaysia. It examines the nature of forced migration, the challenges faced by Malaysia, the policy responses and their impact on the country and upon the forced migrants. It considers forced migration as an event hosting multifaceted issues related and relevant to forced migrants and suggests that Malaysia has been preoccupied with the issue of forced migration movements. This is largely seen in various responses invoked from Malaysi...

  3. Union Dissolution and Migration


    Cooke, Thomas; Mulder, Clara H.; Thomas, Michael


    BACKGROUND While there is a limited body of research regarding residential mobility and migration following union dissolution, there is a particular dearth of studies that go into detail about the factors that shape how union dissolution may result in long-distance migration. OBJECTIVE This research isolates and identifies the processes that influence inter-state migration in the period immediately following the dissolution of a marital union. METHODS Multilevel logit models of the probabilit...

  4. Regional Redistribution and Migration

    DEFF Research Database (Denmark)

    Manasse, Paolo; Schultz, Christian

    We study a model with free migration between a rich and a poor region. Since there is congestion, the rich region has an incentive to give the poor region a transfer in order to reduce immigration. Faced with free migration, the rich region voluntarily chooses a transfer, which turns out...... to be equal to that a social planner would choose. Provided migration occurs in equilibrium, this conclusion holds even in the presence of moderate mobility costs. However, large migration costs will lead to suboptimal transfers in the market solution...

  5. International Migration of Couples

    DEFF Research Database (Denmark)

    Junge, Martin; Munk, Martin D.; Poutvaara, Panu


    Migrant self-selection is important to both origin and destination countries. We develop a theoretical model regarding the migration of dual-earner couples and test it in the context of international migration, using population-wide administrative data from Denmark. Our model predicts...

  6. Migrating Art History

    DEFF Research Database (Denmark)

    Ørum, Tania


    Review of Hiroko Ikegami, The Great Migrator. Robert Rauschenberg and the Global Rise of American Art. Cambridge Mass., The MIT Press, 2010. 277 pages. ISBN 978-0-262-01425-0.......Review of Hiroko Ikegami, The Great Migrator. Robert Rauschenberg and the Global Rise of American Art. Cambridge Mass., The MIT Press, 2010. 277 pages. ISBN 978-0-262-01425-0....

  7. Migration, klima og sundhed

    DEFF Research Database (Denmark)

    Tellier, Siri; Carballo, Manuel


    Many tentative connections have been postulated between migration and climate. This article points to rural-urban migration, particularly into low elevation urban slums prone to flooding as an issue needing urgent attention by health professionals. It also notes the no-man's land in which...

  8. Migration in Burkina Faso

    NARCIS (Netherlands)

    Wouterse, F.S.


    Migration plays an important role in development and as a strategy for poverty reduction. A recent World Bank investigation finds a significant positive relationship between international migration and poverty reduction at the country level (Adams and Page 2003). Burkina Faso, whose conditions for a

  9. Geography of European Migration

    Directory of Open Access Journals (Sweden)

    Zhitin Dmitry V.


    Full Text Available In recent decades, the role of international migration has increased dramatically in most European countries. The growth in migration has made some authors proclaim the beginning of a second Migration Period that could transform the social and cultural identity of Europe. The article presents an analysis of international migration geography in Europe in the last twenty-five years. The authors identify the main trends in migration, provide migration profiles of European countries, and propose a classification based on the recent changes in the migrant stock. Changes in the migrant stock (total emigration and immigration reflect the level of involvement in international and global processes. They can serve as an indicator of a country’s attractiveness for both foreigners and the country’s citizens. The study shows that European countries are increasingly split into ‘immigrant’ and ‘emigrant’ states. The authors describe spatial patterns of migration. The volume and localisation of migration flows in Europe are affected not only by cultural and historical circumstance, such as a colonial past or a common language. The scale of immigrant influx often does not depend on a donor country’s demographic potential or the level of its socio-economic development. The links between the place of origin and destination are often more complex than it might initially seem. The authors stress the importance of a differentiated immigration policy taking into account ethnic and cultural features of host societies.

  10. Model Migration Schedules



    This report draws on the fundamental regularity exhibited by age profiles of migration all over the world to develop a system of hypothetical model schedules that can be used in multiregional population analyses carried out in countries that lack adequate migration data.

  11. Samtidskunst og migration

    DEFF Research Database (Denmark)

    Petersen, Anne Ring


    "Samtidskunst og migration. En oversigt over faglitteraturen" er en forskningsoversigt der gør status over hvad der hidtil er skrevet inden for det kunsthistoriske område om vor tids billedkunst og migration som politisk, socialt og kulturelt fænomen, primært i forbindelse med immigration til...

  12. World Migration Degree Global migration flows in directed networks

    CERN Document Server

    Porat, Idan


    In this article we analyze the global flow of migrants from 206 source countries to 145 destination countries (2006-2010) and focus on the differences in the migration network pattern between destination and source counters as represented by its degree and weight distribution. Degree represents the connectivity of a country to the global migration network, and plays an important role in defining migration processes and characteristics. Global analysis of migration degree distribution offers a strong potential contribution to understanding of migration as a global phenomenon. In regard to immigration, we found that it is possible to classify destination countries into three classes: global migration hubs with high connectivity and high migration rate; local migration hubs with low connectivity and high migration rate; and local migration hubs with opposite strategy of high connectivity and low migration rate. The different migration strategies of destination countries are emerging from similar and homogenies p...

  13. Malaysia and forced migration

    Directory of Open Access Journals (Sweden)

    Arzura Idris


    Full Text Available This paper analyzes the phenomenon of “forced migration” in Malaysia. It examines the nature of forced migration, the challenges faced by Malaysia, the policy responses and their impact on the country and upon the forced migrants. It considers forced migration as an event hosting multifaceted issues related and relevant to forced migrants and suggests that Malaysia has been preoccupied with the issue of forced migration movements. This is largely seen in various responses invoked from Malaysia due to “south-south forced migration movements.” These responses are, however, inadequate in terms of commitment to the international refugee regime. While Malaysia did respond to economic and migration challenges, the paper asserts that such efforts are futile if she ignores issues critical to forced migrants.

  14. On marriage and migration. (United States)

    Stark, O


    Marriage, migration, and related phenomena such as marital stability, fertility, and investment in human capital may be better explained by studying marriage and migration jointly. This paper examines the role of migration in obtaining joint labor market and marriage market equilibrium. When broadly interpreted, marriage and migration share a number of common features. Both involve search and its resolution (pairing of mates in the former and matching of labor and firms in the latter). In both cases, success in finding a partner is sensitive to the availability of partners and to the distribution of their endowments and traits. Almost always, and along with separation and divorce, marriage mandates spatial relocation which may translate into migration. Both involve a movement that is associated with adjustment costs from 1 state into another. The decisions to enter marriage and undertake employment or the decisions to divorce and quit a job depend on exogenous parameters, some of which are determined by the marriage market and the labor market. Since both marriage and divorce take place in the context of broadly defined markets, they may and often are analyzed applying market concepts, theorems, and solutions. Yet the authors could not pinpoint 1 single, systematic attempt that checks through the interactions between marriage and migration, so this paper attempts to rectify this state of research. Essentially, this paper 1) discusses individual decision making pending possible migration prior to or following marriage, 2) examines whether it is easier for a married couple or a single person to migrate, and 3) considers whether marriage dissolution could cause migration when marriage is the only reason that has kept a spouse from moving. This integrated research agenda for both marriage and migration can delineate interesting new implications to examine.

  15. Migration without migraines

    Energy Technology Data Exchange (ETDEWEB)

    Lines, L.; Burton, A.; Lu, H.X. [Memorial Univ. of Newfoundland, St. John`s (Canada)


    Accurate velocity models are a necessity for reliable migration results. Velocity analysis generally involves the use of methods such as normal moveout analysis (NMO), seismic traveltime tomography, or iterative prestack migration. These techniques can be effective, and each has its own advantage or disadvantage. Conventional NMO methods are relatively inexpensive but basically require simplifying assumptions about geology. Tomography is a more general method but requires traveltime interpretation of prestack data. Iterative prestack depth migration is very general but is computationally expensive. In some cases, there is the opportunity to estimate vertical velocities by use of well information. The well information can be used to optimize poststack migrations, thereby eliminating some of the time and expense of iterative prestack migration. The optimized poststack migration procedure defined here computes the velocity model which minimizes the depth differences between seismic images and formation depths at the well by using a least squares inversion method. The optimization methods described in this paper will hopefully produce ``migrations without migraines.``

  16. Peripheral 5-HT 1A and 5-HT 7 Serotonergic Receptors Modulate Parasympathetic Neurotransmission in Long-Term Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Beatriz Restrepo


    Full Text Available We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT, effect reproduced by 5-carboxamidotryptamine maleate (5-CT, a 5-HT1/7 agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT1A agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT and abolished by WAY-100,635, 5-HT1A antagonist. Pretreatment with 5-HT1 antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT7 antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5-HT1A receptors induces enhancement, whereas attenuation is due to 5-HT7 receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels.

  17. Peripheral 5-HT1A and 5-HT7 Serotonergic Receptors Modulate Parasympathetic Neurotransmission in Long-Term Diabetic Rats (United States)

    Restrepo, Beatriz; Martín, María Luisa; San Román, Luis; Morán, Asunción


    We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT1/7 agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT1A agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) and abolished by WAY-100,635, 5-HT1A antagonist. Pretreatment with 5-HT1 antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT7 antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5-HT1A receptors induces enhancement, whereas attenuation is due to 5-HT7 receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels. PMID:21403818

  18. Migration og etnicitet

    DEFF Research Database (Denmark)

    Christiansen, Connie Carøe


    Migration og etnicitet er aktuelle og forbundne fænomener, idet migration øger berøringsfladerne mellem befolkningsgrupper. Etniciteter formes i takt med at grænser drages imellem disse grupper. Imod moderniserings-teoriernes forventning forsvandt etnicitet ikke som en traditionel eller oprindelig...... måde at skabe tilhørsforhold på; globalt set fremstår vor tid istedet som en "migrationens tidsalder", der tilsyneladende også er en tidsalder, hvor kulturelle særtræk, i form af etnicitet, udgør vigtige linjer, hvorefter grupper skilller sig ud fra hinanden. Både migration og etnicitet bringer fokus...... den finder sted i modtagerlandet, men nyere perspektiver på migration, som begreber om medborgerskab, transnationalisme og diaspora er eksponenter for, søger udover den nationalstatslige ramme og inddrager konsekvenserne af migrationen for afsenderlande....

  19. Global Governance of Migration



    The aim of this thesis is to analyze the recently formed global governance of migration, which has got an unprecedented trans-boundary nature due to the impacts og globalization in the post Cold War era. 

  20. 5-HT4-receptors modulate induction of long-term depression but not potentiation at hippocampal output synapses in acute rat brain slices.

    Directory of Open Access Journals (Sweden)

    Matthias Wawra

    Full Text Available The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD. In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4 receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1, 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output.

  1. Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration


    Thomas Walcher; Peter Bernhardt; Dusica Vasic; Helga Bach; Renate Durst; Wolfgang Rottbauer; Daniel Walcher


    Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD...

  2. Indonesia's migration transition. (United States)

    Hugo, G


    This article describes population movements in Indonesia in the context of rapid and marked social and economic change. Foreign investment in Indonesia is increasing, and global mass media is available to many households. Agriculture is being commercialized, and structural shifts are occurring in the economy. Educational levels are increasing, and women's role and status are shifting. Population migration has increased over the decades, both short and long distance, permanent and temporary, legal and illegal, and migration to and between urban areas. This article focuses specifically on rural-to-urban migration and international migration. Population settlements are dense in the agriculturally rich inner areas of Java, Bali, and Madura. Although the rate of growth of the gross domestic product was 6.8% annually during 1969-94, the World Bank ranked Indonesia as a low-income economy in 1992 because of the large population size. Income per capita is US $670. Indonesia is becoming a large exporter of labor to the Middle East, particularly women. The predominance of women as overseas contract workers is changing women's role and status in the family and is controversial due to the cases of mistreatment. Malaysia's high economic growth rate of over 8% per year means an additional 1.3 million foreign workers and technicians are needed. During the 1980s urban growth increased at a very rapid rate. Urban growth tended to occur along corridors and major transportation routes around urban areas. It is posited that most of the urban growth is due to rural-to-urban migration. Data limitations prevent an exact determination of the extent of rural-to-urban migration. More women are estimated to be involved in movements to cities during the 1980s compared to the 1970s. Recruiters and middlemen have played an important role in rural-to-urban migration and international migration.

  3. Astrocytes in Migration. (United States)

    Zhan, Jiang Shan; Gao, Kai; Chai, Rui Chao; Jia, Xi Hua; Luo, Dao Peng; Ge, Guo; Jiang, Yu Wu; Fung, Yin-Wan Wendy; Li, Lina; Yu, Albert Cheung Hoi


    Cell migration is a fundamental phenomenon that underlies tissue morphogenesis, wound healing, immune response, and cancer metastasis. Great progresses have been made in research methodologies, with cell migration identified as a highly orchestrated process. Brain is considered the most complex organ in the human body, containing many types of neural cells with astrocytes playing crucial roles in monitoring normal functions of the central nervous system. Astrocytes are mostly quiescent under normal physiological conditions in the adult brain but become migratory after injury. Under most known pathological conditions in the brain, spinal cord and retina, astrocytes are activated and become hypertrophic, hyperplastic, and up-regulating GFAP based on the grades of severity. These three observations are the hallmark in glia scar formation-astrogliosis. The reactivation process is initiated with structural changes involving cell process migration and ended with cell migration. Detailed mechanisms in astrocyte migration have not been studied extensively and remain largely unknown. Here, we therefore attempt to review the mechanisms in migration of astrocytes.

  4. Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration

    Directory of Open Access Journals (Sweden)

    Thomas Walcher


    Full Text Available Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0±0.1 fold increase in cell migration (P<.01; n=7. Pretreatment of cells with ivabradine reduces this effect to a maximal 1.2±0.1 fold induction at 0.1 µmol/L ivabradine (P<.01 compared to SDF-1-treated cells, n=7. The effect of ivabradine on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, ivabradine inhibits activation of the small GTPase Rac and phosphorylation of the Myosin Light Chain (MLC. Moreover, ivabradine treatment reduces f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. Conclusion. Ivabradine inhibits chemokine-induced migration of CD4-positive lymphocytes. Given the crucial importance of chemokine-induced T-cell migration in early atherogenesis, ivabradine may be a promising tool to modulate this effect.

  5. Migration to the Horizon Integrated Library System at the Parke-Davis Pharmaceutical Research Library: Project Implementation and System Overview. (United States)

    Zorn, Peggy; And Others


    Reports how the Parke-Davis Pharmaceutical Research Library migrated to the Horizon integrated library system. Discusses migration processes including project planning and implementation, client/server issues, data migration, and staff/end-user training. Reviews system modules including acquisitions, cataloging, serials control, public access, and…

  6. Draxin, an axon guidance protein, affects chick trunk neural crest migration. (United States)

    Su, Yuhong; Naser, Iftekhar B; Islam, Shahidul M; Zhang, Sanbing; Ahmed, Giasuddin; Chen, Sandy; Shinmyo, Yohei; Kawakami, Minoru; Yamamura, Ken-ichi; Tanaka, Hideaki


    The neural crest is a multipotent population of migratory cells that arises in the central nervous system and subsequently migrates along defined stereotypic pathways. In the present work, we analyzed the role of a repulsive axon guidance protein, draxin, in the migration of neural crest cells. Draxin is expressed in the roof plate of the chick trunk spinal cord and around the early migration pathway of neural crest cells. Draxin modulates chick neural crest cell migration in vitro by reducing the polarization of these cells. When exposed to draxin, the velocity of migrating neural crest cells was reduced, and the cells changed direction so frequently that the net migration distance was also reduced. Overexpression of draxin also caused some early migrating neural crest cells to change direction to the dorsolateral pathway in the chick trunk region, presumably due to draxin's inhibitory activity. These results demonstrate that draxin, an axon guidance protein, can also affect trunk neural crest migration in the chick embryo.

  7. Planet Formation with Migration

    CERN Document Server

    Chambers, J E


    In the core-accretion model, gas-giant planets form solid cores which then accrete gaseous envelopes. Tidal interactions with disk gas cause a core to undergo inward type-I migration in 10^4 to 10^5 years. Cores must form faster than this to survive. Giant planets clear a gap in the disk and undergo inward type-II migration in <10^6 years if observed disk accretion rates apply to the disk as a whole. Type-II migration times exceed typical disk lifetimes if viscous accretion occurs mainly in the surface layers of disks. Low turbulent viscosities near the midplane may allow planetesimals to form by coagulation of dust grains. The radius r of such planetesimals is unknown. If r<0.5 km, the core formation time is shorter than the type-I migration timescale and cores will survive. Migration is substantial in most cases, leading to a wide range of planetary orbits, consistent with the observed variety of extrasolar systems. When r is of order 100m and midplane alpha is of order 3 times 10^-5, giant planets si...

  8. Biometrics and international migration. (United States)

    Redpath, Jillyanne


    This paper will focus on the impact of the rapid expansion in the use of biometric systems in migration management on the rights of individuals; it seeks to highlight legal issues for consideration in implementing such systems, taking as the starting point that the security interests of the state and the rights of the individual are not, and should not be, mutually exclusive. The first part of this paper briefly describes the type of biometric applications available, how biometric systems function, and those used in migration management. The second part examines the potential offered by biometrics for greater security in migration management, and focuses on developments in the use of biometrics as a result of September 11. The third part discusses the impact of the use of biometrics in the management of migration on the individual's right to privacy and ability to move freely and lawfully. The paper highlights the increasing need for domestic and international frameworks to govern the use of biometric applications in the migration/security context, and proposes a number of issues that such frameworks could address.

  9. Migration = cloning; aliasiing

    DEFF Research Database (Denmark)

    Hüttel, Hans; Kleist, Josva; Nestmann, Uwe


    In Obliq, a lexically scoped, distributed, object-oriented programming language, object migration was suggested as the creation of a copy of an object’s state at the target site, followed by turning the object itself into an alias, also called surrogate, for the remote copy. We consider the creat......In Obliq, a lexically scoped, distributed, object-oriented programming language, object migration was suggested as the creation of a copy of an object’s state at the target site, followed by turning the object itself into an alias, also called surrogate, for the remote copy. We consider...... the creation of object surrogates as an abstraction of the abovementioned style of migration. We introduce Øjeblik, a distribution-free subset of Obliq, and provide three different configuration-style semantics, which only differ in the respective aliasing model. We show that two of the semantics, one of which...... matches Obliq’s implementation, render migration unsafe, while our new proposal for a third semantics is provably safe. Our work suggests a straightforward repair of Obliq’s aliasing model such that it allows programs to safely migrate objects....

  10. En fornemmelse for migration

    DEFF Research Database (Denmark)

    Schütze, Laura Maria

    Afhandlingen undersøger, hvordan sted, museets rolle som aktør og religion er relevante for produktionen af migration på Immigrantmuseet (2012) og i Københavns Museums udstilling At blive københavner (2010). Afhandlingen er baseret på udstillingsanalyse samt interview med relevant museumsfagligt......, anvendes som virkemidler til at nuancere migration og distancere udstillingen fra den offentlige debat om indvandring. Afhandlingen peger på, at produktionen af den nyere danske historie på museum er præget af et fravær af religion. Det skyldes, at de museumsfaglige praksisser og traditioner afspejler en...... identiteter, som vi tager for givet: nationer, byer, kvinder - såvel som migration og religion. Afhandlingen argumenterer følgelig for, at museernes produktion af (materiel) religion er et særdeles relevant, men kun ringe udforsket, genstandsfelt for religionssociologien....

  11. The effects of nabumetone, a cyclooxygenase-2 inhibitor, on cisplatin-induced 5-hydroxytryptamine release from the isolated rat ileum. (United States)

    Kudo, C; Minami, M; Hirafuji, M; Endo, T; Hamaue, N; Akita, K; Murakami, T; Kawaguchi, H


    In order to elucidate 5-HT release influenced by PGE2 in the background of the anticancer drug-induced emesis, the effect of nabumetone, a COX-2 inhibitor, on the release of 5-HT from the isolated rat ileum was investigated. PGE2 produced a concentration-dependent increase (10(-9) to 10 M) and decrease (10(-8) to 10(-6) M) in 5-HT release. Arachidonic acid also demonstrated a similar bell-shaped 5-HT release. The arachidonic acid-induced 5-HT release at 3 x 10(-6) M (313.04 +/- 25.90%) was significantly inhibited by the concomitant perfusion with BRL10720 (10(-6) M) (161.98 +/- 19.4%, pnabumetone, or indomethacin (3 x 10(-7) M)(190.01 +/- 16.19%, pnabumetone or BRL10720, but was not affected by the 3-day administration of dexamethasone. After 72 hours, however, the in vivo 3-days administration of nabumetone, BRL10720 or dexamethasone had no effect on the increase in ileal 5-HT levels induced by cisplatin. The use of COX-2 inhibitors to ameliorate delayed emesis induced by cisplatin-based anticancer chemotherapy has been proposed. On the other hand, there is a possibility that dexamethasone works through a mechanism other than 5-HT release in delayed emesis.

  12. Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5-hydroxytryptamine reuptake inhibitors in mice

    DEFF Research Database (Denmark)

    Kreilgaard, Mads; Smith, D. G.; Brennum, L. T.;


    Bridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady-state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) mod...

  13. Analysing immune cell migration. (United States)

    Beltman, Joost B; Marée, Athanasius F M; de Boer, Rob J


    The visualization of the dynamic behaviour of and interactions between immune cells using time-lapse video microscopy has an important role in modern immunology. To draw robust conclusions, quantification of such cell migration is required. However, imaging experiments are associated with various artefacts that can affect the estimated positions of the immune cells under analysis, which form the basis of any subsequent analysis. Here, we describe potential artefacts that could affect the interpretation of data sets on immune cell migration. We propose how these errors can be recognized and corrected, and suggest ways to prevent the data analysis itself leading to biased results.

  14. What's driving migration? (United States)

    Kane, H


    During the 1990s investment in prevention of international or internal migration declined, and crisis intervention increased. The budgets of the UN High Commissioner for Refugees and the UN Development Program remained about the same. The operating assumption is that war, persecution, famine, and environmental and social disintegration are inevitable. Future efforts should be directed to stabilizing populations through investment in sanitation, public health, preventive medicine, land tenure, environmental protection, and literacy. Forces pushing migration are likely to increase in the future. Forces include depletion of natural resources, income disparities, population pressure, and political disruption. The causes of migration are not constant. In the past, migration occurred during conquests, settlement, intermarriage, or religious conversion and was a collective movement. Current migration involves mass movement of individuals and the struggle to survive. There is new pressure to leave poor squatter settlements and the scarcities in land, water, and food. The slave trade between the 1500s and the 1800s linked continents, and only 2-3 million voluntarily crossed national borders. Involuntary migration began in the early 1800s when European feudal systems were in a decline, and people sought freedom. Official refugees, who satisfy the strict 1951 UN definition, increased from 15 million in 1980 to 23 million in 1990 but remained a small proportion of international migrants. Much of the mass movement occurs between developing countries. Migration to developed countries is accompanied by growing intolerance, which is misinformed. China practices a form of "population transfer" in Tibet in order to dilute Tibetan nationalism. Colonization of countries is a new less expensive form of control over territory. Eviction of minorities is another popular strategy in Iraq. Public works projects supported by foreign aid displace millions annually. War and civil conflicts

  15. Unix Application Migration Guide

    CERN Document Server

    Microsoft. Redmond


    Drawing on the experience of Microsoft consultants working in the field, as well as external organizations that have migrated from UNIX to Microsoft® Windows®, this guide offers practical, prescriptive guidance on the issues you are likely to face when porting existing UNIX applications to the Windows operating system environment. Senior IT decision makers, network managers, and operations managers will get real-world guidance and best practices on planning and implementation issues to understand the different methods through which migration or co-existence can be accomplished. Also detailing

  16. Making Migration Meaningful

    DEFF Research Database (Denmark)

    Benwell, Ann Fenger


    . The article focuses on changing patterns of mobility in the Mongolian ‘age of the market’ and its effects on population groups. Internal and international migration has continually risen as individuals and families have moved to places of opportunity. Connections are believed to be maintained during periods...... of absence by migrant family members, as both men and women are culturally permitted to be separate from their families. Migration is understood to contribute to prosperity, and separations contribute to generate growth and hishig (good fortune) for the good of the family. However, such mobility is also...

  17. Polybinary modulation for bandwidth limited optical links

    DEFF Research Database (Denmark)

    Vegas Olmos, Juan José; Jurado-Navas, Antonio


    Optical links using traditional modulation formats are reaching a plateau in terms of capacity, mainly due to bandwidth limitations in the devices employed at the transmitter and receivers. Advanced modulation formats, which boost the spectral efficiency, provide a smooth migration path towards e...

  18. Migration strategies of insects. (United States)

    Dingle, H


    Physiological and ecological results from a variety of species are consistent with what seem to be valid general statements concerning insect migration. These are as follows: (i)During migration locomotory functions are enhanced and vegetative functions such as feeding and reproduction are suppressed. (ii) Migration usually occurs prereproductively in the life of the adult insect (the oogenesis-flight syndrome). (iii)Since migrant individuals are usually prereproductive, their reproductive values, and hence colonizing abilities, are at or near maximum. (iv) Migrants usually reside in temporary habitats. (v)Migrants have a high potential for population increase, r, which is also advantageous for colonizers. (vi)Both the physiological and ecological parameters of migration are modifiable by environmental factors (that is, phenotypically modifiable)to suit the prevailing conditions. Taken together, these criteria establish a comprehensive theory and adumbrate the basic strategy for migrant insects. This basic strategy is modified to suit the ecological requirements of individual species. Comparative studies of these modifications are of considerable theoretical and practical interest, the more so since most economically important insects are migrants. No satisfactory general statements can as yet be made with respect to the genotype and migration. Certainly we expect colonizing populiations to possess genotypes favoring a high r, but genotypic variation in r depends on the heritabilities of life table statistics, and such measurements are yet to be made (10, 53). The fact that flight duration can be increased by appropriate selection in Oncopeltus fasciatus, and the demonstration of additive genetic variance for this trait in Lygaeus kalmii, suggest that heritability studies of migratory behavior would also be worth pursuing. Most interesting of course, will be possible genetic correlations between migration and life history parameters. Also, migration often

  19. Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions? (United States)

    Aznar, Susana; Klein, Anders B


    The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

  20. Migration scenarii in extrasolar systems

    Directory of Open Access Journals (Sweden)

    Crida A.


