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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.

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

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

    2014-01-01

    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

  3. 5-Hydroxytryptamine 1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception.

    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

    2016-03-01

    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. PMID:26749090

  4. The interplay between brain 5-hydroxytryptamine levels and cocaine addiction.

    Nonkes, L.J.P.; Bussel, I.P. van; Verheij, M.M.M.; Homberg, J.R.

    2011-01-01

    Cocaine addiction is a major health problem that affects millions of people. Cocaine acts by inhibiting dopamine, noradrenaline and serotonin [5-hydroxytryptamine(5-HT)] reuptake. The dopaminergic system is generally assumed to be involved in the reinforcing aspects of the drug, but the role of 5-HT

  5. NMR studies of 5-hydroxytryptamine transport through large unilamellar vesicle membranes.

    Viscio, D B; Prestegard, J H

    1981-01-01

    Nuclear magnetic resonance techniques developed to study membrane permeability in closed membrane systems have been used to investigate transport of 5-hydroxytryptamine across the phospholipid membranes of large unilamellar vesicles. The vesicles, modeling the 5-hydroxytryptamine storage organelles of blood platelets, contained a high internal level of ATP buffered at a pH low relative to the external solution. The resultant pH gradient drove accumulation of 5-hydroxytryptamine to a level con...

  6. Old and new pharmacology: positive allosteric modulation of the alpha7 nicotinic acetylcholine receptor by the 5-hydroxytryptamine(2B/C) receptor antagonist SB-206553 (3,5-dihydro-5-methyl-N-3-pyridinylbenzo[1,2-b:4,5-b']di pyrrole-1(2H)-carboxamide).

    Dunlop, John; Lock, Tim; Jow, Brian; Sitzia, Fabrizio; Grauer, Steven; Jow, Flora; Kramer, Angela; Bowlby, Mark R; Randall, Andrew; Kowal, Dianne; Gilbert, Adam; Comery, Thomas A; Larocque, James; Soloveva, Veronica; Brown, Jon; Roncarati, Renza

    2009-03-01

    The alpha7 nicotinic acetylcholine receptor (nAChR) has been implicated in Alzheimer's disease and schizophrenia, leading to efforts targeted toward discovering agonists and positive allosteric modulators (PAMs) of this receptor. In a Ca2+ flux fluorometric imaging plate reader assay, SB-206553 (3,5-dihydro-5-methyl -N-3-pyridinylbenzo [1, 2-b:4,5 -b']-di pyrrole-1(2H)-carboxamide), a compound known as a 5-hydroxytryptamine(2B/2C) receptor antagonist, produced an 8-fold potentiation of the evoked calcium signal in the presence of an EC(20) concentration of nicotine and a corresponding EC(50) of 1.5 muM for potentiation of EC(20) nicotine responses in GH4C1 cells expressing the alpha7 receptor. SB-206553 was devoid of direct alpha7 receptor agonist activity and selective against other nicotinic receptors. Confirmation of the PAM activity of SB-206553 on the alpha7 nAChR was obtained in patch-clamp electrophysiological experiments in GH4C1 cells, where it failed to evoke any detectable currents when applied alone, yet dramatically potentiated the currents evoked by an EC(20) (17 microM) and EC(100) (124 microM) of acetylcholine (ACh). Native nicotinic receptors in CA1 stratum radiatum interneurons of rat hippocampal slices could also be activated by ACh (200 microM), an effect that was entirely blocked by the alpha7-selective antagonist methyllycaconitine (MLA). These ACh currents were potentiated by SB-206553, which increased the area of the current response significantly, resulting in a 40-fold enhancement at 100 microM. In behavioral experiments in rats, SB-206553 reversed an MK-801 (dizocilpine maleate)-induced deficit in the prepulse inhibition of acoustic startle response, an effect attenuated in the presence of MLA. This latter observation provides further evidence in support of the potential therapeutic utility of alpha7 nAChR PAMs in schizophrenia. PMID:19050173

  7. Effect of hemorrhagic shock on 5-hydroxytryptamine removal by the lung

    The biogenic amine, radioactive 5-hydroxytryptamine, is removed from the blood during passage through the pulmonary vasculature. After one hour of hemorrhagic shock, the extraction rate increased from 74 to 89 per cent. One and two hours after resuscitation, the lung extracted only 30 per cent of the 5-hydroxytryptamine. The relationship between the pathophysiologic state and altered amine removal is a reflection of prolonged exposure to receptor sites or increased diffusion of serotonin across the endothelium

  8. Norepinephrine triggers Ca2+-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture.

    Yamada, Hiroshi; Hayashi, Mitsuko; Uehara, Shunsuke; Kinoshita, Mika; Muroyama, Akiko; Watanabe, Masami; Takei, Koji; Moriyama, Yoshinori

    2002-05-01

    5-hydroxytryptamine (5-HT) is a precursor and a putative modulator for melatonin synthesis in mammalian pinealocytes. 5-HT is present in organelles distinct from l-glutamate-containing synaptic-like microvesicles as well as in the cytoplasm of pinealocytes, and is secreted upon stimulation by norepinephrine (NE) to enhance serotonin N-acetyltransferase activity via the 5-HT2 receptor. However, the mechanism underlying the secretion of 5-HT from pinealocytes is unknown. In this study, we show that NE-evoked release of 5-HT is largely dependent on Ca2+ in rat pinealocytes in culture. Omission of Ca2+ from the medium and incubation of pineal cells with EGTA-tetraacetoxymethyl-ester inhibited by 59 and 97% the NE-evoked 5-HT release, respectively. Phenylephrine also triggered the Ca2+-dependent release of 5-HT, which was blocked by phentolamine, an alpha antagonist, but not by propranolol, a beta antagonist. Botulinum neurotoxin type E cleaved 25 kDa synaptosomal-associated protein and inhibited by 50% of the NE-evoked 5-HT release. Bafilomycin A1, an inhibitor of vacuolar H+-ATPase, and reserpine and tetrabenazine, inhibitors of vesicular monoamine transporter, all decreased the storage of vesicular 5-HT followed by inhibition of the NE-evoked 5-HT release. Agents that trigger L-glutamte exocytosis such as acetylcholine did not trigger any Ca2+-dependent 5-HT release. Vice versa neither NE nor phenylephrine caused synaptic-like microvesicle-mediated l-glutamate exocytosis. These results indicated that upon stimulation of a adrenoceptors pinealocytes secrete 5-HT through a Ca2+-dependent exocytotic mechanism, which is distinct from the exocytosis of synaptic-like microvesicles. PMID:12065661

  9. beta-Adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses.

    Cowen, P. J.; Grahame-Smith, D.G.; Green, A R; Heal, D. J.

    1982-01-01

    The beta-adrenoceptor agonists, salbutamol, terbutaline and clenbuterol, were investigated for their effect on 5-hydroxytryptamine-mediated (5-HT) hyperactivity. 2 The lipophilic beta-adrenoceptor agonist, clenbuterol (5 mg/kg) enhanced the behaviours induced by quipazine (25 mg/kg), including headweaving, forepaw treading and hind-limb abduction and thus increased automated activity recording. Clenbuterol (5 mg/kg) also enhanced the hyperactivity syndrome produced by the 5-HT agonist, 5-meth...

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

    Red wine, at a final dilution of 1/50, caused released of (14C)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

  11. Role of 5-hydroxytryptamine in platelet thrombus formation and mechanisms of inhibition of thrombus formation by 5-hydroxytryptamine2A antagonists in rabbits.

    Takano, S

    1995-01-01

    The role of 5-hydroxytryptamine (5-HT) in platelet thrombus formation and in the mechanisms of inhibition of thrombus formation by 5-HT2A antagonists was investigated using a turbidimetric method. Collagen-induced platelet aggregation occurred simultaneously with a release of 5-HT from the platelets. The supernatant of collagen-aggregated platelets induced a further aggregation volume-dependently. This supernatant-induced aggregation was inhibited by either 5-HT2A antagonists or adenosine-diphosphate (ADP) scavenging. 5-Hydroxytryptamine and a small amount of the supernatant shifted the dose-response curves of collagen to the left. The aggregation velocity and the onset of aggregation by collagen were significantly increased by the supernatant, but not by 5-HT. The 5-HT2A antagonists, ketanserin and MCI-9042, returned the dose-response curves of the maximum aggregation and of the aggregation velocity of collagen, which were already amplified by the supernatant, to the original values. The onset of aggregation was delayed by the antagonists, but was not completely returned to the original points. There were distinct differences between the effects of endogenous 5-HT, derived from platelets which were stimulated by collagen, and those of exogenous 5-HT on both extensive platelet activation and amplification of the collagen-induced aggregation. These findings suggest that endogenous 5-HT activates platelets in synergism with ADP. The 5-HT2A antagonists used, block the synergism via 5-HT2A receptors and lead to inhibition of a positive feedback loop of thrombus formation. PMID:8836449

  12. Influence of 5-hydroxytryptamine (serotonin) on blood flow in the dog pulp

    The effect of intra-arterial injection of 5-hydroxytryptamine (5-HT) on pulpal blood flow of the dog was determined using the 15-micron radioisotope-labeled microsphere injection method. Pulpal blood flow was significantly reduced following the 5-HT injection. This decrease in blood flow appeared to be due to vasoconstriction as determined by an increase in pulpal vascular hindrance. However, our findings do not preclude the possibility that blood flow was reduced as a result of passive compression of venules produced by vasodilation in a low-compliance environment

  13. Digital blood flow and 5-hydroxytryptamine receptor blockade after ketanserin in patients with Raynaud's phenomenon.

    Marasini, B; Bassani, C.

    1990-01-01

    1. The effect of ketanserin on digital blood flow and 5-hydroxytryptamine (5-HT)-induced platelet aggregation was studied in 18 patients with Raynaud's phenomenon. 2. Measurements were made before and after a single dose of 20 mg ketanserin and again after 1 month of continuous treatment with 20 mg ketanserin three times a day. 3. Digital blood flow was assessed by changes in digital pulse volume; platelet aggregation by changes in light transmission after challenge with 10(-5) M 5-HT. 4. Ket...

  14. The stimulus-induced release of 5-hydroxytryptamine and tryptophan from superfused rat brain synaptosomes

    The synthesis of 5-hydroxytryptamine (5-HT) from 3H-tryptophan in rat forebrain synaptosomes was studied. Synaptosomes which had been preincubated with 3H-tryptophan were perfused with Krebs solution and the release of tryptophan, 5-HT and 5-hydroxyindoleactic acid (5-HIAA) was determined. K+ depolarization induced a Ca2+ -dependent release of 5-HT and tryptophan but had no effect on 5-HIAA efflux. This finding suggests that the release of tryptophan is unlikely to be a non-specific effect of depolarization. (Author)

  15. Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain.

    Erlander, M G; Lovenberg, T W; Baron, B M; de Lecea, L; Danielson, P E; Racke, M; Slone, A L; Siegel, B W; Foye, P. E.; Cannon, K

    1993-01-01

    We report two serotonin (5-hydroxytryptamine, 5-HT) receptors, MR22 and REC17, that belong to the G-protein-associated receptor superfamily. MR22 and REC17 are 371 and 357 amino acids long, respectively, as deduced from nucleotide sequence and share 68% mutual amino acid identity and 30-35% identity with known catecholamine and 5-HT receptors. Saturable binding of 125I-labeled (+)-lysergic acid diethylamide to transiently expressed MR22 in COS-M6 cells was inhibited by ergotamine > methiothep...

  16. 5-Hydroxytryptamine stimulation of phospholipase D activity in the rabbit isolated mesenteric artery

    Hinton, J. M.; ADAMS, D.; Garland, C J

    1999-01-01

    The involvement of phospholipase D (PLD) in the 5-hydroxytryptamine 5-HT1B/5-HT1D-signalling pathway was assessed in the rabbit isolated mesenteric artery.RT–PCR analysis of mesenteric smooth muscle cells revealed a strong signal corresponding to mRNA transcript for the 5-HT1B receptor. The PCR fragment corresponded to the known sequence for the 5-HT1B receptor. No signal corresponding to 5-HT1D mRNA was detected.Neither 5-HT (3 μM) nor KCl (45 mM) individually stimulated any significant incr...

  17. Application of 5-hydroxytryptamine receptor imaging for study of neuropsychiatric disorders and brain functions

    In the central nervous system, the widely distributed 5-hydroxytryptamine (5-HT)receptors are involved in regulating a large number of psychological and physiological functions, including mood, sleep, endocrine and autonomic nervous system. Abnormal 5-HT transmission has been implicated in a variety of neuropsychiatric disorders, such as pain, depression and epilepsy. With the development of radioligands, non-invasive nuclear imaging technique with exquisite sensitivity and specificity has been applied for delineation of neurotransmitter function in vivo. It does great benefit for researches of these diseases and development of drugs. This review provided an overview of 5-HT receptors radioligands and recent findings. (authors)

  18. Effects of radiation and maze performance on brain contents of norepinephrine and 5-hydroxytryptamine in male albino rat

    The objectives of the present study are dealing with the normal patterns of the occurrence of norepinephrine (N E) and 5 - hydroxytryptamine (5-H T) in different brain regions of albino rat and to determine the changes in brain levels of both substances when the rat was subjected to various effects

  19. Evidence that 5-hydroxytryptamine/sub 3/ receptors mediate cytotoxic drug and radiation-evoked emesis

    Miner, W.D.; Sanger, G.J.; Turner, D.H.

    1987-08-01

    The involvement of 5-hydroxytryptamine (5-HT) 5-HT/sub 3/ receptors in the mechanisms of severe emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant and dopamine antagonist at conventional doses, a 5-HT/sub 3/ receptor antagonist at higher doses) and BRL 24924 (a potent gastric motility stimulant and a 5-HT/sub 3/ receptor antagonist). Domperidone or metoclopramide prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924 greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a fundamental role for 5-HT/sub 3/ receptors in the mechanisms mediating severely emetogenic cancer treatment therapies.

  20. 5-Hydroxytryptamine antagonists and the 5-methoxy-N,N-dimethyltryptamine-induced changes of postdecapitation convulsions.

    Archer, T

    1987-01-01

    The ability of various compounds to antagonise the 5-MeODMT induced prolongations of latency and duration of postdecapitation convulsions (PDCs) were compared. The 5-hydroxytryptamine (5-HT) receptor antagonists, mianserin, methergoline, cinanserin and methysergide antagonised the 5-MeODMT (0.5 to 4.0 mg/kg) induced prolongations of latency to onset of convulsions substantially and to a lesser extent the prolongation of duration. The efficacy of the 5-HT antagonists for blocking 5-MeODMT changes of PDCs was roughly of the order mianserin greater than cinanserin greater than methysergide greater than methergoline. Pirenperone, the 5-HT2 antagonist, and pimozide, the dopamine receptor antagonist did not antagonise the 5-MeODMT induced changes. Mianserin, methergoline, cinanserin and methysergide, by themselves, prolonged the duration of PDCs but did not affect latency. Pirenperone (0.25 mg/kg) prolonged both the latency and duration of the PDCs while pimozide (0.5-2.0 mg/kg) had no effect upon PDCs. This evidence suggests that 5-MeODMT induced changes of PDCs are mediated via 5-HT1 receptors and thus a reliable model to combine with other measures of spinal function is suggested. PMID:3562388

  1. Autoradiographic visualization on the role of central 3H-5-hydroxytryptamine in acupuncture analgesia

    The role played by central 5-hydroxytryptamine (5-HT) in electroacupuncture analgesia has been studied in rats by means of autoradiography with isotopic tracers 3H-5-HT. The purpose of the study is to determine the localization of 3H-5-HT in the midbrain raphe nuclei and in the mesencephalon aquaeduct as well as periaquaeductal gray matter. Parallel experiments were studied by freezing microautoradiographic method and histo-fixative microautoradiographic method. The analgesic effect of acupuncture can be enhanced or lowered by the increment or the decrement of the 5-HT level in the midbrain raphe nuclei and in the mesencephalon aquaeduct as well as periaquaeductal gray matter. The results show that when the rats were subjected to electro-acupuncture analgesia, the microautoradiographic intensities of 3H-5-HT both in the midbrain raphe nuclei and in the areas of mesencephalon aqueduct were significantly increased. It may be observed that the release of 5-HT in these regions of the brain is accelerated during acupuncture analgesia. From this it can be concluded that the midbrain raphe nuclei and the mesencephalon aquaeduct as well as the periaquaeductal gray matter are closely related to acupuncture analgesia. The results imply that 5-HT in these areas may be one of the most important neurochemical agents mediating acupuncture analgesia

  2. 5-Hydroxytryptamine Induces Electrogenic Secretion in the Duodenum of Gerbil (Gerbillus cheesmani

    Fawzia Y. Al-Balool

    2007-01-01

    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.

  3. Regional and systemic haemodynamic changes evoked by 5-hydroxytryptamine in awake and anaesthetized rabbits

    The radioactive microsphere method has been used to study the effects of the infusions of 5-hydroxytryptamine (5-HT) on cardiac output and its distribution in both pentobarbital-anaesthetized and conscious rabbits. Doses of 5 and 10 μg kg-1 min-1 caused progressive decreases in diastolic pressure and total peripheral resistance in the anaesthetized rabbits but not in conscious ones. There was no significant effect on systolic pressure, cardiac output or heart rate. However, in spite of minimal systematic changes, in both groups 5-HT evoked increases in blood flow to the brain, heart and stomach at the expense of the kidneys, skin, liver (hepatic artery) and lungs (bronchial artery plus aerteriovenous anastomotic flow). The 10 μg kg-1 min-1 dose of 5-HT also increased blood flow and decreased resistance in the extracerebral tissues of the head. The significance of these findings in relation to the possible role of 5-HT in the migraine syndrome has been discussed. (Auth.)

  4. Central beta-adrenoceptors can modulate 5-hydroxytryptamine-induced tremor in rats.

    Hallberg, H.

    1986-01-01

    The effects of two beta 2-adrenoceptor agonists with different lipophilicities were studied on tremor induced by L-5-hydroxytryptophan (L-5-HTP) in pargyline- and carbidopa-pretreated rats. Tremor was recorded and analysed by an objective method based on accelerometry. Clenbuterol, a lipophilic beta 2-selective agonist, dose-dependently enhanced tremor intensity, whereas the hydrophilic beta 2-agonist terbutaline had no effect. The clenbuterol-induced enhancement of tremor was completely abol...

  5. Peptide displacement of [3H]5-hydroxytryptamine binding to bovine cortical membranes

    Chemical studies have demonstrated that peptides such as the encephalitogenic (EAE) peptide of myelin basic protein (MBP) and luteinizing hormone-releasing hormone (LHRH) can bind serotonin (5-hydroxytryptamine, 5-HT) in vitro. The present research was undertaken to determine whether such binding interferes with 5-HT binding to its 5-HT1 receptors on bovine cerebral cortical membranes. EAE peptide and LHRH displaced [3H]5-HT with IC50s of 4.0 x 10(-4) and 1.8 x 10(-3) M respectively. MBP itself also showed apparent displacing ability with an IC50 of 6.0 x 10(-5) M, though it also caused aggregation of cortical membranes that might have interfered with normal receptor binding. These results support previous suggestions that the tryptophan peptide region of MBP may act as a 5-HT receptor in the neural system. We also tested the effects of muramyl dipeptide (N-acetyl-muramyl-L-Ala-D-isoGln, MD), a bacterial cell-wall breakdown product that acts as a slow-wave sleep promoter, binds to LHRH and EAE peptide, and competes for 5-HT binding sites on macrophages. It showed no significant displacement of 5-HT binding to cortical membranes (IC50 greater than 10(-1) M), but its D-Ala analogue did (IC50 = 1.7 x 10(-3) M). Thus, it seems likely that the 5-HT-related effects of naturally occurring muramyl peptides are physiologically limited by receptor types

  6. 5-Hydroxytryptamine uptake in oxygen radical-mediated acute lung injury

    Pulmonary endothelial cell function (ECF) studies have been shown to be a sensitive indicator of chronic lung injury. We attempted to correlate changes in 5-hydroxytryptamine (5HT) uptake with an acute oxygen radical-mediated lung injury in dogs. Beta-d glucose/glucose oxidase was injected intravenously in an experimental group (n = 10), while the control group (n = 5) received saline. 5HT uptake, measured using a multiple indicator dilution technique before and 20 min after injection, was calculated for both the percent total uptake and the peak extraction ratio of 5HT during a single passage through the lung. The mean pulmonary and systemic arterial pressures (PAP, SAP), total pulmonary resistance (TPR), extravascular lung water (EVLW), and wet-to-dry weight ratios were also determined. The experimental group showed an acute rise in PAP and TPR and a fall in SAP after the injection, all returning to normal by 20 min; total 5HT uptake fell from 81 +/- 2.3% to 47 +/- 6.5% (p = 0.0002) as did the peak extraction ratio from 0.87 +/- 0.013 to 0.44 +/- 0.066 (p = 0.0001). No change in 5HT uptake was observed in the control group. EVLW did not change in either group, but wet-to-dry weight ratio was elevated in the experimental group (5.21 +/- 0.12 versus 4.73 +/- 0.06, p less than 0.01). ECF studies of 5HT uptake appear to be a sensitive indicator of acute lung injury in this large-animal, oxygen radical-induced injury model

  7. Artifactual high-affinity and saturable binding of (3H)5-hydroxytryptamine induced by radioligand oxidation

    Peroutka, S.J.; Ison, P.J.; Liu, D.U.; Barrett, R.W.