    Full Text Available In this review talk, I present the theory of type I migration of small mass planets, and its latest developments that open the possibility of outward migration in the inner part of a protoplanetary disk. I also review the type II migration of giant planets, and mention the runaway, type III. Then, we focus on the migration of pairs of planets in resonance. The eccentricity of the planets raise, and possibly their mutual inclination as well. Also, the migration rate can be changed, and directed outward if the outer planet is the lighter. Last, we present a synthetic scenario of migration for the giant planets of our Solar System.

  1. Enhanced migration of seismic data

    Energy Technology Data Exchange (ETDEWEB)

    Carrion, P.M. (PPPG/UFBA, Instituto de Geociencias, Rua Gaetano Moura 123, Federacao, 40.210 Salvador, Bahia (BR))


    The so-called enhanced migration which uses diffraction tomography as the repair tool for correction of amplitudes (reflection coefficients) of migrated sections is discussed. As with any linearized procedure, diffraction tomography requires knowledge of the initial model. It is suggested that the initial model is taken as the migrated image. It will be demonstrated that diffraction tomography applied to the data residuals improves the amplitudes of the migrated images. Migration is redefined as the reconstruction of the wavefront sets of distributions (reflection interfaces), and the inversion process as tomographic correction of migrated images.

  2. Engineered Models of Confined Cell Migration (United States)

    Paul, Colin D.; Hung, Wei-Chien; Wirtz, Denis; Konstantopoulos, Konstantinos


    Cells in the body are physically confined by neighboring cells, tissues, and the extracellular matrix. Although physical confinement modulates intracellular signaling and the underlying mechanisms of cell migration, it is difficult to study in vivo. Furthermore, traditional two-dimensional cell migration assays do not recapitulate the complex topographies found in the body. Therefore, a number of experimental in vitro models that confine and impose forces on cells in well-defined microenvironments have been engineered. We describe the design and use of microfluidic microchannel devices, grooved substrates, micropatterned lines, vertical confinement devices, patterned hydrogels, and micropipette aspiration assays for studying cell responses to confinement. Use of these devices has enabled the delineation of changes in cytoskeletal reorganization, cell–substrate adhesions, intracellular signaling, nuclear shape, and gene expression that result from physical confinement. These assays and the physiologically relevant signaling pathways that have been elucidated are beginning to have a translational and clinical impact. PMID:27420571

  3. Migration as Adventure

    DEFF Research Database (Denmark)

    Olwig, Karen Fog


    Narratives of adventure constitute a well-established convention of describing travel experiences, yet the significance of this narrative genre in individuals’ accounts of their migration and life abroad has been little investigated. Drawing on Simmel and Bakhtin, among others, this article...

  4. Migrating the Light

    DEFF Research Database (Denmark)

    Sørensen, Bent

    The migration of Blaga’s universalist, even centralist poems from Romanian of the first third of the 20th C. into American of the first fifth of the 21st C. illustrates the uses of Pierre Joris’s nomadic methods. My translations of Blaga read well for a teenage audience whose only exposure to lit...

  5. Migration and Africa

    DEFF Research Database (Denmark)

    Zoppi, Marco


    European powers imposed the nation-state on Africa through colonialism. But even after African independencies, mainstream discourses and government policies have amplified the idea that sedentariness and the state are the only acceptable mode of modernity. Migration is portrayed as a menace...

  6. Practical Data Migration

    CERN Document Server

    Morris, Johny


    This book is for executives and practitioners tasked with the movement of data from old systems to a new repository. It uses a series of steps guaranteed to get the reader from an empty new system to one that is working and backed by the user population. Using this proven methodology will vastly increase the chances of a successful migration.

  7. Describing migration spatial structure

    NARCIS (Netherlands)

    Rogers, A; Willekens, F; Little, J; Raymer, J


    The age structure of a population is a fundamental concept in demography and is generally depicted in the form of an age pyramid. The spatial structure of an interregional system of origin-destination-specific migration streams is, however, a notion lacking a widely accepted definition. We offer a d

  8. Digitizing migration heritage

    DEFF Research Database (Denmark)

    Marselis, Randi


    Museums are increasingly digitizing their collections and making them available to the public on-line. Creating such digital resources may become means for social inclusion. For museums that acknowledge migration history and cultures of ethnic minority groups as important subjects in multiethnic...

  9. Dispersal and migration

    Directory of Open Access Journals (Sweden)

    Schwarz, C.


    Full Text Available Ringing of birds unveiled many aspects of avian migration and dispersal movements. However, there is even much more to be explored by the use of ringing and other marks. Dispersal is crucial in understanding the initial phase of migration in migrating birds as it is to understand patterns and processes of distribution and gene flow. So far, the analysis of migration was largely based on analysing spatial and temporal patters of recoveries of ringed birds. However, there are considerable biases and pitfalls in using recoveries due to spatial and temporal variation in reporting probabilities. Novel methods are required for future studies separating the confounding effects of spatial and temporal heterogeneity of recovery data and heterogeneity of the landscape as well. These novel approaches should aim a more intensive and novel use of the existing recovery data by taking advantage of, for instance, dynamic and multistate modeling, should elaborate schemes for future studies, and should also include other marks that allow a more rapid data collection, like telemetry, geolocation and global positioning systems, and chemical and molecular markers. The latter appear to be very useful in the delineating origin of birds and connectivity between breeding and non–breeding grounds. Many studies of migration are purely descriptive. However, King and Brooks (King & Brooks, 2004 examine if movement patterns of dolphins change after the introduction of a gillnet ban. Bayesian methods are an interesting approach to this problem as they provide a meaningful measure of the probability that such a change occurred rather than simple yes/no response that is often the result of classical statistical methods. However, the key difficulty of a general implementation of Bayesian methods is the complexity of the modelling —there is no general userfriendly package that is easily accessible to most scientists. Drake and Alisauskas (Drake & Alisauskas, 2004 examine the

  10. World Migration Degree Global migration flows in directed networks



    In this article we analyze the global flow of migrants from 206 source countries to 145 destination countries (2006-2010) and focus on the differences in the migration network pattern between destination and source counters as represented by its degree and weight distribution. Degree represents the connectivity of a country to the global migration network, and plays an important role in defining migration processes and characteristics. Global analysis of migration degree distribution offers a...

  11. Globalization, Migration and Development

    Directory of Open Access Journals (Sweden)

    George, Susan


    Full Text Available EnglishMigration may become the most important branch of demography in the earlydecades of the new millennium in a rapidly globalizing world. This paper discusses the causes, costsand benefits of international migration to countries of the South and North, and key issues of commonconcern. International migration is as old as national boundaries, though its nature, volume,direction, causes and consequences have changed. The causes of migration are rooted in the rate ofpopulation growth and the proportion of youth in the population, their education and training,employment opportunities, income differentials in society, communication and transportationfacilities, political freedom and human rights and level of urbanization. Migration benefits the Souththrough remittances of migrants, improves the economic welfare of the population (particularly womenof South countries generally, increases investment, and leads to structural changes in the economy.However, emigration from the South has costs too, be they social or caused by factors such as braindrain. The North also benefits by migration through enhancement of economic growth, development ofnatural resources, improved employment prospects, social development and through exposure toimmigrants' new cultures and lifestyles. Migration also has costs to the North such as of immigrantintegration, a certain amount of destabilization of the economy, illegal immigration, and socialproblems of discrimination and exploitation. Issues common to both North and South include impact onprivate investment, trade, international cooperation, and sustainable development. Both North andSouth face a dilemma in seeking an appropriate balance between importing South's labour or itsproducts and exporting capital and technology from the North.FrenchLa migration est sans doute devenue la partie la plus importante de la démographie des premières décennies du nouveau millénaire dans un monde qui change rapidement. Ce

  12. The International Organization for Migration in Global Migration Governance



    This project focuses on the IOM, the notion of global governance of migration and the interaction between these two. The point of departure has been an attempt to grasp the current global approach to migration and comprehend whether, or to what degree, there is governance of migration issues taking place at a global level.

  13. Faster and Efficient Web Crawling with Parallel Migrating Web Crawler

    Directory of Open Access Journals (Sweden)

    Akansha Singh


    Full Text Available A Web crawler is a module of a search engine that fetches data from various servers. Web crawlers are an essential component to search engines; running a web crawler is a challenging task. It is a time-taking process to gather data from various sources around the world. Such a single process faces limitations on the processing power of a single machine and one network connection. This module demands much processing power and network consumption. This paper aims at designing and implementing such a parallel migrating crawler in which the work of a crawler is divided amongst a number of independent and parallel crawlers which migrate to different machines to improve network efficiency and speed up the downloading. The migration and parallel working of the proposed design was experimented and the results were recorded.


    Directory of Open Access Journals (Sweden)

    Daniela DĂNĂCICĂ


    Full Text Available The aim of this research is to study the patterns of migration in Romania. Labor migration in Romania has seen major growth after 1989. Permanent migration rapidly increased in the early years after the revolution, decreasing rapidly thereafter, due to difficulties of obtaining long term residence and work permit in the host countries. However, temporary migration has been found to evolve very dynamically, requiring economic analysis of potential externalities, whether positive or the negative of this phenomenon.



    Daniela DĂNĂCICĂ


    The aim of this research is to study the patterns of migration in Romania. Labor migration in Romania has seen major growth after 1989. Permanent migration rapidly increased in the early years after the revolution, decreasing rapidly thereafter, due to difficulties of obtaining long term residence and work permit in the host countries. However, temporary migration has been found to evolve very dynamically, requiring economic analysis of potential externalities, whet...

  16. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe


    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  17. Making Migration Meaningful

    DEFF Research Database (Denmark)

    Benwell, Ann Fenger


    . The article focuses on changing patterns of mobility in the Mongolian ‘age of the market’ and its effects on population groups. Internal and international migration has continually risen as individuals and families have moved to places of opportunity. Connections are believed to be maintained during periods......Mongolia has experienced two decades since the demise of the Soviet Union and has implemented strategies to strengthen its economy and its democratic practices. Transitions from being a nomadic society to a Soviet satellite state and onwards to liberal democracy have greatly impacted family life...... of absence by migrant family members, as both men and women are culturally permitted to be separate from their families. Migration is understood to contribute to prosperity, and separations contribute to generate growth and hishig (good fortune) for the good of the family. However, such mobility is also...

  18. Religion, migration og integration

    DEFF Research Database (Denmark)

    Borup, Jørn


    Sammenhængen mellem religion og integration har de sidste år været genstand for debat. Artiklen kommer ind på begreber og sammenhænge relateret til området (migration, diaspora, assimilation, etnicitet, kultur) og ser på religionens mulige rolle som negativ eller positiv ressource i integrationss......Sammenhængen mellem religion og integration har de sidste år været genstand for debat. Artiklen kommer ind på begreber og sammenhænge relateret til området (migration, diaspora, assimilation, etnicitet, kultur) og ser på religionens mulige rolle som negativ eller positiv ressource i...

  19. Computational model of mesenchymal migration in 3D under chemotaxis. (United States)

    Ribeiro, F O; Gómez-Benito, M J; Folgado, J; Fernandes, P R; García-Aznar, J M


    Cell chemotaxis is an important characteristic of cellular migration, which takes part in crucial aspects of life and development. In this work, we propose a novel in silico model of mesenchymal 3D migration with competing protrusions under a chemotactic gradient. Based on recent experimental observations, we identify three main stages that can regulate mesenchymal chemotaxis: chemosensing, dendritic protrusion dynamics and cell-matrix interactions. Therefore, each of these features is considered as a different module of the main regulatory computational algorithm. The numerical model was particularized for the case of fibroblast chemotaxis under a PDGF-bb gradient. Fibroblasts migration was simulated embedded in two different 3D matrices - collagen and fibrin - and under several PDGF-bb concentrations. Validation of the model results was provided through qualitative and quantitative comparison with in vitro studies. Our numerical predictions of cell trajectories and speeds were within the measured in vitro ranges in both collagen and fibrin matrices. Although in fibrin, the migration speed of fibroblasts is very low, because fibrin is a stiffer and more entangling matrix. Testing PDGF-bb concentrations, we noticed that an increment of this factor produces a speed increment. At 1 ng mL(-1) a speed peak is reached after which the migration speed diminishes again. Moreover, we observed that fibrin exerts a dampening behavior on migration, significantly affecting the migration efficiency.

  20. Enforcement and illegal migration


    Orrenius, Pia


    Border enforcement of immigration laws attempts to raise the costs of illegal immigration, while interior enforcement also lowers the benefits. Border and interior enforcement therefore reduce the net benefits of illegal immigration and should lower the probability that an individual will decide to migrate. While some empirical studies find that border and interior enforcement serve as significant deterrents to illegal immigration, immigration enforcement is costly and carries significant uni...

  1. Migration with fiscal externalities. (United States)

    Hercowitz, Z; Pines, D


    "This paper analyses the distribution of a country's population among regions when migration involves fiscal externalities. The main question addressed is whether a decentralized decision making [by] regional governments can produce an optimal population distribution...or a centralized intervention is indispensable, as argued before in the literature.... It turns out that, while with costless mobility the fiscal externality is fully internalized by voluntary interregional transfers, with costly mobility, centrally coordinated transfers still remain indispensable for achieving the socially optimal allocation."

  2. Managing the Mass Migration

    Institute of Scientific and Technical Information of China (English)

    Lan Xinzhen


    Big crowds and foul air on the train,frighteningly long queues and fierce clashes at the station...these are common scenes during China's Spring Festival travel rush.The annual travel peak is known as the world's biggest human migration.This year's stampede is still ongoing.Lasting over 40 days,people began retuming to their hometowns on January 8 and the final stragglers will make their way back to the cities by February 16.

  3. Functorial Data Migration

    CERN Document Server

    Spivak, David I


    In this paper we present a simple database definition language: that of categories and functors. A database schema is a category and a state is a set-valued functor. We show that morphisms of schemas induce three "data migration functors" that translate states from one schema to the other in canonical ways. Database states form a boolean topos of which the classical "relational algebra" is a fragment. These ideas thus create a new denotational semantics for database theory.

  4. Conservation physiology of animal migration. (United States)

    Lennox, Robert J; Chapman, Jacqueline M; Souliere, Christopher M; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D; Cooke, Steven J


    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

  5. Gender and migration from Albania. (United States)

    Stecklov, Guy; Carletto, Calogero; Azzarri, Carlo; Davis, Benjamin


    This article examines the dynamics and causes of the shift in the gender composition of migration, and more particularly, in women's access to migration opportunities and decision-making. Our analysis focuses on Albania, a natural laboratory for studying international migration where out-migration was essentially nonexistent from the end of World War II to the end of the 1980s. Interest in the Albanian case is heightened because of the complex layers of inequality existing at the time when migration began: relatively low levels of inequality within the labor market and educational system-a product of the Communist era-while household relations remained heavily steeped in tradition and patriarchy. We use micro-level data from the Albania 2005 Living Standards Measurement Study, including migration histories for family members since migration began. Based on discrete-time hazard models, the analysis shows a dramatic increase in male migration and a gradual and uneven expansion of the female proportion of this international migration. Female migration, which is shown to be strongly associated with education, wealth, and social capital, appears responsive to economic incentives and constraints. Using information on the dependency of female migration to the household demographic structure as well as the sensitivity of female migration to household-level shocks, we show how household-level constraints and incentives affect male and female migration differently. Throughout this period, however, women's migration behavior appears more directly aligned with household-level factors, and there is little evidence to suggest that increased female migration signals rising behavioral independence among Albanian women.

  6. Many Faces of Migrations

    Directory of Open Access Journals (Sweden)

    Milica Antić Gaber


    We believe that in the present thematic issue we have succeeded in capturing an important part of the modern European research dynamic in the field of migration. In addition to well-known scholars in this field several young authors at the beginning their research careers have been shortlisted for the publication. We are glad of their success as it bodes a vibrancy of this research area in the future. At the same time, we were pleased to receive responses to the invitation from representatives of so many disciplines, and that the number of papers received significantly exceeded the maximum volume of the journal. Recognising and understanding of the many faces of migration are important steps towards the comprehensive knowledge needed to successfully meet the challenges of migration issues today and even more so in the future. It is therefore of utmost importance that researchers find ways of transferring their academic knowledge into practice – to all levels of education, the media, the wider public and, of course, the decision makers in local, national and international institutions. The call also applies to all authors in this issue of the journal.

  7. -Regular Modules

    Directory of Open Access Journals (Sweden)

    Areej M. Abduldaim


    Full Text Available We introduced and studied -regular modules as a generalization of -regular rings to modules as well as regular modules (in the sense of Fieldhouse. An -module is called -regular if for each and , there exist and a positive integer such that . The notion of -pure submodules was introduced to generalize pure submodules and proved that an -module is -regular if and only if every submodule of is -pure iff   is a -regular -module for each maximal ideal of . Many characterizations and properties of -regular modules were given. An -module is -regular iff is a -regular ring for each iff is a -regular ring for finitely generated module . If is a -regular module, then .

  8. Migrations in Slovenian geography textbooks

    Directory of Open Access Journals (Sweden)

    Jurij Senegačnik


    Full Text Available In Slovenia, the migrations are treated in almost all geographical textbooks for different levels of education. In the textbooks for the elementary school from the sixth to ninth grade, students acquire knowledge of the migrations by the inductive approach. Difficulty level of treatment and quantity of information are increasing by the age level. In the grammar school program a trail of gaining knowledge on migration is deductive. Most attention is dedicated to migrations in general geography textbooks. The textbooks for vocational and technical school programs deal with migrations to a lesser extent and with different approaches.

  9. Lines of evidence for environmentally driven human migration (United States)

    Davis, K. F.; D'Odorico, P.


    determine additional factors that may help explain migration at global, regional, continental and community-based (i.e. maximized module) scales. Lastly, we explore the relationship between migration and natural disasters (e.g. drought, flooding) to identify instances in which the environment is a proximate cause of human displacement and in turn use this information to determine if a subsequent cascade of human movements appears in neighboring countries as a result of the elevated inflow of migrants from the initial country of interest. In this way, we seek to gain a fuller picture of the environmental factors driving the dynamics of modern human migration.

  10. Population, desertification, and migration. (United States)

    Westing, A H


    When an imbalance develops between population numbers and the carrying capacity of the land, the persons thereby displaced are referred to as environmental refugees. The utilization of the land beyond sustainability leads to land degradation and ultimately, desertification. The social and political impacts of long-term environmental migration can be distinguished: a) at the site of origin of the displaced persons by the residual population; b) at rural sites of destination within the nation between the new arrivals and preestablished populations; c) in the cities within the nation; d) in the nonindustrialized foreign countries; and e) in the industrialized foreign countries. In the event that an area which had previously been devoted to pastoralism is converted to agriculture, the displaced pastoralists might respond through armed rebellion. In some instances, the disenchanted urban squatters become a politically restive and even a destabilizing force, as occurred in Sudan in the 1980s, especially in Khartoum and Port Sudan. The foreign countries to which many of the displaced persons are migrating are subjected to increasing levels of migrant-induced economic, cultural, and political strains. The growing problems associated with south-to-north migration across the Mediterranean Sea have recently led France, Italy, Portugal, and Spain to enter into a consultative arrangement with Algeria, Libya, Mauritania, Morocco, and Tunisia. All foreign aid to the nonindustrialized countries that attempts to ameliorate the problem of desertification must adopt integrated approaches that: a) address population issues; b) support environmental education; c) provide for the protection of biodiversity; d) encourage participatory forms of local and national government; e) provide opportunities for income generation outside the livestock sector; and f) foster political security and facilitate ecogeographical (subregional) cooperation.

  11. ILO - International Migration Programme. (United States)

    Boudraa, Miriam


    In a wide International Context characterised not only by the economical development but also by the social, cultural, political and individual development, we witness more and more to a exchange between the developed and the developing countries, which can be translated especially in the migration of the work force. In theory, all countries are either countries of origin either countries of transit or destination, and they are all responsible for the rights of migrant workers by promoting the rights, by monitoring and by preventing the abusive conditions. The process of migration of the workforce can be divided into three stages: the first coincides with the period prior to departure, the second is represented by the aftermath of the departure and the period of stay in the country of destination, the third stage corresponds to the return in the country of origin. The workers must be protected throughout this process by the international organizations that perform the catalytic role of communication and exchange between countries, for the only purpose of protecting the rights of immigrant and/or immigrants workers. The responsibility for the protection of workers is divided among the various players in the International Labour Organisation. Every country has to apply measures according to the international standards regarding workers' rights, standards that guide the various countries in the formulation and implementation of their policies and legislation. These standards are suggested by International Conventions, the ILO Conventions and other international instruments such as the human rights instrument. There has been a big step forward once the ILO Fundamental Conventions and Conventions on Migrant Workers where implemented and this implementation represented the use of the Guidelines "ILO Multilateral Framework on Labour Migration".

  12. [Obesity, migration and adolescence]. (United States)

    Chamay-Weber, Catherine; Shehu-Brovina, Shqipe; Narring, Françoise


    Weight management interventions during adolescence are challenging. Migration adds complexity to this problem, making migrant families more vulnerable. Teenagers confront families to new values transmitted by the host society: opulence, junk food, video games. Obesity should not be seen as a single issue of calories-excess, but must be considered as being part of a larger problem, which takes into account the context of the familial and societal life of the migrants. The caregivers must have an overall view of the situation to provide appropriate approaches to weight management.

  13. HIV-1-infection of T lymphocytes and macrophages affects their migration via Nef

    Directory of Open Access Journals (Sweden)

    Christel eVérollet


    Full Text Available The human immunodeficiency virus (HIV-1 disseminates in the body and is found in several organs and tissues. While HIV-1 mainly targets both CD4+ T lymphocytes and macrophages, it has contrasting effects between these cell populations. HIV-1 infection namely reduces the viability of CD4+ T cells, whereas infected macrophages are long-lived. In addition, the migration of T cells is reduced by the infection, while HIV-1 differentially modulates the migration modes of macrophages. In 2-dimensions (2D assays, infected macrophages are less motile compared to the control counterparts. In 3D environments, macrophages use two migration modes that are dependent on the matrix architecture: amoeboid and mesenchymal migration. HIV-1 infected macrophages exhibit a reduced amoeboid migration but an enhanced mesenchymal migration, via the viral protein Nef. Indeed, the mesenchymal migration involves podosomes, and Nef stabilizes these cell structures through the activation of the tyrosine kinase Hck, which in turn phosphorylates the Wiskott Aldrich Syndrome Protein (WASP. WASP is a key player in actin remodeling and cell migration. The reprogramed motility of infected macrophages observed in vitro correlates in vivo with enhanced macrophage infiltration in experimental tumors in Nef-transgenic mice compared to control mice.In conclusion, HIV infection of host target cells modifies their migration capacity; we infer that HIV-1 enhances virus spreading in confined environments by reducing T cells migration, and facilitates virus dissemination into different organs and tissues of the human body by enhancing macrophage mesenchymal migration.

  14. Inhibitory modulation of chemoreflex bradycardia by stimulation of the nucleus raphe obscurus is mediated by 5-HT3 receptors in the NTS of awake rats. (United States)

    Weissheimer, Karin Viana; Machado, Benedito H


    Several studies demonstrated the involvement of 5-hydroxytryptamine (5-HT) and its different receptor subtypes in the modulation of neurotransmission of cardiovascular reflexes in the nucleus tractus solitarii (NTS). Moreover, anatomic evidence suggests that nucleus raphe obscurus (ROb) is a source of 5-HT-containing terminals within the NTS. In the present study we investigated the possible changes in the cardiovascular responses to peripheral chemoreceptor activation by potassium cyanide (KCN, i.v.) following ROb stimulation with L-glutamate (10 nmol/50 nL) and also whether 5-HT3 receptors in the caudal commissural NTS are involved in this neuromodulation. The results showed that stimulation of the ROb with L-glutamate in awake rats (n=15) produced a significant reduction in the bradycardic response 30 s after the microinjection (-182+/-19 vs -236+/-10 bpm; Wilcoxon test) but no changes in the pressor response to peripheral chemoreceptor activation (43+/-4 vs 51+/-3 mmHg; two-way ANOVA) in relation to the control. Microinjection of 5--HT3 receptors antagonist granisetron (500 pmol/50 nL), but not the vehicle, into the caudal commissural NTS bilaterally prevented the reduction of chemoreflex bradycardia in response to microinjection of L-glutamate into ROb. These data indicate that 5-HT-containing projections from ROb to the NTS play an inhibitory neuromodulatory role in the chemoreflex evoked bradycardia by releasing 5-HT and activating 5-HT3 receptors in the caudal NTS.

  15. Network migration for printers

    CERN Multimedia


    Further to the recent General Purpose (office) Network reorganisation (as announced in the Bulletin - see here), please note that the majority of print devices will be automatically migrated to the new network IP address range on Tuesday 27 September.   This change should be transparent for these devices and therefore end-users, provided you have installed the printers from the Print Service website. A small number of devices will require manual intervention from the Printer Support team in order to migrate correctly. These devices will not change their IP address until the manual intervention, which will be carried out before Monday 3rd October. However, if you have mistakenly connected directly to the printer’s IP address, then your printing will be affected – please uninstall the printer (for help, see: KB3785), and re-install it from the Print Service website (or follow instructions for visitor machines). Please do this as soon as possible in order to avoid printing issues, t...

  16. Electrochemically induced nanocluster migration

    Energy Technology Data Exchange (ETDEWEB)

    Hartl, Katrin [Lehrstuhl Physikalische Chemie, Technische Universitaet Muenchen, Lichtenbergstr. 4, D-85748 Garching (Germany); Department of Chemistry, CS06, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen O (Denmark); Nesselberger, Markus [Department of Chemistry, CS06, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen O (Denmark); Mayrhofer, Karl J.J. [MPI fuer Eisenforschung, Abt. Grenzflaechenchemie und Oberflaechentechnik, Max-Planck-Strasse 1, D-40237 Duesseldorf (Germany); Kunz, Sebastian; Schweinberger, Florian F.; Kwon, GiHan [Lehrstuhl Physikalische Chemie, Technische Universitaet Muenchen, Lichtenbergstr. 4, D-85748 Garching (Germany); Hanzlik, Marianne [Institut fuer Elektronenmikroskopie, Technische Universitaet Muenchen, Lichtenbergstr. 4, D-85748 Garching (Germany); Heiz, Ueli [Lehrstuhl Physikalische Chemie, Technische Universitaet Muenchen, Lichtenbergstr. 4, D-85748 Garching (Germany); Arenz, Matthias, E-mail: m.arenz@kemi.ku.d [Department of Chemistry, CS06, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen O (Denmark)


    In the presented study the influence of electrochemical treatments on size-selected Pt nanoclusters (NCs) supported on amorphous carbon is investigated by means of transmission electron microscopy (TEM). Well-defined Pt NCs are prepared by an ultra-high vacuum (UHV) laser vaporization source and deposited with low kinetic energy ({<=}10 eV/cluster) onto TEM gold grids covered by a thin (2 nm) carbon film. After transfer out of UHV Pt NCs are verified to be uniform in size and randomly distributed on the support. Subsequently, the TEM grids are employed as working electrodes in a standard electrochemical three electrode setup and the Pt nanoclusters are subjected to different electrochemical treatments. It is found that the NC arrangement is not influenced by potential hold conditions (at 0.40 V vs. RHE) or by potential cycling in a limited potential window (V{sub max} = 0.55 V vs. RHE). Upon potential cycling to 1.05 V vs. RHE, however, the NCs migrate on the carbon support. Interestingly, migration in oxygen or argon saturated electrolyte leads to NC coalescence, a mechanism discussed for being responsible for performance degradation of low temperature fuel cells, whereas in carbon monoxide saturated electrolyte the Pt NC agglomerate, but remain separated from each other and thus form distinctive structures.

  17. The challenges of managing migration

    Energy Technology Data Exchange (ETDEWEB)

    Tacoli, Cecilia


    Migration and urbanisation are driven by economic growth and social change, but also by deepening inequalities. Managing migration should not be equated with curbing it, as this inevitably reduces migrants' rights. But managing population movement whilst respecting the rights of migrants and nonmigrants, supporting the contribution of migration to poverty reduction and economic growth in sending and receiving areas and reducing the human and material costs of movement means that fundamental challenges need to be addressed.

  18. Gender and Migration from Albania



    This article examines the dynamics and causes of the shift in the gender composition of migration, and more particularly, in women's access to migration opportunities and decision-making. Our analysis focuses on Albania, a natural laboratory for studying international migration where outmigration was essentially nonexistent from the end of World War II to the end of the 1980s. Interest in the Albanian case is heightened because of the complex layers of inequality existing at the time when mig...

  19. Gender and Migration: Overview Report


    Jolly, Susie; Reeves, Hazel; Piper, Nicola


    Abstract. Over the past four decades total numbers of international migrants have more than doubled but the percentage of the world population migrating has remained fairly constant. There are now 175 million international migrants worldwide or approximately 3.5 per cent of the global population – about half of whom are women, despite the common misconception that men are the migrants. This Overview Report on Gender and Migration takes a broad approach to migration – it looks at the gender dy...

  20. Migration control: a distance compensation strategy in ants. (United States)

    O'Shea-Wheller, Thomas A; Sendova-Franks, Ana B; Franks, Nigel R


    Migratory behaviour forms an intrinsic part of the life histories of many organisms but is often a high-risk process. Consequently, varied strategies have evolved to negate such risks, but empirical data relating to their functioning are limited. In this study, we use the model system of the house-hunting ant Temnothorax albipennis to demonstrate a key strategy that can shorten migration exposure times in a group of social insects. Colonies of these ants frequently migrate to new nest sites, and due to the nature of their habitat, the distances over which they do so are variable, leading to fluctuating potential costs dependent on migration parameters. We show that colonies of this species facultatively alter the dynamics of a migration and so compensate for the distance over which a given migration occurs. Specifically, they achieve this by modulating the rate of 'tandem running', in which workers teach each other the route to a new nest site. Using this method, colonies are able to engage a larger number of individuals in the migration process when the distance to be traversed is greater, and furthermore, the system appears to be based on perceived encounter rate at the individual level. This form of decentralised control highlights the adaptive nature of a behaviour of ecological importance, and indicates that the key to its robustness lies in the use of simple rules. Additionally, our results suggest that such coordinated group reactions are central to achieving the high levels of ecological success seen in many eusocial organisms.

  1. Gender and Migration from Albania



    This article examines the dynamics and causes of the shift in the gender composition of migration, and more particularly, in women’s access to migration opportunities and decision-making. Our analysis focuses on Albania, a natural laboratory for studying international migration where out-migration was essentially nonexistent from the end of World War II to the end of the 1980s. Interest in the Albanian case is heightened because of the complex layers of inequality existing at the time when mi...

  2. Les questions de migrations internationales (Questions of International Migrations). (United States)

    Samman, Mouna Liliane


    Education about international migration should (1) utilize a framework of historical evolution; (2) stress the growing interdependence of nations; (3) emphasize universal moral values and the role of the individual in human rights; and (4) consider the complementary or competing portraits of international migration presented by the media. (DMM)

  3. Individualisation of Migration from the East? Comparison of Different Socio-Demographic Groups and their Migration Intentions

    Directory of Open Access Journals (Sweden)

    Maarja Saar


    Full Text Available Recent studies on Eastern European migration argue that moving for self-development reasons is becoming increasingly common among this group. Furthermore, it is suggested that migration from the East is becoming individualised and less dependent on social surroundings. Nevertheless, most such results rely on interviews conducted among certain social groups, such as the young and highly skilled. Hence, the comparison between different social groups and their motivations is rarely provided and, therefore, the claims about increased individualisation might be premature. This article uses the Estonian Household Module Survey, including responses from 620 Estonians intending to migrate, to evaluate if migration flows are indeed becoming more individualised and less dependent on social surroundings. Using cluster analysis, three different groups — self-development, economic and life quality migrants — are formed, which are then tested using regression analysis to check for the influence of socio-demographic variables. The article concludes that socio-demographic variables such as gender, age, ethnicity, family status and socio-economic status are still relevant for migration intentions. Indeed, a new group of Eastern European migrants, mainly oriented towards self-development, is emerging; however, it is small and consists mostly of young, Estonian-speaking females. The results complicate the notions of free mobility and liquid migration from Eastern Europe and illustrate that there is a need to pay attention to the increasing group differences in these societies

  4. Do serotonin(1-7) receptors modulate short and long-term memory? (United States)

    Meneses, A


    Evidence from invertebrates to human studies indicates that serotonin (5-hydroxytryptamine; 5-HT) system modulates short- (STM) and long-term memory (LTM). This work is primarily focused on analyzing the contribution of 5-HT, cholinergic and glutamatergic receptors as well as protein synthesis to STM and LTM of an autoshaping learning task. It was observed that the inhibition of hippocampal protein synthesis or new mRNA did not produce a significant effect on autoshaping STM performance but it did impair LTM. Both non-contingent protein inhibition and 5-HT depletion showed no effects. It was basically the non-selective 5-HT receptor antagonist cyproheptadine, which facilitated STM. However, the blockade of glutamatergic and cholinergic transmission impaired STM. In contrast, the selective 5-HT(1B) receptor antagonist SB-224289 facilitated both STM and LTM. Selective receptor antagonists for the 5-HT(1A) (WAY100635), 5-HT(1D) (GR127935), 5-HT(2A) (MDL100907), 5-HT(2C/2B) (SB-200646), 5-HT(3) (ondansetron) or 5-HT(4) (GR125487), 5-HT(6) (Ro 04-6790, SB-399885 and SB-35713) or 5-HT(7) (SB-269970) did not impact STM. Nevertheless, WAY100635, MDL100907, SB-200646, GR125487, Ro 04-6790, SB-399885 or SB-357134 facilitated LTM. Notably, some of these changes shown to be independent of food-intake. Concomitantly, these data indicate that '5-HT tone via 5-HT(1B) receptors' might function in a serial manner from STM to LTM, whereas working in parallel using 5-HT(1A), 5-HT(2A), 5-HT(2B/2C), 5-HT(4), or 5-HT(6) receptors.


    Directory of Open Access Journals (Sweden)

    Perla Shiomara del Carpio Ovando


    Full Text Available This research is focused on the migratory movements that have characterized Simojovel de Allende, Chiapas. Both indigenous Tsotsil communities as well as mestizos from different municipalities live in Simojovel, which is a town that has had multiple migratory movements due to different reasons. For example, economical struggle that has led to poverty, the lack of opportunities; the political situation, religious and ethnic persecutions, insecurity and the communitarian division between zapatistas and non-zapatistas. There are also cultural factors that have caused migration in Simojovel such as tradition, generational gaps, young people’s interests for new types of work and ways of living. Simojovel has been characterized by its coffee, tobacco and amber, but also by its migratory activity.

  6. Osteoactivin Promotes Migration of Oral Squamous Cell Carcinomas. (United States)

    Arosarena, Oneida A; Dela Cadena, Raul A; Denny, Michael F; Bryant, Evan; Barr, Eric W; Thorpe, Ryan; Safadi, Fayez F


    Nearly 50% of patients with oral squamous cell carcinoma (OSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell adhesion, migration, and invasion. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies. The aims were to determine how integrin interactions modulate OA-induced OSCC cell migration; and to investigate OA effects on cell survival and proliferation. We confirmed OA mRNA and protein overexpression in OSCC cell lines. We assessed OA's interactions with integrins using adhesion inhibition assays, fluorescent immunocytochemistry and co-immunoprecipitation. We investigated OA-mediated activation of mitogen-activated protein kinases (MAPKs) and cell survival. Integrin inhibition effects on OA-mediated cell migration were determined. We assessed effects of OA knock-down on cell migration and proliferation. OA is overexpressed in OSCC cell lines, and serves as a migration-promoting adhesion molecule. OA co-localized with integrin subunits, and co-immunoprecipitated with the subunits. Integrin blocking antibodies, especially those directed against the β1 subunit, inhibited cell adhesion (P = 0.03 for SCC15 cells). Adhesion to OA activated MAPKs in UMSCC14a cells and OA treatment promoted survival of SCC15 cells. Integrin-neutralizing antibodies enhanced cell migration with OA in the extracellular matrix. OA knock-down resulted in decreased proliferation of SCC15 and SCC25 cells, but did not inhibit cell migration. OA in the extracellular matrix promotes OSCC cell adhesion and migration, and may be a novel target in the prevention of HNSCC spread. J. Cell. Physiol. 231: 1761-1770, 2016. © 2015 Wiley Periodicals, Inc.

  7. Migration and the Wage Curve:

    DEFF Research Database (Denmark)

    Brücker, Herbert; Jahn, Elke J.

      Based on a wage curve approach we examine the labor market effects of migration in Germany. The wage curve relies on the assumption that wages respond to a change in the unemployment rate, albeit imperfectly. This allows one to derive the wage and employment effects of migration simultaneously...

  8. Africa: Setting for Human Migration (United States)

    Buuba, Babacar Diop


    Analysis of African migrations can help to understand prehistoric, historical, ancient modern and contemporaneous migrations. Movements of populations were and continue to be so intense that, for some analysts, they constitute one of the dominant trends of the history and destiny of the very old continent. African and non-African states, whether…

  9. New dimensions in cell migration

    NARCIS (Netherlands)

    Friedl, P.; Sahai, E.; Weiss, S.; Yamada, K.M.


    Studies of cell migration in three-dimensional (3D) cell culture systems and in vivo have revealed several differences when compared with cell migration in two dimensions, including their morphology and mechanical and signalling control. Here, researchers assess the contribution of 3D models to our

  10. The migration of university graduates

    DEFF Research Database (Denmark)

    Drejer, Ina; Holm, Jacob Rubæk; Nielsen, Kristian

    of university graduates is an important issue for regional policy makers. The present paper analyzes the migration patterns of university graduates from two very different regions in Denmark: the Greater Capital region around Copenhagen and the peripheral region of North Denmark. Studies of the migration...

  11. Modelling Rho GTPase biochemistry to predict collective cell migration (United States)

    Merchant, Brian; Feng, James

    The collective migration of cells, due to individual cell polarization and intercellular contact inhibition of locomotion, features prominently in embryogenesis and metastatic cancers. Existing methods for modelling collectively migrating cells tend to rely either on highly abstracted agent-based models, or on continuum approximations of the group. Both of these frameworks represent intercellular interactions such as contact inhibition of locomotion as hard-coded rules defining model cells. In contrast, we present a vertex-dynamics framework which predicts polarization and contact inhibition of locomotion naturally from an underlying model of Rho GTPase biochemistry and cortical mechanics. We simulate the interaction between many such model cells, and study how modulating Rho GTPases affects migratory characteristics of the group, in the context of long-distance collective migration of neural crest cells during embryogenesis.

  12. Glycine Receptor α2 Subunit Activation Promotes Cortical Interneuron Migration

    Directory of Open Access Journals (Sweden)

    Ariel Avila


    Full Text Available Glycine receptors (GlyRs are detected in the developing CNS before synaptogenesis, but their function remains elusive. This study demonstrates that functional GlyRs are expressed by embryonic cortical interneurons in vivo. Furthermore, genetic disruption of these receptors leads to interneuron migration defects. We discovered that extrasynaptic activation of GlyRs containing the α2 subunit in cortical interneurons by endogenous glycine activates voltage-gated calcium channels and promotes calcium influx, which further modulates actomyosin contractility to fine-tune nuclear translocation during migration. Taken together, our data highlight the molecular events triggered by GlyR α2 activation that control cortical tangential migration during embryogenesis.

  13. Controlled levels of canonical Wnt signaling are required for neural crest migration. (United States)

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette


    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells.

  14. Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model.

    Directory of Open Access Journals (Sweden)

    Dongyuan Lü

    Full Text Available Keratinocyte migration during re-epithelization is crucial in wound healing under biochemical and biomechanical microenvironment. However, little is known about the underlying mechanisms whereby mechanical tension and cocultured fibroblasts or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we applied a tensile device together with a modified transwell assay to determine the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or HF fibroblasts. A novel pattern of asymmetric migration was observed for keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the accumulative distance of HaCaT cells was significantly higher when moving away from HF cells or migrating from down to up cross the membrane than that when moving close to HF cells or when migrating from up to down, whereas HF migration was symmetric. This asymmetric migration was mainly regulated by EGF derived from fibroblasts, but not transforming growth factor α or β1 production. Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion, while no role of mechanical stretch was found for EGF secretion by keratinocytes. These results provided a new insight into understanding the regulating mechanisms of two- or three-dimensional migration of keratinocytes or fibroblasts along or across dermis and epidermis under biomechanical microenvironment.

  15. Data Migration for Ontology Evolution

    Institute of Scientific and Technical Information of China (English)

    赵彦; 张雷; 林晨曦; 张卓; 俞勇


    Ontology is the conceptual backbone that provides meaning to data on the semantic web. However, ontology is not a static resource and may evolve over time, which often leaves the meaning of data in an undefined or inconsistent state. It is thus very important to have a method to preserve the data and its meaning when ontology changes. This paper proposed a general method that solves the problem using data migration. It analyzed some of the issues in the method including separation of ontology and data, migration specification, migration result and migration algorithm. The paper also instantiates the general mothod in RDF(S) as an example. The RDF(S) example itself is a simple but complete method for migrating RDF data when RDFS ontology changes.

  16. Traction Stresses and Translational Distortion of the Nucleus During Fibroblast Migration on a Physiologically Relevant ECM Mimic


    Pan, Zhi; Ghosh, Kaustabh; Liu, Yajie; Clark, Richard A.F.; Rafailovich, Miriam H.


    Cellular traction forces, resulting in cell-substrate physical interactions, are generated by actin-myosin complexes and transmitted to the extracellular matrix through focal adhesions. These processes are highly dynamic under physiological conditions and modulate cell migration. To better understand the precise dynamics of cell migration, we measured the spatiotemporal redistribution of cellular traction stresses (force per area) during fibroblast migration at a submicron level and correlate...

  17. Current Migration Movements in Europe

    Directory of Open Access Journals (Sweden)

    Jelena Zlatković Winter


    Full Text Available After a brief historical review of migrations in Europe, the paper focuses on current migration trends and their consequences. At the end of the 1950s, Western Europe began to recruit labour from several Mediterranean countries – Italy, Spain, Portugal and former Yugoslavia, and later from Morocco, Algeria, Tunisia and Turkey. Some countries, such as France, Great Britain and the Netherlands, recruited also workers from their former colonies. In 1970 Germany had the highest absolute number of foreigners, followed by France, and then Switzerland and Belgium. The total number of immigrants in Western Europe was twelve million. During the 1970s mass recruitment of foreign workers was abandoned, and only the arrival of their family members was permitted, which led to family reunification in the countries of employment. Europe closed its borders, with the result that clandestine migration increased. The year 1989 was a turning point in the history of international migrations. The political changes in Central and Eastern Europe brought about mass migration to the West, which culminated in the so-called “mass movement of 1989–1990”. The arrival of ethnic Germans in Germany, migration inside and outside of the territory of the former Soviet Union, an increase in the number of asylum seekers and displaced persons, due to armed conflicts, are – according to the author – the main traits of current migration. The main part of the paper discusses the causes and effects of this mass wave, as well as trends in labour migration, which is still present. The second part of the paper, after presenting a typology of migrations, deals with the complex processes that brought about the formation of new communities and led to the phenomenon of new ethnic minorities and to corresponding migration policies in Western European countries that had to address these issues.

  18. Musei del migration heritage

    Directory of Open Access Journals (Sweden)

    Patrizia Dragoni


    Since the second half of the 1960s of the 20th century, a profound cultural innovation was accompanied to the radical change in the social, political and economic climate. The anthropological notion of culture as opposed to idealistic vision, the unusual and strong interest in material culture, the enunciation of the concept of cultural property by the Franceschini Commission, the luck of the Public History bring a change of the disciplinary statutes of historical sciences, which begin to attend to social history, focusing on the spontaneous sources of information and initiating experiences of oral history. To all this a remarkable transformation of the themes and of the social function of museums is added. This paper illustrates, in relation to this more general context, the foundation and the dissemination of museums dedicated to the history of migration in Italy and in the world, enunciates their possible social utility for the integration of present migrants in Italy and illustrates, by way of example, the museum recently opened in Recanati.


    Directory of Open Access Journals (Sweden)

    Virginia COJOCARU


    Full Text Available This paper presents recent trends and flows of labor migration and its impact on economic and social life. Main aim of this research sets up the influence of the migration on the European economics and its competitiveness. Methods of research are: method of comparison, analysis method, method of deduction, method of statistics, modeling method. The economic impact of migration has been intensively studied but is still often driven by ill-informed perceptions, which, in turn, can lead to public antagonism towards migration. These negative views risk jeopardising efforts to adapt migration policies to the new economic and demographic challenges facing many countries. Migration Policy looks at the evidence for how immigrants affect the economy in three main areas: The labour market, public purse and economic growth. In Europe, the scope of labour mobility greatly increased within the EU/EFTA zones following the EU enlargements of 2004, 2007 and 2014-2015. This added to labour markets’ adjustment capacity. Recent estimates suggest that as much as a quarter of the asymmetric labour market shock – that is occurring at different times and with different intensities across countries – may have been absorbed by migration within a year.

  20. Simple rules guide dragonfly migration (United States)

    Wikelski, Martin; Moskowitz, David; Adelman, James S; Cochran, Jim; Wilcove, David S; May, Michael L


    Every year billions of butterflies, dragonflies, moths and other insects migrate across continents, and considerable progress has been made in understanding population-level migratory phenomena. However, little is known about destinations and strategies of individual insects. We attached miniaturized radio transmitters (ca 300 mg) to the thoraxes of 14 individual dragonflies (common green darners, Anax junius) and followed them during their autumn migration for up to 12 days, using receiver-equipped Cessna airplanes and ground teams. Green darners exhibited distinct stopover and migration days. On average, they migrated every 2.9±0.3 days, and their average net advance was 58±11 km in 6.1±0.9 days (11.9±2.8 km d−1) in a generally southward direction (186±52°). They migrated exclusively during the daytime, when wind speeds were less than 25 km h−1, regardless of wind direction, but only after two nights of successively lower temperatures (decrease of 2.1±0.6 °C in minimum temperature). The migratory patterns and apparent decision rules of green darners are strikingly similar to those proposed for songbirds, and may represent a general migration strategy for long-distance migration of organisms with high self-propelled flight speeds. PMID:17148394

  1. UK Migration Policy and Migration from Eastern Partnership Countries



    This paper examines UK migration policy and recent migration flows from Eastern Partnership (EaP) countries to the UK. Although inflows of migrant workers were relatively large in the mid-2000s, especially amongst Ukrainians, these have fallen following changes to UK immigration policy, especially the Seasonal Agricultural Workers Scheme and the introduction of the Points Based System. As a result, the stock of migrants from EaP countries resident in the UK is small, especially in comparison ...

  2. Palaearctic-African Bird Migration

    DEFF Research Database (Denmark)

    Iwajomo, Soladoye Babatola

    investigated the relationship between the timing of autumn migration and climatic variations at local and spatial scale. The first three papers focused on speciesspecific analysis. In them I described the age-specific patterns in biometrics, phenology and migration strategies as well as trends...... of birds from Europe to Africa and opens up the possibility of studying intra-African migration. I have used long-term, standardized autumn ringing data from southeast Sweden to investigate patterns in biometrics, phenology and population trends as inferred from annual trapping totals. In addition, I...... also molt their flight feathers at this location and intraspecific interactions are non-aggressive. The second manuscript investigates whether variations in the timing of migration of wader species at a stopover site in southeast Sweden is influence by local or regional climatic variables...

  3. Quantifying global international migration flows. (United States)

    Abel, Guy J; Sander, Nikola


    Widely available data on the number of people living outside of their country of birth do not adequately capture contemporary intensities and patterns of global migration flows. We present data on bilateral flows between 196 countries from 1990 through 2010 that provide a comprehensive view of international migration flows. Our data suggest a stable intensity of global 5-year migration flows at ~0.6% of world population since 1995. In addition, the results aid the interpretation of trends and patterns of migration flows to and from individual countries by placing them in a regional or global context. We estimate the largest movements to occur between South and West Asia, from Latin to North America, and within Africa.

  4. Interregional migration flows in Indonesia

    NARCIS (Netherlands)

    Wajdi, N.; van Wissen, L.J.G.; Mulder, C.H.


    Population Census and Intercensal Population Survey data permit description of the origin–destination patterns that characterize interregional migration flows in Indonesia. Application of the framework of population redistribution proposed by Long (1985) results in indications of over-urbanization,

  5. Migration and Deforestation in Indonesia


    Darmawan, Rivayani; Klasen, Stephan; Nuryartono, Nunung


    Indonesia now has the highest deforestation rate in the world, with an average increase of about 47,600 ha per year. As a result, the nation is one of the largest emitters of greenhouse gases in the world and putting its rich biodiversity at risk. Although the literature discussing the political economy of Indonesia commercial's logging is growing, only a small amount focuses on the relationship between migration and deforestation. Migration may contribute to the forest cover change, as migra...

  6. Homeward bound: Yemeni return migration. (United States)

    Colton, N A


    The author discusses the return migration of Yemenis from Saudi Arabia during the period 1970-1989. "Through the use of original, empirical data collected in Yemen, this article sheds light on who these returning migrants are, where they have come from, and what sort of future awaits them.... The survey conducted on return migration was administered in the winter and spring of 1989 in a region of North Yemen called al-Hujariyya."

  7. articles: Describing migration spatial structure


    Andrei Rogers; Frans Willekens; James Raymer; Jani Little


    The age structure of a population is a fundamental concept in demography and is generally depicted in the form of an age pyramid. The spatial structure of an interregional system of origin-destination-specific migration streams is, however, a notion lacking a widely accepted definition. We offer a definition in this article, one that draws on the log-linear specification of the geographer's spatial interaction model. We illustrate our definition with observed migration data, we discuss extens...

  8. Integrated modeling of European migration


    Raymer, James; Wiśniowski, Arkadiusz; Forster, Jonathan J.; Peter W. F. Smith; Bijak, Jakub


    International migration data in Europe are collected by individual countries with separate collection systems and designs. As a result, reported data are inconsistent in availability, definition and quality. In this paper, we propose a Bayesian model to overcome the limitations of the various data sources. The focus is on estimating recent international migration flows amongst 31 countries in the European Union and European Free Trade Association from 2002 to 2008, using data collated by Euro...

  9. Simple rules guide dragonfly migration


    Wikelski, Martin; Moskowitz, David; Adelman, James S; Cochran, Jim; Wilcove, David S; May, Michael L


    Every year billions of butterflies, dragonflies, moths and other insects migrate across continents, and considerable progress has been made in understanding population-level migratory phenomena. However, little is known about destinations and strategies of individual insects. We attached miniaturized radio transmitters (ca 300 mg) to the thoraxes of 14 individual dragonflies (common green darners, Anax junius) and followed them during their autumn migration for up to 12 days, using receiver-e...

  10. European Integration and Labour Migration

    Directory of Open Access Journals (Sweden)

    Julda Kielyte


    Full Text Available The present paper studies how European integration might affect the migration of workers in the enlarged EU. Unlike the reduced-form migration models, we base our empirical analysis on the theory of economic geography à la Krugman (1991, which provides an alternative modelling of migration pull and push factors. Parameters of the theoretical model are estimated econometrically using historical migration data. Our empirical findings suggest that European integration would trigger selective migration between the countries in the enlarged EU. In the Baltics, Lithuania would gain about 7.25% of the total work force. In the Visegrád Four, the share of the mobile labour force would increase the most in Hungary, 8.35%, compared to the pre-integration state. Our predictions for the East-West migration are moderate and lower than those of reduced-form models: between 5.44% (from the Baltics and 3.61% (from the Visegrád Four would emigrate to the EU North. Because migrants not only follow market potential, but also shape the region’s market potential, the long-run agglomeration forces are sufficiently weak to make a swift emergence of a core-periphery pattern in the enlarged EU very unlikely.