    1986-07-01

    The binding of (3H)5-hydroxytryptamine (5-HT, serotonin) to cerebellar membranes was examined after preincubation of (/sup 3/H)5-HT in the presence or absence of ascorbate. The tissue preparation was identical in all experiments and consisted of rat cerebellar homogenates in Tris-HCl buffer with 0.1% ascorbate. Cerebellar membranes were used because of their low density of 5-HT1 binding sites. In the presence of ascorbate during a 4-h preincubation period, minimal specific binding of 2 nM (/sup 3/H)5-HT is detected. Similar results are obtained with equimolar concentrations of other antioxidants (butylated hydroxytoluene, sodium dithionite, and sodium metabisulfite). Apparent specific binding increases 14-fold following a 4-h preincubation of (/sup 3/H)5-HT in the absence of ascorbate. The increase in apparent specific (/sup 3/H)5-HT binding is time-dependent and plateaus after 4-6 h of preincubation. When ascorbate is present during the 4-h preincubation, Scatchard analysis of (/sup 3/H)5-HT binding reveals a KD value of 3.0 +/- 0.3 nM and a Bmax value of 1.9 +/- 0.2 pmol/g tissue. When ascorbate is absent during the preincubation, the KD is essentially unchanged at 3.6 +/- 0.1 nM but the Bmax is significantly increased to 36.5 +/- 7 pmol/g tissue. Drug competition studies reveal that the apparent specific (/sup 3/H)5-HT binding in the absence of ascorbate appears to be displaced by nanomolar concentrations of hydroxylated tryptamines (5-HT, bufotenine) but not by nonhydroxylated tryptamines (5-methoxytryptamine, tryptamine). HPLC analysis demonstrates that (3H)5-HT is essentially destroyed by a 4-h incubation at 22/sup 0/C in the absence of ascorbate.

  8. Parallel Functional Activity Profiling Reveals Valvulopathogens Are Potent 5-Hydroxytryptamine2B Receptor Agonists: Implications for Drug Safety Assessment

    Huang, Xi-Ping; Setola, Vincent; Yadav, Prem N.; Allen, John A.; Rogan, Sarah C.; Hanson, Bonnie J; Revankar, Chetana; Robers, Matt; Doucette, Chris; Roth, Bryan L.

    2009-01-01

    Drug-induced valvular heart disease (VHD) is a serious side effect of a few medications, including some that are on the market. Pharmacological studies of VHD-associated medications (e.g., fenfluramine, pergolide, methysergide, and cabergoline) have revealed that they and/or their metabolites are potent 5-hydroxytryptamine2B (5-HT2B) receptor agonists. We have shown that activation of 5-HT2B receptors on human heart valve interstitial cells in vitro induces a proliferative response reminiscen...

  9. Behavioural hyperactivity in rats treated with selective monoamine oxidase inhibitors and LM 5008, a selective 5-hydroxytryptamine uptake blocker.

    Ashkenazi, R.; Finberg, J. P.; Youdim, M. B.

    1983-01-01

    The administration of 4-[2-(3-indolyl)ethyl]piperidine (LM 5008), a selective 5-hydroxytryptamine (5-HT) uptake blocker to rats pretreated with tranylcypromine (Tcp) resulted in a behavioural syndrome of locomotor hyperactivity which is indistinguishable from that following combined treatment with Tcp and L-tryptophan. A similar behavioural response was elicited by the administration of LM 5008 to rats pretreated with 5-hydroxytryptophan. The response to LM 5008 after monoamine oxidase (MAO) ...

  10. The ionization of 5-hydroxytryptamine and related compounds and an appraisal of methods for the estimation of zwitterion constants.

    Barlow, R B; Burston, K. N.

    1980-01-01

    1 The dissociation constants of 5-hydroxytryptamine and 5-hydroxy-N,N-dimethyltryptamine have been measured and the zwitterion constants have been estimated from the pKas of analogous methoxyamines and the phenolic quaternary ammonium salt. 2 Direct measurement of zwitterion constants has been made by a spectroscopic method which has been used also with several phenolic amines previously studied electrometrically. It make fewer assumptions and so should be more reliable but an appraisal of th...

  11. The effect of selective 5-hydroxytryptamine uptake inhibitors on 5-methoxy-N,N-dimethyltryptamine-induced ejaculation in the rat.

    Rényi, L.

    1986-01-01

    The ejaculatory response and the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1 i.p.) were studied following acute and repeated treatment of rats with the selective uptake inhibitors of 5-HT, fluoxetine, zimeldine, alaproclate, and citalopram. The oral doses used were based on the respective ED50 values for uptake inhibition. Acute doses of fluoxetine and zimeldine significantly reduced the ejaculatory response when given 48 h...

  12. Phenolphthalein stimulates the formation of histamine, 5-hydroxytryptamine and prostaglandin-like material by rat jejunum, ileum and colon.

    Autore, G.; Capasso, F.; Mascolo, N.

    1984-01-01

    The effects of phenolphthalein on the formation of histamine, 5-hydroxytryptamine(5-HT) and prostaglandin-like material by rat intestine were examined in vivo. Phenolphthalein, in a dose that causes laxation increased the formation of histamine, 5-HT and prostaglandin-like material, and indomethacin reduced these increases. The data support the idea that the laxative effect of phenolphthalein is due to increased intestinal production of prostaglandin, histamine and 5-HT.

  13. CORTICOTROPIN-RELEASING FACTOR INCREASES GABA SYNAPTIC ACTIVITY AND INDUCES INWARD CURRENT IN 5-HYDROXYTRYPTAMINE DORSAL RAPHE NEURONS

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

    2008-01-01

    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 t...

  14. Increased contractile responses to 5-hydroxytryptamine and Angiotensin II in high fat diet fed rat thoracic aorta

    Ghatta Srinivas

    2004-08-01

    Full Text Available Abstract Background Feeding normal rats with high dietary levels of saturated fat leads to pathological conditions, which are quite similar to syndrome X in humans. These conditions such as hypertriglyceridemia, hypercholesterolemia, obesity, and hyperglycemia might induce hypertension through various mechanisms. Metabolic syndrome and the resulting NIDDM represent a major clinical challenge because implementation of treatment strategies is difficult. Vascular abnormalities probably contribute to the etiology of many diabetic complications including nephropathy, neuropathy, retinopathy, and cardiomyopathy. It has been shown that in Streptozotocin induced diabetic animals there is an increase in maximal responses to 5-Hydroxytryptamine and Angiotensin II. The purpose of this study was to evaluate High fat diet fed rats for the development of hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperglycemia and to assess their vascular responses to 5-Hydroxytryptamine and Angiotensin II. Methods Male Sprague Dawley rats were used for this study and were divided into two equal groups. One of the groups was fed with normal pellet diet and they served as the control group, whereas the other group was on a high fat diet for 4 weeks. Body weight, plasma triglycerides, plasma cholesterol, and plasma glucose were measured every week. Intraperitoneal glucose tolerance test was performed after 4 weeks of feeding. At the end of fourth week of high fat diet feeding, thoracic aortae were removed, and cut into helical strips for vascular reactivity studies. Dose-response curves of 5-Hydroxytryptamine and Angiotensin II were obtained. Results There was no significant difference in pD2, with 5-Hydroxytryptamine and Angiotensin II in both groups but Emax was increased. Conclusions These results suggest that hypertension in high fat diet rats is associated with increased in vitro vascular reactivity to 5-HT and Ang II.

  15. Effects of metformin on intestinal 5-hydroxytryptamine (5-HT) release and on 5-HT3 receptors.

    Cubeddu, L X; Bönisch, H; Göthert, M; Molderings, G; Racké, K; Ramadori, G; Miller, K J; Schwörer, H

    2000-01-01

    Nearly 30% of patients treated with metformin experience gastrointestinal side effects. Since release of 5-hydroxytryptamine (5-HT) from the intestine is associated with nausea, vomiting, and diarrhea, we examined whether metformin induces 5-HT release from the intestinal mucosa. In 40% of tissue biopsy specimens of human duodenal mucosa, metformin (1, 10, and 30 microM) caused an increase in 5-HT outflow by 35, 70, and 98%, respectively. Peak increases in 5-HT outflow were observed after 10-15 min exposure to metformin, returning to baseline levels after 25 min. Tetrodotoxin (1 microM) reduced by about 50% the metformin-evoked increase in 5-HT outflow (Pnaloxone, or the NK1 receptor antagonist L703606. In the presence of tetrodotoxin (1 microM), somatostatin (1 microM) further reduced metformin-induced 5-HT release by 15-20%. In view of the 5-HT releasing effects of selective 5-HT3 receptor agonists to which metformin (N-N-dimethylbiguanide) is structurally related, we investigated whether metformin directly interacts with 5-HT3 receptors. Receptor binding (inhibition of [3H]-GR65630 binding) and agonist effects (stimulation of [14C]-guanidinium influx) at 5-HT3 receptors were studied in murine neuroblastoma N1E-115 cells, which express functional 5-HT3 receptors. Metformin up to 0.3 mM failed to inhibit [3H]-GR65630 binding and to modify displacement of [3H]-GR65630 binding induced by 5-HT. 5-HT (3 microM) stimulated the influx of [14C]-guanidinium in intact N1E-115 cells. Metformin up to 1 mM failed to modify basal influx, 5-HT-induced influx, and 5-HT+ substance P-induced influx of [14C]-guanidinium. Our results indicate that metformin induces 5-HT3 receptor-independent release of 5-HT from human duodenal mucosa via neuronal and non-neuronal mechanisms. Part of the gastrointestinal side effects observed during treatment with metformin could, thus, be produced by the release of 5-HT and other neurotransmitter substances within the duodenal mucosa. PMID:10651152

  16. Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist.

    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

    2011-11-01

    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. PMID:21825000

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

    Nakayama H

    2014-02-01

    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

  18. Characterization of the 5-hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureter

    Hernández, Medardo; Barahona, María Victoria; Simonsen, Ulf; Recio, Paz; Rivera, Luis; Martínez, Ana Cristina; García-Sacristán, Albino; Orensanz, Luis M; Prieto, Dolores

    2003-01-01

    This study was designed to investigate the effect of 5-hydroxytryptamine (5-HT) and to characterize the 5-HT receptors involved in 5-HT responses in the pig intravesical ureter. 5-HT (0.01–10 μM) concentration-dependently increased the tone of intravesical ureteral strips, whereas the increases in phasic contractions were concentration-independent. The 5-HT2 receptor agonist α-methyl 5-HT, mimicked the effect on tone whereas weak or no response was obtained with 5-CT, 8-OH-DPAT, m-chlorophenylbiguanide and RS 67333, 5-HT1, 5-HT1A, 5-HT3 and 5-HT4 receptor agonists, respectively. 5-HT did not induce relaxation of U46619-contracted ureteral preparations. Pargyline (100 μM), a monoaminooxidase A/B activity inhibitor, produced leftward displacements of the concentration-response curves for 5-HT. 5-HT-induced tone was reduced by the 5-HT2 and 5-HT2A receptor antagonists ritanserine (0.1 μM) and spiperone (0.2 μM), respectively. However, 5-HT contraction was not antagonized by cyanopindolol (2 μM), SDZ–SER 082 (1 μM), Y-25130 (1 μM) and GR 113808 (0.1 μM), which are respectively, 5-HT1A/1B, 5-HT2B/2C, 5-HT3, and 5-HT4 selective receptor antagonists. Removal of the urothelium did not modify 5-HT-induced contractions. Blockade of neuronal voltage-activated sodium channels, α-adrenergic receptors and adrenergic neurotransmission with tetrodotoxin (1 μM), phentolamine (0.3 μM) and guanethidine (10 μM), respectively, reduced the contractions to 5-HT. However, physostigmine (1 μM), atropine (0.1 μM) and suramin (30 μM), inhibitors of cholinesterase activity, muscarinic- and purinergic P2-receptors, respectively, failed to modify the contractions to 5-HT. These results suggest that 5-HT increases the tone of the pig intravesical ureter through 5-HT2A receptors located at the smooth muscle. Part of the 5-HT contraction is indirectly mediated via noradrenaline release from sympathetic nerves. PMID:12522083

  19. Toward Selective Drug Development for the Human 5-Hydroxytryptamine 1E Receptor: A Comparison of 5-Hydroxytryptamine 1E and 1F Receptor Structure-Affinity RelationshipsS⃞

    Klein, Michael T.; Dukat, Małgorzata; Glennon, Richard A.; Teitler, Milt

    2011-01-01

    The 5-hydroxytryptamine (5-HT) 1E receptor is highly expressed in the human frontal cortex and hippocampus, and this distribution suggests the function of 5-HT1E receptors might be linked to memory. To test this hypothesis, behavioral experiments are needed. Because rats and mice lack a 5-HT1E receptor gene, knockout strategies cannot be used to elucidate this receptor's functions. Thus, selective pharmacological tools must be developed. The tryptamine-related agonist BRL54443 [5-hydroxy-3-(1...

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

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

    2009-01-01

    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

  1. Gamma-aminobutyric acid and 5-hydroxytryptamine in the nervous system of an annelid worm (Nereis diversicolor)

    Autoradiographic techniques have been employed to define the cellular elements involved in the elaboration of gamma-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) in the nervous system of Nereis. This procedure is described. Results concerning the distribution of 5-HT and GABA in Nereis are still incomplete. Nevertheless, as a result of these initial autoradiographic data, it seems possible to postulate an effect of 5-HT and GABA in the neuropil and in the peripheral nerves. 5-HT would also act in certain endplates located in the pharynx of Nereis, for instance. This monoamine, however, probably does not act the level of the infracerebral complex

  2. 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.

    2012-01-01

    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...

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

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

    2012-09-19

    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.

  4. Protein kinase mediated upregulation of endothelin A, endothelin B and 5-hydroxytryptamine 1B/1D receptors during organ culture in rat basilar artery

    Hansen-Schwartz, Jacob; Svensson, Carl-Lennart; Xu, Cang-Bao;

    2002-01-01

    1. Organ culture has been shown to upregulate both endothelin (ET) and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptors in rat cerebral arteries. The purpose of the present study was to investigate the involvement of protein kinases, especially protein kinases C (PKC) and A (PKA) in this process...

  5. Acute and chronic effects of citalopram on postsynaptic 5-hydroxytryptamine(1A) receptor-mediated feedback : a microdialysis study in the amygdala

    Bosker, FJ; Cremers, TIFH; Jongsma, ME; Westerink, BHC; Wikstrom, VH; den Boer, JA

    2001-01-01

    Microdialysis was used to assess the involvement of postsynaptic 5-hydroxytryptamine(1A) (5-HT1A) receptors in the regulation of extracellular 5-HT in the amygdala. Local infusion of the 5-HT1A receptor agonist flesinoxan (0.3, 1, 3 muM) for 30 min into the amygdala maximally decreased 5-HT to 50% o

  6. Enhanced transcription of contractile 5-hydroxytryptamine 2A receptors via extracellular signal-regulated kinase 1/2 after organ culture of rat mesenteric artery

    Cao, Yong-Xiao; He, Lang-Chong; Xu, Cang-Bao;

    2005-01-01

    5-Hydroxytryptamine (5-HT) has been found to elicit enhanced contractile effects in some vascular disorders. The present study was designed to examine if vascular 5-HT2A receptors are up-regulated during organ culture and if the extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathways ...

  7. Mechanism of decline in rat brain 5-hydroxytryptamine after induction of liver tryptophan pyrrolase by hydrocortisone: roles of tryptophan catabolism and kynurenine synthesis

    Young, Simon N.

    1981-01-01

    1 Two mechanisms have been proposed to explain the decline in brain tryptophan and 5-hydroxytryptamine (5-HT) after administration of hydrocortisone and the subsequent induction of liver pyrrolase. These are depletion of tryptophan by high rates of tryptophan catabolism and inhibition of tryptophan uptake by elevated levels of the tryptophan catabolite, kynurenine.

  8. 5-Hydroxytryptamine 1A and 2B serotonin receptors in neurite outgrowth: involvement of early growth response protein 1.

    Anelli, Tonino; Cardarelli, Silvia; Ori, Michela; Nardi, Irma; Biagioni, Stefano; Poiana, Giancarlo

    2013-01-01

    Neurotransmitters play important roles in neurogenesis; in particular, acetylcholine and serotonin may regulate neurite elongation. Acetylcholine may also activate transcription factors such as early growth response protein 1 (EGR-1), which plays a role in neurite extension. N18TG2 neuroblastoma cells (which do not produce neurotransmitters and constitutively express muscarinic acetylcholine receptors) were transfected with constructs containing the cDNA for choline acetyltransferase, 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2B serotonin receptors to study acetylcholine and serotonin interplay in neurite outgrowth. 5-HT1A receptor stimulation causes a decrease in EGR-1 levels and inhibition of neurite outgrowth; 5-HT2B stimulation, however, has no effect. Muscarinic cholinergic stimulation, on the other end, increases EGR-1 levels and fiber outgrowth. Inhibition of EGR-1 binding reduces fiber outgrowth activity. When both cholinergic and 5-HT1A receptors are stimulated, fiber outgrowth is restored; therefore, acetylcholine counterbalances the inhibitory effect of serotonin on neurite outgrowth. These results suggest that EGR-1 plays a role in the interplay of acetylcholine and serotonin in the regulation of neurite extension during development. PMID:24158140

  9. Cinitapride protects against ethanol-induced gastric mucosal injury in rats: role of 5-hydroxytryptamine, prostaglandins and sulfhydryl compounds.

    Alarcón-de-la-Lastra Romero, C; López, A; Martín, M J; la Casa, C; Motilva, V

    1997-04-01

    This study was designed to determine the gastroprotective properties of cinitapride (CNT), a novel prokinetic benzamide derivative agonist of 5-HT4 and 5-HT1 receptors and 5-HT2 antagonist, on mucosal injury produced by 50% (v/v) ethanol. Results were compared with those for 5-hydroxytryptamine (5-HT: 10 mg kg-1). The possible involvements of gastric mucus secretion, endogenous prostaglandins (PGs) and sulfhydryl compounds (SH) in the protection mediated by CNT were also examined. Intraperitoneal administration of CNT (0.50 and 1 mg kg-1), 30 min before ethanol, significantly prevented gastric ulceration and increased the hexosamine content of gastric mucus. CNT (1 mg kg-1) also produced a significant increase in gastric mucosal levels of PGE2, but did not induce any significant changes in SH values. On the contrary, pretreatment with 5-HT worsened ethanol-induced erosions, however, did not affect gastric mucus secretion, glycoprotein content or PGE2 levels, although the non-protein SH fraction was significantly decreased. The present results demonstrate that the gastroprotective effects of CNT could be partly explained by a complex PG dependent mechanism. We suggest that 5-HT dependent mechanisms through 5-HT2 receptor blockade and 5-HT1 receptor activation could be also involved. PMID:9211565

  10. Increased extracellular dopamine and 5-hydroxytryptamine levels contribute to enhanced subthalamic nucleus neural activity during exhausting exercise.

    Hu, Y; Liu, X; Qiao, D

    2015-09-01

    The purpose of the study was to explore the mechanism underlying the enhanced subthalamic nucleus (STN) neural activity during exhausting exercise from the perspective of monoamine neurotransmitters and changes of their corresponding receptors. Rats were randomly divided into microdialysis and immunohistochemistry study groups. For microdialysis study, extracellular fluid of the STN was continuously collected with a microdialysis probe before, during and 90 min after one bout of exhausting exercise. Dopamine (DA) and 5-hydroxytryptamine (5-HT) levels were subsequently detected with high-performance liquid chromatography (HPLC). For immunohistochemistry study, the expression of DRD2 and HT2C receptors in the STN, before, immediately after and 90 min after exhaustion was detected through immunohistochemistry technique. Microdialysis study results showed that the extracellular DA and 5-HT neurotransmitters increased significantly throughout the procedure of exhausting exercise and the recovery period (Prat STN immediately after exhausting exercise and at the time point of 90 min after exhaustion were both higher than those of the rest condition, but the difference was not significant (P>0.05). Our results suggest that the increased extracellular DA and 5-HT in the STN might be one important factor leading to the enhanced STN neural activity and the development of fatigue during exhausting exercise. This study may essentially offer useful evidence for better understanding of the mechanism of the central type of exercise-induced fatigue. PMID:26424920

  11. 5-Hydroxytryptamine-induced bladder hyperactivity via the 5-HT2A receptor in partial bladder outlet obstruction in rats.

    Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

    2013-04-01

    We investigated the effects of partial bladder outlet obstruction (BOO) on the function and gene expression of 5-hydroxytryptamine (5-HT) receptor subtypes in rat bladder. Isometric contractions of the isolated bladders from sham-operated control and BOO rats were examined. The contractile responses to 5-HT were significantly increased in BOO rat bladder strips, while the responses to KCl, carbachol, or phenylephrine were not different from the control. The 5-HT-induced hypercontraction in BOO rat bladder strips was inhibited by ketanserin, a 5-HT(2A) receptor antagonist. The contractile responses to 5-HT in bladder strips were not affected by urothelium removal from the intact bladder. The gene expression of 5-HT receptor subtypes in the bladders was analyzed by RT-PCR. The mRNA expression of the 5-HT(2A), 5-HT(2B), 5-HT(2C), 5-HT(4), and 5-HT(7) receptors was detected in both the control and BOO rat bladders. Quantitative RT-PCR analysis showed there was a significant increase of 5-HT(2A) receptor mRNA in the BOO rat bladder compared with the control bladder. On the other hand, the gene expression of the 5-HT(4) receptor was not changed in the BOO rat bladder. These results suggest that the increased contractile responses to 5-HT in BOO rat bladder may be partly caused by 5-HT(2A) receptor upregulation in the detrusor smooth muscles. PMID:23344575

  12. Effect of ethanol on thrombin-induced platelet phospholipid breakdown and release of [3H]-5-hydroxytryptamine

    Ethanol has been reported previously to inhibit chemically-induced platelet aggregation and the release of platelet contents. In platelet suspensions the mechanical stimulus of stirring can induce slow aggregation and the loss of endogenous arachidonic acid from phospholipids by activation of platelet phospholipases. These changes are prevented by the presence of ethanol 20-100 mM, whereas, in unstirred suspensions, ethanol alone has no effect on platelet phospholipids. Under similar conditions of reduced platelet: platelet contact, chemical stimuli, such as thrombi, although unable to produce visible aggregation, still cause the release of [3H]-5-hydroxytryptamine from platelets and also initiate the breakdown of platelet phospholipids. Ethanol does not now inhibit the thrombin-induced release of platelet contents and has little effect on phosphatidylinositol breakdown, though it inhibits phosphatidylcholine breakdown. Ethanol may therefore inhibit platelet aggregation by reducing the effect of mechanical and chemical stimuli on the activation of phospholipase A2. In contrast ethanol has rather little effect on the receptor-mediated breakdown of phosphatidylinositol which is apparently sufficient to trigger the release of platelet contents

  13. Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment.

    Huang, Xi-Ping; Setola, Vincent; Yadav, Prem N; Allen, John A; Rogan, Sarah C; Hanson, Bonnie J; Revankar, Chetana; Robers, Matt; Doucette, Chris; Roth, Bryan L

    2009-10-01

    Drug-induced valvular heart disease (VHD) is a serious side effect of a few medications, including some that are on the market. Pharmacological studies of VHD-associated medications (e.g., fenfluramine, pergolide, methysergide, and cabergoline) have revealed that they and/or their metabolites are potent 5-hydroxytryptamine(2B) (5-HT(2B)) receptor agonists. We have shown that activation of 5-HT(2B) receptors on human heart valve interstitial cells in vitro induces a proliferative response reminiscent of the fibrosis that typifies VHD. To identify current or future drugs that might induce VHD, we screened approximately 2200 U.S. Food and Drug Administration (FDA)-approved or investigational medications to identify 5-HT(2B) receptor agonists, using calcium-based high-throughput screening. Of these 2200 compounds, 27 were 5-HT(2B) receptor agonists (hits); 14 of these had previously been identified as 5-HT(2B) receptor agonists, including seven bona fide valvulopathogens. Six of the hits (guanfacine, quinidine, xylometazoline, oxymetazoline, fenoldopam, and ropinirole) are approved medications. Twenty-three of the hits were then "functionally profiled" (i.e., assayed in parallel for 5-HT(2B) receptor agonism using multiple readouts to test for functional selectivity). In these assays, the known valvulopathogens were efficacious at concentrations as low as 30 nM, whereas the other compounds were less so. Hierarchical clustering analysis of the pEC(50) data revealed that ropinirole (which is not associated with valvulopathy) was clearly segregated from known valvulopathogens. Taken together, our data demonstrate that patterns of 5-HT(2B) receptor functional selectivity might be useful for identifying compounds likely to induce valvular heart disease. PMID:19570945

  14. The effect of selective 5-hydroxytryptamine uptake inhibitors on 5-methoxy-N,N-dimethyltryptamine-induced ejaculation in the rat.

    Rényi, L

    1986-04-01

    The ejaculatory response and the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1 i.p.) were studied following acute and repeated treatment of rats with the selective uptake inhibitors of 5-HT, fluoxetine, zimeldine, alaproclate, and citalopram. The oral doses used were based on the respective ED50 values for uptake inhibition. Acute doses of fluoxetine and zimeldine significantly reduced the ejaculatory response when given 48 h before 5-MeODMT. This blockade was prevented by treatment of the rats with the postsynaptic 5-HT receptor antagonist methergoline. An acute dose of fluoxetine given 7 and 14 days before 5-MeODMT significantly enhanced the ejaculatory response. On day 24, the response returned to the control level. Repeated treatment every second day (5 times over 9 days and 10 times over 19 days) with fluoxetine caused a longer blockade of the ejaculatory response and the sensitization of the response came later than after an acute dose. Parallel with the ejaculatory response three other components of the 5-HT behavioural syndrome also decreased significantly. Acute doses of alaproclate and citalopram significantly blocked the ejaculatory response at 1 h, but they failed to affect the response at any other time point after either acute or repeated treatment. Neither did these drugs attentuate the 5-HT syndrome. It is concluded that acute and repeated treatment of rats with different selective 5-HT uptake inhibitors does not produce a common alteration in 5-HT2-receptor functions. PMID:2939912

  15. Lack of systematic effects of the 5-hydroxytryptamine 3 receptor antagonist ICS 205-930 on gastric emptying and antral motor activity in patients with primary anorexia nervosa.

    Stacher, G; Bergmann, H; Granser-Vacariu, G V; Wiesnagrotzki, S; Wenzelabatzi, T A; Gaupmann, G; Kugi, A; Steinringer, H; Schneider, C; Höbart, J

    1991-01-01

    1. The 5-hydroxytryptamine 3 receptor antagonist, ICS 205-930, has been reported to have potent effects on gastric smooth muscle and to enhance gastric emptying in animals, but findings in man have been inconsistent. 2. This study investigated the effects of ICS 205-930 on gastric emptying of an isotopically labelled semisolid 1168 kJ meal and on antral contractility in patients with primary anorexia nervosa, a condition frequently associated with impaired gastric motor function. 3. Thirteen ...

  16. Antidepressant treatments: effects in rodents on dose-response curves of 5-hydroxytryptamine- and dopamine-mediated behaviours and 5-HT2 receptor number in frontal cortex.

    Green, A. R.; Heal, D. J.; Johnson, P.; Laurence, B. E.; Nimgaonkar, V. L.

    1983-01-01

    The effects of repeated electroconvulsive shock (ECS) administration, repeated desmethylimipramine injection (5 mg kg-1, twice daily for 14 days) and acute administration of the beta-adrenoceptor, clenbuterol, on 5-hydroxytryptamine (5-HT)- and dopamine-mediated behaviours in mice have been examined. All three treatments enhanced the carbidopa/5-hydroxytryptophan (5-HTP)-induced head-twitch response at all doses of 5-HTP examined, producing a parallel shift in the dose-response curve. A singl...

  17. A Meta-Analysis of the Effects of the 5-Hydroxytryptamine Transporter Gene-Linked Promoter Region Polymorphism on Susceptibility to Lifelong Premature Ejaculation

    Zhu, Lijie; Mi, Yuanyuan; You, Xiaoming; Wu, Sheng; Shao, Hongbao; Dai, Feng; Peng, Tao; Qin, Feng; Feng, Ninghan

    2013-01-01

    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 studie...

  18. Drugs targeting 5-hydroxytryptamine receptors in acute treatments of migraine attacks. A review of new drugs and new administration forms of established drugs

    Tfelt-Hansen, Peer C; Pihl, Thomas Peter Boye; Hougaard, Anders; Mitsikostas, Dimos D

    2014-01-01

    Introduction: The development of sumatriptan, more than 20 years ago, added substantially to the characterization of 5-hydroxytryptamine (5-HT) receptors and their relevance to acute migraine therapy. Recently, 5-HT1F receptor agonists, with no vascular effects, have shown efficacy in the treatme...... low incidence of recurrence. None of these reviewed treatments are likely to fulfill patients' expectations, and the advancement of acute migraine drugs should likely depend on different mechanisms from current 5-HT-related drugs....

  19. The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting

    To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. We identified 1,832 palonosetron and 2,387 other 5-HT3 RA (“other”) patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs

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

    Chen Ya-qiong; Wu Wei-guang

    2007-01-01

    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

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

    Huipeng Li; Fengli An; Shucheng An

    2009-01-01

    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

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

    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))

    1992-11-01

    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).

  3. Neural control of the sphincter of Oddi. A physiological role of 5-hydroxytryptamine in the regulation of basal sphincter of Oddi motor activity in the cat.

    Behar, J; Biancani, P

    1983-01-01

    The effect of 5-hydroxytryptamine (5-HT) on the sphincter of Oddi (SO) was studied in the cat. The SO had two motor responses to 5-HT: the most common was an initial contraction followed by a more prolonged relaxation, and the other was an exclusive relaxation. Tetrodotoxin did not impair the magnitude of the net contraction induced by 5-HT, but it completely blocked the relaxation. Methysergide partially inhibited the SO contraction in response to submaximal doses of 5-HT (5-20 micrograms/kg...

  4. The 5-HT1 receptor agonist RU-24969 decreases 5-hydroxytryptamine (5-HT) release and metabolism in the rat frontal cortex in vitro and in vivo.

    Brazell, M. P.; Marsden, C. A.; Nisbet, A. P.; Routledge, C.

    1985-01-01

    K+-stimulated release of [3H]-5-hydroxytryptamine ( [3H]-5-HT) from rat frontal cortex slices was decreased by the 5-HT receptor agonists 5-methoxy-n1N-dimethyltryptamine and 5-methoxy-3(1,2,3,6,-tetrahydro-4-pyrindinyl)-1H-indole (RU-24969) (1 X 10(-5)M). RU-24969 (10 mg kg-1, i.p.) decreased extracellular 5-HT and its metabolite 5-hydroxyindoleacetic acid measured in vivo by use of intracerebral dialysis combined with high performance liquid chromatography and electrochemical detection. The...

  5. Capsaicin modulates proliferation, migration, and activation of hepatic stellate cells.

    Bitencourt, Shanna; Mesquita, Fernanda; Basso, Bruno; Schmid, Júlia; Ferreira, Gabriela; Rizzo, Lucas; Bauer, Moises; Bartrons, Ramon; Ventura, Francesc; Rosa, Jose Luis; Mannaerts, Inge; van Grunsven, Leo Adrianus; Oliveira, Jarbas

    2014-03-01

    Capsaicin, the active component of chili pepper, has been reported to have antiproliferative and anti-inflammatory effects on a variety of cell lines. In the current study, we aimed to investigate the effects of capsaicin during HSC activation and maintenance. Activated and freshly isolated HSCs were treated with capsaicin. Proliferation was measured by incorporation of EdU. Cell cycle arrest and apoptosis were investigated using flow cytometry. The migratory response to chemotactic stimuli was evaluated by a modified Boyden chamber assay. Activation markers and inflammatory cytokines were determined by qPCR, immunocytochemistry, and flow cytometry. Our results show that capsaicin reduces HSC proliferation, migration, and expression of profibrogenic markers of activated and primary mouse HSCs. In conclusion, the present study shows that capsaicin modulates proliferation, migration, and activation of HSC in vitro. PMID:23955514

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

    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

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

    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: Edward.Chow@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2012-01-01

    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

  8. Characterization of poly(5-hydroxytryptamine)-modified glassy carbon electrode and applications to sensing of norepinephrine and uric acid in preparations and human urines

    Graphical abstract: A 5-hydroxytryptamine (5-HT) modified electrode was fabricated by electro-polymerization of 5-HT on a glassy carbon electrode (GCE) by cyclic voltammetry (CV) in 0.05 M PBS (pH 7). The characterization of the modified electrode was carried out by atomic force microscopy (AFM), voltammetry and electrochemical impedance spectroscopy (EIS). The mechanism of electro-deposition of 5-HT at GCE was discussed based on electrochemical studies and quantum chemical calculations. The poly(5-HT)-modified electrode could separately detect NE and UA, even in the presence of 10-fold concentration of ascorbic acid (AA) and was applied successfully to the analysis of NE preparations and healthy human urines. Due to the favorable functionalized groups (-NH2 and -OH), electroactivity, biocompatibility and stability, the poly(5-HT) film could be a promising immobilization matrix for anchoring interested biological molecules in the fabrication of sensors and biosensors. Highlights: ► A poly(5-HT)-modified electrode was fabricated originally by CV. ► The electro-deposition mechanism of 5-HT at GCE was proposed. ► The polymer film shows favorable electrocatalytic properties to NE and UA. ► The modified GCE was applied to the sensing analysis of real samples. -- Abstract: A poly(5-hydroxytryptamine) (poly(5-HT)) modified electrode was fabricated by electropolymerization of 5-hydroxytryptamine (5-HT) on a glassy carbon electrode (GCE) by cyclic voltammetry (CV) in 0.05 M PBS (pH 7). The characterization of poly(5-HT)-modified electrode was carried out by atomic force microscopy (AFM), voltammetry and electrochemical impedance spectroscopy (EIS). Results showed that a brown and heterogeneous film was formed on the surface of the modified electrode. The mechanism of electro-deposition of 5-HT at GCE was discussed. The modified electrode showed good affinity and electrocatalytic properties to some species, such as norepinephrine (NE) and uric acid (UA). Furthermore

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

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

    1984-08-01

    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.

  10. About the research progress of the relation between the aggressive behavior and 5-hydroxytryptamine and dopamine%5-羟色胺和多巴胺与攻击行为关系的研究进展

    胡晨; 马泽兵; 冯晓琪; 罗强

    2015-01-01

    This paper summarizes the certain studies of 5-hydroxytryptamine(5-HT) and dopamine(DA) influence on aggressive behavior through the literature material, in order to provide the theoretical basis for using 5-hydroxytryptamine(5-HT) and dopamine(DA)to reduce aggression.%通过文献资料法,对5-羟色胺与多巴胺对攻击行为的影响的相关研究进行综述,从而为通过调控5-羟色胺和多巴胺来减少攻击行为提供理论依据。

  11. 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

    Pierce D

    2015-02-01

    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

  12. Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation

    2016-01-01

    Purpose: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. Methods: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2ʹ- deoxyuridine and doublecortin (DCX) in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT1A) in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) levels in the hippocampus were evaluated by western blot analysis. Results: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT1A expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. Conclusions: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT1A activation in offspring rats. PMID:27230461

  13. Depressive behavior and alterations in receptors for dopamine and 5-hydroxytryptamine in the brain of the senescence accelerated mouse (SAM)-P10.

    Onodera, T; Watanabe, R; Tha, K K; Hayashi, Y; Murayama, T; Okuma, Y; Ono, C; Oketani, Y; Hosokawa, M; Nomura, Y

    2000-08-01

    The senescence accelerated mouse (SAM) is known as a murine model of aging. SAM consists of senescence accelerated-prone mouse (SAMP) and senescence accelerated-resistant mouse (SAMR). Previous studies reported that SAMP10 exhibits age-related learning impairments and behavioral depression in a tail suspension test after 7 months. We investigated the changes in emotional behavior in a forced swimming test and in receptors for dopamine and 5-hydroxytryptamine (5-HT) in SAMP10. SAMP10 at 8 months showed an increase of immobility in the test compared with SAMR1. Treatment with desipramine (25 mg/kg, i.p., 3 days) in SAMP10 caused a decrease in immobility. In the cortex from SAMP10, [3H]quinpirole binding to D2/D3 dopamine receptors increased significantly compared with control SAMR1. In the hippocampus from SAMP10, [3H]8-hydroxy DPAT binding to 5-HT1A receptor increased. In midbrains from SAMP10, bindings of [3H]quinpirole and [3H]8-hydroxy DPAT increased. [3H]SCH23390 binding to D1/D5 receptors and [3H]ketanserin binding to 5-HT2 receptor in brain regions examined in SAMP10 were similar to those in SAMR1. The present findings represent the first neurochemical evidence of an increase of D2/D3 and 5-HT1A receptors in SAMP10. SAMP10 may be a useful model of aging associated depressive behavior. PMID:11001177

  14. Migrants and the labour process: a module for migration surveys.

    Standing G

    1981-01-01

    ILO pub-wep pub. Working paper comprising a draft chapter from an anticipated guide to survey data collecting on internal migration, labour mobility and employment (esp. In developing countries - develops a questionnaire to determine basic household activities (wages and unpaid work, occupational status, etc.) And labour force participation (pre and post migration, recent and return migrant, etc.). References.

  15. [3H]-DOB(4-bromo-2,5-dimethoxyphenylisopropylamine) and [3H] ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor

    The binding properties of the 5-hydroxytryptamine2 (5-HT2) receptor have been the subject of much interest and debate in recent years. The hallucinogenic amphetamine derivative 4-bromo-2,5-dimethoxyphenylisopropylamine (DOB) has been shown to bind to a small number of binding sites with properties very similar to [3H]ketanserin-labeled 5-HT2 receptors, but with much higher agonist affinities. Some researchers have interpreted this as evidence for the existence of a new subtype of 5-HT2 receptor (termed 5-HT2A), whereas others have interpreted these data as indicative of agonist high affinity and agonist low affinity states for the 5-HT2 receptor. In this investigation, a cDNA clone encoding the serotonin 5-HT2 receptor was transiently transfected into monkey kidney Cos-7 cells and stably transfected into mouse fibroblast L-M(TK-) cells. In both systems, expression of this single serotonin receptor cDNA led to the appearance of both [3H]DOB and [3H]ketanserin binding sites with properties that matched their binding characteristics in mammalian brain homogenates. Addition of guanosine 5'-(beta, gamma-imido) triphosphate [Gpp(NH)p] to this system caused a rightward shift and steepening of agonist competition curves for [3H] ketanserin binding, converting a two-site binding curve to a single low affinity binding state. Gpp(NH)p addition also caused a 50% decrease in the number of high affinity [3H]DOB binding sites, with no change in the dissociation constant of the remaining high affinity states. These data on a single human 5-HT2 receptor cDNA expressed in two different transfection host cells indicate that [3H]DOB and [3H]ketanserin binding reside on the same gene product, apparently interacting with agonist and antagonist conformations of a single human 5-HT2 receptor protein

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

    Yan-qi LIANG; Xi-can TANG

    2006-01-01

    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.

  17. Emetic responses to T-2 toxin, HT-2 toxin and emetine correspond to plasma elevations of peptide YY3-36 and 5-hydroxytryptamine.