  11. Rab, Arf, and Arl-Regulated Membrane Traffic in Cortical Neuron Migration. (United States)

    Tang, Bor Luen


    The migration of projection neurons from its birthplace in the subventricular zone to their final destination in the cortical plate is a complex process that requires a series of highly coordinated cellular events. Amongst the key factors involved in the processes are modulators of cytoskeletal dynamics, as well as cellular membrane traffic. Members of the small GTPases family responsible for the latter process, the Rabs and Arfs, have been recently implicated in cortical neuron migration. Rab5 and Rab11, which are key modulators of endocytosis and endocytic recycling respectively, ensure proper surface expression and distribution of N-cadherin, a key adhesion protein that tethers migrating neurons to the radial glia fiber tracts during pia-directed migration. Rab7, which is associated with lysosomal biogenesis and function, is important for the final step of terminal translocation when N-cadherin is downregulated by lysosomal degradation. Arf6 activity, which is known to be important in neuronal processes outgrowth, may negatively impact the multipolar-bipolar transition of cortical neurons undergoing radial migration, but the downstream effector of Arf6 in this regard is not yet known. In addition to the above, members of the Arl family which have been recently shown to be important in radial glia scaffold formation, would also be important for cortical neuron migration. In this short review, we discuss recent advances in our understanding of the importance of membrane traffic regulated by the Rab, Arf, and Arl family members in cortical neuron migration.

  12. Kinematic artifacts in prestack depth migration.

    NARCIS (Netherlands)

    Stolk, C.C.; Symes, W.W.


    Strong refraction of waves in the migration velocity model introduces kinematic artifacts¿coherent events not corresponding to actual reflectors¿into the image volumes produced by prestack depth migration applied to individual data bins. Because individual bins are migrated independently, the migrat

  13. Distance and Intrastate College Student Migration (United States)

    Alm, James; Winters, John V.


    Most studies of student migration focus on "interstate" migration of college students, largely because the aggregate data typically used are limited in geographic specificity to states. However, interstate migration is only a small part of the total student migration. Public institutions generally get most of their students from within their…

  14. Distance and Intrastate College Student Migration (United States)

    Alm, James; Winters, John V.


    Most studies of student migration focus on "interstate" migration of college students, largely because the aggregate data typically used are limited in geographic specificity to states. However, interstate migration is only a small part of the total student migration. Public institutions generally get most of their students from within…

  15. Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients. (United States)

    Neziri, Alban Y; Dickenmann, Martina; Scaramozzino, Pasquale; Andersen, Ole K; Arendt-Nielsen, Lars; Dickenson, Anthony H; Curatolo, Michele


    The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2mg, and tropisetron 5mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.

  16. International migration: a global challenge. (United States)

    Martin, P; Widgren, J


    Trends in international migration are presented in this multiregional analysis. Seven of the world's wealthiest countries have about 33% of the world's migrant population, but under 16% of the total world population. Population growth in these countries is substantially affected by the migrant population. The migration challenge is external and internal. The external challenge is to balance the need for foreign labor and the commitment to human rights for those migrants seeking economic opportunity and political freedom. The internal challenge is to assure the social adjustment of immigrants and their children and to integrate them into society as citizens and future leaders. Why people cross national borders and how migration flows are likely to evolve over the next decades are explained. This report also presents some ways that countries can manage migration or reduce the pressures which force people to migrate. It is recommended that receiving nations control immigration by accelerating global economic growth and reducing wars and human rights violations. This report examines the impact of immigration on international trade, aid, and direct intervention policies. Although migration is one of the most important international economic issues, it is not coordinated by an international group. The European experience indicates that it is not easy to secure international cooperation on issues that affect national sovereignty. It is suggested that countries desiring control of their borders should remember that most people never cross national borders to live or work in another country, that 50% of the world's migrants move among developing countries, and that countries can shift from being emigration to immigration countries. The author suggests that sustained reductions in migration pressure are a better alternative than the "quick fixes" that may invite the very much feared mass and unpredictable movements.

  17. Challenges in Polybinary Modulation for Bandwidth Limited Optical Links

    DEFF Research Database (Denmark)

    Vegas Olmos, Juan José; Tafur Monroy, Idelfonso; Madsen, Peter;


    Optical links using traditional modulation formats are reaching a plateau in terms of capacity, mainly due to bandwidth limitations in the devices employed at the transmitter and receivers. Advanced modulation formats, which boost the spectral efficiency, provide a smooth migration path towards e...... of the current research status of the key building blocks in polybinary systems. The results clearly show how polybinary modulation effectively reduces the bandwidth requirements on optical links while providing high spectral efficiency....

  18. Migration and sustainability - compatible or contradictory?

    DEFF Research Database (Denmark)

    Røpke, Inge


    When the migration issue is discussed in a sustainability perspective, two questions are vital: 1) What is the relationship between migration and the global population growth? 2) What is the relationship between migration and consumption growth, and how does migration influence the distribution o...... of consumption possibilities both between and within industrialized and developing countries? Based on responses to these questions, it is argued that reasonably managed migration will be compatible with sustainable development....

  19. International migration in Serbia: Facts and policies


    Bobić Mirjana; Babović Marija


    In the absence of comprehensive, systematic and precize data on international migration in Serbia, and consequently the analysis of migration trends, their drivers and outcomes, the objective of this paper is to offer the review of contemporary migration flows in Serbia. International migration flows are observed in the context of semi-peripheral position of Serbia in the global system, and hindered transformation and development. Migrations are analyzed at the macro level, according to...

  20. Irreducible Specht modules are signed Young modules


    Hemmer, David J.


    Recently Donkin defined signed Young modules as a simultaneous generalization of Young and twisted Young modules for the symmetric group. We show that in odd characteristic, if a Specht module $S^\\lambda$ is irreducible, then $S^\\lambda$ is a signed Young module. Thus the set of irreducible Specht modules coincides with the set of irreducible signed Young modules. This provides evidence for our conjecture that the signed Young modules are precisely the class of indecomposable self-dual module...

  1. Cell migration in confined environments. (United States)

    Irimia, Daniel


    We describe a protocol for measuring the speed of human neutrophils migrating through small channels, in conditions of mechanical confinement comparable to those experienced by neutrophils migrating through tissues. In such conditions, we find that neutrophils move persistently, at constant speed for tens of minutes, enabling precise measurements at single cells resolution, for large number of cells. The protocol relies on microfluidic devices with small channels in which a solution of chemoattractant and a suspension of isolated neutrophils are loaded in sequence. The migration of neutrophils can be observed for several hours, starting within minutes after loading the neutrophils in the devices. The protocol is divided into four main steps: the fabrication of the microfluidic devices, the separation of neutrophils from whole blood, the preparation of the assay and cell loading, and the analysis of data. We discuss the practical steps for the implementation of the migration assays in biology labs, the adaptation of the protocols to various cell types, including cancer cells, and the supplementary device features required for precise measurements of directionality and persistence during migration.

  2. Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task. (United States)

    Meneses, Alfredo


    Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the

  3. Lateral/Basolateral Amygdala Serotonin Type-2 Receptors Modulate Operant Self-administration of a Sweetened Ethanol Solution via Inhibition of Principal Neuron Activity

    Directory of Open Access Journals (Sweden)

    Brian eMccool


    Full Text Available The lateral/basolateral amygdala (BLA forms an integral part of the neural circuitry controlling innate anxiety and learned fear. More recently, BLA dependent modulation of self-administration behaviors suggests a much broader role in the regulation of reward evaluation. To test this, we employed a self-administration paradigm that procedurally segregates ‘seeking’ (exemplified as lever-press behaviors from consumption (drinking directed at a sweetened ethanol solution. Microinjection of the nonselective serotonin type-2 receptor agonist, alpha-methyl-5-hydroxytryptamine (-m5HT into the BLA reduced lever pressing behaviors in a dose-dependent fashion. This was associated with a significant reduction in the number of response-bouts expressed during non-reinforced sessions without altering the size of a bout or the rate of responding. Conversely, intra-BLA -m5HT only modestly effected consumption-related behaviors; the highest dose reduced the total time spent consuming a sweetened ethanol solution but did not inhibit the total number of licks, number of lick bouts, or amount of solution consumed during a session. In vitro neurophysiological characterization of BLA synaptic responses showed that -m5HT significantly reduced extracellular field potentials. This was blocked by the 5-HT2A/C antagonist ketanserin suggesting that 5-HT2-like receptors mediate the behavioral effect of -m5HT. During whole-cell patch current-clamp recordings, we subsequently found that -m5HT increased action potential threshold and hyperpolarized the resting membrane potential of BLA pyramidal neurons. Together, our findings show that the activation of BLA 5-HT2A/C receptors inhibits behaviors related to reward-seeking by suppressing BLA principal neuron activity. These data are consistent with the hypothesis that the BLA modulates reward-related behaviors and provides specific insight into BLA contributions during operant self-administration of a

  4. Central 5-HT2A receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats

    Directory of Open Access Journals (Sweden)

    H.A. Futuro Neto


    Full Text Available Activation of 5-hydroxytryptamine (5-HT 5-HT1A, 5-HT2C, 5-HT3, and 5-HT7 receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT2A/2B receptors in these phenomena is unclear. We report here the effects of intracisternal (ic administration of selective 5-HT2A/2B antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group. The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT2A antagonist; 0.1 µmol/kg, SB-204741 (a 5-HT2B antagonist; 0.1 µmol/kg or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT2A receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05. Neither the 5-HT2B receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT2A receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.

  5. Brownian Motion in Planetary Migration

    CERN Document Server

    Murray-Clay, R A; Murray-Clay, Ruth A.; Chiang, Eugene I.


    A residual planetesimal disk of mass 10-100 Earth masses remained in the outer solar system following the birth of the giant planets, as implied by the existence of the Oort cloud, coagulation requirements for Pluto, and inefficiencies in planet formation. Upon gravitationally scattering planetesimal debris, planets migrate. Orbital migration can lead to resonance capture, as evidenced here in the Kuiper and asteroid belts, and abroad in extra-solar systems. Finite sizes of planetesimals render migration stochastic ("noisy"). At fixed disk mass, larger (fewer) planetesimals generate more noise. Extreme noise defeats resonance capture. We employ order-of-magnitude physics to construct an analytic theory for how a planet's orbital semi-major axis fluctuates in response to random planetesimal scatterings. To retain a body in resonance, the planet's semi-major axis must not random walk a distance greater than the resonant libration width. We translate this criterion into an analytic formula for the retention effi...

  6. Planet migration and magnetic torques (United States)

    Strugarek, A.; Brun, A. S.; Matt, S. P.; Reville, V.


    The possibility that magnetic torques may participate in close-in planet migration has recently been postulated. We develop three dimensional global models of magnetic star-planet interaction under the ideal magnetohydrodynamic (MHD) approximation to explore the impact of magnetic topology on the development of magnetic torques. We conduct twin numerical experiments in which only the magnetic topology of the interaction is altered. We find that magnetic torques can vary by roughly an order of magnitude when varying the magnetic topology from an aligned case to an anti-aligned case. Provided that the stellar magnetic field is strong enough, we find that magnetic migration time scales can be as fast as ~100 Myr. Hence, our model supports the idea that magnetic torques may participate in planet migration for some close-in star-planet systems.

  7. The International-Migration Network

    CERN Document Server

    Fagiolo, Giorgio


    This paper studies international migration from a complex-network perspective. We define the international-migration network (IMN) as the weighted-directed graph where nodes are world countries and links account for the stock of migrants originated in a given country and living in another country at a given point in time. We characterize the binary and weighted architecture of the network and its evolution over time in the period 1960-2000. We find that the IMN is organized around a modular structure characterized by a small-world pattern displaying disassortativity and high clustering, with power-law distributed weighted-network statistics. We also show that a parsimonious gravity model of migration can account for most of observed IMN topological structure. Overall, our results suggest that socio-economic, geographical and political factors are more important than local-network properties in shaping the structure of the IMN.

  8. Rural migration and health care

    DEFF Research Database (Denmark)

    Svendsen, Gunnar Lind Haase; Jensen, Marit Vatn

    This literature study focuses on possible links between access to health services and migration in rural areas. Why do people move to or from rural areas or why do they stay? What determines where people settle? And, in this context, do local health care services play an important or minor role......, or no role at all? First, the paper reports on key findings from rural migration studies, in order to shed light on two migration trends: urbanization and counter-urbanization. Then we take a closer look on settlement preferences in rural areas, including the impact of health care facilities. Finally, we end...... up with a more deepgoing review of the relatively small number of studies, which explicitly deal with settlement preferences related to access to health care....

  9. Optogenetic toolkit reveals the role of Ca2+ sparklets in coordinated cell migration. (United States)

    Kim, Jin Man; Lee, Minji; Kim, Nury; Heo, Won Do


    Cell migration is controlled by various Ca(2+) signals. Local Ca(2+) signals, in particular, have been identified as versatile modulators of cell migration because of their spatiotemporal diversity. However, little is known about how local Ca(2+) signals coordinate between the front and rear regions in directionally migrating cells. Here, we elucidate the spatial role of local Ca(2+) signals in directed cell migration through combinatorial application of an optogenetic toolkit. An optically guided cell migration approach revealed the existence of Ca(2+) sparklets mediated by L-type voltage-dependent Ca(2+) channels in the rear part of migrating cells. Notably, we found that this locally concentrated Ca(2+) influx acts as an essential transducer in establishing a global front-to-rear increasing Ca(2+) gradient. This asymmetrical Ca(2+) gradient is crucial for maintaining front-rear morphological polarity by restricting spontaneous lamellipodia formation in the rear part of migrating cells. Collectively, our findings demonstrate a clear link between local Ca(2+) sparklets and front-rear coordination during directed cell migration.

  10. Rural migration in southern Nevada

    Energy Technology Data Exchange (ETDEWEB)

    Mosser, D.; Soden, D.L.


    This study reviews the history of migration in two rural counties in Southern Nevada. It is part of a larger study about the impact of a proposed high-level nuclear waste repository on in- and out-migration patterns in the state. The historical record suggests a boom and bust economic cycle has predominated in the region for the past century creating conditions that should be taken into account by decision makers when ascertaining the long-term impacts of the proposed repository.

  11. Women’s football migration

    DEFF Research Database (Denmark)

    Agergaard, Sine

    What is intriguing about women’s football as a cultural phenomenon is that unlike men’s football the finances and media interest for the game are sparse. Nevertheless we have found that migration of female football players is growing steadily and women’s football is becoming global in nature....... The question is then what drives this globalization process? According to our study of women’s football migration into Scandinavia, one of the centers of women’s football, transnational networks play a crucial role in mobilizing global migratory moves. Using the concept of friends-of-friends networks from Bale...

  12. Full wavefield migration: utilization of multiples in seismic migration

    NARCIS (Netherlands)

    Berkhout, A.J.; Verschuur, D.J.


    The next generation migration technology considers multiple scattering as vital information, allowing the industry to generate significantly better images of the subsurface. The proposed full wavefield algorithm (FWM) makes use of two-way wave theory that is formulated in terms of one-way wavefields

  13. [International migration in the Americas: intraregional migration grows]. (United States)

    Zlotnik, H


    The principal destinations for intraregional migrants in South America in recent decades have been Argentina, Brazil, and Venezuela, while in North America the U.S. has exerted a growing attraction since 1965. Intraregional migration in Latin America has been irregular and difficult to quantify, and reliable statistics on migratory flows are nonexistent. Census data indicate that most migration to Argentina and Brazil occurred before 1960, while most migration to Venezuela occurred during the 1970s. Between 1960 and 1980, the proportion of migrants from other Latin American countries showed a tendency to increase, despite decreases in the overall level of immigration. The effect of the economic crisis of the 1980s on immigration from Latin American countries will become more apparent as census data for the 1990s become available. Selectivity according to country of origin is an important characteristic of intraregional migration in South America. The U.S. has, however, been the principal destination of Latin American migrants for the past three decades. Between 1965 and 1991 the U.S. granted resident status to more than 7.4 million persons of Latin American and Caribbean origin, and they constituted 47% of immigrants during those years. The great majority of the Latin American immigrants in the U.S. are Mexican. The 3.5 million Mexicans admitted to the U.S. as immigrants between 1965 and 1991 accounted for 22% of all immigrants during this period.

  14. *-Modules, co-*-modules and cotilting modules over Noetherian rings

    Institute of Scientific and Technical Information of China (English)

    汪明义; 许永华


    Let R be a Noetherian ring. The projectivity and injectivity of modules over R are discussed. The concept of modules is introduced and the descriptions for co-*-modules over R are given. At last, cotilting modules over R are characterized by means of co-*-modules.

  15. Thruster Module (United States)

    Andersson, G.


    The thruster module described in this paper provides a low but controlled acceleration in a mission which would normally be labelled “microgravity”. The first mission was Cryofenix, where tanks containing liquid hydrogen were used in the experiment. The experiment utilizing the low acceleration is using liquids and requires a precise acceleration profile throughout the mission. Acceleration obtained by payload rotation is not feasible due to that the transversal forces required to change the acceleration will cause undesired liquid turbulence. In order to satisfy the experiment requirements a thruster module was developed by SSC for the Cryofenix mission funded by CNES. The Cryofenix mission had a payload weight of 380 kg and an apogee of about 260 km. The module produces a controlled thrust in flight direction by means of a cold gas system.

  16. Depth migration and de-migration for 3-D migration velocity analysis; Migration profondeur et demigration pour l'analyse de vitesse de migration 3D

    Energy Technology Data Exchange (ETDEWEB)

    Assouline, F.


    3-D seismic imaging of complex geologic structures requires the use of pre-stack imaging techniques, the post-stack ones being unsuitable in that case. Indeed, pre-stack depth migration is a technique which allows to image accurately complex structures provided that we have at our disposal a subsurface velocity model accurate enough. The determination of this velocity model is thus a key element for seismic imaging, and to this end, migration velocity analysis methods have met considerable interest. The SMART method is a specific migration velocity analysis method: the singularity of this method is that it does not rely on any restrictive assumptions on the complexity of the velocity model to determine. The SMART method uses a detour through the pre-stack depth migrated domain for extracting multi-offset kinematic information hardly accessible in the time domain. Once achieved the interpretation of the pre-stack depth migrated seismic data, a kinematic de-migration technique of the interpreted events enables to obtain a consistent kinematic database (i.e. reflection travel-times). Then, the inversion of these travel-times, by means of reflection tomography, allows the determination of an accurate velocity model. To be able to really image geologic structures for which the 3-D feature is predominant, we have studied the implementation of migration velocity analysis in 3-D in the context of the SMART method, and more generally, we have developed techniques allowing to overcome the intrinsic difficulties in the 3-D aspects of seismic imaging. Indeed, although formally the SMART method can be directly applied to the case of 3-D complex structures, the feasibility of its implementation requires to choose well the imaging domain. Once this choice done, it is also necessary to conceive a method allowing, via the associated de-migration, to obtain the reflection travel-times. We first consider the offset domain which constitutes, still today, the strategy most usually used

  17. [Family reunification, family-formation migration, and return migration of Turks and Moroccans]. (United States)

    De Beer, J; Kuijper, H; Noordam, R


    The authors analyze migration patterns to the Netherlands from Turkey and Morocco for the period 1977-1989. Three distinct phases emerge: labor migration, family-reunification migration, and family-formation migration. The rise in migration from Turkey and Morocco during the second half of the 1980s is attributed to family-formation migration, which is defined as a member of the second generation marrying a partner from the country of origin. (SUMMARY IN ENG)

  18. Migration cost externality and interregional equilibrium. (United States)

    Shin, C


    "This paper will investigate the characteristics of population allocation between two regions in the presence of migration cost. It will also examine both populations and the non-migration range of the initial population in which migration does not occur, in social optimum and market equilibrium with central government intervention, to reveal migration cost externality, and to propose a remedy for it." The author finds that "migration cost gives the social planner an additional burden of population reallocation, and it has an important effect upon an individual's decisions on migration in a decentralized market mechanism."

  19. Signed Young Modules and Simple Specht Modules


    Danz, Susanne; Lim, Kay Jin


    By a result of Hemmer, every simple Specht module of a finite symmetric group over a field of odd characteristic is a signed Young module. While Specht modules are parametrized by partitions, indecomposable signed Young modules are parametrized by certain pairs of partitions. The main result of this article establishes the signed Young module labels of simple Specht modules. Along the way we prove a number of results concerning indecomposable signed Young modules that are of independent inter...

  20. Using Virtual ATE Model to Migrate Test Programs

    Institute of Scientific and Technical Information of China (English)

    王晓明; 杨乔林


    Bacause of high development costs of IC (Integrated Circuit)test programs,recycling existing test programs from one kind of ATE (Automatic Test Equipment) to another or generating directly from CAD simulation modules to ATE is more and more valuable.In this paper,a new approach to migrating test programs is presented.A virtual ATE model based on object-oriented paradigm is developed;it runs Test C++ (an intermediate test control language) programs and TeIF(Test Inftermediate Format-an intermediate pattern),migrates test programs among three kinds of ATE (Ando DIC8032,Schlumberger S15 and GenRad 1732) and generates test patterns from two kinds of CAD 9Daisy and Panda) automatically.

  1. Migration of accreting giant planets (United States)

    Crida, A.; Bitsch, B.; Raibaldi, A.


    We present the results of 2D hydro simulations of giant planets in proto-planetary discs, which accrete gas at a more or less high rate. First, starting from a solid core of 20 Earth masses, we show that as soon as the runaway accretion of gas turns on, the planet is saved from type I migration : the gap opening mass is reached before the planet is lost into its host star. Furthermore, gas accretion helps opening the gap in low mass discs. Consequently, if the accretion rate is limited to the disc supply, then the planet is already inside a gap and in type II migration. We further show that the type II migration of a Jupiter mass planet actually depends on its accretion rate. Only when the accretion is high do we retrieve the classical picture where no gas crosses the gap and the planet follows the disc spreading. These results impact our understanding of planet migration and planet population synthesis models. The e-poster presenting these results in French can be found here: L'e-poster présentant ces résultats en français est disponible à cette adresse:

  2. A Discrete Cell Migration Model

    Energy Technology Data Exchange (ETDEWEB)

    Nutaro, James J [ORNL; Kruse, Kara L [ORNL; Ward, Richard C [ORNL; O' Quinn, Elizabeth [Wofford College; Woerner, Matthew M [ORNL; Beckerman, Barbara G [ORNL


    Migration of vascular smooth muscle cells is a fundamental process in the development of intimal hyperplasia, a precursor to development of cardiovascular disease and a potential response to injury of an arterial wall. Boyden chamber experiments are used to quantify the motion of cell populations in response to a chemoattractant gradient (i.e., cell chemotaxis). We are developing a mathematical model of cell migration within the Boyden chamber, while simultaneously conducting experiments to obtain parameter values for the migration process. In the future, the model and parameters will be used as building blocks for a detailed model of the process that causes intimal hyperplasia. The cell migration model presented in this paper is based on the notion of a cell as a moving sensor that responds to an evolving chemoattractant gradient. We compare the results of our three-dimensional hybrid model with results from a one-dimensional continuum model. Some preliminary experimental data that is being used to refine the model is also presented.

  3. Vortex migration in protoplanetary disks

    CERN Document Server

    Paardekooper, S -J; Papaloizou, J C B


    We consider the radial migration of vortices in two-dimensional isothermal gaseous disks. We find that a vortex core, orbiting at the local gas velocity, induces velocity perturbations that propagate away from the vortex as density waves. The resulting spiral wave pattern is reminiscent of an embedded planet. There are two main causes for asymmetries in these wakes: geometrical effects tend to favor the outer wave, while a radial vortensity gradient leads to an asymmetric vortex core, which favors the wave at the side that has the lowest density. In the case of asymmetric waves, which we always find except for a disk of constant pressure, there is a net exchange of angular momentum between the vortex and the surrounding disk, which leads to orbital migration of the vortex. Numerical hydrodynamical simulations show that this migration can be very rapid, on a time scale of a few thousand orbits, for vortices with a size comparable to the scale height of the disk. We discuss the possible effects of vortex migrat...

  4. Externality, migration, and urban crises. (United States)

    Kanemoto, Y


    The author analyzes a special aspect of the short-run dynamics of an urban area which arises when there is a contrast between different types of households. The possibility of cumulative or catastrophic processes because of migration by poor families and then by rich families in or out of an urban area is discussed

  5. [Migration of dentists within Hungary]. (United States)

    Balázs, Péter


    Concerning the human resource management in the health care, Hungarian analysts focus mainly on cross-national migration, which was instigated considerably by joining the European Union in 2004. Contrasted to other health care professionals, dentists emphasized also the importance of in-country migration (mobility) indicating serious dangers of developing inequalities in the dental service. From the point of view of health system planning, the main problem is to balance the needs and the number of professionals in regions and areas with extremely different socio-economic conditions. Under dictatorial governments, this "balancing" (which was experienced also in Hungary) is a forced allocation of young professionals to the target regions. In political freedom and free market economy, these measures are unthinkable. The present domestic area distribution, concerning also the supply through vacancies by old age inactivity and cross-national migration, is ruled by personal decisions of actually graduated and immigrant professionals respectively. Therefore, it is unavoidable to investigate the interrelation of factors (dentists' births place, study migration and decisions for practice allocation) ruling the in-country geographic patterns of dental practices. This evidence-based knowledge can only explain the present situation and provide guidelines for health policy decision makers.

  6. Essays on growth and migration

    NARCIS (Netherlands)

    Stryszowski, P.K.