    Wu, Wenda; Zhou, Hui-Ren; Bursian, Steven J; Link, Jane E; Pestka, James J

    2016-04-01

    Trichothecene mycotoxins are a family of potent translational inhibitors that are associated with foodborne outbreaks of human and animal gastroenteritis in which vomiting is a clinical hallmark. Deoxynivalenol (DON, vomitoxin) and other Type B trichothecenes have been previously demonstrated to cause emesis in the mink (Neovison vison), and this response has been directly linked to secretion of both the satiety hormone peptide YY3-36 (PYY3-36) and neurotransmitter 5-hydroxytryptamine (5-HT). Here, we characterized the emetic responses in the mink to T-2 toxin (T-2) and HT-2 toxin (HT-2), two highly toxic Type A trichothecenes that contaminate cereals, and further compared these effects to those of emetine, a natural alkaloid that is used medicinally and also well known to block translation and cause vomiting. Following intraperitoneal (IP) and oral exposure, all three agents caused vomiting with evident dose-dependent increases in both duration and number of emetic events as well as decreases in latency to emesis. T-2 and HT-2 doses causing emesis in 50 % of treated animals (ED50s) were 0.05 and 0.02 mg/kg BW following IP and oral administration, respectively, whereas the ED50s for emetine were 2.0 and 1.0 mg/kg BW for IP and oral exposure, respectively. Importantly, oral administration of all three toxins elicited marked elevations in plasma concentrations of PYY3-36 and 5-HT that corresponded to emesis. Taken together, the results suggest that T-2 and HT-2 were much more potent than emetine and that emesis induction by all three translational inhibitors co-occurred with increases in circulating levels of PYY3-36 and 5-HT. PMID:25855062

  18. Cross-talk between 5-hydroxytryptamine and substance P in the melanogensis and apoptosis of B16F10 melanoma cells.

    Zhou, Jia; Geng, Kun-kun; Ping, Feng-feng; Gao, Yue-ying; Liu, Lei; Feng, Bai-nian

    2016-03-15

    Skin pigmentation is a complex process controlled by many different factors. Substance P (SP) regulates many biological functions, including melanogenesis and stress. Our previous study indicated that regulation of SP on melanocyte function was mediated by neurokinin 1 receptor (NK1 receptor). Substantial evidence has accumulated that psychological stress can be associated with skin pigmentation, so that the impact of 5-hydroxytryptamine (5-HT), one of the important factors participating in stress process, on melanogenesis has also been concerned. It has been reported that 5-HT induces melanin synthesis via 5-HT2A receptor. Furthermore, 5-HT2A receptor and NK1 receptor are G-protein coupled receptors (GPCRs) and both expressed on melanocyte, the present study was designed to investigate whether SP has influence on the adjustment function of 5-HT. Our data demonstrated that, SP inhibited 5-HT2A receptor expression to neutralize the pro-melanogenesis effect of 5-HT on B16F10 cells. The up-regulation of NK1 receptor expression was simultaneous with the down-regulation of 5-HT2A receptor treated by SP. This inhibition of 5-HT2A receptor expression by SP could be reversed by NK1 receptor antagonist Spantide I. Our studies indicated that SP could directly induce B16F10 cells apoptosis in vitro. 5-HT and 5-HT2A receptor agonist could mitigate this apoptotic effect of SP. It is the strong evidence of possible cross-talk between GPCRs and giving enlightenments when screening desirable drugs for target receptors. PMID:26872989

  19. Early detection of oxygen-induced lung injury in conscious rabbits. Reduced in vivo activity of angiotensin converting enzyme and removal of 5-hydroxytryptamine

    Changes in lung endothelial metabolic function, determined in vitro, have been proposed as sensitive indexes of hyperoxic lung damage. However, it is unclear whether these changes are also seen in vivo. We studied the possibility, using conscious rabbits in which jugular and carotid catheters had previously been placed under halothane anesthesia. Approximately 24 h later, test animals were exposed to normobaric hyperoxia (96 +/- 2%), while a second group was maintained in room air. Multiple indicator dilution methods were used to study (1) metabolism of 3H-benzoyl-phe-ala-pro (BPAP), a synthetic substrate for angiotensin converting enzyme (ACE), and (2) removal of 14C-5-hydroxytryptamine (5-HT) during a single transpulmonary passage in conscious animals. Lungs of air-exposed animals hydrolyzed 81 +/- 2% of injected BPAP (0.1 to 0.15 nmoles) during a single passage. Percent metabolism was unaltered during the next 72 h. However, in test animals, ACE activity, as reflected by BPAP metabolism, was significantly reduced after 16 h of exposure to oxygen (77 +/- 2%, p less than 0.01) and continued to decrease to a nadir of 66 +/- 3% at 40 h. Single-pass lung uptake of 14C-5-HT (77 +/- 2%) was unchanged throughout the 72-h period in air-exposed rabbits. In test animals, 14C-5-HT removal decreased to 65 +/- 4% (p less than 0.01) after 24 h of oxygen exposure; 5-HT removal remained depressed compared with the 0 h control determination for the oxygen group at all subsequent measurement intervals. Light and electron microscopy of lungs from oxygen-exposed rabbits demonstrating reduced 5-HT removal and ACE activity at 24 h revealed normal endothelial and type I cell morphologic features

  20. Substrate stiffness modulates lung cancer cell migration but not epithelial to mesenchymal transition.

    Shukla, V C; Higuita-Castro, N; Nana-Sinkam, P; Ghadiali, S N

    2016-05-01

    Biomechanical properties of the tumor microenvironment, including matrix/substrate stiffness, play a significant role in tumor evolution and metastasis. Epithelial to Mesenchymal Transition (EMT) is a fundamental biological process that is associated with increased cancer cell migration and invasion. The goal of this study was to investigate (1) how substrate stiffness modulates the migration behaviors of lung adenocarcinoma cells (A549) and (2) if stiffness-induced changes in cell migration correlate with biochemical markers of EMT. Collagen-coated polydimethylsiloxane (PDMS) substrates and an Ibidi migration assay were used to investigate how substrate stiffness alters the migration patterns of A549 cells. RT-PCR, western blotting and immunofluorescence were used to investigate how substrate stiffness alters biochemical markers of EMT, that is, E-cadherin and N-cadherin, and the phosphorylation of focal adhesion proteins. Increases in substrate stiffness led to slower, more directional migration but did not alter the biochemical markers of EMT. Interestingly, growth factor (i.e., Transforming Growth Factor-β) stimulation resulted in similar levels of EMT regardless of substrate stiffness. We also observed decreased levels of phosphorylated focal adhesion kinase (FAK) and paxillin on stiffer substrates which correlated with slower cell migration. These results indicate that substrate stiffness modulates lung cancer cell migration via focal adhesion signaling as opposed to EMT signaling. PMID:26779779

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

    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

  2. Nudt3 is an mRNA decapping enzyme that modulates cell migration.

    Grudzien-Nogalska, Ewa; Jiao, Xinfu; Song, Man-Gen; Hart, Ronald P; Kiledjian, Megerditch

    2016-05-01

    Removal of the 5'-end 7-methylguanosine cap structure is a critical step in the highly regulated process of mRNA decay. The Nudix hydrolase, Dcp2, was identified as a first decapping enzyme and subsequently shown to preferentially modulate stability of only a subset of mRNAs. This observation led to the hypothesis that mammalian cells possess multiple decapping enzymes that may function in distinct pathways. Here we report Nudt3 is a Nudix protein that possesses mRNA decapping activity in cells and is a modulator of MCF-7 breast cancer cell migration. Reduction of Nudt3 protein levels in MCF-7 cells promotes increased cell migration and corresponding enhanced filopodia extensions. Importantly, this phenotype was reversed by complementation with wild type, but not catalytically inactive Nudt3 protein indicating Nudt3 decapping activity normally functions to control cell migration. Genome-wide analysis of Nudt3 compromised cells identified elevated levels of transcripts involved in cell motility including integrin β6, lipocalin-2, and fibronectin. The observed increase in mRNA abundance was dependent on Nudt3 decapping activity where integrin β6 and lipocalin-2 were modulated directly through mRNA stability, while fibronectin was indirectly controlled. Moreover, increased cell migration observed in Nudt3 knockdown cells was mediated through the extracellular integrin β6 and fibronectin protein nexus. We conclude that Nudt3 is an mRNA decapping enzyme that orchestrates expression of a subset of mRNAs to modulate cell migration and further substantiates the existence of multiple decapping enzymes functioning in distinct cellular pathways in mammals. PMID:26932476

  3. The palmitoylation state of PMP22 modulates epithelial cell morphology and migration

    David A. Zacharias

    2012-12-01

    Full Text Available PMP22 (peripheral myelin protein 22, also known as GAS 3 (growth-arrest-specific protein 3, is a disease-linked tetraspan glycoprotein of peripheral nerve myelin and constituent of intercellular junctions in epithelia. To date, our knowledge of the post-translational modification of PMP22 is limited. Using the CSS-Palm 2.0 software we predicted that C85 (cysteine 85, a highly conserved amino acid located between the second and third transmembrane domains, is a potential site for palmitoylation. To test this, we mutated C85S (C85 to serine and established stable cells lines expressing the WT (wild-type or the C85S-PMP22. In Schwann and MDCK (Madin–Darby canine kidney cells mutating C85 blocked the palmitoylation of PMP22, which we monitored using 17-ODYA (17-octadecynoic acid. While palmitoylation was not necessary for processing the newly synthesized PMP22 through the secretory pathway, overexpression of C85S-PMP22 led to pronounced cell spreading and uneven monolayer thinning. To further investigate the functional significance of palmitoylated PMP22, we evaluated MDCK cell migration in a wound-healing assay. While WT-PMP22 expressing cells were resistant to migration, C85S cells displayed lamellipodial protrusions and migrated at a similar rate to vector control. These findings indicate that palmitoylation of PMP22 at C85 is critical for the role of the protein in modulating epithelial cell shape and motility.

  4. 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

    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

  5. 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

    Jahn, Franziska, E-mail: franziska.jahn@uk-halle.de [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)

    2015-08-01

    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.

  6. Migrating Motor Complex in Colectomized Ileo Stoma Patients

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

    2011-01-01

    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...... 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 < 0.05) but not in healthy subjects. Atropine reduced 5-HT-induced frequency of MMC phase...

  7. 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

    Martino Matteo

    2010-12-01

    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.

  8. Modulators of estrogen receptor inhibit proliferation and migration of prostate cancer cells.

    Piccolella, Margherita; Crippa, Valeria; Messi, Elio; Tetel, Marc J; Poletti, Angelo

    2014-01-01

    In the initial stages, human prostate cancer (PC) is an androgen-sensitive disease, which can be pharmacologically controlled by androgen blockade. This therapy often induces selection of androgen-independent PC cells with increased invasiveness. We recently demonstrated, both in cells and mice, that a testosterone metabolite locally synthetized in prostate, the 5α-androstane-3β, 17β-diol (3β-Adiol), inhibits PC cell proliferation, migration and invasion, acting as an anti-proliferative/anti-metastatic agent. 3β-Adiol is unable to bind androgen receptor (AR), but exerts its protection against PC by specifically interacting with estrogen receptor beta (ERβ). Because of its potential retro-conversion to androgenic steroids, 3β-Adiol cannot be used "in vivo", thus, the aims of this study were to investigate the capability of four ligands of ERβ (raloxifen, tamoxifen, genistein and curcumin) to counteract PC progression by mimicking the 3β-Adiol activity. Our results demonstrated that raloxifen, tamoxifen, genistein and curcumin decreased DU145 and PC3 cell proliferation in a dose-dependent manner; in addition, all four compounds significantly decreased the detachment of cells seeded on laminin or fibronectin. Moreover, raloxifen, tamoxifen, genistein and curcumin-treated DU145 and PC3 cells showed a significant decrease in cell migration. Notably, all these effects were reversed by the anti-estrogen, ICI 182,780, suggesting that their actions are mediated by the estrogenic pathway, via the ERβ, the only isoform present in these PCs. In conclusion, these data demonstrate that by selectively activating the ERβ, raloxifen, tamoxifen, genistein and curcumin inhibit human PC cells proliferation and migration favoring cell adesion. These synthetic and natural modulators of ER action may exert a potent protective activity against the progression of PC even in its androgen-independent status. PMID:24184124

  9. HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes▿

    Nobile, Cinzia; Rudnicka, Dominika; Hasan, Milena; Aulner, Nathalie; Porrot, Françoise; Machu, Christophe; Renaud, Olivier; Prévost, Marie-Christine; Hivroz, Claire; Schwartz, Olivier; Sol-Foulon, Nathalie

    2010-01-01

    The HIV-1 Nef protein is a pathogenic factor modulating the behavior of infected cells. Nef induces actin cytoskeleton changes and impairs cell migration toward chemokines. We further characterized the morphology, cytoskeleton dynamics, and motility of HIV-1-infected lymphocytes. By using scanning electron microscopy, confocal immunofluorescence microscopy, and ImageStream technology, which combines flow cytometry and automated imaging, we report that HIV-1 induces a characteristic remodeling of the actin cytoskeleton. In infected lymphocytes, ruffle formation is inhibited, whereas long, thin filopodium-like protrusions are induced. Cells infected with HIV with nef deleted display a normal phenotype, and Nef expression alone, in the absence of other viral proteins, induces morphological changes. We also used an innovative imaging system to immobilize and visualize living individual cells in suspension. When combined with confocal “axial tomography,” this technique greatly enhances three-dimensional optical resolution. With this technique, we confirmed the induction of long filopodium-like structures in unfixed Nef-expressing lymphocytes. The cytoskeleton reorganization induced by Nef is associated with an important impairment of cell movements. The adhesion and spreading of infected cells to fibronectin, their spontaneous motility, and their migration toward chemokines (CXCL12, CCL3, and CCL19) were all significantly decreased. Therefore, Nef induces complex effects on the lymphocyte actin cytoskeleton and cellular morphology, which likely impacts the capacity of infected cells to circulate and to encounter and communicate with bystander cells. PMID:20015995

  10. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with\\ increased motor disability.

    Iravani, Mahmoud M; Tayarani-Binazir, Kayhan; Chu, Wing B; Jackson, Michael J; Jenner, Peter

    2006-12-01

    5-Hydroxytryptamine 1a (5-HT(1a)) receptor agonists, such as sarizotan and tandospirone, are reported to reduce levodopa-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques and in Parkinson's disease without worsening motor disability. However, these compounds are not specific for 5-HT(1a) receptors and also possess dopamine antagonist actions. We now report on the effects of (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin [(R)-(+)-8-OHDPAT], a selective 5-HT(1a) agonist lacking dopaminergic activity, on motor disability and dyskinesia (chorea and dystonia) in levodopa-primed MPTP-treated common marmosets. Administration of (R)-(+)-8-OHDPAT (0.2, 0.6, and 2.0 mg/kg s.c), in conjunction with levodopa/carbidopa (12.5 mg/kg each p.o.) to levodopa-primed animals, dose-dependently reduced levodopa-induced chorea but did not affect dystonic movements. However, (R)-(+)-8-OHDPAT treatment also reduced locomotor activity and the reversal of motor disability. Administration of (R)-(+)-8-OHDPAT alone had no effects of motor behaviors. The effects of (R)-(+)-8-OHDPAT on levodopa-induced motor behaviors were antagonized by the 5-HT(1a) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate (WAY-100635) (1.0 mg/kg s.c.). Administration of (R)-(+)-8-OHDPAT (0.6 mg/kg s.c.) also reduced chorea produced by the administration of the D(2)/D(3) dopamine receptor agonist pramipexole (0.06 mg/kg p.o.) to levodopa-primed MPTP-treated animals. However, again the increase in locomotor activity and reversal of motor disability produced by pramipexole were also inhibited. These data suggest that selective 5-HT(1a) agonists do not provide an effective means of suppressing levodopa-induced dyskinesia, except with worsening of parkinsonism. PMID:16959959

  11. Migration Speed of Cajal-Retzius Cells Modulated by Vesicular Trafficking Controls the Size of Higher-Order Cortical Areas.

    Barber, Melissa; Arai, Yoko; Morishita, Yoshihiro; Vigier, Lisa; Causeret, Frédéric; Borello, Ugo; Ledonne, Fanny; Coppola, Eva; Contremoulins, Vincent; Pfrieger, Frank W; Tissir, Fadel; Govindan, Subashika; Jabaudon, Denis; Proux-Gillardeaux, Véronique; Galli, Thierry; Pierani, Alessandra

    2015-10-01

    In the neocortex, higher-order areas are essential to integrate sensory-motor information and have expanded in size during evolution. How higher-order areas are specified, however, remains largely unknown. Here, we show that the migration and distribution of early-born neurons, the Cajal-Retzius cells (CRs), controls the size of higher-order areas in the mouse somatosensory, auditory, and visual cortex. Using live imaging, genetics, and in silico modeling, we show that subtype-specific differences in the onset, speed, and directionality of CR migration determine their differential invasion of the developing cortical surface. CR migration speed is cell autonomously modulated by vesicle-associated membrane protein 3 (VAMP3), a classically non-neuronal mediator of endosomal recycling. Increasing CR migration speed alters their distribution in the developing cerebral cortex and leads to an expansion of postnatal higher-order areas and congruent rewiring of thalamo-cortical input. Our findings thus identify novel roles for neuronal migration and VAMP3-dependent vesicular trafficking in cortical wiring. PMID:26387718

  12. Neurotransmitters and brain maturation: early paracrine actions of GABA and glutamate modulate neuronal migration.

    Manent, Jean-Bernard; Represa, Alfonso

    2007-01-01

    International audience Migration of neurons from their birthplace to their final destination is an extremely important step in brain maturation, and cortical migration disorders are the most common brain developmental alteration observed in human patients. Among the mechanisms that govern neuronal migration, the neurotransmitters GABA and glutamate deserve particular attention: 1) neurotransmitters and receptors are expressed early in the developing brain, 2) neurotransmitters may act as p...

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

    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

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

    Thiebot, Jean-Baptiste; Cherel, Yves; Crawford, Robert J M; Makhado, Azwianewi B; Trathan, Philip N; Pinaud, David; Bost, Charles-André

    2013-01-01

    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 subsequent migration

  15. Modulation of sulfated proteoglycan synthesis by bovine aortic endothelial cells during migration

    1986-01-01

    The rates of 35S-sulfate incorporation into proteoglycan were compared in multi-scratch wounded and confluent cultures of bovine aortic endothelial cells to determine whether proteoglycan synthesis is altered as cells are stimulated to migrate and proliferate. Incorporation was found to be stimulated in a time-dependent manner, reaching maximal levels 44-50 h after wounding, as cells migrated into wounded areas of the culture dish. Quantitative autoradiography of 35S- sulfate-labeled single-s...

  16. Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex.

    Crandall, James E; McCarthy, Deirdre M; Araki, Kiyomi Y; Sims, John R; Ren, Jia-Qian; Bhide, Pradeep G

    2007-04-01

    GABA neurons of the cerebral cortex and other telencephalic structures are produced in the basal forebrain and migrate to their final destinations during the embryonic period. The embryonic basal forebrain is enriched in dopamine and its receptors, creating a favorable environment for dopamine to influence GABA neuron migration. However, whether dopamine receptor activation can influence GABA neuron migration is not known. We show that dopamine D1 receptor activation promotes and D2 receptor activation decreases GABA neuron migration from the medial and caudal ganglionic eminences to the cerebral cortex in slice preparations of embryonic mouse forebrain. Slice preparations from D1 or D2 receptor knock-out mouse embryos confirm the findings. In addition, D1 receptor electroporation into cells of the basal forebrain and pharmacological activation of the receptor promote migration of the electroporated cells to the cerebral cortex. Analysis of GABA neuron numbers in the cerebral wall of the dopamine receptor knock-out mouse embryos further confirmed the effects of dopamine receptor activation on GABA neuron migration. Finally, dopamine receptor activation mobilizes striatal neuronal cytoskeleton in a manner consistent with the effects on neuronal migration. These data show that impairing the physiological balance between D1 and D2 receptors can alter GABA neuron migration from the basal forebrain to the cerebral cortex. The intimate relationship between dopamine and GABA neuron development revealed here may offer novel insights into developmental disorders such as schizophrenia, attention deficit or autism, and fetal cocaine exposure, all of which are associated with dopamine and GABA imbalance. PMID:17409246

  17. Modulation of p75 neurotrophin receptor under hypoxic conditions induces migration and invasion of C6 glioma cells.

    Wang, Ting-Chung; Luo, Sheng-Jie; Lin, Chun-Liang; Chang, Pey-Jium; Chen, Miao-Fen

    2015-01-01

    p75 neurotrophin receptor (p75NTR) has been reported to play important roles in various cancer types. However, the exact mechanism of tumorigenesis involving p75NTR is unknown. In this study, we investigated the relationship between the expression of p75NTR in malignant glioma and the impact on tumor cell migration and invasion. p75NTR and hypoxia-inducible factor-1α (HIF-1α) expression was down-regulated by short-hairpin RNA and up-regulated with expression vectors. By immunohistochemical staining and Western blot analysis, we found that p75NTR was expressed in both human and rat malignant gliomas. Knockdown of p75NTR increased the expression of vimentin, vascular endothelial growth factor, Matrix metalloproteinase 9, and TWIST, and enhanced the invasion and migration abilities assessed by transwell assay in the C6 tumor cells. Inverse expressions of p75NTR and HIF-1α were detected in glioma cell lines under hypoxic conditions, while increased HIF-1α significantly downregulated the expression of p75NTR, suggesting a HIF-1α-p75NTR-EMT pathway that may regulate glioma cells invasion and migration. Downregulation of p75NTR increased phosphorylation of Src, focal adhesion kinase (FAK) and paxillin. Knockdown of p75NTR also dysregulated β-catenin-mediated cell junctions, and up-regulated the expressions of fibronectin and L1CAM in the cell-cell junctions, thus suggesting that p75NTR knockdown contributed to a more aggressive migration phenotype via FAK signaling pathway. Our studies suggested that modulation of p75NTR under hypoxic condition could enhance C6 cells migration and invasion by induction of EMT, and activation of the FAK pathway. The HIF-1α-p75NTR-EMT axis may play a central role in glioma tumorigenesis. PMID:25527128

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

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

    2009-01-01

    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.

  19. Modulation of cell adhesion and migration by the histone methyltransferase subunit mDpy-30 and its interacting proteins.

    Bin Xia

    Full Text Available We have previously shown that a subset of mDpy-30, an accessory subunit of the nuclear histone H3 lysine 4 methyltransferase (H3K4MT complex, also localizes at the trans-Golgi network (TGN, where its recruitment is mediated by the TGN-localized ARF guanine nucleotide exchange factor (ArfGEF BIG1. Depletion of mDpy-30 inhibits the endosome-to-TGN transport of internalized CIMPR receptors and concurrently promotes their accumulation at the cell protrusion. These observations suggest mDpy-30 may play a novel role at the crossroads of endosomal trafficking, nuclear transcription and adhesion/migration. Here we provide novel mechanistic and functional insight into this association. First, we demonstrate a direct interaction between mDpy-30 and BIG1 and locate the binding region in the N-terminus of BIG1. Second, we provide evidence that the depletion or overexpression of mDpy-30 enhances or inhibits cellular adhesion/migration of glioma cells in vitro, respectively. A similar increase in cell adhesion/migration is observed in cells with reduced levels of BIG1 or other H3K4MT subunits. Third, knockdown of mDpy-30, BIG1, or the RbBP5 H3K4MT subunit increases the targeting of beta1 integrin to cell protrusions, and suppression of H3K4MT activity by depleting mDpy-30 or RbBP5 leads to increased protein and mRNA levels of beta1 integrin. Moreover, stimulation of cell adhesion/migration via mDpy-30 knockdown is abolished after treating cells with a function-blocking antibody to beta1 integrin. Taken together, these data indicate that mDpy-30 and its interacting proteins function as a novel class of cellular adhesion/migration modulators partially by affecting the subcellular distribution of endosomal compartments as well as the expression of key adhesion/migration proteins such as beta1 integrin.

  20. NEUROBIOLOGICAL MODULATORS OF ANXIETY

    Mohale Deepak S.

    2012-01-01

    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.

  1. Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor

    Ashcroft, Gillian S.; Stuart J. Mills; Lei, Kejian; Gibbons, Linda; Jeong, Moon-Jin; Taniguchi, Marisu; Burow, Matthew; Horan, Michael A.; Wahl, Sharon M.; Nakayama, Toshinori

    2003-01-01

    Characteristic of both chronic wounds and acute wounds that fail to heal are excessive leukocytosis and reduced matrix deposition. Estrogen is a major regulator of wound repair that can reverse age-related impaired wound healing in human and animal models, characterized by a dampened inflammatory response and increased matrix deposited at the wound site. Macrophage migration inhibitory factor (MIF) is a candidate proinflammatory cytokine involved in the hormonal regulation of inflammation. We...

  2. Breast tumor kinase BRK requires kinesin-2 subunit KAP3A in modulation of cell migration.

    Lukong, Kiven E; Richard, Stéphane

    2008-02-01

    BReast tumor Kinase (BRK) also known as protein kinase 6 (PTK6) is a nonreceptor tyrosine kinase overexpressed in the majority of human breast tumors. Although some studies have implicated BRK in signalling, cell proliferation and migration, the precise intracellular role of BRK has not been fully elucidated. The RNA-binding protein Sam68, and adaptor proteins paxillin and STAT3 are the only BRK substrates that link BRK to signal transduction. To identify new BRK substrates, we screened high-density protein filter arrays by large-scale in vitro kinase assays using active recombinant BRK. We identified at least 4 BRK targets comprising the alpha-subunit of stimulatory guanine nucleotide binding protein (GNAS), FL139441, beta-tubulin and kinesin associated protein 3A (KAP3A) and validated them as BRK substrates using a secondary assay. Further characterization revealed that KAP3A is an in vivo substrate of BRK and associates with BRK in breast cancer cells. We show that BRK specifically phosphorylated tyrosine residues at the C-terminus of KAP3A and induces delocalization of KAP3A from punctate nuclear localization to a diffuse nucleo-cytoplasmic pattern. Functionally, we demonstrate that KAP3A knockdown results in suppression of BRK-induced migration of breast cancer cells and show that the C-terminal deletion mutant of KAP3A acts as a dominant negative in BRK-induced cell migration. Our findings therefore reveal new substrates of BRK and define KAP3A as a physiological substrate of BRK during cell migration. PMID:18077133

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

    Dionysia Lymperatou

    2013-01-01

    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. The Wnt gatekeeper SFRP4 modulates EMT, cell migration and downstream Wnt signalling in serous ovarian cancer cells.

    Caroline E Ford

    Full Text Available Aberrant Wnt signalling is implicated in numerous human cancers, and understanding the effects of modulation of pathway members may lead to the development of novel therapeutics. Expression of secreted frizzled related protein 4 (SFRP4, an extracellular modulator of the Wnt signalling pathway, is progressively lost in more aggressive ovarian cancer phenotypes. Here we show that recombinant SFRP4 (rSFRP4 treatment of a serous ovarian cancer cell line results in inhibition of β-catenin dependent Wnt signalling as measured by TOP/FOP Wnt reporter assay and decreased transcription of Wnt target genes, Axin2, CyclinD1 and Myc. In addition, rSFRP4 treatment significantly increased the ability of ovarian cancer cells to adhere to collagen and fibronectin, and decreased their ability to migrate across an inflicted wound. We conclude that these changes in cell behaviour may be mediated via mesenchymal to epithelial transition (MET, as rSFRP4 treatment also resulted in increased expression of the epithelial marker E-cadherin, and reduced expression of Vimentin and Twist. Combined, these results indicate that modulation of a single upstream gatekeeper of Wnt signalling can have effects on downstream Wnt signalling and ovarian cancer cell behaviour, as mediated through epithelial to mesenchymal plasticity (EMP. This raises the possibility that SFRP4 may be used both diagnostically and therapeutically in epithelial ovarian cancer.

  5. TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration.

    Adrien Rousseau

    2013-12-01

    Full Text Available Tumor necrosis factor (TNF receptor-associated factor 4 (TRAF4 is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs in normal mammary epithelial cells (MECs, it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6 is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration.

  6. Transmembrane collagen XVII modulates integrin dependent keratinocyte migration via PI3K/Rac1 signaling.

    Stefanie Löffek

    Full Text Available The hemidesmosomal transmembrane component collagen XVII (ColXVII plays an important role in the anchorage of the epidermis to the underlying basement membrane. However, this adhesion protein seems to be also involved in the regulation of keratinocyte migration, since its expression in these cells is strongly elevated during reepithelialization of acute wounds and in the invasive front of squamous cell carcinoma, while its absence in ColXVII-deficient keratinocytes leads to altered cell motility. Using a genetic model of murine Col17a1⁻/⁻ keratinocytes we elucidated ColXVII mediated signaling pathways in cell adhesion and migration. Col17a1⁻/⁻ keratinocytes exhibited increased spreading on laminin 332 and accelerated, but less directed cell motility. These effects were accompanied by increased expression of the integrin subunits β4 and β1. The migratory phenotype, as evidenced by formation of multiple unstable lamellipodia, was associated with enhanced phosphoinositide 3-kinase (PI3K activity. Dissection of the signaling pathway uncovered enhanced phosphorylation of the β4 integrin subunit and the focal adhesion kinase (FAK as activators of PI3K. This resulted in elevated Rac1 activity as a downstream consequence. These results provide mechanistic evidence that ColXVII coordinates keratinocyte adhesion and directed motility by interfering integrin dependent PI3K activation and by stabilizing lamellipodia at the leading edge of reepithelializing wounds and in invasive squamous cell carcinoma.

  7. Plasminogen N-terminal activation peptide modulates the activity of angiostatin-related peptides on endothelial cell proliferation and migration.

    Hayashi, Moyuru; Tamura, Yosuke; Dohmae, Naoshi; Kojima, Soichi; Shimonaka, Motoyuki

    2008-05-01

    Angiostatin, a potent inhibitor of angiogenesis, is derived from the fibrinolytic proenzyme, plasminogen, by enzymatic processing. Plasminogen N-terminal activation peptide (PAP) is one of the products concomitantly released aside from angiostatin (kringles 1-4) and mini-plasminogen (kringle 5 plus the catalytic domain) when plasminogen is processed. To determine whether PAP alone or together with the angiostatin-related peptides derived from the processing of plasminogen modulate the proliferation and motility of endothelial cells, we have generated a recombinant PAP and used it to study its effects on endothelial cells in the presence and absence of the angiostatin-related peptides. Our results showed that PAP alone slightly increased the migration but not the proliferation of endothelial cells. However, in the presence of the angiostatin-related peptides, PAP attenuated the inhibitory activity of the angiostatin-related peptides on the proliferation and migration of endothelial cells. The inhibitory effect of PAP on the angiostatin-related peptides could be due to its binding to the kringle domains of the latter peptides. PMID:18294956

  8. Plasminogen N-terminal activation peptide modulates the activity of angiostatin-related peptides on endothelial cell proliferation and migration

    Angiostatin, a potent inhibitor of angiogenesis, is derived from the fibrinolytic proenzyme, plasminogen, by enzymatic processing. Plasminogen N-terminal activation peptide (PAP) is one of the products concomitantly released aside from angiostatin (kringles 1-4) and mini-plasminogen (kringle 5 plus the catalytic domain) when plasminogen is processed. To determine whether PAP alone or together with the angiostatin-related peptides derived from the processing of plasminogen modulate the proliferation and motility of endothelial cells, we have generated a recombinant PAP and used it to study its effects on endothelial cells in the presence and absence of the angiostatin-related peptides. Our results showed that PAP alone slightly increased the migration but not the proliferation of endothelial cells. However, in the presence of the angiostatin-related peptides, PAP attenuated the inhibitory activity of the angiostatin-related peptides on the proliferation and migration of endothelial cells. The inhibitory effect of PAP on the angiostatin-related peptides could be due to its binding to the kringle domains of the latter peptides

  9. Understanding attitudes to immigration: The migration and minority module of the first European Social Survey

    Card, D.; Dustmann, C.; Preston, I

    2005-01-01

    Immigration control is an issue that figures prominently in public policy discussions and election campaigns throughout Europe. Although immigration may have positive effects on economic efficiency and growth in the receiving economy, it is often the negative aspects -or perceived negative aspects - of immigration that attract the most attention. In this paper, we use the immigration module of the European Social Survey (ESS), which we developed in collaboration with the ESS survey team, to i...

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

    Yan QY

    2016-03-01

    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

  11. Cell proliferation and migration are modulated by Cdk-1-phosphorylated endothelial-monocyte activating polypeptide II.

    Margaret A Schwarz

    Full Text Available BACKGROUND: Endothelial-Monocyte Activating Polypeptide (EMAP II is a secreted protein with well-established anti-angiogenic activities. Intracellular EMAP II expression is increased during fetal development at epithelial/mesenchymal boundaries and in pathophysiologic fibroproliferative cells of bronchopulmonary dysplasia, emphysema, and scar fibroblast tissue following myocardial ischemia. Precise function and regulation of intracellular EMAP II, however, has not been explored to date. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that high intracellular EMAP II suppresses cellular proliferation by slowing progression through the G2M cell cycle transition in epithelium and fibroblast. Furthermore, EMAP II binds to and is phosphorylated by Cdk1, and exhibits nuclear/cytoplasmic partitioning, with only nuclear EMAP II being phosphorylated. We observed that extracellular secreted EMAP II induces endothelial cell apoptosis, where as excess intracellular EMAP II facilitates epithelial and fibroblast cells migration. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that EMAP II has specific intracellular effects, and that this intracellular function appears to antagonize its extracellular anti-angiogenic effects during fetal development and pulmonary disease progression.

  12. Sulfated proteoglycans as modulators of neuronal migration and axonal decussation in the developing midbrain

    L.A. Cavalcante

    2003-08-01

    Full Text Available Proteoglycans are abundant in the developing brain and there is much circumstantial evidence for their roles in directional neuronal movements such as cell body migration and axonal growth. We have developed an in vitro model of astrocyte cultures of the lateral and medial sectors of the embryonic mouse midbrain, that differ in their ability to support neuritic growth of young midbrain neurons, and we have searched for the role of interactive proteins and proteoglycans in this model. Neurite production in co-cultures reveals that, irrespective of the previous location of neurons in the midbrain, medial astrocytes exert an inhibitory or nonpermissive effect on neuritic growth that is correlated to a higher content of both heparan and chondroitin sulfates (HS and CS. Treatment of astrocytes with chondroitinase ABC revealed a growth-promoting effect of CS on lateral glia but treatment with exogenous CS-4 indicated a U-shaped dose-response curve for CS. In contrast, the growth-inhibitory action of medial astrocytes was reversed by exogenous CS-4. Treatment of astrocytes with heparitinase indicated that the growth-inhibitory action of medial astrocytes may depend heavily on HS by an as yet unknown mechanism. The results are discussed in terms of available knowledge on the binding of HS proteoglycans to interactive proteins, with emphasis on the importance of unraveling the physiological functions of glial glycoconjugates for a better understanding of neuron-glial interactions.

  13. A Leishmania Ortholog of Macrophage Migration Inhibitory Factor Modulates Host Macrophage Responses

    Kamir,D.; Zierow, S.; Leng, L.; Cho, Y.; Diaz, Y.; Griffith, J.; McDonald, C.; Merk, M.; Mitchell, R.; et al

    2008-01-01

    Parasitic organisms have evolved specialized strategies to evade immune defense mechanisms. We describe herein an ortholog of the cytokine, macrophage migration inhibitory factor (MIF), which is produced by the obligate intracellular parasite, Leishmania major. The Leishmania MIF protein, Lm1740MIF, shows significant structural homology with human MIF as revealed by a high-resolution x-ray crystal structure (1.03 A). Differences between the two proteins in the N-terminal tautomerization site are evident, and we provide evidence for the selective, species-specific inhibition of MIF by small-molecule antagonists that target this site. Lm1740MIF shows significant binding interaction with the MIF receptor, CD74 (K(d) = 2.9 x 10(-8) M). Like its mammalian counterpart, Lm1740MIF induces ERK1/2 MAP kinase activation in a CD74-dependent manner and inhibits the activation-induced apoptosis of macrophages. The ability of Lm1740MIF to inhibit apoptosis may facilitate the persistence of Leishmania within the macrophage and contribute to its evasion from immune destruction.

  14. Light Emitting Diode-Generated Blue Light Modulates Fibrosis Characteristics: Fibroblast Proliferation, Migration Speed, and Reactive Oxygen Species Generation

    Mamalis, Andrew; Garcha, Manveer; Jagdeo, Jared

    2016-01-01

    Background and Objective Blue light is part of the visible light spectrum that does not generate harmful DNA adducts associated with skin cancer and photoaging, and may represent a safer therapeutic modality for treatment of keloid scars and other fibrotic skin diseases. Our laboratory previously demonstrated that light-emitting diode (LED) red and infrared light inhibits proliferation of skin fibroblasts. Moreover, different wavelengths of light can produce different biological effects. Furthermore, the effects of LED blue light (LED-BL) on human skin fibroblasts are not well characterized. This study investigated the effects of LED-BL on human skin fibroblast proliferation, viability, migration speed, and reactive oxygen-species (ROS) generation. Methods and Materials Irradiation of adult human skin fibroblasts using commercially-available LED-BL panels was performed in vitro, and modulation of proliferation and viability was quantified using the trypan blue dye exclusion assay, migratory speed was assessed using time-lapse video microscopy, and intracellular ROS generation was measured using the dihydrorhodamine flow cytometry assay. Statistical differences between groups were determined by ANOVA and Student s t-test. Results Human skin fibroblasts treated with LED-BL fluences of 5, 30, 45, and 80 J/cm2 demonstrated statistically significant dose-dependent decreases in relative proliferation of 8.4%, 29.1%, 33.8%, 51.7%, and 55.1%, respectively, compared to temperature and environment matched bench control plates, respectively. LED-BL fluences of 5, 30, 45 and 80 J/cm2 decreased fibroblast migration speed to 95 ± 7.0% (p = 0.64), 81.3 ± 5.5% (p = 0.021), 48.5 ± 2.7% (p migration speed, and is associated with increased reactive oxygen species generation in a dose-dependent manner without altering viability. LED-BL has the potential to contribute to the treatment of keloids and other fibrotic skin diseases and is worthy of further translational and clinical

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

    Gadelha, H.

    2010-05-12

    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.

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

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

    2016-08-01

    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

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

    2015-01-01

    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. 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

    陆征宇; 赵虹; 陈洁; 程波; 宗蕾

    2011-01-01

    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.

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

    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.

  20. 5-Hydroxytryptamine 4 Receptor in the Endothelial Cells

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

    2006-01-01

    central nervous system (CNS). We have recently demonstrated that 5-HT4 receptor couples to G13 protein to induce RhoA-dependent gene transcription, neurite retraction, and neuronal cell rounding (Ponimaskin et al, 2002). Although multiple studies were focused on the function of the 5-HT4 receptor in the...

  1. 5-Hydroxytryptamine3 receptor antagonists and cardiac side effects

    Brygger, Louise; Herrstedt, Jørn

    2014-01-01

    clinical trials. Furthermore, polypharmacy is frequent and drug-drug interactions between chemotherapy and other QTc-prolonging drugs may influence the pharmacokinetics and pharmacodynamics of the 5-HT3-RAs. During the next 10 - 15 years a huge increase in the number of cancer patients is expected...

  2. Ganglioside GM2 mediates migration of tumor cells by interacting with integrin and modulating the downstream signaling pathway.

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

    2016-07-01

    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. PMID:27066976

  3. miR-194 targets RBX1 gene to modulate proliferation and migration of gastric cancer cells.

    Chen, Xiaonan; Wang, Yuanyuan; Zang, Wenqiao; Du, Yuwen; Li, Min; Zhao, Guoqiang

    2015-04-01

    RING box protein1 (RBX1), an essential component of SCF E3 ubiquitin ligases, plays an important role in gastric cancer. In the study, miR-194 and RBX1 expression was evaluated in 76 pairs of gastric tumor and non-tumor tissue samples by qRT-PCR, and clinicopathological characteristics were analyzed. CCK8, transwell assay, wound healing assay, and flow cytometry assay were performed to evaluate the effect of miR-194 on gastric cancer (GC) cellular proliferation, invasion, migration, apoptosis, and cell cycle, respectively. Luciferase reporter assays and Western blotting were used to evaluate whether RBX1 is a direct target of miR-194. The Kaplan-Meier method and log-rank test were used to evaluate the correlation between miR-194 or RBX1 expression and patient survival. Then, we found that miR-194 was significantly downregulated and RBX1 upregulated in GC tissues; both of which showed significant association with tumor size, location, invasion, and tumor node metastasis. Cell proliferation, invasion, and migration were significantly restricted with miR-194 overexpression. miR-194 downregulated RBX1 protein expression, and luciferase assays showed that binding sites in the RBX1 3'UTR were required for miR-194-mediated repression of RBX1, indicating that RBX1 was a direct target of miR-194. Transfection of RBX1 without the 3'UTR restored the miR-194-inhibiting migration function. miR-194 overexpression or RBX1 lowexpression was associated with prolonged survival of GC patients. In conclusion, upregulation of miR-194 can inhibit proliferation, migration, and invasion of GC cells, possibly by targeting RBX1. Aberrant expression of miR-194 and RBX1 is correlated to GC patient survival time. PMID:25412959

  4. 脊髓损伤亚急性期移植神经干细胞:损伤脊髓5-羟色胺的表达%Neural stem cells transplantation in subacute stage of spinal cord injury: Expression of 5-hydroxytryptamine injured spinal cord

    巴迎春; 唐建中; 范艳; 李仲铭; 王金德; 王廷华

    2012-01-01

    背景:5-羟色胺能纤维可以作为评价脊髓损伤后再生的指标之一.目的:观察神经干细胞在脊髓损伤的亚急性期(第7天)脊髓内移植对大鼠受损伤脊髓再生修复的影响.方法:将正常成年SD雌性大鼠分为3组,单纯脊髓全横断组、假手术组(仅仅打开椎板,但不横断脊髓)、神经干细胞移植组.神经干细胞移植组在脊髓全横断后第7天时进行神经干细胞移植,其他两组不移植神经干细胞.结果与结论:神经干细胞移植组瘢痕上1至2节段5-羟色胺的阳性纤维数量多于单纯脊髓全横断组.提示神经干细胞亚急性期移植能部分促进脊髓损伤后脊髓神经的再生.%BACKGROUND: 5-hydroxytryptamine (5-HT) serotonergic fibers are evaluated as one of regenerative indice after spinal cord injury.OBJECTIVE: To study effects of neural stem cells (NSCs) transplantation on the recovery of the rats injured spinal cord in subacute stage (on the 7th day).METHODS: The normal adult SD female rats were divided into 3 groups: merely spinal cord transection group, sham operation group (just opened the lamina, but not transected the spinal cord), NSCs transplantation group. NSCs transplantation group was performed on the 7th day after spinal cord transection, the other two groups were not performed with transplantation.RESULTS AND CONCLUSION: In 1-2 segments above scar of spinal cord, the number of 5-HT positive fibers in NSCs transplantation group was more than that in merely spinal cord transection group. It indicates that NSCs transplantation group in subacute stage can promote the nerve regeneration after spinal cord injury.