    Essays on Growth and Migration is a collection of papers that analyze how two particular factors, the brain drain and the intellectual property rights (IPR), affect the economic performance of a given country. The theoretical models are constructed and illustrative empirical examples are provided in

  7. [Moroccan international migration: recent trends]. (United States)

    Lazaar, M


    Recent trends in emigration from Morocco are analyzed. The author describes the policies developed by the Moroccan government regarding emigration and the changing characteristics of the emigrants, as emigrants are becoming younger and are increasingly female. The author concludes that the increasing demand for migrant labor in Europe will result in increased emigration despite the development of restrictive migration policies.

  8. Planetary migration in protoplanetary disks

    CERN Document Server

    Popolo, A D


    In the current paper, we further develop the model for the migration of planets introduced in Del Popolo et al. (2001) and extended to time-dependent accretion discs in Del Popolo and Eksi (2002). We use a method developed by Stepinski and Valageas (1996, 1997), that is able to simultaneously follow the evolution of gas and solid particles for up to $10^7 {\\rm yr}$. The disc model is coupled to the migration model introduced in Del Popolo et al. (2001) in order to obtain the migration rate of the planet in the planetesimal disc. We find that in the case of discs having total mass of $10^{-3}-0.1 M_{\\odot}$, and $0.1<\\alpha<0.0001$, planets can migrate inward a large distance while if $M<10^{-3} M_{\\odot}$ the planets remain almost in their initial position for $0.1<\\alpha<0.01$ and only in the case $\\alpha<0.001$ the planets move to a minimum value of orbital radius of $\\simeq 2 {\\rm AU}$. The model gives a good description of the observed distribution of planets in the period range 0-20 day...

  9. Marriage migration in the Netherlands

    NARCIS (Netherlands)

    Leen Sterckx; Jaco Dagevos; Willem Huijnk; Jantine van Lisdonk


    Original title: Huwelijksmigratie in Nederland When a man or woman living in the Netherlands embarks on a relationship with a partner from another country and the couple decide to build a married life together in the Netherlands, we call this marriage migration. The foreign partner who moves to the

  10. Job Migration: A Collaborative Effort (United States)

    Wagoner, Cynthia L.


    Music teachers often change jobs several times during their careers. Reasons for job changes vary, but regardless, these changes bring a different set of challenges. Sharing knowledge and learning are part and parcel of collaboration. So what if, as education professionals, music teachers decided to collaborate during job migrations? For all music…

  11. [Haitian migration to Santo Domingo]. (United States)

    Latortue, P R


    This work examines the history of Haitian migration to the Dominican Republic, the central role of Haitian migration in Dominican society, working conditions of Haitian migrants in the Dominican Republic, and the relationship of the migration to economic development on the island of Hispaniola. Lack of data, the difficulty of measuring illegal movement, and the problem of defining Haitians in Santo Domingo have impeded understanding of migration to the Dominican Republic. It is believed by many authorities that Haitian migration to Santo Domingo is considerable and perhaps exceeds that to the US. Haitian migration to the Dominican Republic began after 1915 with the fall of the Haitian president, a worsening of economic conditions partly caused by stagnation in the agricultural sector, and the newly dominant role of the US in Haitian economic affairs. The Great Depression of the 1930s was a direct antecedent of the massacre of Haitians by Dominican police in which some 30 thousand persons were killed; the economic recession of the early 1980s has also caused an outburst of antiHaitian feeling in the Dominican Republic although 80% of laborers in the sugar industry are Haitians. Sugar is extremely important to the Dominican economy: in 1974, sugar covered 12% of cultivated land, produced 40% of foreign exchange earnings, and was responsable for 21% of taxable income. Dominicans however refuse to work in sugar plantations under the current technological. conditions and wage system. Although the government periodically demands the Dominicanization of the sugar work force, no such changes have been made. Sugar will probably continue to play a decisive role in the generation of foreign exchange despite introduction of more technologically advanced sectors which benefit from better prices in the international market. Possibilities of mechanizing sugar production in the Dominican Republic appear remote, and failure to modernize an important sector of the economy has

  12. Memory Modulation

    NARCIS (Netherlands)

    Roozendaal, Benno; McGaugh, James L.


    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evi

  13. Controlled surface topography regulates collective 3D migration by epithelial-mesenchymal composite embryonic tissues. (United States)

    Song, Jiho; Shawky, Joseph H; Kim, YongTae; Hazar, Melis; LeDuc, Philip R; Sitti, Metin; Davidson, Lance A


    Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topography. Most studies on surface topography and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multi-cellular tissues to topographical cues. Here, we examine the response to complex topographical cues of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis. We control topography using fabricated micropost arrays (MPAs) and investigate the collective 3D migration of these multi-cellular systems in these MPAs. We find that the topography regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing of the MPAs we uncover how 3D topographical cues disrupt collective cell migration. We find surface topography can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement.

  14. Depth migration and de-migration for 3-D migration velocity analysis; Migration profondeur et demigration pour l'analyse de vitesse de migration 3D

    Energy Technology Data Exchange (ETDEWEB)

    Assouline, F.


    3-D seismic imaging of complex geologic structures requires the use of pre-stack imaging techniques, the post-stack ones being unsuitable in that case. Indeed, pre-stack depth migration is a technique which allows to image accurately complex structures provided that we have at our disposal a subsurface velocity model accurate enough. The determination of this velocity model is thus a key element for seismic imaging, and to this end, migration velocity analysis methods have met considerable interest. The SMART method is a specific migration velocity analysis method: the singularity of this method is that it does not rely on any restrictive assumptions on the complexity of the velocity model to determine. The SMART method uses a detour through the pre-stack depth migrated domain for extracting multi-offset kinematic information hardly accessible in the time domain. Once achieved the interpretation of the pre-stack depth migrated seismic data, a kinematic de-migration technique of the interpreted events enables to obtain a consistent kinematic database (i.e. reflection travel-times). Then, the inversion of these travel-times, by means of reflection tomography, allows the determination of an accurate velocity model. To be able to really image geologic structures for which the 3-D feature is predominant, we have studied the implementation of migration velocity analysis in 3-D in the context of the SMART method, and more generally, we have developed techniques allowing to overcome the intrinsic difficulties in the 3-D aspects of seismic imaging. Indeed, although formally the SMART method can be directly applied to the case of 3-D complex structures, the feasibility of its implementation requires to choose well the imaging domain. Once this choice done, it is also necessary to conceive a method allowing, via the associated de-migration, to obtain the reflection travel-times. We first consider the offset domain which constitutes, still today, the strategy most usually used

  15. Partial migration in fishes: causes and consequences. (United States)

    Chapman, B B; Hulthén, K; Brodersen, J; Nilsson, P A; Skov, C; Hansson, L-A; Brönmark, C


    Partial migration, where only some individuals from a population migrate, has been widely reported in a diverse range of animals. In this paper, what is known about the causes and consequences of partial migration in fishes is reviewed. Firstly, the ultimate and proximate drivers of partial migration are reflected upon: what ecological factors can shape the evolution of migratory dimorphism? How is partial migration maintained over evolutionary timescales? What proximate mechanisms determine whether an individual is migratory or remains resident? Following this, the consequences of partial migration are considered, in an ecological and evolutionary context, and also in an applied sense. Here it is argued that understanding the concept of partial migration is crucial for fisheries and ecosystem managers, and can provide information for conservation strategies. The review concludes with a reflection on the future opportunities in this field, and the avenues of research that are likely to be fruitful to shed light on the enduring puzzle of partial migration in fishes.

  16. Migration Helps Spread Bird Flu Worldwide (United States)

    ... page: Migration Helps Spread Bird Flu Worldwide Scientists recommend keeping ... birds can spread bird flu worldwide and monitoring migration routes could provide early warning of outbreaks, researchers ...

  17. Migration policies and return migration with particular reference to Yugoslavia. (United States)

    Chepulis, R L


    "The essay analyses some of the most recent migratory trends in Europe in the light of labour turnover, integration and assimilation. The author states that [since] World War II the expansion of the European and international capitalistic system has encouraged or discouraged, according to the various circumstances, the transferral of workers to different countries. "Particular attention has been given to the case of Yugoslavia. The changing of its migration policies has often coincided with the different modalities of flows." (summary in FRE)

  18. Globalization and formal sector migration in Brazil


    Aguayo-Tellez, Ernesto; Muendler, Marc-Andreas; Poole, Jennifer Pamela


    We use novel linked employer–employee data to study the relationship between globalization and formal sector interstate migration for Brazil. We estimate the worker’s multichoice migration problem and document that previously unobserved employer covariates are significant predictors associated with migration flows. Our results provide support for the idea that globalization acts on internal migration through the growth of employment opportunities at locations with a high concentration of fore...

  19. Theoretical aspects of studying the migration processes

    Directory of Open Access Journals (Sweden)

    Dilfuza Rasulova


    Full Text Available In conditions of continuous growth of population in Uzbekistan the issue of managing the labor migration processes is becoming more important. Effective coordination of migration processes requires comprehensive study of theory and methodology of labour migration, particularly considering cases of transition countries. The paper considers some theoretic concepts that seem important for understanding the mechanism of migration princesses, suggests practical recommendations for the associated decision-making.

  20. Undocumented migration in response to climate change


    Nawrotzki, Raphael J.; Riosmena, Fernando; HUNTER, LORI M.; Runfola, Daniel M.


    In the face of climate change induced economic uncertainty, households may employ migration as an adaptation strategy to diversify their livelihood portfolio through remittances. However, it is unclear whether such climate migration will be documented or undocumented. In this study we combine detailed migration histories with daily temperature and precipitation information for 214 weather stations to investigate whether climate change more strongly impacts undocumented or documented migration...

  1. Migration and security : history, practice, and theory


    Aslan, Nazlı Sinem


    Cataloged from PDF version of article. Receiving states viewed international migration as a means of economic development well until late 20th century. Since then policy makers around the world have increasingly associated migration to security and sought to meet this ‘threat’ through ‘control’. In the 21st century, the significance of international migration increased further as migration flows increased and took on new forms affecting the world as a whole. This thesis look...

  2. Helicobacter pylori : migrations humaines et cancer gastrique


    Breurec, Sébastien


    Helicobacter pylori is associated with severe gastroduodenal disorders but is also a bacterial genetic marker of human migrations. First, we provide evidence that distinct H. pylori genetic populations accompanied at least four ancient human migrations into Oceania and Southeast Asia: i) an expansion of Austronesian speaking people about 5000 years ago from Taiwan into Oceania, ii) a migration from India into Southeast Asia within the last 2000 years, iii) a migration of Austro-Asiatic speaki...


    Institute of Scientific and Technical Information of China (English)


    Headcut migration is studied by using empirical and numerical modeling approaches. Empirical formulas for the headcut migration are established using available measurement data, which consider not only the flow strength but also the properties of soil. Numerical model for the headcut migration is proposed. The influences of dynamic pressure gradient, downward flow, and bed slope on sediment entrainment are considered. The local erosion patterns and migration speeds of headcut calculated by the numerical model agree reasonably well with observed data.

  4. Nanoparticles migration in fractured rocks and affects on contaminant migration (United States)

    Missana, Tiziana; Garcia-Gutierrez, Miguel; Alonso, Ursula


    In previous studies, the transport behavior of artificial (gold and latex) and natural (smectite clay) colloids, within a planar fracture in crystalline rock, was analyzed. In order to better understand the effects of colloid size, shape and surface charge on nanoparticle migration and especially on filtration processes on natural rock surfaces, different clay colloids and oxide nanoparticles were selected and their transport studied as a function of the residence time. In all the cases, (a fraction of) the nanoparticles travelled in the fracture as fast as or faster than water (with a retardation factor, Rf ≤ 1) and the observed Rf, was related to the Taylor dispersion coefficient, accounting for colloid size, water velocity and fracture width. However, under most of the cases, in contrast to the behavior of a conservative tracer, colloids recovery was much lower than 100 %. Differences in recovery between different nanoparticles, under similar residence times, were analyzed. In order to evaluate the possible consequences, on contaminant migration, of the presence of nanoparticles in the system, transport tests were carried out with both colloids and sorbing radionuclides. The overall capacity for colloids of enhancing radionuclide migration in crystalline rock fractures is discussed. Acknowledgments: The research leading to these results received funding from EU FP7/2007-2011 grant agreement Nº 295487 (BELBAR, Bentonite Erosion: effects on the Long term performance of the engineered Barrier and Radionuclide Transport) and by the Spanish Government under the project NANOBAG (CTM2011-2797).

  5. Module Evaluation (United States)


    MODULES IN LIFE TEST CHAMBER (LEFT SIDE) 68 MODULE TRANSMIT TEMP CA1 54.8°C CB1 65.3°C CC1 70.5°C CD1 75.2°C CE1 68.5°C CA2 72.1°C CB2 ...NO. PA (Contractor) PA (MELTS) DRV (Contractor) DRV (MELTS) CA1 058 +11.0 VOLTS +10.3 VOLTS + 7.5 VOLTS + 3.64 VOLTS CB1 085 +11.0 VOLTS +10.13...CE1 032 +11.0 VOLTS + 7.02 VOLTS + 7.5 VOLTS + 4.23 VOLTS CA2 065 +11.0 VOLTS +11.03 VOLTS + 7.5 VOLTS + 7.53 VOLTS CB2 057 +11.0 VOLTS + 9.49

  6. Migration on Wings Aerodynamics and Energetics

    CERN Document Server

    Kantha, Lakshmi


    This book is an effort to explore the technical aspects associated with bird flight and migration on wings. After a short introduction on the birds migration, the book reviews the aerodynamics and Energetics of Flight and presents the calculation of the Migration Range. In addition, the authors explains aerodynamics of the formation flight and finally introduces great flight diagrams.

  7. Migration in Asia-Europe Relations

    DEFF Research Database (Denmark)

    Juego, Bonn


    There is a remarkable difference between viewing migration as a 'social integration' issue, on the one hand, and migration as a 'social relation'. The idea of ‘social integration’ has unrealistic assumptions that see migration as a one-way process, that societies and human relations are static, a...

  8. [Urban employment and internal migration in Peru]. (United States)

    Cotlear, D


    The relationship between internal migration and employment problems in Peru is examined. The author argues that regional differences in income distribution are the primary causes of migration, particularly to urban areas. A model of the migration process is developed and tested using data from official sources, surveys, and the published literature.

  9. Migration Flows: Measurement, Analysis and Modeling

    NARCIS (Netherlands)

    Willekens, F.J.; White, Michael J.


    This chapter is an introduction to the study of migration flows. It starts with a review of major definition and measurement issues. Comparative studies of migration are particularly difficult because different countries define migration differently and measurement methods are not harmonized. Insigh

  10. Step-Wise Migration : Evidence from Indonesia

    NARCIS (Netherlands)

    Pardede, Elda; McCann, Philip; Venhorst, Viktor


    The objective of this paper is to study multiple internal migration trajectories in Indonesia, with special attention to step-wise migration. Step-wise migration involves moves with smaller steps from village to nearby small town, to larger town, and then to big cities rather than a direct move from

  11. Module descriptor

    DEFF Research Database (Denmark)

    Vincenti, Gordon; Klausen, Bodil; Kjær Jensen, Jesper


    The Module Descriptor including a Teacher’s Guide explains and describes how to work innovatively and co-creatively with wicked problems and young people. The descriptor shows how interested educators and lecturers in Europe can copy the lessons of the Erasmus+ project HIP when teaching their own...... students how to include marginalized young people and practitioners in the education of future social workers and social educators....

  12. Physicists' Forced Migrations under Hitler (United States)

    Beyerchen, Alan


    When the Nazis came to power in early 1933 they initiated formal and informal measures that forced Jews and political opponents from public institutions such as universities. Some physicists retired and others went into industry, but most emigrated. International communication and contact made emigration a viable option despite the desperate economic times in the Great Depression. Another wave of emigrations followed the annexation of Austria in 1938. Individual cases as well as general patterns of migration and adaptation to new environments will be examined in this presentation. One important result of the forced migrations was that many of the physicists expelled under Hitler played important roles in strengthening physics elsewhere, often on the Allied side in World War II.

  13. Monomer Migration and Annihilation Processes

    Institute of Scientific and Technical Information of China (English)

    KE Jian-Hong; LIN Zhen-Quan; ZHUANG You-Yi


    We propose a two-species monomer migration-annihilation model, in which monomer migration reactions occur between any two aggregates of the same species and monomer annihilation reactions occur between two different species. Based on the mean-field rate equations, we investigate the evolution behaviors of the processes. For the case with an annihilation rate kernel proportional to the sizes of the reactants, the aggregation size distribution of either species approaches the modified scaling form in the symmetrical initial case, while for the asymmetrical initial case the heavy species with a large initial data scales according to the conventional form and the light one does not scale. Moreover,at most one species can survive finally. For the case with aconstant annihilation rate kernel, both species may scale according to the conventional scaling law in the symmetrical case and survive together at the end.


    CERN Multimedia


    Restricted services from 3 to 7 November 2001 Due to the migration of the Oracle HR application to the Web, some services which rely on the application's availability may be disturbed from Friday 2 November at 17:30 until Thursday 8 November at 08:30. Amongst those services: HR Division: records office, recruitment, claims and benefits. FI Division: personnel accounting, advances and claims. ST Division: registration office (access cards). SPL Division: external firm staff records. EP Division: users' office. Experiments' secretariats: PIE, Greybook. Divisional secretariats: externals, internal addresses. All information concerning this migration is available at: We apologize for any inconvenience and thank you in advance for your understanding.

  15. ProBDNF inhibits collective migration and chemotaxis of rat Schwann cells. (United States)

    Ding, You-Quan; Li, Xuan-Yang; Xia, Guan-Nan; Ren, Hong-Yi; Zhou, Xin-Fu; Su, Bing-Yin; Qi, Jian-Guo


    Schwann cell migration, including collective migration and chemotaxis, is essential for the formation of coordinate interactions between Schwann cells and axons during peripheral nerve development and regeneration. Moreover, limited migration of Schwann cells imposed a serious obstacle on Schwann cell-astrocytes intermingling and spinal cord repair after Schwann cell transplantation into injured spinal cords. Recent studies have shown that mature brain-derived neurotrophic factor, a member of the neurotrophin family, inhibits Schwann cell migration. The precursor form of brain-derived neurotrophic factor, proBDNF, was expressed in the developing or degenerating peripheral nerves and the injured spinal cords. Since "the yin and yang of neurotrophin action" has been established as a common sense, proBDNF would be expected to promote Schwann cell migration. However, we found, in the present study, that exogenous proBDNF also inhibited in vitro collective migration and chemotaxis of RSC 96 cells, a spontaneously immortalized rat Schwann cell line. Moreover, proBDNF suppressed adhesion and spreading of those cells. At molecular level, proBDNF inhibits F-actin polymerization and focal adhesion dynamics in cultured RSC 96 cells. Therefore, our results suggested a special case against the classical opinion of "the yin and yang of neurotrophin action" and implied that proBDNF might modulate peripheral nerve development or regeneration and spinal cord repair through perturbing native or transplanted Schwann cell migration.

  16. Population forecasting with endogenous migration: an application to trans-Tasman migration. (United States)

    Gorbey, S; James, D; Poot, J


    "This article focuses on forecasting migration between Australia and New Zealand (trans-Tasman migration), which is largely visa-free and therefore resembles internal migration. Net trans-Tasman migration is a major component of New Zealand population change and is embedded in this article in a Bayesian or unrestricted vector autoregression (VAR) model, which includes foreign and domestic economic variables. When time series of net migration are available, this approach provides a useful input into forecasting population growth in the short run in the absence of major policy changes. This conclusion applies equally to interregional migration and to unrestricted international migration between economically integrated nations."

  17. Developing a new resource on international nurse migration: the international centre on nurse migration. (United States)

    Nichols, Barbara; Oulton, Judith


    A new collaborative project on nurse migration was recently launched by the International Council of Nurses and the Commission on Graduates of Foreign Nursing Schools. This collaboration, the International Centre on Nurse Migration, guided by the principles of ethical recruitment and equitable treatment of migrating nurses, focuses on promoting, collecting, creating, and disseminating data and information on nurse migration; acting as a resource center; tracking trends and patterns of global health care workforce migration; analyzing policy; generating policy options; advocating for sound policy concerning nurse migration; promoting, undertaking, and disseminating research; providing consultant and expert advice; and offering continuing education about migration.

  18. Mexican Migration: Assessing Root Causes (United States)


    66 Figure 4 is derived from John Scott, “Metas y Mecanismo ,” Centro de Investigacion y Docencia Economicas...John Scott, “Metas y Mecanismo ,” 4. 31 Another explanation for the increase in migration concerns neither the Mexican economy nor the Mexican...Dominant Regime,” 135. 82 John Scott, “Metas y Mecanismo ,” 5. 83 World Bank: Mexican Health Foundation, “Trends and Empirical Causes of Violent

  19. Incentives and disincentives: international migration. (United States)

    Bhagwati, J N


    International migration is largely controlled by disincentives, or quotas, on immigration rather than checks on emigrations. Societies generally feel they have a right to exclude others from their boundaries, but they also usually feel that they do not have a right to control emigration. The single-planetary approach holds that people have the right to live wherever they like on the planet, and the cosmopolitan-utilitarian approach believes the same for reasons of world efficiency. The current feeling that societies have the right to exclude others may be explained best by territoriality in human animals. People also believe that their culture will be diluted if too many outsiders enter. In many cases, immigration systems cannot really control immigration, as in the cases of long landlocked borders between the US and Mexico and between Bangladesh and Assam. Immigration systems also contain legal loopholes. For example, in the US it is easier to get a student visa and convert to immigrant status than to gain immigrant status directly. Loopholes lead to plugs, which lead in turn to more loopholes. An upsurge in requests for political asylum followed increased restrictions on immigration in Western Europe. The US has investigated foreign aid and foreign investments to Mexico and Haiti to curb the flow of illegal migrants. The author suggests that foreign investments may lead to more migration because of the creation of a new proletariat used to the ways of developed countries. An estimate of what would happen if all immigration control were removed worldwide concludes that efficiency and income distribution would improve worldwide. Most migration from developing to developed countries currently consists of the migration of skilled professionals, the brain drain. The author proposes a tax on these professionals to be paid to the country of origin to compensate them for the loss in education and training. The author summarizes the differences between the West German

  20. Marriage migration in the Netherlands


    Leen Sterckx; Jaco Dagevos; Willem Huijnk; Jantine van Lisdonk


    Original title: Huwelijksmigratie in Nederland When a man or woman living in the Netherlands embarks on a relationship with a partner from another country and the couple decide to build a married life together in the Netherlands, we call this marriage migration. The foreign partner who moves to the Netherlands for a lasting relationship is then known as marriage migrant. In this publication we present a statistical picture of marriage migrants, but above all we allow them and their partners t...

  1. Live Migration Of Parallel Applications


    Romero, Raul Fabian


    Romero, Raul F. M.S., Purdue University, August, 2010. Live Migration of Parallel Applications. Major Professor: Thomas J. Hacker. It has been observed on engineering and scientific data centers that the absence of a clear separation between software and hardware can severely affect parallel applications. Applications that run across several nodes tend to be greatly affected because a single computational failure present in one of the nodes often leads the entire application to produce ...

  2. Influences of environmental cues, migration history and habitat familiarity on partial migration

    DEFF Research Database (Denmark)

    Skov, Christian; Aarestrup, Kim; Baktoft, Henrik;


    The factors that drive partial migration in organisms are not fully understood. Roach (Rutilus rutilus), a freshwater fish, engage in partial migration where parts of populations switch between summer habitats in lakes and winter habitats in connected streams. To test if the partial migration trait...... is phenotypically plastic or has genetic components, we translocated roach from 2 populations with different opportunities for migration to a lake with migration opportunity, containing a local roach population. This enabled monitoring of partial migration of fish in 3 different situations: 1) previous opportunity...... decisions. Individuals without previous migration opportunity migrated at a lower proportion and with different small-scale migration patterns, suggesting that also genetic components are involved in the expression of the partial migration trait....


    Energy Technology Data Exchange (ETDEWEB)

    Socrates, Aristotle; Katz, Boaz; Dong Subo; Tremaine, Scott [Institute for Advanced Study, Princeton, NJ 08540 (United States)


    An important class of formation theories for hot Jupiters involves the excitation of extreme orbital eccentricity (e = 0.99 or even larger) followed by tidal dissipation at periastron passage that eventually circularizes the planetary orbit at a period less than 10 days. In a steady state, this mechanism requires the existence of a significant population of super-eccentric (e > 0.9) migrating Jupiters with long orbital periods and periastron distances of only a few stellar radii. For these super-eccentric planets, the periastron is fixed due to conservation of orbital angular momentum and the energy dissipated per orbit is constant, implying that the rate of change in semi-major axis a is a-dot {proportional_to}a{sup 1/2} and consequently the number distribution satisfies dN/d log a{proportional_to}a{sup 1/2}. If this formation process produces most hot Jupiters, Kepler should detect several super-eccentric migrating progenitors of hot Jupiters, allowing for a test of high-eccentricity migration scenarios.

  4. Super-Eccentric Migrating Jupiters

    CERN Document Server

    Socrates, Aristotle; Dong, Subo; Tremaine, Scott


    An important class of formation theories for hot Jupiters involves the excitation of extreme orbital eccentricity (e=0.99 or even larger) followed by tidal dissipation at periastron passage that eventually circularizes the planetary orbit at a period less than 10 days. In a steady state, this mechanism requires the existence of a significant population of super-eccentric (e>0.9) migrating Jupiters with long orbital periods and periastron distances of only a few stellar radii. For these super-eccentric planets, the periastron is fixed due to conservation of orbital angular momentum and the energy dissipated per orbit is constant, implying that the rate of change in semi-major axis a is \\dot a \\propto a^0.5 and consequently the number distribution satisfies dN/dlog a\\propto a^0.5. If this formation process produces most hot Jupiters, Kepler should detect several super-eccentric migrating progenitors of hot Jupiters, allowing for a test of high-eccentricity migration scenarios.


    Directory of Open Access Journals (Sweden)



    Full Text Available Illegal migration is a mobile phenomenon, which ignores national borders, a threat that originates outside the community and extends to Western societies. This phenomenon is becoming larger and irregular migrants are often in a precarious situation and exposed to the criminals involved in various manifestations of organized crime. The future risk factors of the illegal migration are the demographic bomb, because the population is decreasing in European countries and increasing rapidly in poorer countries, droughts, floods, deforestation, that cause conflicts between climate refugees , extreme poverty, totalitarian regimes, epidemics, can trigger millions of people, the elderly and the working population imbalance which leads to the permanent import of immigrants To combat this phenomenon, states must engage and cooperate with each other. Measures taken by states must balance their integration policy for immigrants, legally residents and asylum policy to comply with international conventions. Also, states must adopt anti-immigrant policies, consisting of subordination visa policy to the interests of international security and exchange of information and, not least, to continue the Schengen process, as a value of humanitarian law applied in the field. The aim of the research is to characterize this dangerous phenomenon for the society and the goal is to identify strategies to combat illegal migration.

  6. National and international graduate migration flows. (United States)

    Mosca, Irene; Wright, Robert E


    This article examines the nature of national and international graduate migration flows in the UK. Migration equations are estimated with microdata from a matched dataset of Students and Destinations of Leavers from Higher Education, information collected by the Higher Education Statistical Agency. The probability of migrating is related to a set of observable characteristics using multinomial logit regression. The analysis suggests that migration is a selective process with graduates with certain characteristics having considerably higher probabilities of migrating, both to other regions of the UK and abroad.


    Directory of Open Access Journals (Sweden)



    Full Text Available Return migration is probably the aspect of the migration cycle, which was granted the lowest attention, perhaps because most research resources are located in highly developed countries, while most of the returning most returnees return to developing countries. This is especially unfortunate because perceptions about the process of returning to the country of origin and attitudes towards returning migrants have a significant impact on migrants and their host communities. Rollback, sometimes called remigration, is considered by some authors as the final stage of the migration process, which further comprises the step preparation / decision to migrate and actual migration phase or installation of migrant destination country selected.

  8. Photovoltaic module and module arrays (United States)

    Botkin, Jonathan; Graves, Simon; Lenox, Carl J. S.; Culligan, Matthew; Danning, Matt


    A photovoltaic (PV) module including a PV device and a frame. The PV device has a PV laminate defining a perimeter and a major plane. The frame is assembled to and encases the laminate perimeter, and includes leading, trailing, and side frame members, and an arm that forms a support face opposite the laminate. The support face is adapted for placement against a horizontal installation surface, to support and orient the laminate in a non-parallel or tilted arrangement. Upon final assembly, the laminate and the frame combine to define a unitary structure. The frame can orient the laminate at an angle in the range of from horizontal, and can be entirely formed of a polymeric material. Optionally, the arm incorporates integral feature(s) that facilitate interconnection with corresponding features of a second, identically formed PV module.

  9. Conditioned taste aversion: modulation by 5-HT receptor activity and corticosterone

    DEFF Research Database (Denmark)

    Boris, Gorzalka; Hanson, Laura; Harrington, J


    Two experiments were designed to elucidate the involvement of the hypothalamic-pituitary-adrenal axis and the 5-hydroxytryptamine (5-HT) system in the acquisition of lithium chloride-conditioned taste aversion. In Experiment 1, rats were administered either vehicle or 50 mg/kg nefazodone daily fo......, corticosterone-treated animals required more trials to reach extinction. These results suggest the involvement of both the 5-HT system and the hypothalamic-pituitary-adrenal axis in lithium chloride-conditioned taste aversion....

  10. Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway


    Marcelo Franchin; Marcos Guilherme da Cunha; Carina Denny; Marcelo Henrique Napimoga; Thiago Mattar Cunha; Bruno Bueno-Silva; Severino Matias de Alencar; Masaharu Ikegaki; Pedro Luiz Rosalen


    The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial...

  11. Social Physics and China's Population Migration (United States)

    Wang, Yun-Lin; Li, Ding

    Based on the social physics theory, this paper analyzes the economic disparities between different regions in China, and contributes a conceptual model of population migration among eastern, central, western and north-eastern regions. The national 1% population sample investigation data is adopted to build a network of inter-provincial population migration, and the population migration network is analyzed with social network analysis. The results are shown that there is a very strong correlation between migrant population and economy disparity in China, and the migration with obviously geographical characteristics. The eastern region is the main areas for migration-inflow; the central region is the main areas of migration-outflow; the western region is relatively “locked-up”, with a little of population flow; and the migration of the northeast is mainly within its own regional territory.

  12. Migration from New EU Member Countries

    DEFF Research Database (Denmark)

    Pytlikova, Mariola


    The main purpose of the paper is to give predictions of the migration potential from the 7 new EU member countries to the EEA/EU-13 countries. Being able to analyze 'real' migration behavior from these particular countries over the period 1990-2000 helps me to avoid problems related to (double) out......-of sample forecasts and to the assumption of invariance of migration behavior across a space that previous studies had to hold. Results of the econometric analyses reveal the importance of controlling for pairs of countries unobserved heterogeneity. Preliminary results regarding the predictions of future...... gross and net migration flows show that the magnitude of the estimated gross and net migration flows is relatively high and lower, respectively, compared to forecasts from previous studies. Such a development in gross and net migration flows indicates that migration from the new EU member countries...

  13. Tracing The Largest Seasonal Migration on Earth

    CERN Document Server

    Wang, Xianwen; Mao, Wenli; Hu, Zhigang; Gu, Li


    It is estimated that over 3.6 billion passengers are travelling during the Chinese Spring Festival travel season. They leave their working cities and return their hometowns to enjoy annual family time, and back to cities after the holiday. In this study, with the massive location-based data collected from millions of smartphone users, we propose a novel method to trace the migration flow and explore the migration patterns of Chinese people. From the temporal perspective, we explore the migration trend over time during a 34-days period, about half a month before and after the Spring Festival. From the spatial perspective, the migration directions and routes are estimated and quantified, and the migration flow is visualized. The spatial range of influence of developed regions could be reflected with the destinations of migration, the migration destinations and originations have obvious characteristic of geographical proximity.

  14. Trends in return migration to the South. (United States)

    Long, L H; Hansen, K A


    The rate of return migration to the South rose by nearly 19 percent between the late 1950's and the late 1960's and was an important factor in changing the South's overall migration pattern. But an increase in the rate of return migration was somewhat less important in changing Southern migration than (1) a decline in the rate of out-migration of native Southerners and (2) an increase in the rate at which non-Southern-born persons move to the South. The probability of former migrants returning to the South was over four times greater for whites than for blacks in the 1955-1960 period and three and one-fourth times greater in the 1965-1970 period. Since 1970 the rate of return migration has apparently continued to rise at a faster rate for blacks, but the black rate of return migration is still below the white rate.

  15. An economic analysis of migration in Mexico. (United States)

    Greenwood, M J; Ladman, J R


    This paper analyzes internal migration in Mexico over the 1960-70 period. A model of the determinants of migration is specified and estimated for aggregated interstate migration flows. Results show that distance serves as a significant deterrent to migration, that higher destination earning levels are attractive to migrants, and that regions with high unemployment rates experience lower rates of inmigration. An unanticipated finding is that regions with higher earning levels have greater rates of outmigration. The data are disaggregated to examine separate migration relationships for each state. The results are that distance is a lesser deterrent for those migrants with more accessible alternatives, that higher earning levels reduce the deterring effects of distance, and that regions with higher earning levels have lower associated elasticities of migration. It is concluded that economic factors have played a crucial role in internal migration and thus in the changing occupational and geographic structure of the Mexican labor force.

  16. European Perspectives Approach to Asylum and Migration

    Directory of Open Access Journals (Sweden)

    Georgeta Modiga


    Full Text Available Migration is a complex process, with a multinational character that can not be managed onlyunilaterally or bilaterally, but through effective management to take into account the benefit of all involvedand changing characteristics of the migration process. Regarding the European Union, framed in the generalcontext, it aims to promote a comprehensive migration policy, to provide a coherent and efficient manner tomeet the challenges and opportunities that migration presents. Multilateral approach under considerationcovers all phases of migration, aiming to seize them and present it at the same time, to implement effectivepolicies and measures concerning illegal migration and human trafficking. It is based on generally acceptedprinciples relating to subsidiary, proportionality, solidarity and respect for law and the economic and social.From this perspective, the present study examines the quantitative aspects of migration as well as qualitativeaspects, with emphasis on the challenges that they face Romania, from the status of EU member country.

  17. Type I Planetary Migration with MHD Turbulence

    CERN Document Server

    Laughlin, G; Adams, F; Laughlin, Gregory; Steinacker, Adriane; Adams, Fred


    This paper examines how type I planet migration is affected by the presence of turbulent density fluctuations in the circumstellar disk. For type I migration, the planet does not clear a gap in the disk and its secular motion is driven by torques generated by the wakes it creates in the surrounding disk fluid. MHD turbulence creates additional density perturbations that gravitationally interact with the planet and can dominate the torques produced by the migration mechanism itself. This paper shows that conventional type I migration can be readily overwhelmed by turbulent perturbations and hence the usual description of type I migration should be modified in locations where the magnetorotational instability is active. In general, the migrating planet does not follow a smooth inward trned, but rather exhibits a random walk through phase space. Our main conclusion is that MHD turbulence will alter the time scales for type I planet migration and -- because of chaos -- requires the time scales to be described by ...

  18. Drugs targeting 5-hydroxytryptamine receptors in acute treatments of migraine attacks. A review of new drugs and new administration forms of established drugs

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer C; Pihl, Thomas Peter Boye; Hougaard, Anders


    of migraines. Areas covered: This evaluation reviews the recent advances in acute migraine therapy targeting the 5-HT receptor. Specifically, the authors review the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of 5-HT1F receptor agonists and new formulations of sumatriptan...

  19. [Innervation of the anterior byssus retractor muscle (ABRM) in Mytilus edulis L. III. Histochemical localisation of the terminal nerves through 5-hydroxytryptamine (author's transl)]. (United States)

    Gilloteaux, J


    Detection of nerve structures containing 5-HT were described in the anterior byssus retractor muscle (ABRM) in Mytilus edulis L. after using the fluorescence microscope technique of Flack. We are able to confirm our previous results and assumptions given by histology and electron microscope studies: the neuromuscular "en passage" junctions, largely distributed within the ABRM, contain 5-HT.

  20. Localization of serotoni (5-hydroxytryptamine, 5-HT) with partial purification and characterization of a serotonin binding protein in the intestinal tissue of the nematode Ascaris suum

    Energy Technology Data Exchange (ETDEWEB)

    Martin, R.E.


    An intracellular 5-HT binding protein (SBP) from intestinal tissue was partially purified and characterized. Binding of ({sup 3}H) 5-HT to the protein appeared to be Fe{sup +2}-sensitive and maximal (20.8pmol/mg protein) at 5 {times} 10{sup {minus}4}M Fe{sup +2} and 10{sup {minus}7}M ({sup 3}H) 5-HT. There were two 5-HT binding sites present at optimum Fe{sup +2} concentrations. The Bmax values of these sites were more sensitive to Fe{sup +2} than Kd values. Sulfhydryl reducing agents, cation chelators, Fe{sup +3}, Ca{sup +2} and antagonists of 5-HT uptake and storage inhibited binding of 5-HT to SBP. Gel exclusion chromatography indicated the presence of a 45Kda SBP that in 5 {times} 10{sup {minus}5}M Fe{sup +2} may form aggregates ranging in size from approximately 80 to >1000Kda. The data indicate these in vitro aggregates may correspond to the electron-opaque patches observed in situ. Ascaris suum may provide a model system to further elucidate the physiological role of analogous serotonin binding proteins that have been identified in mammalian systems.

  1. Protein kinase mediated upregulation of endothelin A, endothelin B and 5-hydroxytryptamine 1B/1D receptors during organ culture in rat basilar artery

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Svensson, Carl-Lennart; Xu, Cang-Bao;


    had an enhancing effect on the induced changes giving rise to a 7-25% increase in E(max) in response to ET-1, S6c and 5-CT as compared to the cultured control. 5. Staurosporine inhibited the culture induced upregulation of the response of both the ET(A) and the 5-HT(1B/1D) receptors, but had...

  2. Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex. (United States)

    Egashira, Nobuaki; Iwasaki, Katsunori; Ishibashi, Ayumi; Hayakawa, Kazuhide; Okuno, Ryoko; Abe, Moe; Uchida, Naoki; Mishima, Kenichi; Takasaki, Kotaro; Nishimura, Ryoji; Oishi, Ryozo; Fujiwara, Michihiro


    Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with Alzheimer's disease (AD) and other forms of senile dementia. BPSD have a serious impact on the quality of life of dementia patients, as well as their caregivers. However, an effective drug therapy for BPSD has not been established. Recently, the traditional Japanese medicine Yokukansan (YKS, Yi-gan san in Chinese) has been reported to improve BPSD in a randomized, single-blind, placebo-controlled study. Moreover, abnormalities of the serotonin (5-HT) system such as 5-HT2A receptors have been reported to be associated with BPSD of AD patients. In the present study, we investigated the effect of YKS on head-twitch response induced by 2,5-dimethoxy-4-iodoamphetamine (DOI, 5 mg/kg, i.p.) in mice, a behavioral response that is mediated, in part, by 5-HT2A receptors. Acute treatment with YKS (100 and 300 mg/kg, p.o.) had no effect on the DOI-induced head-twitch response, whilst 14 days repeated treatment with YKS (300 mg/kg, p.o.) significantly inhibited this response. Moreover, repeated treatment with YKS (300 mg/kg, p.o.) decreased expression of 5-HT2A receptors in the prefrontal cortex, which is part of the circuitry mediating the head-twitch response. These findings suggest that the inhibition of DOI-induced head-twitch response by YKS may be mediated, in part, by altered expression of 5-HT2A receptors in the prefrontal cortex, which suggests the involvement of the 5-HT system in psychopharmacological effects of YKS.

  3. Risperidone-Induced Weight Gain in Referred Children with Autism Spectrum Disorders Is Associated with a Common Polymorphism in the 5-Hydroxytryptamine 2C Receptor Gene

    NARCIS (Netherlands)

    Hoekstra, Pieter J.; Troost, Pieter W.; Lahuis, Bertine E.; Mulder, Hans; Mulder, Erik J.; Franke, Barbara; Buitelaar, Jan K.; Anderson, George M.; Scahill, Lawrence; Minderaa, Ruud B.


    Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age-and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-label, fle

  4. Risperidone-Induced Weight Gain in Referred Children with Autism Spectrum Disorders Is Associated with a Common Polymorphism in the 5-Hydroxytryptamine 2C Receptor Gene.

    NARCIS (Netherlands)

    Hoekstra, P.J.; Troost, P.W.; Lahuis, B.E.; Mulder, H.; Mulder, E.J.H.; Franke, B.; Buitelaar, J.K.; Anderson, G.M.; Scahill, L.; Minderaa, R.B.


    Abstract Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age- and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-

  5. Selectivity of (3)H-MADAM binding to 5-hydroxytryptamine transporters in vitro and in vivo in mice; correlation with behavioural effects. (United States)

    Larsen, A K; Brennum, L T; Egebjerg, J; Sánchez, C; Halldin, C; Andersen, P H


    1. Binding of the novel radioligand (3)H-2-(2-dimethylaminomethyl-phenylsulphanyl)-5-methyl-phenylamine ((3)H-MADAM) to the serotonin transporter (SERT) was used to characterise a range of selective serotonin re-uptake inhibitors (SSRIs) in vitro and in vivo. 2. (3)H-MADAM bound with high affinity in a saturable manner to both human SERT expressed in CHO cells (K(d)=0.20 nm (pK(d)=9.74+/-0.12), B(max)=35+/-4 fmol mg(-1) protein) and mouse cerebral cortex membranes (K(d)=0.21 nm (pK(d)=9.66+/-0.10), B(max)=50+/-24 fmol mg(-1) protein). 3. Binding of (3)H-MADAM was highly selective for SERT in vitro as demonstrated by the in vitro profile of MADAM tested at 75 different receptors, ion channels and transporters. This was further substantiated by the pharmacological profile of the binding. Hence, the binding of (3)H-MADAM was potently inhibited by SSRIs but not by selective inhibitors of noradrenaline transport and dopamine transport. Likewise, a 5-HT(2A/2C) receptor antagonist did not inhibit (3)H-MADAM binding. 4. (3)H-MADAM binding in vivo was inhibited only by compounds which also inhibited the binding of (3)H-MADAM in vitro (the SSRIs, mixed SERT/noradrenaline transport inhibitors and clomipramine), confirming the selectivity of (3)H-MADAM for SERT also in vivo. Moreover, compounds effective in inhibiting (3)H-MADAM binding were the only ones found to be active in the mouse 5-HTP potentiation test confirming the model as a behavioural correlate to in vivo 5-HT uptake. 5. Finally, it was found that a SERT occupancy of 85-95% was necessary to produce 50% of the maximum behavioural response (ED(50)).

  6. Hydrogen peroxide (H/sub 2/O/sub 2/) stimulates the active transport of 5-hydroxytryptamine (5-HT) into platelets

    Energy Technology Data Exchange (ETDEWEB)

    Bosin, T.R.


    Platelets function in a variety of physiological and pathological processes which may be altered by oxidant injury. One such process is the active transport 5-HT, which is an important mechanism in the control of circulating 5-HT levels. Exposure of mouse platelets (10/sup 8//ml) to H/sub 2/O/sub 2/ caused a time-dependent and dose-dependent increase in 5-HT (10/sup -7/M) uptake. The uptake 4 and 10 min following H/sub 2/O/sub 2/ (50 was 228% and 145% of control values, respectively. Fluoxetine (10/sup -6/M) blocked all 5-HT uptake and catalase (1500 U/ml) blocked the H/sub 2/O/sub 2/-stimulated uptake. Enzymatically produced H/sub 2/O/sub 2/ (glucose/glucose oxidase) and xanthine (X)/xanthine oxidase (XO) generated oxygen radicals produced quantitatively and qualitatively similar results. The stimulatory response of platelets to X/XO generated oxidants was unaffected by superoxide dismutase (250 U/ml) but, was inhibited using heat-denatured XO, allopurinol (0.5 mM) and catalase; fluoxetine inhibited all 5-HT uptake. Platelets exposed to X/XO in the presence of chelated (EDTA, 100 or unchelated FeSO/sub 4/, FeNH/sub 4/(SO/sub 4/)/sub 2/ or CuCl (50 did not have altered 5-HT uptake. These data indicate that brief exposure of platelets to physiological levels of H/sub 2/O/sub 2/ results in marked, reversible stimulation of active 5-HT uptake which may represent a homeostatic defense mechanism when H/sub 2/O/sub 2/ is elevated in the platelet microenvironment.

  7. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, D.J.; Guan, X.M.; Shulgin, A.T. (Department of Neurology Neurological Sciences, Stanford University Medical Center, CA (USA))


    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.

  8. 5-Hydroxytryptamine potentiates neurogenic contractions of rat isolated urinary bladder through both 5-HT(7) and 5-HT(2C) receptors. (United States)

    Rekik, Moèz; Lluel, Philippe; Palea, Stefano


    Serotonin (5-HT) enhances the neurogenic contractile response induced by electrical field stimulation (EFS) in the rat isolated urinary bladder. The aim of this study was to functionally characterize the receptors involved in this effect by using a range of 5-HT receptor subtype selective agonists and antagonists. 5-HT produced a concentration-dependent potentiation of contractile responses to EFS with a pEC(50) value of 6.86±0.24. SB-269970 (0.01, 0.1 and 1μM), a selective 5-HT(7) receptor antagonist, caused a concentration-dependent rightward shift of the 5-HT-induced response. The pA(2) value was 8.16 with a slope of 0.46±0.08. Neither ketanserine nor SB-204741, 5-HT(2A) and 5-HT(2B) receptors antagonists, respectively, affected the concentration-response curve to 5-HT. However, 5-HT response was antagonized by the selective 5-HT(2C) receptor antagonist SB-242084 (0.1 and 1μM). In the presence of 1μM of both antagonists SB-269970 and SB-242084, 5-HT response was almost fully inhibited. 5-CT, a 5-HT(7) receptor agonist, induced a biphasic concentration-dependent potentiation of neurogenic contractions. SB-269970 concentration-dependently antagonized the first phase of 5-CT response with a pA(2) value of 8.77 and a slope not significantly different from unity (0.91±0.11) that suggests a competitive antagonism. WAY-161503, a 5-HT(2C) receptor agonist (0.01-10μM), induced a concentration-dependent potentiation of contractile response to EFS while DOI (a selective 5-HT(2A) agonist) had no effect. SB-242084 (0.1 and 1μM) antagonized the effect of WAY-161503 in a concentration-dependent manner. The current results demonstrate that 5-HT potentiates neurogenic contractions of rat isolated detrusor muscle through both 5-HT(7) and 5-HT(2c) receptors.

  9. 5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis. (United States)

    Matsumoto, T; Maeno, Y; Kato, H; Seko-Nakamura, Y; Monma-Ohtaki, J; Ishiba, A; Nagao, M; Aoki, Y


    Using in vivo microdialysis, a comparative study was conducted to examine the effects of amphetamine-related compounds (methamphetamine, MAP; 3,4-methylenedioxymethamphetamine, MDMA; p-methoxyamphetamine, PMA; p-methoxymethamphetamine, PMMA; 4-methylthioamphetamine, 4-MTA; 3,4,5-trimethoxyamphetamine, TMA; 2,5-dimethoxy-4-iodoamphetamine, DOI) on extracellular levels of serotonin (5-HT) and dopamine (DA). Dialysates were assayed using HPLC equipped with electrochemical detector following i.p. administration with each drug at a dose of 5 mg/kg. MAP was found to drastically and rapidly increase 5-HT and DA levels (870% and 1460%, respectively). PMA, PMMA, and 4-MTA slightly increased DA levels (150-290%) but remarkably increased 5-HT levels (540-900%). In contrast, TMA and DOI caused no detectable changes in levels of both monoamines. We observed that the potent DA-releasing action of MAP was remarkably decreased by introduction of methoxy or methylthio group at the para position (MAP vs. PMMA or 4-MTA), but introduction of two additional adjacent methoxy groups into PMA totally abolished its 5-HT-/DA-releasing action (PMA vs. TMA). In addition, para-mono-substituted compounds inhibited both monoamine oxidase (MAO) enzymes more strongly than other compounds; PMA and 4-MTA exhibited submicromolar IC50 values for MAO-A. On the other hand, TMA scarcely affected the activity of both MAO enzymes as well as extracellular levels of 5-HT and DA. In this comparative study, MDMA, PMA, and 4-MTA functioned similar to PMMA, a typical empathogen; these findings therefore could be helpful in clarifying the psychopharmacological properties of amphetamine-related, empathogenic designer drugs.

  10. Development of Plate Reader and On-Line Microfluidic Screening to Identify Ligands of the 5-Hydroxytryptamine Binding Protein in Venoms

    Directory of Open Access Journals (Sweden)

    Reka A. Otvos


    Full Text Available The 5-HT3 receptor is a ligand-gated ion channel, which is expressed in the nervous system. Its antagonists are used clinically for treatment of postoperative- and radiotherapy-induced emesis and irritable bowel syndrome. In order to better understand the structure and function of the 5-HT3 receptor, and to allow for compound screening at this receptor, recently a serotonin binding protein (5HTBP was engineered with the Acetylcholine Binding Protein as template. In this study, a fluorescence enhancement assay for 5HTBP ligands was developed in plate-reader format and subsequently used in an on-line microfluidic format. Both assay types were validated using an existing radioligand binding assay. The on-line microfluidic assay was coupled to HPLC via a post-column split which allowed parallel coupling to a mass spectrometer to collect MS data. This high-resolution screening (HRS system is well suitable for compound mixture analysis. As a proof of principle, the venoms of Dendroapsis polylepis, Pseudonaja affinis and Pseudonaja inframacula snakes were screened and the accurate masses of the found bioactives were established. To demonstrate the subsequent workflow towards structural identification of bioactive proteins and peptides, the partial amino acid sequence of one of the bioactives from the Pseudonaja affinis venom was determined using a bottom-up proteomics approach.

  11. Simultaneous measurements of capillary filtration and diffusion capacities during graded infusions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT) into the rat hindquarter vascular bed. (United States)

    Rippe, B; Folkow, B


    The relationships between capillary diffusion capacity (PS) for Cr-EDTA respective capillary filtration capacity (CFC) and vascular resistance during graded intraarterial infusions of NA and 5-HT into the artificially constant flow perfused rat hindquarter vascular bed were investigated. During maximal vasodilatation PS for Cr-EDTA was some 5.5--5.7 ml/min x 100 g, CFC some 0.04 ml/min x mmHg x 100 g, while vascular resistance was 2.8 mmHg x ml-1 x min x 100 g (PRU100) and isogravimetric capillary pressure 12.8 mmHg on an average. Setting out from maximal vasodilatation, increasing doses of NA and 5-HT produced graded reductions in capillary surface area as reflected by progressive decreases in both PS for Cr-EDTA and CFC. These changes occurred simultaneously with progressive increases in both pre- and postcapillary resistances, causing elevations in both arterial and capillary hydrostatic pressures and hance in capillary fluid filtration at constant flow. Capillary hydrostatic pressure increased maximally to 45 mmHg (calculated for NA) and vascular resistance to some 21 mmHg x ml-1 x min x 100 g on an average. PS for Cr-EDTA decreased maximally to some 0.7--1 ml/min x 100 g for both NA and 5-HT and furthermore, the relationships between PS for Cr-EDTA and PRU100 for NA respective 5-HT were almost identical. This was taken to indicate that capillary surface area for nutritional exchange is affected similarly by both drugs. However, the CFU-PRU100 relationship was shifted towards some 30--50% higher CFC values for 5-HT than for NA at almost every level of vasoconstriction. This might suggest that 5-HT besides reducing capillary surface area also induced moderate increases in capillary permeability though increases in number and/or radius of large pores (gaps) (cf. Rippe, Kamiya & Folkow 1978). Even during NA-induced vasoconstriction, when virtually no changes in capillary permeability occurred, PS for Cr-EDTA was reduced to a relatively greater extent than CFC, the discrepancy being most pronounced during marked vasoconstriction. The significance of this finding is discussed.