  5. MicroRNA-193b modulates proliferation, migration, and invasion of non-small cell lung cancer cells

    Huajun Hu; Shangao Li; Jun Liu; Bin Ni

    2012-01-01

    MicroRNAs have been reported to be closely related to the development of human lung cancers.However,the functions of microRNAs in non-small cell lung cancer (NSCLC) remain largely undefined.Here,we investigated the role of microRNA-193b (miR-193b) in NSCLC.Our data showed that miR-193b was markedly down-regulated in NSCLC cancer tissues compared with adjacent normal tissues.The NSCLC cell line (A549) transfected with the miR-193b exhibited significantly decreased proliferation,migration,and invasion capacities when compared with the control cells.In contrast,inhibition of miR-193bincreased the proliferation,migration,and invasion of A549 cells.Moreover,miR-193b repressed the expressions of cyclin D1 and urokinase-type plasminogen activator in A549 cells.These data suggest that miR-193b is a tumor suppressor in NSCLC.

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

    Cheng Cui

    2013-11-01

    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

  7. Three-dimensional matrix fiber alignment modulates cell migration and MT1-MMP utility by spatially and temporally directing protrusions

    Fraley, Stephanie I.; Wu, Pei-Hsun; He, Lijuan; Feng, Yunfeng; Krisnamurthy, Ranjini; Longmore, Gregory D.; Wirtz, Denis

    2015-10-01

    Multiple attributes of the three-dimensional (3D) extracellular matrix (ECM) have been independently implicated as regulators of cell motility, including pore size, crosslink density, structural organization, and stiffness. However, these parameters cannot be independently varied within a complex 3D ECM protein network. We present an integrated, quantitative study of these parameters across a broad range of complex matrix configurations using self-assembling 3D collagen and show how each parameter relates to the others and to cell motility. Increasing collagen density resulted in a decrease and then an increase in both pore size and fiber alignment, which both correlated significantly with cell motility but not bulk matrix stiffness within the range tested. However, using the crosslinking enzyme Transglutaminase II to alter microstructure independently of density revealed that motility is most significantly predicted by fiber alignment. Cellular protrusion rate, protrusion orientation, speed of migration, and invasion distance showed coupled biphasic responses to increasing collagen density not predicted by 2D models or by stiffness, but instead by fiber alignment. The requirement of matrix metalloproteinase (MMP) activity was also observed to depend on microstructure, and a threshold of MMP utility was identified. Our results suggest that fiber topography guides protrusions and thereby MMP activity and motility.

  8. 金丝桃素对抑郁大鼠行为及脑内5-羟色胺和去甲肾上腺素表达的影响%Effects of hypericin on behavior and brain 5-hydroxytryptamine and noradrenalin expression in rats with depression

    司银楚; 孙建宁; 谢春娥

    2004-01-01

    目的:研究贯叶连翘提取物对抑郁大鼠行为学及脑内5-羟色胺、去甲肾上腺素(noradrenaline,NA)表达的影响.方法:选用雄性Wistar大鼠72只.制作大鼠慢性应激抑郁模型,应用敞箱法、跳台法、免疫组织化学染色研究贯叶连翘提取物对抑郁大鼠行为学、脑病理学的影响.结果:慢性应激抑郁大鼠的走格数与站立数显著少于对照组(P<0.01),贯叶连翘提取物150.0,75.0 mg/kg组大鼠走格数与站立数明显多于模型组(P<0.05,P<0.01);贯叶连翘提取物37.5 mg/kg组大鼠走格数(27±14)明显多于模型组(18±5)(P<0.05).慢性应激抑郁大鼠跳台行为学出现明显变化,表现为逃避反应的获得欠缺而停留期显著延长(P<0.05),贯叶连翘提取物150.0,75.0mg/kg组大鼠错误反应的停留期明显少于模型大鼠(P<0.05).5-羟色胺、NA在贯叶连翘提取物150.0,75.0 mg/kg组大鼠脑内的表达明显强于模型组(P<0.01).结论:贯叶连翘提取物通过增强抑郁大鼠脑内5-羟色胺、NA表达,改善抑郁症状.%AIM: To study the effects of hypericin on the behavior and expressions of5-hydroxytryptamine(5-HT), noradrenaline(NA) in the brain of rats withdepression.METHODS: Totally 72 male Wistar rats were selected in this experiment toestablish models of chronic stress-induced depression. Open-field test,step-down avoidance test and immunohistochemstry staining were employedto study the effects of the extract of the fruit of Hyperieum perforatum(EFHP) on praxiology and cerebral pathology in the rat models.RESULTS: In open-field test, the number of crossing and rearing was sig-nificantly lower in chronic stress-induced depression rats than the control rats( P < 0. 01). At the doses of 150.0 and 75.0 mg/kg, EFHP increased thenumber of crossing and rearing( P < 0. 05 and P < 0.01, respectively) incomparison with the model group; at the dose of 37.5 mg/kg, EFHP in-creased the number of crossings to 27 ± 14

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

    Likui Wang

    2014-09-01

    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.

  10. ZIC1 modulates cell-cycle distributions and cell migration through regulation of sonic hedgehog, PI3K and MAPK signaling pathways in gastric cancer

    ZIC1, a vital transcription factor with zinc finger domains, has been implicated in the process of neural development. We previously showed that ZIC1 may function as a tumour suppressor in gastrointestinal cancers. However, the molecular mechanism underlying ZIC1 participation in tumour progression remains unknown. The role of ZIC1 on cell proliferation and migration was examined. The regulation of sonic hedgehog (Shh), phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways after ectopic expression of ZIC1 in gastric cancer cells were evaluated. Overexpression of ZIC1 contributes to the inhibition of cell proliferation migration and cell-cycle distribution in gastric cancer. The modulation of G1/S checkpoint by ZIC1 is mainly mediated through the regulation of cyclin-dependent kinases (p21 Waf1/Cip1, p27 Kip1 and cyclin D1). In addition, ZIC1 can inactivate the level of phospholated Akt and Erk1/2, and transcriptionally regulate sonic hedgehog (Shh) signaling, thus leading to regulate the expression of p21 Waf1/Cip1 and cyclin D1. Finally, we have systemically identified ZIC1 downstream targets by cDNA microarray analysis and revealed that 132 genes are down-regulated and 66 genes are up-regulated after transfection with ZIC1 in gastric cancer cells. These candidate genes play critical roles in cell proliferation, cell cycle and cell motility. Overexpression of ZIC1 results in inactivation of Shh, PI3K and MAPK signaling pathways, as well as regulation of multiple downstream targets which are essential for the development and progression of gastric cancer. ZIC1 serves as a potential therapeutic target for gastric cancer

  11. 周围血5-羟色胺与手传振动接触水平及末梢血管损伤的相关性%Correlation of Peripheral Blood 5-Hydroxytryptamine with Hand-Arm Vibration Exposure and Peripheral Vascular Damage

    郎丽; 林瀚生; 陈青松; 肖斌; 曾繁松

    2016-01-01

    [Objective] To explore the correlation of peripheral blood 5-hydroxytryptamine (5-HT) levels with vibration exposure levels and peripheral vascular damage in hand-ann vibration exposed workers.[Methods] Seventy-seven workers exposed to hand-ann vibration from a sports equipment manufacturing company in Guangdong were selected for this study.General information,upper limb symptoms,and vibration-induced white finger (VWF) of the workers were collected by questionnaire.Cumulative vibration exposure level (CVEL) was calculated through on-site tested hand-ann vibration levels of the selected workers.Level of 5-HT in peripheral blood was detected by enzyme-linked immunosorbent assay.Cool water loading test (CWLT) was also conducted for the workers.The association of 5-HT level with hand-arm vibration exposure level and peripheral vascular damage was analyzed using binary non-conditional logistic regression models.[Results] The high CVEL group showed a higher 5-HT level than the low CVEL group (z=-2.352,P=0.034).The 5-HT level in the abnormal CWLT group was much higher than that in the normal CWLT group (z=-3.211,P=0.001).After adjusted for age,smoking,and drinking,according to the logistic regression model,5-HT level was associated with CVEL and CWLT:ORs (95%CIs) were 3.17 (1.12,8.94) for high CVEL vs.low CVEL and 7.34 (1.44,37.30) for abnormal CWLT vs.normal CWLT.The 5-HT level was not correlated with VWF results with OR (95%CI) as 1.92 (0.74,5.00).[Conclusion] The results suggests that hand-arm vibration exposure might result in elevated 5-HT levels,and the level of 5-HT correlates to vibration exposure level or hand peripheral vascular damage degree.%[目的]研究手传振动接触工人周围血5-羟色胺水平与振动接触水平及末梢血管损伤的相关性. [方法]选取广东某运动器材厂77名手传振动作业工人作为研究对象,对其进行问卷调查了解一般情况、手臂自觉症状、是否出现振动性白指(VWF)等;现场检

  12. 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

    高雪屏; 苏林雁; 谢光荣; 黄春香; 李雪荣

    2005-01-01

    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

  13. 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

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

    2005-01-01

    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

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

    Yamashita Shunichi

    2011-03-01

    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

  15. 慢性锰中毒大鼠5-羟色胺、脑源性营养因子的表达变化%Expression changes of 5-hydroxytryptamine and brain-derived neurotrophic factor in rats with chronic manganism

    黄婉媚; 王进; 黄坚毅; 庞霖霖

    2015-01-01

    Objective To observe the expression changes of 5-hydroxytryptamine (5-HT),brainderived neurotrophic factor (BDNF) in rats with chronic manganism.Methods Sixty healthy male Sprague-Dawley rats were randomly divided into control group (n =15) and experimental group (n =45).The experimental group was divided into three subgroups:low-dose group (n =15),middle-dose group (n =15),high-dose group (n =15).The rats in control group were given intraperitoneal injection of normal saline while the rats in low-dose group,middle-dose group,high-dose group were given intraperitoneal injection of 5 mg/kg,15 mg/kg and 25 mg/kg manganese chloride tetrahydrate,respectively for 5 days oncea week and lasted for 12 weeks.The depressive behavior changes of rats were observed by sucrose preference test and open field test.The concentrations of manganese in the striatum of rats were detected by inductively coupled plasma-atomic emission spectrometry.The expression of 5-HT in frontal cortex,hippocampus of rats was determined by high performance liquid chromatography.The expression of BDNF in frontal cortex,hippocampus of rats was examined by Western blotting.The expression of BDNF mRNA was detected using real-time fluorescence quantitative polymerase chain reaction.Results The chronic manganese poisoning rats presented depression-like behavior based on the sucrose preference test and open field test,which was more distinct in high-dose rats.As compared with the control group (frontal cortex (459.65 ± 16.81) ng/g,hippocampus (323.92 ± 17.41) ng/g;tissue wet weight),the expressions of 5-HT were significantly decreased in frontal cortex ((423.45 ± 17.19) ng/g,(376.89 ± 18.87) ng/g,(280.17 ± 25.46) ng/g),hippocampus ((265.71 ± 17.89) ng/g,(214.35 ±23.63) ng/g,(172.67 ± 18.24) ng/g) of the experimental group (F =132.68,69.66,both P < 0.05).As compared with the control group (frontal cortex 0.962 ±0.111,hippocampus 0.873 ± 0.101;the expressions of BDNF were significantly decreased in

  16. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

    Muki S Shey

    Full Text Available HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β or agonists for TLR4 (LPS, TLR2/1 (PAM3 and TLR7/8 (R848. Migration (frequency and activation (HLA-DR expression of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833. There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77. Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

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

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

    2016-01-01

    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. PMID:27294913

  18. 缬草对慢性应激导致的抑郁大鼠大脑海马5-羟色胺水平、细胞增殖及神经元数量的影响%Effects of Valerian on the level of 5-hydroxytryptamine, cell proliferation and neurons in cerebral hippocampus of rats with depression induced by chronic mild stress

    唐久余; 曾园山; 陈巧格; 秦雅静; 陈穗君; 钟志强

    2008-01-01

    目的:探讨缬草对慢性应激导致的抑郁大鼠大脑海马5-羟色胺(5-hydroxytryptamine,5-HT)水平、细胞增殖及神经元数量的影响.方法:70只大鼠被分成正常对照组、未用药模型组、阴性对照模型组、阳性对照模型组和低、中、高剂量缬草治疗组,每组10只.除正常对照组外,给予其余6组大鼠4周慢性应激建立抑郁症模型.除未用药模型组大鼠正常饲养外,其余6组大鼠在模型建立后分别灌服5%羧甲基纤维素钠、氟西汀以及低、中、高剂量缬草,灌药周期均为3周.灌药结束后,体内注射5-溴脱氧尿嘧啶核苷(bromodeoxyuridine,BrdU)标记海马增殖细胞,应用高效液相色谱法检测海马组织5-羟色胺水平,采用形态计量学方法计数海马神经元数量.结果:与正常对照组比较,低、中剂量缬草治疗组的海马5-HT含量增加,并恢复至正常水平.灌服低剂量缬草3周后,抑郁大鼠海马BrdU阳性细胞数目和神经元数量恢复性增加至正常对照组大鼠的水平.结论:小剂量缬草能够促进抑郁大鼠大脑海马5-HT水平及细胞增殖数量恢复至正常状况,同时具有保护海马受损伤神经元的作用.

  19. Medical migration.

    Loefler, I J

    2001-10-01

    The issue of professional migration, however emotional it may have become, ought not to be regarded in moralizing terms. The history of western medicine is the history of migrating physicians. A doctor who moves from a locality to another to take up a new assignment there cannot be said to have "abandoned his patients". This emotional bond has become the victim of specialization and of depersonalization of medical services and not of medical migration, brain drain or otherwise. The primary reason for medical migration is not financial; the desire to migrate usually begins with the desire to learn. Professionals crave in the first line for professional satisfaction. The migration of medical manpower cannot be stopped with administrative measures and will not be stopped by exhortations and appeals, moralization and condemnations. Brain drain is a global phenomenon and has always been so. A country which loses its professionals, its doctors, should examine the social relationships within the profession and should investigate whether the opportunities for deriving professional satisfaction from everyday work exist or whether these have been thwarted by the hierarchy, conservatism, cronyism and the general lack of comprehension of what good medical care is about. PMID:11593497

  20. Migration chemistry

    Migration chemistry, the influence of chemical -, biochemical - and physico-chemical reactions on the migration behaviour of pollutants in the environment, is an interplay between the actual natur of the pollutant and the characteristics of the environment, such as pH, redox conditions and organic matter content. The wide selection of possible pollutants in combination with varying geological media, as well as the operation of different chemical -, biochemical - and physico-chemical reactions compleactes the prediction of the influence of these processes on the mobility of pollutants. The report summarizes a wide range of potential pollutants in the terrestrial environment as well as a variety of chemical -, biochemical - and physico-chemical reactions, which can be expected to influence the migration behaviour, comprising diffusion, dispersion, convection, sorption/desorption, precipitation/dissolution, transformations/degradations, biochemical reactions and complex formation. The latter comprises the complexation of metal ions as well as non-polar organics to naturally occurring organic macromolecules. The influence of the single types of processes on the migration process is elucidated based on theoretical studies. The influence of chemical -, biochemical - and physico-chemical reactions on the migration behaviour is unambiguous, as the processes apparently control the transport of pollutants in the terrestrial environment. As the simple, conventional KD concept breaks down, it is suggested that the migration process should be described in terms of the alternative concepts chemical dispersion, average-elution-time and effective retention. (AB) (134 refs.)

  1. A novel microtubule-modulating agent EM011 inhibits angiogenesis by repressing the HIF-1α axis and disrupting cell polarity and migration

    Karna, Prasanthi; Rida, Padmashree C. G.; Turaga, Ravi Chakra; Gao, Jinmin; Gupta, Meenakshi; Fritz, Andreas; Werner, Erica; Yates, Clayton; Zhou, Jun; Aneja, Ritu

    2012-01-01

    Endothelial tubular morphogenesis relies on an exquisite interplay of microtubule dynamics and actin remodeling to propel directed cell migration. Recently, the dynamicity and integrity of microtubules have been implicated in the trafficking and efficient translation of the mRNA for HIF-1α (hypoxia-inducible factor), the master regulator of tumor angiogenesis. Thus, microtubule-disrupting agents that perturb the HIF-1α axis and neovascularization cascade are attractive anticancer drug candida...

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

    Kawakami Minoru

    2011-11-01

    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.

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

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

    1988-01-01

    cultured subconfluent cells actively synthesizing matrix. Endothelial cells express a 69-kD laminin-binding protein that is membrane associated and appears to colocalize with actin microfilaments. The topological distribution of 69 kD and its cytoskeletal associations can be modulated by the cell during...

  4. Monarch Migration.

    Williamson, Brad; Taylor, Orley

    1996-01-01

    Describes the Monarch Watch program that tracks the migration of the monarch butterfly. Presents activities that introduce students to research and international collaboration between students and researchers. Familiarizes students with monarchs, stimulates their interest, and helps them generate questions that can lead to good research projects.…

  5. AMPK-dependent signaling modulates the suppression of invasion and migration by fenofibrate in CAL 27 oral cancer cells through NF-κB pathway.

    Tsai, Shih-Chang; Tsai, Ming-Hsui; Chiu, Chang-Fang; Lu, Chi-Cheng; Kuo, Sheng-Chu; Chang, Nai-Wen; Yang, Jai-Sing

    2016-07-01

    Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist and lipid-lowering agent, has been used worldwide for treatment of hyperlipidemia. The clinical trials demonstrate that fenofibrate possesses multiple pharmacological activities, including antitumor effects. However, the precise mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we investigated the anticancer effects of fenofibrate on the migration and invasion of human oral cancer CAL 27 cells. Fenofibrate inhibited the cell migration and invasion of CAL 27 cells by the wound healing and Boyden chamber transwell assays, respectively. In addition, fenofibrate reduced the protein expressions of MMP-1, MMP-2, MMP-7, and MMP-9 by Western blotting and inhibited enzyme activities of MMP-2/-9 using gelatin zymography assay. Results from immunoblotting analysis showed that the proteins of p-LKB1 (Ser428), LKB1, p-AMPKα (Thr172), p-AMPKα1/α2 (Ser425/Ser491), p-AMPKβ1 (Ser108), and AMPKγ1 were upregulated by fenofibrate; the levels of p-IKKα/β (Ser176) and p-IκBα were reduced in fenofibrate-treated cells. Also, fenofibrate suppressed the expressions of nuclear NF-κB p65 and p50 by immunoblotting and NF-κB DNA binding activity by EMSA assay. The anti-invasive effect of fenofibrate was attenuated by compound C [an adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor] or dominant negative form of AMPK (DN-AMPKα1). Thus, fenofibrate considerably inhibited metastatic behaviors of CAL 27 cells might be mediated through blocking NF-κB signaling, resulting in the inhibition of MMPs; these effects were AMPK-dependent rather than PPARα signaling. Our findings provide a molecular rationale, whereby fenofibrate exerts anticancer effects and additional beneficial effects for the treatment of cancer patients. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 866-876, 2016. PMID:25545733

  6. Gideon's Migration

    Eagly, Ingrid

    2013-01-01

    For the past fifty years, immigration law has resisted integration of Gideon v.Wainwright’s legacy of appointed counsel for the poor. Today, however, this resistance has given way to Gideon’s migration. At the level of everyday practice, criminal defense attorneys appointed pursuant to Gideon now advise clients on the immigration consequences of convictions, negotiate “immigration safe” plea bargains, defend clients charged with immigration crimes, and, in some model programs, even represent ...

  7. A preference for migration

    Stark, Oded

    2007-01-01

    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...

  8. 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

    Hägg, Sara

    2009-12-04

    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

  9. 5-hydroxytryptamine and Lyme disease. Opportunity for a novel therapy to reduce the cerebellar tremor?

    Maximov, G K; Maximov, K G; Chokoeva, A A; Lotti, T; Wollina, U; Patterson, J W; Guarneri, C; Tana, C; Fioranelli, M; Roccia, M G; Kanazawa, N; Tchernev, G

    2016-01-01

    Lyme boreliosis is caused by the spirochete Borrelia burdorferi, which is transmitted by ticks. A 59 year-old woman developed pyrexia, strong headaches, ataxia, dysarthria and tremor of the limbs after a tick bite. She was unable to work and eat on her own. She was hospitalized three times and diagnosed with cerebellar intention tremor, cerebellar ataxia, dysarthria, bilateral horizontal gaze paralysis and a central lesion of the left facial nerve. There were no pyramidal, sensory or psychiatric disturbances. The brain MRI showed multifocal leucoencephalopathy with many hyperintense areas in both hemispheres, as well as in the left superior pedunculus cerebellaris. Diagnosis was confirmed by serologic examination. Treatment with cephtriaxone, doxycycline, methylprednisolone, cephixime and ciprofloxacine was administered without effect on the tremor, ataxia and horizontal gaze paralysis. Treatment was then administered with 5-hydroxytriptamine (5-HT) in increased doses. The result of the three-month treatment with 5-HT was a gradual diminution of the tremor and the ataxia and an increase in the ability to eat, walk and work independently. PMID:27373127

  10. Effect of two non tricyclic antidepressant drugs on [14C]5-hydroxytryptamine uptake by rat platelets

    The uptake of 14C-5-HT by rat blood platelets was examined in vitro in experimental conditions which allowed measurement of the initial velocity and excluded other passive processes across the cell membrane. In these conditions, the effect of two non tricyclic antidepressant drugs (Lilly110140 and trazodone) was investigated. Lilly 110140 was as active as chlorimipramine and several times more active than imipramine as an inhibitor of 14C-5-HT uptake. Like chlorimipramine, Lilly 110140 appeared to be either a non-competitive or an uncompetitive inhibitor, according to the concentration of drug used. Trazodone also inhibited 14C-5-HT uptake by platelets but to a lesser extent than chlorimipramine, imipramine or Lilly 110140. m-chlorophenylpiperazine, a possible metabolite of trazodone, was about 3 times more potent an inhibitor than the parent molecule. Both compounds acted non-competitively. Compared with published data on the effect of Lilly 110140 and trazodone on brain 5-Ht, the present results support the suggestion that rat platelets are a useful pharmacological model of serotoninergic nerve endings. (author)

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

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

    2012-01-01

    Genetic variation in 5-HT transporter (5-HTT) expression is a key risk factor for psychiatric disorder and has been linked to changes in the expression of certain 5-HT receptor subtypes. This study investigated the effect of variation in 5-HTT expression on 5-HT4 receptor levels in both 5-HTT kno......). Together, these findings suggest that variation in 5-HTT expression causes adaptive changes in 5-HT4 receptor levels which are directly linked to alterations in 5-HT availability.......Genetic variation in 5-HT transporter (5-HTT) expression is a key risk factor for psychiatric disorder and has been linked to changes in the expression of certain 5-HT receptor subtypes. This study investigated the effect of variation in 5-HTT expression on 5-HT4 receptor levels in both 5-HTT...

  12. Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues.

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

    2005-01-01

    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. PMID:16095048

  13. Secondhand smoke exposure causes bronchial hyperreactivity via transcriptionally upregulated endothelin and 5-hydroxytryptamine 2A receptors

    Cao, Lei; Zhang, Yaping; Cao, Yong-Xiao; Edvinsson, Lars; Xu, Cang-Bao

    2012-01-01

    secondhand cigarette smoke (SHS) exposure upregulates the bronchial contractile receptors via activation of the Raf/ERK/MAPK pathway. METHODOLOGY/PRINCIPAL FINDINGS: Rats were exposed to SHS for 3 h daily for up to 8 weeks. The receptor agonists-induced bronchial contractile reactivity was analyzed with a......BACKGROUND: Cigarette smoke exposure is strongly associated with airway hyperreactivity (AHR) which is the main characteristic seen in asthma. The intracellular MAPK signaling pathways are suggested to be associated with the airway damage to the AHR. In the present study, we hypothesize that...

  14. Characterization of 5-Hydroxytryptamine, adrenergic and CGRP receptors in relation to migraine

    S. Mehrotra (Suneet)

    2006-01-01

    textabstractMigraine affects a substantial fraction of the world population and is a major cause of disability in the work place. Migraine is a recurrent incapacitating neurovascular disorder characterized by attacks of debilitating pain associated with photophobia, phonophobia, nausea and vomiting.

  15. Characterization of 5-Hydroxytryptamine, adrenergic and CGRP receptors in relation to migraine

    Mehrotra, Suneet

    2006-01-01

    textabstractMigraine affects a substantial fraction of the world population and is a major cause of disability in the work place. Migraine is a recurrent incapacitating neurovascular disorder characterized by attacks of debilitating pain associated with photophobia, phonophobia, nausea and vomiting. Though the pathophysiology of migraine is still unclear, it is believed to be a neurovascular disorder. The drugs used in the treatment of migraine affect vascular receptors. In earlier days, α-ad...

  16. The chemical coding of 5-hydroxytryptamine containing enteroendocrine cells in the mouse gastrointestinal tract.

    Reynaud, Yohan; Fakhry, Josiane; Fothergill, Linda; Callaghan, Brid; Ringuet, Mitchell; Hunne, Billie; Bravo, David M; Furness, John B

    2016-06-01

    The majority of 5-HT (serotonin) in the body is contained in enteroendocrine cells of the gastrointestinal mucosa. From the time of their discovery over 80 years ago, the 5-HT-containing cells have been regarded as a class of cell that is distinct from enteroendocrine cells that contain peptide hormones. However, recent studies have cast doubt on the concept of there being distinct classes of enteroendocrine cells, each containing a single hormone or occasionally more than one hormone. Instead, data are rapidly accumulating that there are complex patterns of colocalisation of hormones that identify multiple subclasses of enteroendocrine cells. In the present work, multiple labelling immunohistochemistry is used to investigate patterns of colocalisation of 5-HT with enteric peptide hormones. Over 95 % of 5-HT cells in the duodenum also contained cholecystokinin and about 40 % of them also contained secretin. In the jejunum, about 75 % of 5-HT cells contained cholecystokinin but not secretin and 25 % contained 5-HT plus both cholecystokinin and secretin. Small proportions of 5-HT cells contained gastrin or somatostatin in the stomach, PYY or GLP-1 in the small intestine and GLP-1 or somatostatin in the large intestine. Rare or very rare 5-HT cells contained ghrelin (stomach), neurotensin (small and large intestines), somatostatin (small intestine) and PYY (in the large intestine). It is concluded that 5-HT-containing enteroendocrine cells are heterogeneous in their chemical coding and by implication in their functions. PMID:26803512

  17. EU Migration Policy

    Kleinschmidt, Harald

    2004-01-01

    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. Neuronal Migration Disorders

    ... Enhancing Diversity Find People About NINDS NINDS Neuronal Migration Disorders Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What are Neuronal Migration Disorders? Neuronal migration disorders (NMDs) are a group ...

  19. Migration of birds

    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. Research on Protocol Migration

    汪芸; 顾冠群; 等

    1996-01-01

    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.

  1. Migration and trade

    Peter H. Egger; Ehrlich, Maximilian von; Nelson, Douglas R.

    2011-01-01

    Theoretical and empirical research in economics suggests that bilateral migration triggers bilateral trade through a number of channels. This paper assesses the functional form of the impact of migration on trade flows in a quasi-experimental setting. We provide evidence that the relationship is not log-linear. In particular, at small levels of migration (stocks) the elasticity of trade to migration is quite high, and it declines to zero at about 4,000 immigrants. If migration stocks exceed s...

  2. Migration and revolution

    Nando Sigona

    2012-06-01

    Full Text Available The Arab Spring has not radically transformed migration patterns in the Mediterranean, and the label ‘migration crisis’ does not do justice to the composite and stratified reality.

  3. Migration, Remittances and Growth

    Nurgul Ukueva

    2011-01-01

    This paper analyzes the effect of migration and remittances on a small, open, migrant-sending country in the context of an endogenous growth model with technology transfers. The paper demonstrates that, due to a dynamic feedback effect from economic conditions to migration and from migration to economic development in an economy exposed to migration, initial conditions can determine its long-run steady state, leading to the rise of vicious or virtues circles of development. Countries with a l...

  4. International Migration and Remittances

    Dattatray Sitaram Bagade

    2012-01-01

    Human migration is a physical movement by human beings from one geographical areato another geographical area. Migration is internal as well as external. At theinternational level, no universally accepted definition for “Migrant” exists. The UniteNations defines “migration as an individual who has resided in a foreign country formore than one year irrespective of the causes, voluntary or involuntary, and the means,regular or irregular, used migrate”. Key terms of migrations is documented migr...

  5. Essays on temporary migration

    Mestres Domenech, J.

    2012-01-01

    My thesis dissertation focuses on the temporariness of migration, its diverse effects as well as on migration selection. The first paper, A Dynamic Model of Return Migration analyzes the decision process underlying return migration using a dynamic model. We explain how migrants decide whether to stay or to go back to their home country together with their savings and consumption decisions. We simulate our model with return intentions and perform policy simulations. The se...

  6. On Marriage and Migration

    Stark, Oded

    1988-01-01

    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. We thus proceed in this paper to explore the role of migration in obtaining joint labour-market and marriage-market equilibrium. This facilitates identification of several novel and testable hypotheses.

  7. Patterns of migration in Tanzania.

    Bernstein, H

    1981-01-01

    ILO pub-wep pub. Working paper identifying internal migration patterns and employment implications in Tanzania - discusses reasons for migration, types (seasonal workers, permanent, etc.), Migration within rural areas or urban areas, rural migration, land settlement trends, etc. References.)

  8. The Novel Small Leucine-Rich Repeat Protein Podocan is a Negative Regulator of Migration and Proliferation of Smooth Muscle Cells, Modulates Neointima Formation and is Expressed in Human Atheroma

    Hutter, Randolph; Huang, Li; Speidl, Walter S.; Giannarelli, Chiara; Trubin, Paul; Bauriedel, Gerhard; Klotman, Mary E.; Fuster, Valentin; Badimon, Juan J.; Klotman, Paul E.

    2014-01-01

    Background SMC migration and proliferation critically influence the clinical course of vascular disease. We tested the effect of the novel small leucine-rich repeat protein podocan on SMC migration and proliferation using a podocan deficient mouse in combination with a model of arterial injury and aortic explant SMC culture. In addition, we examined the effect of overexpression of the human form of podocan on human SMC and tested for podocan expression in human atherosclerosis. In all these conditions we evaluated concomitantly the Wnt-TCF-pathway. Methods and Results Podocan was strongly and selectively expressed in arteries of WT mice after injury. Podocan−/− mice showed increased arterial lesion formation as compared to WT littermates in response to injury (P<0.05). Also, SMC proliferation was increased in arteries of podocan −/− mice compared to WT (P<0.05). In vitro, migration and proliferation were increased in podocan−/− SMC and were normalized by transfection with the WT podocan gene (P<0.05). In addition, upregulation of the Wnt-TCF-pathway was found in SMC of podocan−/− mice both in vitro and in vivo. On the other hand, podocan overexpression in human SMC significantly reduced SMC migration and proliferation inhibiting the Wnt-TCF-pathway. Podocan and a Wnt-TCF-pathway marker were differently expressed in human coronary restenotic versus primary lesions. Conclusions Podocan appears to be a potent negative regulator of the migration and proliferation of both murine and human SMC. The lack of podocan results in excessive arterial repair and prolonged SMC proliferation, which likely is mediated by the Wnt-TCF-pathway. PMID:24043300

  9. Radon depth migration

    A depth migration method is presented that used Radon-transformed common-source seismograms as input. It is shown that the Radon depth migration method can be extended to spatially varying velocity depth models by using asymptotic ray theory (ART) to construct wavefield continuation operators. These operators downward continue an incident receiver-array plane wave and an assumed point-source wavefield into the subsurface. The migration velocity model is constrain to have longer characteristic wavelengths than the dominant source wavelength such that the ART approximations for the continuation operators are valid. This method is used successfully to migrate two synthetic data examples: (1) a point diffractor, and (2) a dipping layer and syncline interface model. It is shown that the Radon migration method has a computational advantage over the standard Kirchhoff migration method in that fewer rays are computed in a main memory implementation

  10. Bystander effects of ionizing radiation can be modulated by signaling amines

    Actual risk and risk management of exposure to ionizing radiation are among the most controversial areas in environmental health protection. Recent developments in radiobiology especially characterization of bystander effects have called into question established dogmas and are thought to cast doubt on the scientific basis of the risk assessment framework, leading to uncertainty for regulators and concern among affected populations. In this paper we test the hypothesis that small signaling molecules widely used throughout the animal kingdom for signaling stress or environmental change, such as 5-Hydroxytryptamine (5-HT, serotonin), L-DOPA, glycine or nicotine are involved in bystander signaling processes following ionizing radiation exposure. We report data which suggest that nano to micromolar concentrations of these agents can modulate bystander-induced cell death. Depletion of 5-HT present in tissue culture medium, occurred following irradiation of cells. This suggested that 5-HT might be bound by membrane receptors after irradiation. Expression of 5-HT type 3 receptors which are Ca2+ ion channels was confirmed in the cells using immunocytochemistry and receptor expression could be increased using radiation or 5-HT exposure. Zofran and Kitryl, inhibitors of 5-HT type 3 receptors, and reserpine a generic serotonin antagonist block the bystander effect induced by radiation or by serotonin. The results may be important for the mechanistic understanding of how low doses of radiation interact with cells to produce biological effects

  11. TYPES OF MODERN MIGRATION

    KAITMAZOVA KARINA RUSLANOVNA; CABERTI ALINA NODAROVNA

    2016-01-01

    The detailed classification of migration is analyzed, also a conclusion is drawn according to the fact that migration contributes to the development of the population of countries and regions, appearing to be a driving force and an important factor of globalization in the XXI century. Russia, also as other countries, strongly depends on migration: future of the Russian Federation depends on the fact how socially-spiritual community of Russian people will change, and also culture and values of...

  12. Malaysia and forced migration

    Arzura Idris

    2012-01-01

    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...

  13. Unemployment, migration, and growth

    Valerie R. Bencivenga; Bruce D. Smith

    1995-01-01

    Economic development is typically accompanied by a very pronounced migration of labor from rural to urban employment. This migration, in turn, is often associated with large scale urban underemployment. Both factors appear to play a very prominent role in the process of development. We consider a model in which rural-urban migration and urban underemployment are integrated into an otherwise conventional neoclassical growth model. Unemployment arises not from any exogenous rigidities, but from...

  14. Many Faces of Migrations

    Milica Antić Gaber; Marko Krevs

    2013-01-01

    Temporary or permanent, local or international, voluntary or forced, legal or illegal, registered or unregistered migrations of individuals, whole communities or individual groups are an important factor in constructing and modifying (modern) societies. The extent of international migrations is truly immense. At the time of the preparation of this publication more than 200 million people have been involved in migrations in a single year according to the United Nations. Furthermore, three time...

  15. Regional Redistribution and Migration

    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...

  16. From Immigration to Migration Systems: New Concepts in Migration History.

    Hoerder, Dirk

    1999-01-01

    Describes the characteristics of migration systems where two or more societies are connected through migration patterns. Identifies the four major migration systems that populated North America. Reviews the literature in relation to migration systems and discusses autobiographical accounts of migration. Provides an extensive bibliography. (CMK)

  17. Migration, klima og sundhed

    Tellier, Siri; Carballo, Manuel

    2009-01-01

    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...

  18. Migration to Windows NT.

    Doles, Daniel T.

    In the constantly changing world of technology, migration is not only inevitable but many times necessary for survival, especially when the end result is simplicity for both users and IT support staff. This paper describes the migration at Franklin College (Indiana). It discusses the reasons for selecting Windows NT, the steps taken to complete…

  19. International Migration of Couples

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

    2016-01-01

    We develop a theoretical model regarding the migration of dual-earner couples and test it in the context of international migration. Our model predicts that the probability that a couple emigrates increases with the income of the primary earner, whereas the income of the secondary earner may affect...

  20. Migration, Narration, Identity

    Leese, Peter

    (co-editor with Carly McLaughlin and Wladyslaw Witalisz) This book presents articles resulting from joint research on the representations of migration conducted in connection with the Erasmus Intensive Programme entitled «Migration and Narration» taught to groups of international students over...

  1. Migrating Art History

    Ørum, Tania

    2012-01-01

    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....

  2. Migrating for a Profession

    Olwig, Karen Fog

    2015-01-01

    Youths from the Global South migrating for further education often face various forms of discrimination. This Caribbean case study discusses how conditions in the home country can provide a foundation for educational migration that helps the migrants overcome such obstacles and even develop a...

  3. Samtidskunst og migration

    Petersen, Anne Ring

    2010-01-01

    "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...

  4. Environmental change and migration

    Stojanov, Robert

    Santa Barbara, Calif : Praeger, 2012 - (Segal, U.; Elliot, D.), s. 55-89 ISBN 978-0-313-37807-2 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073 Institutional research plan: CEZ:AV0Z60870520 Keywords : migration processes * environmental change * climate change * environmental migrants * human migration Subject RIV: AO - Sociology, Demography

  5. Migration and Rural Development

    Robert E. B. Lucas

    2007-01-01

    The paper summarizes the key routes through which internal and international migration impact rural development and some of the evidence pertaining to these effects in low income countries. It concludes that, although the study of migration impacts on rural economies has come a long way from the early dual theories of development, some of the potentially more important aspects remain to be investigated systematically.

  6. World Migration Degree Global migration flows in directed networks

    Porat, Idan

    2015-01-01

    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...

  7. Migration of health workers.

    Buchan, James

    2008-01-01

    The discussion and debate stimulated by these papers focused across a range of issues but there were four main areas of questioning: "measuring" and monitoring migration (issues related to comparability, completeness and accuracy of data sets on human resources); the impact of migration of health workers on health systems; the motivations of individual health workers to migrate (the "push" and "pull" factors) and the effect of policies designed either to reduce migration (e.g "self ufficiency") or to stimulate it (e.g active international recruitment). It was recognised that there was a critical need to examine migratory flows within the broader context of all health care labour market dynamics within a country, that increasing migration of health workers was an inevitable consequence of globalisation, and that there was a critical need to improve monitoring so as to better inform policy formulation and policy testing in this area. PMID:18561695

  8. Malaysia and forced migration

    Arzura Idris

    2012-06-01

    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.

  9. Power Module

    Gang Fang

    2009-01-01

    Abstract: In this paper, we discuss the upgrade problem of module, and introduce the concepts of the power module, regular power module and uniform power module. We give some results of them. Key words: power group; power module; regular power module; uniform power module

  10. Modular Sequence: Puerto Rican Pupils in Mainland Schools. TTP 003.02. Migration Patterns of the Puerto Rican. Teacher Corps Bilingual Project.

    Hartford Univ., West Hartford, CT. Coll. of Education.

    This module presents an overview of the background of Puerto Rican migration to the U.S. and an explanation of the migrant's current situation. Upon completion of this module the participant will be able to (a) describe the cultural roots of the migrants, (b) list reasons for the migration after 1898, (c) characterize the migration since 1950, and…

  11. Migration, Skills and Productivity

    Robert Hierländer; Peter Huber; Anna Iara; Michael Landesmann; Klaus Nowotny; Mary O'Mahony; Fei Peng; Catherine Robinson; Robert Stehrer

    2010-01-01

    The literature on international migration has repeatedly emphasized that the extent and structure of migration has an important impact on the competitiveness of regions and countries. This report provides an overview of the extent and the potential effects of high-skill migration to the EU27. It shows how many high-skilled migrants live in the EU, where these migrants come from, and how the European Union is positioned in the international competition for talent. Second, we examine how high-s...

  12. Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

    Brinkman, C. Colin; Iwami, Daiki; Hritzo, Molly K.; Xiong, Yanbao; Ahmad, Sarwat; Simon, Thomas; Hippen, Keli L.; Blazar, Bruce R.; Bromberg, Jonathan S.

    2016-01-01

    Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NFκB signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression. PMID:27323847

  13. Dioscorea nipponica Makino inhibits migration and invasion of human oral cancer HSC-3 cells by transcriptional inhibition of matrix metalloproteinase-2 through modulation of CREB and AP-1 activity.