  12. Hearing loss alters serotonergic modulation of intrinsic excitability in auditory cortex. (United States)

    Rao, Deepti; Basura, Gregory J; Roche, Joseph; Daniels, Scott; Mancilla, Jaime G; Manis, Paul B


    Sensorineural hearing loss during early childhood alters auditory cortical evoked potentials in humans and profoundly changes auditory processing in hearing-impaired animals. Multiple mechanisms underlie the early postnatal establishment of cortical circuits, but one important set of developmental mechanisms relies on the neuromodulator serotonin (5-hydroxytryptamine [5-HT]). On the other hand, early sensory activity may also regulate the establishment of adultlike 5-HT receptor expression and function. We examined the role of 5-HT in auditory cortex by first investigating how 5-HT neurotransmission and 5-HT(2) receptors influence the intrinsic excitability of layer II/III pyramidal neurons in brain slices of primary auditory cortex (A1). A brief application of 5-HT (50 μM) transiently and reversibly decreased firing rates, input resistance, and spike rate adaptation in normal postnatal day 12 (P12) to P21 rats. Compared with sham-operated animals, cochlear ablation increased excitability at P12-P21, but all the effects of 5-HT, except for the decrease in adaptation, were eliminated in both sham-operated and cochlear-ablated rats. At P30-P35, cochlear ablation did not increase intrinsic excitability compared with shams, but it did prevent a pronounced decrease in excitability that appeared 10 min after 5-HT application. We also tested whether the effects on excitability were mediated by 5-HT(2) receptors. In the presence of the 5-HT(2)-receptor antagonist, ketanserin, 5-HT significantly decreased excitability compared with 5-HT or ketanserin alone in both sham-operated and cochlear-ablated P12-P21 rats. However, at P30-P35, ketanserin had no effect in sham-operated and only a modest effect cochlear-ablated animals. The 5-HT(2)-specific agonist 5-methoxy-N,N-dimethyltryptamine also had no effect at P12-P21. These results suggest that 5-HT likely regulates pyramidal cell excitability via multiple receptor subtypes with opposing effects. These data also show that

  13. Chapter 10 the primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair

    DEFF Research Database (Denmark)

    Christensen, Søren T; Pedersen, Stine F; Satir, Peter


    Cell cycle control and migration are critical processes during development and maintenance of tissue functions. Recently, primary cilia were shown to take part in coordination of the signaling pathways that control these cellular processes in human health and disease. In this review, we present...... an overview of the function of primary cilia and the centrosome in the signaling pathways that regulate cell cycle control and migration with focus on ciliary signaling via platelet-derived growth factor receptor alpha (PDGFRalpha). We also consider how the primary cilium and the centrosome interact...... with the extracellular matrix, coordinate Wnt signaling, and modulate cytoskeletal changes that impinge on both cell cycle control and cell migration....

  14. Area 2: Inexpensive Monitoring and Uncertainty Assessment of CO2 Plume Migration using Injection Data

    Energy Technology Data Exchange (ETDEWEB)

    Srinivasan, Sanjay [Univ. of Texas, Austin, TX (United States)


    In-depth understanding of the long-term fate of CO₂ in the subsurface requires study and analysis of the reservoir formation, the overlaying caprock formation, and adjacent faults. Because there is significant uncertainty in predicting the location and extent of geologic heterogeneity that can impact the future migration of CO₂ in the subsurface, there is a need to develop algorithms that can reliably quantify this uncertainty in plume migration. This project is focused on the development of a model selection algorithm that refines an initial suite of subsurface models representing the prior uncertainty to create a posterior set of subsurface models that reflect injection performance consistent with that observed. Such posterior models can be used to represent uncertainty in the future migration of the CO₂ plume. Because only injection data is required, the method provides a very inexpensive method to map the migration of the plume and the associated uncertainty in migration paths. The model selection method developed as part of this project mainly consists of assessing the connectivity/dynamic characteristics of a large prior ensemble of models, grouping the models on the basis of their expected dynamic response, selecting the subgroup of models that most closely yield dynamic response closest to the observed dynamic data, and finally quantifying the uncertainty in plume migration using the selected subset of models. The main accomplishment of the project is the development of a software module within the SGEMS earth modeling software package that implements the model selection methodology. This software module was subsequently applied to analyze CO₂ plume migration in two field projects – the In Salah CO₂ Injection project in Algeria and CO₂ injection into the Utsira formation in Norway. These applications of the software revealed that the proxies developed in this project for quickly assessing the dynamic characteristics of the reservoir were

  15. Trefoil factor 3 peptide regulates migration via a Twist-dependent pathway in gastric cell. (United States)

    Zheng, Qianqian; Gao, Jian; Li, Honglin; Guo, Wendong; Mao, Qi; Gao, Enhui; Zhu, Ya-qin


    Trefoil factor 3 (TFF3) is a member of the TFF-domain peptide family and essential in regulating cell migration and maintaining mucosal integrity in gastrointestinal tract. However, the role of TFF3 and its downstream regulating mechanisms in cancer cell migration remain unclear. We previously reported that TFF3 prolonged the up-regulation of Twist protein to modulate IL-8 secretion in intestinal epithelial cells. In this study, we investigated the role of Twist protein in TFF3-induced migration of SGC7901 cells. While Twist was activated by TFF3, siRNA-mediated knockdown of Twist abolished TFF3-induced cell migration. Furthermore, the migration related marker CK-8 as well as ZO-1 and MMP-9 was also regulated by TFF3 via a Twist-dependent mechanism. Our study suggests that Twist, as an important potential downstream effector, plays a key role in TFF3-modulated metastasis in gastric cancer and can be a promising therapeutic target against intestinal-type gastric cancer.

  16. The role of Serine Proteases and Serine Protease Inhibitors in the migration of Gonadotropin-Releasing Hormone neurons

    Directory of Open Access Journals (Sweden)

    Silverman Ann-Judith


    Full Text Available Abstract Background Mechanisms regulating neuronal migration during development remain largely undefined. Extracellular matrix cues, target site released factors, and components of the migratory neurons themselves are likely all coordinated in time and space directing neurons to their appropriate locations. We have studied the effects of proteases and their inhibitors on the extracellular matrix and the consequences to the migration of gonadotropin releasing hormone (GnRH neurons in the embryonic chick. Chick GnRH neurons differentiate in the olfactory epithelium, migrate along the olfactory nerve and enter the forebrain. The accessibility of this coherent cell group make it amenable for studying protease/inhibitor roles in migratory processes. Results Affigel blue beads were used to deliver a serine protease inhibitor, protease nexin-1 (PN-1, and a target protease, trypsin, to the olfactory epithelium coincident with initiation of GnRH neuronal migration. PN-1 inhibited neuronal migration while trypsin accelerated their transit into the CNS. Prior to initiation of migration, neither PN-1 nor trypsin altered the timing of neuronal exit. Trypsin did, however, accelerate the timing of neuronal crossing into the nerve-forebrain junction. Conclusions These data support the hypothesis that protease activity modulates neuronal movements across barriers. Moreover, the data suggest, for the first time, that aspects of GnRH neuronal migration may be cell autonomous but modulated by ECM alterations.

  17. Return migration as failure or success? : The determinants of return migration intentions among Moroccan migrants in Europe

    NARCIS (Netherlands)

    de Haas, H.; Fokkema, T.; Fihri, M.F.


    Different migration theories generate competing hypotheses with regard to determinants of return migration. While neoclassical migration theory associates migration to the failure to integrate at the destination, the new economics of labour migration sees return migration as the logical stage after

  18. Migrating Applications to IPv6

    CERN Document Server

    York, Dan


    If IPv6 is to be adopted on a large scale, the applications running on desktop systems, laptops, and even mobile devices need to work just as well with this protocol as they do with IPv4. This concise book takes you beyond the network layer and helps you explore the issues you need to address if you are to successfully migrate your apps to IPv6. It's ideal for application developers, system/network architects, product managers, and others involved in moving your network to IPv6. Explore changes you need to make in your application's user interfaceMake sure your application is retrieving corre

  19. Savings, remittances, and return migration. (United States)

    Merkle, L; Zimmermann, K F


    "We use a data set of immigrants to West Germany to simultaneously study both savings and remittances which we relate to individual characteristics, economic variables, migration experiences and remigration plans. Section 2 discusses the basic hypotheses and explains the data. Section 3 presents the empirical study and Section 4 summarizes." The results suggest that "savings and remittances of migrants can be well explained by remigration plans and economic as well as demographic variables. However, the planned future duration of residence in Germany has a negative and significant effect only on remittances."

  20. Soluble EphB4 Inhibition of PDGF-Induced RPE Migration In Vitro


    He, Shikun; Kumar, S. Ram; Zhou, Peng; Krasnoperov, Valery; Ryan, Stephen J.; Gill, Parkash S.; Hinton, David R.


    EphB4 receptor and its ligand, EphrinB2, have been shown to be important regulators of cell adhesion and migration. Although the critical role of this system has been explored in neurobiology and vascular biology, little is known about its role in epithelial biology and especially in the retinal pigment epithelium (RPE). Here the authors show a novel mechanism by which soluble EphB4 modulates the migration of RPE cells mediated by platelet-derived growth factor. These results are relevant to ...

  1. Step-Flow Growth on Vicinal GaAs Surfaces by Migration-Enhanced Epitaxy (United States)

    Yamaguchi, Hiroshi; Horikoshi, Yoshiji


    The mechanism of step-flow growth on vicinal GaAs substrates during migration-enhanced epitaxy are studied using the reflection high-energy electron diffraction technique. Results show that the low As pressure during migration-enhanced epitaxy growth accelerates step-flow growth. In addition, it is also shown that monolayer terraces composed of surface Ga atoms are formed from step edges during the Ga deposition process. A GaAs/AlAs tilted superlattice is established using this growth technique. X-ray diffraction measurement and transmission electron microscopy observations show that the fabricated structure has periodic composition modulation along the axis tilted from the substrate azimuth.

  2. Partial migration in fishes: causes and consequences

    DEFF Research Database (Denmark)

    Chapman, B.B.; Hulthén, K.; Brodersen, J.;


    migration are reflected upon: what ecological factors can shape the evolution of migratory dimorphism? How is partial migration maintained over evolutionary timescales? What proximate mechanisms determine whether an individual is migratory or remains resident? Following this, the consequences of partial...... with a reflection on the future opportunities in this field, and the avenues of research that are likely to be fruitful to shed light on the enduring puzzle of partial migration in fishes......Partial migration, where only some individuals from a population migrate, has been widely reported in a diverse range of animals. In this paper, what is known about the causes and consequences of partial migration in fishes is reviewed. Firstly, the ultimate and proximate drivers of partial...

  3. Efficient cell migration requires global chromatin condensation. (United States)

    Gerlitz, Gabi; Bustin, Michael


    Cell migration is a fundamental process that is necessary for the development and survival of multicellular organisms. Here, we show that cell migration is contingent on global condensation of the chromatin fiber. Induction of directed cell migration by the scratch-wound assay leads to decreased DNaseI sensitivity, alterations in the chromatin binding of architectural proteins and elevated levels of H4K20me1, H3K27me3 and methylated DNA. All these global changes are indicative of increased chromatin condensation in response to induction of directed cell migration. Conversely, chromatin decondensation inhibited the rate of cell migration, in a transcription-independent manner. We suggest that global chromatin condensation facilitates nuclear movement and reshaping, which are important for cell migration. Our results support a role for the chromatin fiber that is distinct from its known functions in genetic processes.

  4. Migration in Asia-Europe Relations

    DEFF Research Database (Denmark)

    Juego, Bonn


    There is a remarkable difference between viewing migration as a 'social integration' issue, on the one hand, and migration as a 'social relation'. The idea of ‘social integration’ has unrealistic assumptions that see migration as a one-way process, that societies and human relations are static......, and that migrants are mechanical. Policies that are founded on unrealistic assumptions are most likely to generate tensions, conflicts, and contradictions. For a migration process to succeed in forging social harmony and development, it is therefore of decisive and crucial importance to regard migration...... as a ‘social relation’. This is simply because successful migration has to be a harmonious synergy between the migrants (and also the sending countries where they come from) and the receiving society (and its people). As indicated, migrants enter into the receiving society not merely as a passive commodity...

  5. Focal Adhesion-Independent Cell Migration. (United States)

    Paluch, Ewa K; Aspalter, Irene M; Sixt, Michael


    Cell migration is central to a multitude of physiological processes, including embryonic development, immune surveillance, and wound healing, and deregulated migration is key to cancer dissemination. Decades of investigations have uncovered many of the molecular and physical mechanisms underlying cell migration. Together with protrusion extension and cell body retraction, adhesion to the substrate via specific focal adhesion points has long been considered an essential step in cell migration. Although this is true for cells moving on two-dimensional substrates, recent studies have demonstrated that focal adhesions are not required for cells moving in three dimensions, in which confinement is sufficient to maintain a cell in contact with its substrate. Here, we review the investigations that have led to challenging the requirement of specific adhesions for migration, discuss the physical mechanisms proposed for cell body translocation during focal adhesion-independent migration, and highlight the remaining open questions for the future.

  6. Study on ecological migration in Xinjiang, China

    Institute of Scientific and Technical Information of China (English)

    Abliz Yusup; Osman Niyaz


    This paper expounds on the meaning of migration and the status quo of studies at home and abroad on migration and ecological migration. It focuses on the discussion of the necessity of ecological migration in Xinjiang, and the problems faced by the ecological emigrants, such as the lack of water, the serious land salination and basification,sand storms, and the adaptation to the environment. Besides, it probes into the problems existing in the ecological migration, including the unscientific design of the moving project, the defects of the reclamation work, and the irrational treatment of the relation between ecological migration and regional development. Based on this, we put forward some suggestions about and countermeasures against those problems.

  7. Migration and Education Inequality in Rural Mexico


    David McKenzie; Hillel Rapoport


    This paper examines the impact of migration on education inequality in rural Mexico. Using data from the 1997 National Survey of Demographic Dynamics (ENADID), we first examine the impact of migration on educational attainment for males and females aged 12-15 and 16-18. We then build on the results on attainments to compute education inequality indicators for a large sample of communities throughout Mexico. After instrumenting, we find no significant impact of migration on educational attainm...

  8. Interregional Migration in Spain: A Semiparametric Analysis


    Maza Fernández, Adolfo Jesús; Villaverde Castro, José


    This paper analyses the determinants of internal migration in Spain between 1995 and 2002. After a brief descriptive study, we present an analytical model of internal migration flows. Subsequently, we estimate this model by applying semiparametric techniques. The general conclusion that we come to is that net migration rates are influenced mainly by income and climatic condition differentials between the regions of origin and destination; in addition, unemployment and housin...

  9. Bayesian Probabilistic Projection of International Migration. (United States)

    Azose, Jonathan J; Raftery, Adrian E


    We propose a method for obtaining joint probabilistic projections of migration for all countries, broken down by age and sex. Joint trajectories for all countries are constrained to satisfy the requirement of zero global net migration. We evaluate our model using out-of-sample validation and compare point projections to the projected migration rates from a persistence model similar to the method used in the United Nations' World Population Prospects, and also to a state-of-the-art gravity model.

  10. Cultural values in international migration and remittances


    Inna Čábelková


    In this paper we study the effects of cultural determinants on the migration flows across countries and the financial flows back to the country of origin of the migrants in the form of remittances. We present econometric models for migration and remittances and test the relations between migration and remittances on one hand and cultural dimensions on the other hand. We find that collectivist countries produce more migrants per one inhabitant. This finding corresponds to social reason for mig...

  11. Guidance cue for cortical radial migration discovered

    Institute of Scientific and Technical Information of China (English)


    @@ The regulatory mechanism for neuronal migration in the developing cortex is a major unsolved problem in developmental neurobiology. It is generally accepted that the migration of newborn pyramidal neurons from the ventricular zone toward upper cortical layers is guided by radial glial fibers in the developing cortex, and that the laminar structure of the cortex is formed through regulated attachment and detachment of migrating neurons with radial glial fibers.

  12. Mediating Migration: New Roles for (Mass) Media


    Kosnick, Kira


    This article aims to expand the scope of studying media in relation to migration and diversity by addressing new forms of media deployment in the interest of regulating migration flows to the European Union and the United States. Beyond constructing representations of minorities and migration processes that impact interethnic relations and politics in countries of immigration, it is argued that media technologies and representations have new roles to play when it comes to targeting potential ...


    Directory of Open Access Journals (Sweden)

    Kadir TEMURÇİN


    Full Text Available Migrations from Turkey to abroad for half a century have proceeded in the recent times by undergoing important changes. Moreover, it has been observed that there exist various types and ways of foreigner migration from abroad to Turkey which began from 1980 onwards and became clarified in the 2000s. This study is aimed to focus on who migrated from abroad to Turkey and where they migrated later on the basis of the 2000 General Census.As in the internal migration, the external migration tends towards the western part of the country, particularly big cities. Thusly, % 44 of the migration occurred in big cities; % 33.4 in the centre of towns and provinces; the rest % 22.5 in the countryside. The fact that % 51.9 of immigrants were born in Turkey gives rise to "comeback migration" thought with regard to the external migration. Moreover, that % 77.7 of them are Turkish nationals supports this judgment. On the other hand, the foreign nationals whose number has reached to 50.251 (% 21.5 are non-negligible. The big cities where the external nationals are grouped and the touristic centers on the Aegean and Mediterranean coasts are also the areas immigrants of foreign origin have settled down.

  14. Nuss bar migrations: occurrence and classification

    Energy Technology Data Exchange (ETDEWEB)

    Binkovitz, Lauren E.; Binkovitz, Larry A. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Zendejas, Benjamin; Moir, Christopher R. [Mayo Clinic, Department of Surgery, Rochester, MN (United States)


    Pectus excavatum results from dorsal deviation of the sternum causing narrowing of the anterior-posterior diameter of the chest. It can result in significant cosmetic deformities and cardiopulmonary compromise if severe. The Nuss procedure is a minimally invasive technique that involves placing a thin horizontally oriented metal bar below the dorsal sternal apex for correction of the pectus deformity. To identify the frequency and types of Nuss bar migrations, to present a new categorization of bar migrations, and to present examples of true migrations and pseudomigrations. We retrospectively reviewed the electronic medical records and all pertinent radiologic studies of 311 pediatric patients who underwent a Nuss procedure. We evaluated the frequency and type of bar migrations. Bar migration was demonstrated in 23 of 311 patients (7%) and occurred within a mean period of 26 days after surgery. Bar migrations were subjectively defined as deviation of the bar from the position demonstrated on the immediate postoperative radiographs and categorized as superior, inferior, rotation, lateral or flipped using a new classification system. Sixteen of the 23 migrations required re-operation. Nuss bar migration can be diagnosed with careful evaluation of serial radiographs. Nuss bar migration has a wide variety of appearances and requires exclusion of pseudomigration resulting from changes in patient positioning between radiologic examinations. (orig.)

  15. Motorized Migrations: the Future or Mere Fantasy? (United States)

    Ellis, D.H.; Sladen, William J. L.; Lishman, W.A.; Clegg, K.R.; Duff, J.W.; Gee, G.F.; Lewis, J.C.


    In 15 experiments from 1993-2002, we led cranes, geese, or swans on their first southward migration with either ultralight aircraft or vehicles on the ground. These experiments reveal that large birds can be readily trained to follow and most will return north (and south) in subsequent migrations unassisted. These techniques can now be used to teach birds new (or forgotten) migration paths. Although we are constantly improving our training techniques, we now have an operational program that can be broadly applied to those species where juveniles learn migration routes from their parents.

  16. Migration processes in SCO member states

    Directory of Open Access Journals (Sweden)

    Valentina Sergeevna Antonyuk


    Full Text Available The article concerns modern state and development of migration processes in SCO member states. As a main method of research statistical analysis was applied. The article shows that migration streams between SCO member states are rather intensive, and the problem of labor migration becomes more and more urgent. The countries of consuming and supplying of labour force are clearly differentiated in the region. For some countries, labor export is the key sector of economy. At the same time, interstate relations between SCO member states sometimes are rather disputed. The most urgent factors causing the development of migration processes in the region were determined. Among them, thefactor of growing outflows from China isespecially noted. It is noted that migration processes are discussed by SCO member states nowadays in terms of illegal migration and international criminality connected with it. It means that the question of labor migration is a real problem. It is indicated that the creation of a specific joint commission on migration policy affiliated with the Council of Foreign Ministers of SCO member states is the necessary condition of effective interaction in migration questions within the framework of Shanghai Cooperation Organization.

  17. Multiregional estimation of gross internal migration flows. (United States)

    Foot, D K; Milne, W J


    "A multiregional model of gross internal migration flows is presented in this article. The interdependence of economic factors across all regions is recognized by imposing a non-stochastic adding-up constraint that requires total inmigration to equal total outmigration in each time period. An iterated system estimation technique is used to obtain asymptotically consistent and efficient parameter estimates. The model is estimated for gross migration flows among the Canadian provinces over the period 1962-86 and then is used to examine the likelihood of a wash-out effect in net migration models. The results indicate that previous approaches that use net migration equations may not always be empirically justified."

  18. From migration to settlement: the pathways, migration modes and dynamics of neurons in the developing brain. (United States)

    Hatanaka, Yumiko; Zhu, Yan; Torigoe, Makio; Kita, Yoshiaki; Murakami, Fujio


    Neuronal migration is crucial for the construction of the nervous system. To reach their correct destination, migrating neurons choose pathways using physical substrates and chemical cues of either diffusible or non-diffusible nature. Migrating neurons extend a leading and a trailing process. The leading process, which extends in the direction of migration, determines navigation, in particular when a neuron changes its direction of migration. While most neurons simply migrate radially, certain neurons switch their mode of migration between radial and tangential, with the latter allowing migration to destinations far from the neurons' site of generation. Consequently, neurons with distinct origins are intermingled, which results in intricate neuronal architectures and connectivities and provides an important basis for higher brain function. The trailing process, in contrast, contributes to the late stage of development by turning into the axon, thus contributing to the formation of neuronal circuits.

  19. Working and Living Conditions of Migrant Workers in the GCC: India Migration Report 2016: Gulf Migration


    Diop, Abdoulaye; Le, Kien T.; Ewers, Michael; S. Irudaya Rajan


    India Migration Report 2016 discusses migration to the Persian Gulf region. This volume: • looks at contemporary labour recruitment and policy, both in India and in the Gulf Cooperation Council (GCC) countries; • explores gender issues in migration to Gulf countries; and • brings together latest field data on migrants across states in India. Part of the prestigious annual series, this volume will interest scholars and researchers of economics, development studies, migration an...



    Simona BUTA; Rozalia Iuliana KICSI


    The paper Empirical reflections on migration phenomenon. Major effects of migration on the human capital analyzes the migration flows of the workforce (as part of the human capital) globally/regionally, especially the highly qualified workforce migration. The qualified manpower processes of attracting on the work market have not been always well understood and, in some cases, have generated a series of difficulties. This is the reason why we will focus on the „waste of brains” phenomenon, whi...

  1. Determinants of the Egyptian labour migration. (United States)

    Kandil, M; Metwally, M


    The objective is to summarize the pattern of Egyptian migration to Arab oil-producing countries (AOPC), to review some factors that are important determinants of labor movement based on theory, and to empirically model the migration rate to AOPC and to Saudi Arabia. Factors are differentiated as to their relative importance. Push factors are the low wages, high inflation rate, and high population density in Egypt; pull factors are higher wages. It is predicted that an increase in income from destination countries has a significant positive impact on the migration rate. An increase in population density stimulates migration. An increase in inflation acts to increase out-migration with a 2-year lag, which accommodates departure preparation. Egypt's experience with labor migration is described for the pre-oil boom, and the post-oil boom. Several estimates of labor migration are given. Government policy toward migration is positive. Theory postulates migration to be determined by differences in the availability of labor, labor rewards between destination and origin, and the cost of migration. In the empirical model, push factors are population density, the current inflation rate, and the ratio of income/capita in AOPC to Egypt. The results indicate that the ratio of income/capita had a strong pull impact and population density had a strong push impact. The inflation rate has a positive impact with a lag estimated at 2 years. Prior to the Camp David Accord, there was a significant decrease in the number of Egyptian migrants due to political tension. The findings support the classical theory of factor mobility. The consequences of migration on the Egyptian economy have been adverse. Future models should disaggregate data because chronic shortages exist in some parts of the labor market. Manpower needs assessment would be helpful for policy makers.

  2. Morphological constraints on changing avian migration phenology. (United States)

    Møller, Anders Pape; Rubolini, Diego; Saino, Nicola


    Many organisms at northern latitudes have responded to climate warming by advancing their spring phenology. Birds are known to show earlier timing of spring migration and reproduction in response to warmer springs. However, species show heterogeneous phenological responses to climate warming, with those that have not advanced or have delayed migration phenology experiencing population declines. Although some traits (such as migration distance) partly explain heterogeneity in phenological responses, the factors affecting interspecies differences in the responsiveness to climate warming have yet to be fully explored. In this comparative study, we investigate whether variation in wing aspect ratio (reflecting relative wing narrowness), an ecomorphological trait that is strongly associated with flight efficiency and migratory behaviour, affects the ability to advance timing of spring migration during 1960-2006 in a set of 80 Eurasian migratory bird species. Species with large aspect ratio (longer and narrower wings) showed smaller advancement of timing of spring migration compared to species with smaller aspect ratio (shorter and wider wings) while controlling for phylogeny, migration distance and other life-history traits. In turn, migration distance positively predicted aspect ratio across species. Hence, species that are better adapted to migration appear to be more constrained in responding phenologically to rapid climate warming by advancing timing of spring migration. Our findings corroborate the idea that aspect ratio is a major evolutionary correlate of migration, and suggest that selection for energetically efficient flights, as reflected by high aspect ratio, somehow hinders phenotypically plastic/microevolutionary adjustments of migration phenology to ongoing climatic changes. This article is protected by copyright. All rights reserved.

  3. Cultural values and international migration

    Directory of Open Access Journals (Sweden)

    Miryam Rodríguez Monter


    Full Text Available Immigration is one of the most controversial social issues debated nowadays. It is an undeniable fact that the phenomenon is lived in Europe with concern because of its consequences. People who live and coexist in Europe represent a huge cultural variety. Therefore, social and cultural gaps that can affect the basic values of the western societies seem to be inevitable due to the dimensions of the current migration phenomenon. The present studies are based on the European Social Survey Questionnaire (2002, and the Portrait Values Questionnaire (Schwartz, 1992, 2001 and focuses on the relevance of cultural values to explain the acceptance or rejection of the immigrant.. Finally, we emphasize the importance of cultural values -like Harmony or Egalitarianism- for any initiative or social policy which aimes at reducing the problems concerning inmigration in the European context.

  4. Migration, Transit and the Informal

    DEFF Research Database (Denmark)

    Juul, Kristine


    In the last couple of years, Copenhagen has been receiving new types of visitors: young, resourceful men from southern Europe in search of job opportunities. Many are of West-African origin, and have lived many years in Spain and Italy. As a result of the economic recession, they are now moving...... a mix of private charity, collection of bottles and informal odd jobs, moving between the Nordic capitals as opportunities for income generation arise. The emergence of such hyper mobile and flexible proletariat challenges many of our perceptions on migration. Conceptions of integration, citizenship...... northwards. Being Schengen residents, their entry is legal, but obtaining a work permit remains almost impossible. Instead, a wide range of geographical areas are being scrutinized for alternative income opportunities. Therefore, they relapse into a position as modern ‘ hunter-gatherers’ surviving through...

  5. Migration for Labor, Migration for Love: Marriage and Family Formation across Borders. (United States)

    Sinke, Suzanne


    Addresses how marriage and migration interacted using migration to the United States as an example; the key variables determining this relationship were demographics, legal policies, cultural perceptions, and information and technology. Maintains that the influence of an international marriage market affected the migration decisions of women who…

  6. Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex. (United States)

    Tabata, Hidenori; Nakajima, Kazunori


    Two distinct modes of radial neuronal migration, locomotion and somal translocation, have been reported in the developing cerebral cortex. Although these two modes of migration have been well documented, the cortical intermediate zone contains abundant multipolar cells, and they do not resemble the cells migrating by locomotion or somal translocation. Here, we report that these multipolar cells express neuronal markers and extend multiple thin processes in various directions independently of the radial glial fibers. Time-lapse analysis of living slices revealed that the multipolar cells do not have any fixed cell polarity, and that they very dynamically extend and retract multiple processes as their cell bodies slowly move. They do not usually move straight toward the pial surface during their radial migration, but instead frequently change migration direction and rate; sometimes they even remain in almost the same position, especially when they are in the subventricular zone. Occasionally, the multipolar cells jump tangentially during their radial migration. Because the migration modality of these cells clearly differs from locomotion or somal translocation, we refer to their novel type of migration as "multipolar migration." In view of the high proportion of cells exhibiting multipolar migration, this third mode of radial migration must be an important type of migration in the developing cortex.

  7. Module theory, extending modules and generalizations

    CERN Document Server

    Tercan, Adnan


    The main focus of this monograph is to offer a comprehensive presentation of known and new results on various generalizations of CS-modules and CS-rings. Extending (or CS) modules are generalizations of injective (and also semisimple or uniform) modules. While the theory of CS-modules is well documented in monographs and textbooks, results on generalized forms of the CS property as well as dual notions are far less present in the literature. With their work the authors provide a solid background to module theory, accessible to anyone familiar with basic abstract algebra. The focus of the book is on direct sums of CS-modules and classes of modules related to CS-modules, such as relative (injective) ejective modules, (quasi) continuous modules, and lifting modules. In particular, matrix CS-rings are studied and clear proofs of fundamental decomposition results on CS-modules over commutative domains are given, thus complementing existing monographs in this area. Open problems round out the work and establish the...

  8. Cofinitely weak supplemented modules


    Alizade, Rafail; Büyükaşık, Engin


    We prove that a module M is cofinitely weak supplemented or briefly cws (i.e., every submodule N of M with M/N finitely generated, has a weak supplement) if and only if every maximal submodule has a weak supplement. If M is a cws-module then every M-generated module is a cws-module. Every module is cws if and only if the ring is semilocal. We study also modules, whose finitely generated submodules have weak supplements.

  9. Skilled Migration: Australia. Working Paper No. 63 (United States)

    Shah, Chandra; Burke, Gerald


    Migration patterns to and from Australia are becoming complex with migration programmes increasingly targeted towards meeting the needs of the labour market and regional development. This paper provides an analysis of the permanent and temporary movements of people to and from Australia in the last three years and their impact on the skilled…

  10. Spurred by resistance: mechanosensation in collective migration. (United States)

    Behrndt, Martin; Heisenberg, Carl-Philipp


    How cells orchestrate their behavior during collective migration is a long-standing question. Using magnetic tweezers to apply mechanical stimuli to Xenopus mesendoderm cells, Weber et al. (2012) now reveal, in this issue of Developmental Cell, a cadherin-mediated mechanosensitive response that promotes cell polarization and movement persistence during the collective mesendoderm migration in gastrulation.

  11. Kinematics of shot-geophone migration

    NARCIS (Netherlands)

    C.C. Stolk; M.V. de Hoop; W.W. Symes


    Recent analysis and synthetic examples have shown that many prestack depth migration methods produce nonflat image gathers containing spurious events, even when provided with a kinematically correct migration velocity field, if this velocity field is highly refractive. This pathology occurs in all m

  12. Intraperitoneal stone migration during percutaneos nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Akif Diri


    Full Text Available Percutaneos nephrolithotomy (PNL is the standard care for renal stones larger than 2 cm. The procedure has some major and minor complications. Renal pelvis laceration and stone migration to the retroperitoneum is one of the rare condition. We report the first case of intraperitoneal stone migration during PNL.

  13. Review Fair migration : Setting an ILO agenda

    NARCIS (Netherlands)

    Cremers, Jan


    The ILO-report Fair migration is intended to offer an opportunity for tripartite global debate on the migration issue. In his review Jan Cremers admits that the analysis is correct. However, he questions how to make these ideas concrete as workers exploited in a foreign constituency live and work fa

  14. The Global Village: Migration and Education. (United States)

    Bhavnagri, Navaz Peshotan


    Introduces this special issue on migration and education, describing the common underlying organizational framework for articles in this issue. Presents five common content strands regarding global immigration and schooling, including multiple reasons for migration, initial marginalization of immigrant groups, gaining resilience from support…

  15. The External Dimension of EU Migration Policy

    Directory of Open Access Journals (Sweden)

    Dorina Gjipali


    Defining the conditions of consistency and flexibility to which the Union’s external action can bring the management of migration - a management which will pursue all objectives of the EU’s migration policy in accordance with the its principles, such as solidarity and the protection of fundamental rights - is the focus of this paper.

  16. Socio-Economic Determinants of International Migration

    Directory of Open Access Journals (Sweden)

    Yaroslav PRYTULA


    Full Text Available Since economic factors cannot fully explain the determinants of bilateral migration, this study explores the social and cultural determinants that influence an individual’s decision to migrate. Values, norms and interests in a given culture, may determine whether an individual’s intention to move translates into actual migration. Work values inherent in different cultures could explain why people move or do not move under the condition of perceived economic advantages of migration. A gravity type migration model is used to incorporate variables related both to economic indicators and work values. It is perhaps the first migration study to use the World Value Survey (WVS and the European Value Survey (EVS. We use 2000 stock bilateral migration dataset collected by the World Bank. Our findings indicate that if more aspects of work are valued in a country, this country sends more migrants. Also we show that countries with higher extrinsic work value orientation tend to send more migrants, while countries with higher intrinsic work value orientation tend to send fewer migrants. Our finding shows that the value of work and the level of job security in a country may significantly change migration decision.

  17. A validatable legacy database migration using ORM

    NARCIS (Netherlands)

    Moes, T.H.; Wijbenga, J.P.; Balsters, H.; Huitema, G.B.


    This paper describes a method used in a real-life case of a legacy database migration. The difficulty of the case lies in the fact that the legacy application to be replaced has to remain fully available during the migration process while at the same time data from the old system is to be integrated

  18. Least-squares Gaussian beam migration (United States)

    Yuan, Maolin; Huang, Jianping; Liao, Wenyuan; Jiang, Fuyou


    A theory of least-squares Gaussian beam migration (LSGBM) is presented to optimally estimate a subsurface reflectivity. In the iterative inversion scheme, a Gaussian beam (GB) propagator is used as the kernel of linearized forward modeling (demigration) and its adjoint (migration). Born approximation based GB demigration relies on the calculation of Green’s function by a Gaussian-beam summation for the downward and upward wavefields. The adjoint operator of GB demigration accounts for GB prestack depth migration under the cross-correlation imaging condition, where seismic traces are processed one by one for each shot. A numerical test on the point diffractors model suggests that GB demigration can successfully simulate primary scattered data, while migration (adjoint) can yield a corresponding image. The GB demigration/migration algorithms are used for the least-squares migration scheme to deblur conventional migrated images. The proposed LSGBM is illustrated with two synthetic data for a four-layer model and the Marmousi2 model. Numerical results show that LSGBM, compared to migration (adjoint) with GBs, produces images with more balanced amplitude, higher resolution and even fewer artifacts. Additionally, the LSGBM shows a robust convergence rate.

  19. Ethical issues in irregular migration research

    NARCIS (Netherlands)

    Duvell, F.; Triandafyllidou, A.; Vollmer, B.


    This paper is concerned with the ethical issues arising for researchers engaged in the study of irregular migration. Irregular migration is by definition an elusive phenomenon as it takes place in violation of the law and at the margins of society. This very nature of the phenomenon raises important

  20. Parental Migration and Children's Outcomes in Romania (United States)

    Robila, Mihaela


    Although Eastern European migration has increased greatly, the research on its impact on children and families has been limited. In this study I examined the impact of parental economic migration on children psychosocial and academic outcomes in Romania, one of largest Eastern European migrant sending country. Surveys were conducted with 382…

  1. Investigation of acetyl migrations in furanosides

    Directory of Open Access Journals (Sweden)

    Migaud ME


    Full Text Available Abstract Standard reaction conditions for the desilylation of acetylated furanoside (riboside, arabinoside and xyloside derivatives facilitate acyl migration. Conditions which favour intramolecular and intermolecular mechanisms have been identified with intermolecular transesterifications taking place under mild basic conditions when intramolecular orthoester formations are disfavoured. In acetyl ribosides, acyl migration could be prevented when desilylation was catalysed by cerium ammonium nitrate.

  2. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jeroen Pouwels


    Full Text Available SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1, a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

  3. The Role of Lipid Rafts in Cancer Cell Adhesion and Migration

    Directory of Open Access Journals (Sweden)

    Toshiyuki Murai


    Full Text Available Lipid rafts are cholesterol-enriched microdomains of the cell membrane and possess a highly dynamic nature. They have been involved in various cellular functions including the regulation of cell adhesion and membrane signaling through proteins within lipid rafts. The dynamic features of the cancer cell surface may modulate the malignant phenotype of cancer, including adhesion disorders and aggressive phenotypes of migration and invasion. Recently, it was demonstrated that lipid rafts play critical roles in cancer cell adhesion and migration. This article summarizes the important roles of lipid rafts in cancer cell adhesion and migration, with a focus on the current state of knowledge. This article will improve the understanding of cancer progression and lead to the development of novel targets for cancer therapy.

  4. On generalized extending modules

    Institute of Scientific and Technical Information of China (English)

    ZENG Qing-yi


    A module M is called generalized extending if for any submodule N of M, there is a direct summand K of M such that N≤K and K/N is singular. Any extending module and any singular module are generalized extending. Any homomorphic image of a generalized extending module is generalized extending. Any direct sum of a singular (uniform) module and a semi-simple module is generalized extending. A ring R is a right Co-H-ring ifand only ifall right R modules are generalized extending modules.

  5. Unusual migration of pulmonary artery catheter

    Directory of Open Access Journals (Sweden)

    Sanjay Kuravinakop


    Full Text Available Pulmonary artery catheter is widely used in intensive care. Distal migration of the catheter is a know complication. Diagnosis of such a migration is made by both clinical criteria and radiographs. A 55 year old septic lady was admitted to the intensive care unit. Pulmonary artery catheter introduced for cardiac output monitoring migrated from right lung to left lung. Diagnosis was made following a chest radiograph the following day of insertion with the clinical criteria remaining unaltered. Migration of pulmonary artery catheter can occur not only distally but from one lung to another. Clinical criteria alone cannot rule out migration. Chest radiographs form an important part in monitoring the position of the pulmonary artery catheter.

  6. Internal migration in Mexico and its determinants

    Directory of Open Access Journals (Sweden)

    Rogelio Varela Llamas


    Full Text Available This paper presents an analysis of internal migration in Mexico. Using micro data from the National Survey on Occupation and Employment (enoe, we estimate a multinomial logit model for the case of intrastate and interstate migration. We also conduct estimations for municipalities of different sizes. The results suggest that the probability of migrating increases with the number of weeks spent searching for a job, regardless of whether the search is conducted while the individual is employed or unemployed. In addition, we find that as the number of hours of work per week increases, the probability of migrating rises. The search process does not increase the probability of migrating in rural communities as it does in urban centers.

  7. Undocumented migration in response to climate change. (United States)

    Nawrotzki, Raphael J; Riosmena, Fernando; Hunter, Lori M; Runfola, Daniel M

    In the face of climate change induced economic uncertainty, households may employ migration as an adaptation strategy to diversify their livelihood portfolio through remittances. However, it is unclear whether such climate migration will be documented or undocumented. In this study we combine detailed migration histories with daily temperature and precipitation information for 214 weather stations to investigate whether climate change more strongly impacts undocumented or documented migration from 68 rural Mexican municipalities to the U.S. during the years 1986-1999. We employ two measures of climate change, the warm spell duration index (WSDI) and the precipitation during extremely wet days (R99PTOT). Results from multi-level event-history models demonstrate that climate-related international migration from rural Mexico was predominantly undocumented. We conclude that programs to facilitate climate change adaptation in rural Mexico may be more effective in reducing undocumented border crossings than increased border fortification.

  8. Extreme swimming: The oceanic migrations of anguillids

    DEFF Research Database (Denmark)

    Righton, David; Aarestrup, Kim; Jellyman, Don;


    Anguillids evolved between 20 and 40 million years ago and, as catadromous fish, migrate between marine and freshwater environments. The migration occurs only twice in the lifetime of most eels: when they migrate as larvae to coastal and river habitats, and again as adult, when they return...... to their natal habitat to spawn. In temperate species, the migrations are extreme, requiring larvae and adults to swim thousands of km before reaching their destination, but the migrations of tropical species (hundreds of km) are still remarkable in comparison with many other fish species. To achieve...... these migratory feats, eel larvae and adults are uniquely adapted to oceanic environments. We describe and discuss these adaptations, and identify the challenges and opportunities ahead for aquaculture and eel conservation...

  9. Collective cell migration during inflammatory response (United States)

    Wu, Di; Stroka, Kimberly; Aranda-Espinoza, Helim


    Wound scratch healing assays of endothelial cell monolayers is a simple model to study collective cell migration as a function of biological signals. A signal of particular interest is the immune response, which after initial wounding in vivo causes the release of various inflammatory factors such as tumor necrosis alpha (TNF-α). TNF-α is an innate inflammatory cytokine that can induce cell growth, cell necrosis, and change cell morphology. We studied the effects of TNF-α on collective cell migration using the wound healing assays and measured several migration metrics, such as rate of scratch closure, velocities of leading edge and bulk cells, closure index, and velocity correlation functions between migrating cells. We observed that TNF-α alters all migratory metrics as a function of the size of the scratch and TNF-α content. The changes observed in migration correlate with actin reorganization upon TNF-α exposure.

  10. Ethnic return migration: an Estonian case. (United States)

    Kulu, H


    "This article examines return migration during the post World War 2 period of descendants of Estonians who emigrated to Russia at the end of the nineteenth and at the beginning of the twentieth century" The focus is on changing migration patterns over time. "The behavioural norm of Estonians born in the 1910s-1920s has been return migration to Estonia, while the migration behaviour of the 1930s-1940s and the 1950s-1960s generations can be characterized by urbanization in West Siberia. The results give reason to assume that ethnic return migration over a long period depends neither directly nor indirectly on momentary environmental changes, but rather on changes in people's values, habits, identity etc., which in the case of an ethnic minority living outside its historical homeland may be followed generation by generation." (EXCERPT)

  11. The mixed effects of migration: community-level migration and birthweight in Mexico. (United States)

    Hamilton, Erin R; Choi, Kate H


    Research on the relationship between migration and infant health in Mexico finds that migration has mixed impacts on the risk of low birthweight (LBW). Whereas the departure and absence of household and community members are harmful, remittances are beneficial. We extend this work by considering a different measure of infant health in addition to LBW: macrosomia (i.e., heavy birthweight), which is associated with infant, child, and maternal morbidities but has a different social risk profile from LBW. We link the 2008 and 2009 Mexican birth certificates with community data from the 2000 Mexican census to analyze the association between various dimensions of community-level migration (i.e., rates of out-migration, receipt of remittances, and return migration) and the risk of LBW and macrosomia. We examine this association using two sets of models which differ in the extent to which they account for endogeneity. We find that the health impacts of migration differ depending not only on the dimension of migration, but also on the measure of health, and that they are robust to potential sources of endogeneity. Whereas community remittances and return migration are associated with lower risk of LBW, they are associated with increased risk of macrosomia. By contrast, out-migration is associated with increased risk of LBW and lower risk of macrosomia. Our analysis of endogeneity suggests that bias resulting from unmeasured differences between communities with different levels of migration may result in an underestimate of the impacts of community migration on birthweight.

  12. From Migration Corridors to Clusters: The Value of Google+ Data for Migration Studies

    CERN Document Server

    Messias, Johnnatan; Weber, Ingmar; Zagheni, Emilio


    Recently, there have been considerable efforts to use online data to investigate international migration. These efforts show that Web data are valuable for estimating migration rates and are relatively easy to obtain. However, existing studies have only investigated flows of people along migration corridors, i.e. between pairs of countries. In our work, we use data about "places lived" from millions of Google+ users in order to study migration "clusters", i.e. groups of countries in which individuals have lived. For the first time, we consider information about more than two countries people have lived in. We argue that these data are very valuable because this type of information is not available in traditional demographic sources which record country-to-country migration flows independent of each other. We show that migration clusters of country triads cannot be identified using information about bilateral flows alone. To demonstrate the additional insights that can be gained by using data about migration c...

  13. Ballasted photovoltaic module and module arrays (United States)

    Botkin, Jonathan; Graves, Simon; Danning, Matt


    A photovoltaic (PV) module assembly including a PV module and a ballast tray. The PV module includes a PV device and a frame. A PV laminate is assembled to the frame, and the frame includes an arm. The ballast tray is adapted for containing ballast and is removably associated with the PV module in a ballasting state where the tray is vertically under the PV laminate and vertically over the arm to impede overt displacement of the PV module. The PV module assembly can be installed to a flat commercial rooftop, with the PV module and the ballast tray both resting upon the rooftop. In some embodiments, the ballasting state includes corresponding surfaces of the arm and the tray being spaced from one another under normal (low or no wind) conditions, such that the frame is not continuously subjected to a weight of the tray.

  14. Cardiotoxin III Inhibits Proliferation and Migration of Oral Cancer Cells through MAPK and MMP Signaling

    Directory of Open Access Journals (Sweden)

    Ching-Yu Yen


    Full Text Available Cardiotoxin III (CTXIII, isolated from the snake venom of Formosan cobra Naja naja atra, has previously been found to induce apoptosis in many types of cancer. Early metastasis is typical for the progression of oral cancer. To modulate the cell migration behavior of oral cancer is one of the oral cancer therapies. In this study, the possible modulating effect of CTXIII on oral cancer migration is addressed. In the example of oral squamous carcinoma Ca9-22 cells, the cell viability was decreased by CTXIII treatment in a dose-responsive manner. In wound-healing assay, the cell migration of Ca9-22 cells was attenuated by CTXIII in a dose- and time-responsive manner. After CTXIII treatment, the MMP-2 and MMP-9 protein expressions were downregulated, and the phosphorylation of JNK and p38-MAPK was increased independent of ERK phosphorylation. In conclusion, CTXIII has antiproliferative and -migrating effects on oral cancer cells involving the p38-MAPK and MMP-2/-9 pathways.

  15. Amitriptyline, clomipramine, and maprotiline attenuate the inflammatory response by inhibiting neutrophil migration and mast cell degranulation

    Directory of Open Access Journals (Sweden)

    José Alves Gurgel


    Full Text Available Objective: Despite the recognized anti-inflammatory potential of heterocyclic antidepressants, the mechanisms concerning their modulating effects are not completely known. Thus, we evaluated the anti-inflammatory effect of amitriptyline, clomipramine, and maprotiline and the possible modulating properties of these drugs on neutrophil migration and mast cell degranulation. Methods: The hind paw edema and air-pouch models of inflammation were used. Male Wistar rats were treated with saline, amitriptyline, clomipramine or maprotiline (10, 30, or 90 mg/kg, per os [p.o.] 1 h before the injection of carrageenan (300 μg/0.1 mL/paw or dextran (500 μg/0.1 mL/paw. Then, edema formation was measured hourly. Neutrophil migration to carrageenan (500 μg/pouch and N-formyl-methionyl-leucyl-phenylalanine (fMLP (10-6 M/mL/pouch was also investigated in 6-day-old air-pouch cavities. Compound 48/80-induced mast cell degranulation was assessed in the mesenteric tissues of antidepressant-treated rats. Results: All tested antidepressants prevented both carrageenan- and dextran-induced edema. The anti-inflammatory effect of these drugs partially depends on the modulation of neutrophil migration, since they significantly counteracted the chemotactic response of both carrageenan and fMLP (p < 0.01. Furthermore, amitriptyline, clomipramine and maprotiline inhibited compound 48/80-induced mast cell degranulation (p < 0.001. Conclusions: These results suggest an important anti-inflammatory role of heterocyclic antidepressants, which is dependent on the modulation of neutrophil migration and mast cell stabilization.

  16. International Migration with Heterogeneous Agents: Theory and Evidence

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Brücker, Herbert

    Temporary migration, though empirically relevant, is often ignored in formal models. This paper proposes a migration model with heterogeneous agents and persistent cross country income differentials that features temporary migration. In equilibrium there exists a positive relation between the stock...

  17. MeltMigrator: A MATLAB-based software for modeling three-dimensional melt migration and crustal thickness variations at mid-ocean ridges following a rules-based approach (United States)

    Bai, Hailong; Montési, Laurent G. J.; Behn, Mark D.


    MeltMigrator is a MATLAB®-based melt migration software developed to process three-dimensional mantle temperature and velocity data from user-supplied numerical models of mid-ocean ridges, calculate melt production and melt migration trajectories in the mantle, estimate melt flux along plate boundaries, and predict crustal thickness distribution on the seafloor. MeltMigrator is also capable of calculating compositional evolution depending on the choice of petrologic melting model. Programmed in modules, MeltMigrator is highly customizable and can be expanded to a wide range of applications. We have applied it to complex mid-ocean ridge model settings, including transform faults, oblique segments, ridge migration, asymmetrical spreading, background mantle flow, and ridge-plume interaction. In this technical report, we include an example application to a segmented mid-ocean ridge. MeltMigrator is available as a supplement to this paper, and it is also available from GitHub and the University of Maryland Geodynamics Group website.

  18. Migration Dynamics in Artificial Agent Societies

    Directory of Open Access Journals (Sweden)

    Harjot Kaur


    Full Text Available An Artificial Agent Society can be defined as a collection of agents interacting with each other for some purpose and/or inhabiting a specific locality, possibly in accordance to some common norms/rules. These societies are analogous to human and ecological societies, and are an expanding and emerging field in research about social systems. Social networks, electronic markets and disaster management organizations can be viewed as such artificial (open agent societies and can be best understood as computational societies. Members of such artificial agent societies are heterogeneous intelligent software agents which are operating locally and cooperating and coordinating with each other in order to achieve goals of an agent society. These artificial agent societies have some kind of dynamics existing in them in terms of dynamics of Agent Migration, Role-Assignment, Norm- Emergence, Security and Agent-Interaction. In this paper, we have described the dynamics of agent migration process, starting from the various types of agent migration, causes or reasons for agent migration, consequences of agent migration, and an agent migration framework to model the its behavior for migration of agents between societies.

  19. Assessing Migration Risk for Scientific Data Formats

    Directory of Open Access Journals (Sweden)

    Chris Frisz


    Full Text Available The majority of information about science, culture, society, economy and the environment is born digital, yet the underlying technology is subject to rapid obsolescence. One solution to this obsolescence, format migration, is widely practiced and supported by many software packages, yet migration has well known risks. For example, newer formats – even where similar in function – do not generally support all of the features of their predecessors, and, where similar features exist, there may be significant differences of interpretation.There appears to be a conflict between the wide use of migration and its known risks. In this paper we explore a simple hypothesis – that, where migration paths exist, the majority of data files can be safely migrated leaving only a few that must be handled more carefully – in the context of several scientific data formats that are or were widely used. Our approach is to gather information about potential migration mismatches and, using custom tools, evaluate a large collection of data files for the incidence of these risks. Our results support our initial hypothesis, though with some caveats. Further, we found that writing a tool to identify “risky” format features is considerably easier than writing a migration tool.

  20. Mitigation of artifacts in rtm with migration kernel decomposition

    KAUST Repository

    Zhan, Ge


    The migration kernel for reverse-time migration (RTM) can be decomposed into four component kernels using Born scattering and migration theory. Each component kernel has a unique physical interpretation and can be interpreted differently. In this paper, we present a generalized diffraction-stack migration approach for reducing RTM artifacts via decomposition of migration kernel. The decomposition leads to an improved understanding of migration artifacts and, therefore, presents us with opportunities for improving the quality of RTM images.