    Chien, Ming-Hsien; Ying, Tsung-Ho; Hsieh, Yih-Shou; Chang, Yu-Chao; Yeh, Chia-Ming; Ko, Jiunn-Liang; Lee, Wen-Sen; Chang, Jer-Hua; Yang, Shun-Fa

    2012-03-01

    Oral cancer mortality has increased during the last decade due to the difficulties in treating related metastasis. Dioscorea nipponica Makino, a popular folk medicine, exerts anti-obesity and anti-inflammation properties. However, the effect of this folk medicine on metastasis of oral cancer has yet to be fully elucidated. The present study demonstrates that D. nipponica extracts (DNE), at a range of concentrations (0-50 μg/mL), concentration-dependently inhibited migration/invasion capacities of human oral cancer cells, HSC-3, without cytotoxic effects. The anti-migration effect of DNE was also observed in two other OSCC cell lines, Ca9-22 and Cal-27. Zymography, real time PCR, and Western blotting analyses revealed that DNE inhibited matrix metalloproteinase-2 (MMP-2) enzyme activity, and RNA and protein expression. The inhibitory effects of DNE on MMP-2 proceeded by up-regulating tissue inhibitor of metalloproteinase-2 (TIMP-2), as well as suppressing nuclear translocation and DNA binding activity of cAMP response element-binding (CREB) and activating protein-1 (AP-1) on the MMP-2 promoter in HSC-3 cells. In conclusion, DNE inhibited the invasion of oral cancer cells and may have potential use as a chemopreventive agent against oral cancer metastasis. PMID:22210353

  14. Marine bromophenol bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane inhibits the proliferation, migration, and invasion of hepatocellular carcinoma cells via modulating β1-integrin/FAK signaling.

    Wu, Ning; Luo, Jiao; Jiang, Bo; Wang, Lijun; Wang, Shuaiyu; Wang, Changhui; Fu, Changqing; Li, Jian; Shi, Dayong

    2015-02-01

    Bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) is a natural bromophenol compound derived from marine algae. Previous reports have shown that BDDPM possesses antimicrobial activity. In the present study, we found that BDDPM has cytotoxic activity on a wide range of tumor cells, including BEL-7402 cells (IC50 = 8.7 μg/mL). Further studies have shown that prior to the onset of apoptosis, the BDDPM induces BEL-7402 cell detachment by decreasing the adherence of cells to the extracellular matrix (ECM). Detachment experiments have shown that the treatment of BEL-7402 cells with low concentrations of BDDPM (5.0 μg/mL) significantly inhibits cell adhesion to fibronectin and collagen IV as well as cell migration and invasion. High doses of BDDPM (10.0 μg/mL) completely inhibit the migration of BEL-7402 cells, and the expression level of MMPs (MMP-2 and MMP-9) is significantly decreased. Moreover, the expression of β1-integrin and focal adhesion kinase (FAK) is found to be down-regulated by BDDPM. This study suggests that BDDPM has a potential to be developed as a novel anticancer therapeutic agent due to its anti-metastatic activity and also indicates that BDDPM, which has a unique chemical structure, could serve as a lead compound for rational drug design and for future development of anticancer agents. PMID:25689564

  15. Marine Bromophenol Bis (2,3-Dibromo-4,5-dihydroxy-phenyl-methane Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Modulating β1-Integrin/FAK Signaling

    Ning Wu

    2015-02-01

    Full Text Available Bis (2,3-dibromo-4,5-dihydroxy-phenyl-methane (BDDPM is a natural bromophenol compound derived from marine algae. Previous reports have shown that BDDPM possesses antimicrobial activity. In the present study, we found that BDDPM has cytotoxic activity on a wide range of tumor cells, including BEL-7402 cells (IC50 = 8.7 μg/mL. Further studies have shown that prior to the onset of apoptosis, the BDDPM induces BEL-7402 cell detachment by decreasing the adherence of cells to the extracellular matrix (ECM. Detachment experiments have shown that the treatment of BEL-7402 cells with low concentrations of BDDPM (5.0 μg/mL significantly inhibits cell adhesion to fibronectin and collagen IV as well as cell migration and invasion. High doses of BDDPM (10.0 μg/mL completely inhibit the migration of BEL-7402 cells, and the expression level of MMPs (MMP-2 and MMP-9 is significantly decreased. Moreover, the expression of β1-integrin and focal adhesion kinase (FAK is found to be down-regulated by BDDPM. This study suggests that BDDPM has a potential to be developed as a novel anticancer therapeutic agent due to its anti-metastatic activity and also indicates that BDDPM, which has a unique chemical structure, could serve as a lead compound for rational drug design and for future development of anticancer agents.

  16. Migration og etnicitet

    Christiansen, Connie Carøe

    2004-01-01

    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....

  17. Indonesia's migration transition.

    Hugo, G

    1995-01-01

    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. PMID:12347370

  18. Labour Migration in Europe

    Menz, Georg; Caviedes, Alexander

    2010-01-01

    Economic migration has been rediscovered by governments across Europe. Highly skilled migrants are actively solicited, irregular migrants are being offered amnesties, and East-West migration is welcomed by business and employer associations. However, this is a highly politicized and contested policy domain. This timely collection of cutting-edge research explores and examines the new realities of economic immigration to Europe. The thematic focus rests on new trends and developments, includin...

  19. Remittances and Return Migration

    Collier, William J.; Piracha, Matloob E; Randozza, Teresa

    2011-01-01

    This paper utilises survey data of return migrants to analyse the determinants of remittances sent while the migrants were abroad. We approach our research question from the perspective of three sending countries in the Maghreb, namely Algeria, Morocco and Tunisia. We investigate the remittance behaviour using the migrants’ conditions before migration as well as during the migration experience. Using a two-part model, we show that the decision to remit and the amount remitted depend on a comb...

  20. Migration of Interplanetary Dust

    Ipatov, S. I.; Mather, J. C.; Taylor, P.A.

    2003-01-01

    We numerically investigate the migration of dust particles with initial orbits close to those of the numbered asteroids, observed trans-Neptunian objects, and Comet Encke. The fraction of silicate asteroidal particles that collided with the Earth during their lifetime varied from 1.1% for 100 micron particles to 0.008% for 1 micron particles. Almost all asteroidal particles with diameter d>4 microns collided with the Sun. The peaks in the migrating asteroidal dust particles' semi-major axis d...

  1. Migration and Culture

    Epstein, Gil S.; Ira N. Gang

    2010-01-01

    Culture is not new to the study of migration. It has lurked beneath the surface for some time, occasionally protruding openly into the discussion, usually under some pseudonym. The authors bring culture into the open. They are concerned with how culture manifests itself in the migration process for three groups of actors: the migrants, those remaining in the sending areas, and people already living in the recipient locations. The topics vary widely. What unites the authors is an understanding...

  2. Effect of prolonged 5-hydroxytryptamine uptake inhibition by paroxetine on cortical β1 and β2-adrenoceptors in rat brain

    The effects of prolonged oral administration of the antidepressants paroxetine and amitriptyline on rat brain cortical β1- and β2-adrenoceptor numbers and affinities were investigated using [3H]-CGP 12177. Although amitriptyline, 27 mg/kg, caused a significant 20% reduction in the number of β1-adrenoceptors, paroxetine, at does up to 8.9 mg/kg p.o., did not influence binding of [3H]-CGP 12177 to cortical β1- or β2-adrenoceptors. This study with paroxetine provides further evidence that the down-regulation of central β1-adrenoceptors in rat brain after repeated administration is not a property of all antidepressant drugs

  3. Partial Purification of the 5-Hydroxytryptamine-Reuptake System from Human Blood Platelets Using a Citalopram-Derived Affinity Resin

    Biessen, E.A.L.; Horn, A.S.; Robillard, G.T.

    1990-01-01

    This paper describes a procedure for the synthesis and application of a citalopram-derived affinity resin in purifying the 5HT-reuptake system from human blood platelets. A two-step scheme has been developed for partial purification, based on wheat germ agglutinin-lectin (WGA) affinity and citalopra

  4. Increased extracellular dopamine and 5-hydroxytryptamine levels contribute to enhanced subthalamic nucleus neural activity during exhausting exercise

    Hu, Y.; Liu, X.; D. QIAO

    2015-01-01

    The purpose of the study was to explore the mechanism underlying the enhanced subthalamic nucleus (STN) neural activity during exhausting exercise from the perspective of monoamine neurotransmitters and changes of their corresponding receptors. Rats were randomly divided into microdialysis and immunohistochemistry study groups. For microdialysis study, extracellular fluid of the STN was continuously collected with a microdialysis probe before, during and 90 min after one bout of exhausting ex...

  5. Effects of conditioned running on plasma, liver and brain tryptophan and on brain 5-hydroxytryptamine metabolism of the rat.

    Chaouloff, F; Elghozi, J. L.; Guezennec, Y.; Laude, D.

    1985-01-01

    An investigation was made into the effects of conditioned running (1 h and 2 h at 20 m min-1), which accelerates lipolysis, on the concentrations of tryptophan (Trp) in plasma, liver and brain and on 5-hydroxytrptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in brain. Running caused time-dependent increases in plasma free Trp and brain Trp of the rat, leading to increased brain 5-HT turnover as revealed by higher amounts of its metabolite, 5-HIAA. The ratio of brain Trp to plasm...

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

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

    2008-01-01

    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...

  7. Increased contractile responses to 5-hydroxytryptamine and Angiotensin II in high fat diet fed rat thoracic aorta

    Ghatta Srinivas; Ramarao Poduri

    2004-01-01

    Abstract Background Feeding normal rats with high dietary levels of saturated fat leads to pathological conditions, which are quite similar to syndrome X in humans. These conditions such as hypertriglyceridemia, hypercholesterolemia, obesity, and hyperglycemia might induce hypertension through various mechanisms. Metabolic syndrome and the resulting NIDDM represent a major clinical challenge because implementation of treatment strategies is difficult. Vascular abnormalities probably contribut...

  8. Return Migration, Wage Differentials, and the Optimal Migration Duration

    Dustmann, Christian

    2001-01-01

    In simple static models, migration increases with the wage differential between host and home country. In a dynamic framework, and if migrations are temporary, the size of the migrant population in the host country depends also on the migration duration. This paper analyses optimal migration durations in a model which rationalises the decision of the migrant to return to his home country, despite persistently higher wages in the host country. The analysis shows that, if migrations are tempora...

  9. Managing Migration: The Brazilian Case

    Eduardo L. G. Rios-Neto

    2005-01-01

    The objective of this paper is to present the Brazilian migration experience and its relationship with migration management. The article is divided into three parts. First, it reviews some basic facts regarding Brazilian immigration and emigration processes. Second, it focuses on some policy and legal issues related to migration. Finally, it addresses five issues regarding migration management in Brazil.

  10. MODERN MIGRATION POLICY OF RUSSIA

    Kobylinsky S. V.

    2014-11-01

    Full Text Available Several peculiarities of the implementation of migration policy in the Russian Federation were considered in this article. We have shown main provisions on refugees and forced migrants from the Ukraine and labor migration. On the basis of the study we have suggested an improvement of migration legislation, in particular, creation of a single codex and migration police

  11. TOWARD MIGRATION TRANSITION IN ROMANIA

    Cristian Incaltarau

    2012-01-01

    Most studies regarding the contribution of migration to development are limited to an isolated analysis of the economic effects of migration. But the migration process is in turn influenced by other processes. So a wider framework including migration and other processes of development would be more appropriate. The experience of South European and East Asian countries have shown us that, during development, countries can change their migration profile from emigration to immigration. The prese...

  12. Prestack depth migration

    Two lines form the southern North Sea, with known velocity inhomogeneities in the overburden, have been pre-stack depth migrated. The pre-stack depth migrations are compared with conventional processing, one with severe distortions and one with subtle distortions on the conventionally processed sections. The line with subtle distortions is also compared with post-stack depth migration. The results on both lines were very successful. Both have already influenced drilling decisions, and have caused a modification of structural interpretation in the respective areas. Wells have been drilled on each of the lines, and well tops confirm the results. In fact, conventional processing led to incorrect locations for the wells, both of which were dry holes. The depth migrated sections indicate the incorrect placement, and on one line reveals a much better drilling location. This paper reports that even though processing costs are high for pre-stack depth migration, appropriate use can save millions of dollars in dry-hole expense

  13. Biometrics and international migration.

    Redpath, Jillyanne

    2007-01-01

    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. PMID:17536151

  14. Co-regulation of cell polarization and migration by caveolar proteins PTRF/Cavin-1 and caveolin-1.

    Michelle M Hill

    Full Text Available Caveolin-1 and caveolae are differentially polarized in migrating cells in various models, and caveolin-1 expression has been shown to quantitatively modulate cell migration. PTRF/cavin-1 is a cytoplasmic protein now established to be also necessary for caveola formation. Here we tested the effect of PTRF expression on cell migration. Using fluorescence imaging, quantitative proteomics, and cell migration assays we show that PTRF/cavin-1 modulates cellular polarization, and the subcellular localization of Rac1 and caveolin-1 in migrating cells as well as PKCα caveola recruitment. PTRF/cavin-1 quantitatively reduced cell migration, and induced mesenchymal epithelial reversion. Similar to caveolin-1, the polarization of PTRF/cavin-1 was dependent on the migration mode. By selectively manipulating PTRF/cavin-1 and caveolin-1 expression (and therefore caveola formation in multiple cell systems, we unveil caveola-independent functions for both proteins in cell migration.

  15. En fornemmelse for migration

    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....

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

    Kjell eFuxe

    2012-06-01

    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. Migration Outflows and Optimal Migration Policy: Rules versus Discretion

    Ismaël Issifou; Francesco Magris

    2015-01-01

    We study the effects of more open borders on return migration and show that migrants are more likely to return to the origin country when migration rules are softer, because this implies that they could more easily re-migrate if return migration is unsuccessful. As a result, softening migration rules leads to lower net inflows than generally acknowledged. We show that if government follows rules to shape the optimal migration policy, it will chose more open borders than in the case its behavi...

  18. Differential migration and proliferation of geometrical ensembles of cell clusters

    Kumar, Girish; Chen, Bo; Co, Carlos C.; Ho, Chia-Chi, E-mail: hocc@email.uc.edu

    2011-06-10

    Differential cell migration and growth drives the organization of specific tissue forms and plays a critical role in embryonic development, tissue morphogenesis, and tumor invasion. Localized gradients of soluble factors and extracellular matrix have been shown to modulate cell migration and proliferation. Here we show that in addition to these factors, initial tissue geometry can feedback to generate differential proliferation, cell polarity, and migration patterns. We apply layer by layer polyelectrolyte assembly to confine multicellular organization and subsequently release cells to demonstrate the spatial patterns of cell migration and growth. The cell shapes, spreading areas, and cell-cell contacts are influenced strongly by the confining geometry. Cells within geometric ensembles are morphologically polarized. Symmetry breaking was observed for cells on the circular pattern and cells migrate toward the corners and in the direction parallel to the longest dimension of the geometric shapes. This migration pattern is disrupted when actomyosin based tension was inhibited. Cells near the edge or corner of geometric shapes proliferate while cells within do not. Regions of higher rate of cell migration corresponded to regions of concentrated growth. These findings demonstrate that multicellular organization can result in spatial patterns of migration and proliferation.

  19. Unix Application Migration Guide

    Microsoft. Redmond

    2003-01-01

    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

  20. [Migration and diabetes].

    Aydinkoc-Tuzcu, Kadriye; Schindler, Karin; Kautzky-Willer, Alexandra; Ludvik, Bernhard; Fasching, Peter

    2016-04-01

    The article deals with the demographic data of migration in Austria and with therapeutic advice concerning drug therapy and diabetes education for patients with migration background. In this context socio-cultural specifics are discussed. These suggestions are seen complementary to the general treatment guidelines of the Austrian Diabetes Association.Especially for the fast months Ramadan there are a lot of informations. The most important point is that the patient care must be highly individualized and the management plan may differ for each patient. PMID:27052237

  1. Migration of seismic data

    Prospecting for oil and gas resources poses the problem of determining the geological structure of the earth's crust from indirect measurements. Seismic migration is an acoustic image reconstruction technique based on the inversion of the scalar wave equation. Extensive computation is necessary before reliable information can be extracted form large sets of recorded data. In this paper a collection of open-quotes industrialclose quotes migration techniques, each giving rise to a data parallel algorithm, is outlined. Computer simulations on synthetic seismic data illustrate the problem and the approach

  2. Making Migration Meaningful

    Benwell, Ann Fenger

    2013-01-01

    . 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...

  3. Migration = cloning; aliasiing

    Hüttel, Hans; Kleist, Josva; Nestmann, Uwe;

    1999-01-01

    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...

  4. Is Migration Feminized?

    Toksöz, Gülay

    2012-01-01

    In the context of Turkey’s accession to the EU, the issue of potential migration from Turkey and its impact upon European labor markets became one of the concerns of the EU, considering Turkey’s growing population and young labor force. In 2011, half a century after the bi-lateral agreement between Turkey and Germany on labor recruitment in 1961, migration plays a key role in relations of Turkey with the EU and will even increase its significance – not necessarily for the next fifty years bu...

  5. [Migration, climate and health].

    Tellier, Siri; Carballo, Manuel; Calballo, Manuel

    2009-10-26

    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 environmental refugees find themselves and the consequences this may have. Finally, it points to the urgent need to reform health systems in both developing and developed countries to adapt to rapidly changing disease patterns and to become more responsive to them. PMID:19857400

  6. [Migration and health].

    Litvinjenko, S

    1997-01-01

    In the last decades of this century we are witnesses of frequent crises in different parts of the world produced by internal disturbance and wars. These crises, together with natural disasters, poverty and hunger, follow the history of mankind often forcing huge population groups to leave their homes. The harmful health consequences are among negative effects of migrations. While stable populations have well-tried routines for maintaining health, migrations mean abandoning such support systems. The increased exposure to harmful factors contributes more to the bad health condition of the migrant population. Setting of newcomers and local people together in the same homes, reduction in food and heating resources, drug shortage as well as importation of new infectious agents, may also endanger health of the native population. These observations have also been confirmed by Yugoslav experience. Depending on the fact whether a migration is elemental or organized i.e. dependent on its place in the large scale between these two extreme endpoints, the size of risk is also dependent on the consequences and degree of their difficulty. Mass health disturbances occur during migrations of the population from war regions, migrations from areas of natural disasters, mass pilgrimage, migrations of seasonal workers and migrations of armies during wars. However, even in these difficult times and conditions, a good organization can contribute to the mitigation of harmful consequences caused by these migrations. For instance, in 1942 there was an epidemic of typhus fever in Bosnia when many refugees crossed the Drina river on the way to Serbia escaping from Ustasha terrorism. At the Serbian side there were checkpoints where the refugees could taka a bath and where their laundry and clothing were depediculated with dry air, and after a two-week quarantine they could continue to Serbian provinces without making new foci of typhus fever. The most vulnerable and numerous group of refugees

  7. Engineered Models of Confined Cell Migration.

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

    2016-07-11

    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

  8. Migration scenarii in extrasolar systems

    Crida A.

    2011-02-01

    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.

  9. Migration pathways in soils

    This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

  10. Fall armyworm migration patterns.

    Fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), infestations in most of North America arise from annual migrations of populations that overwinter in southern Texas and Florida. Cytochrome Oxidase I haplotype profiles within the fall armyworm corn-strain, the subgroup tha...

  11. Practical Data Migration

    Morris, Johny

    2012-01-01

    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.

  12. Migrating the Light

    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...

  13. MEXICAN MIGRATION PROJECT

    The Mexican Migration Project is designed to make timely, high-quality data on documented and undocumented Mexican migrants available to researchers and policy analysts. Each year since 1987 the project has administered a semi-structured interview schedule to representative sampl...

  14. Brain Migration Revisited

    Vinokur, Annie

    2006-01-01

    The "brain drain/brain gain" debate has been going on for the past 40 years, with irresolvable theoretical disputes and unenforceable policy recommendations that economists commonly ascribe to the lack of reliable empirical data. The recent report of the World Bank, "International migration, remittances and the brain drain", documents the…

  15. Migration and Africa

    Zoppi, Marco

    2014-01-01

    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 to the...

  16. Migration as Adventure

    Olwig, Karen Fog

    2016-01-01

    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...

  17. Dispersal and migration

    Schwarz, C.

    2004-06-01

    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

  18. Migration and Narration

    Brigitte Boenisch-Brednich

    2002-05-01

    Full Text Available The following article aims to work out the main narrative techniques of “telling migration”. The conclusions drawn on the subject of migration and narration are based on a one-year field work study, combining participant observation with interviewing. This study took place in New Zealand concentrating on German immigrants between 1936 and 1996. The main source for my analysis given in this paper is provided by 102 people I interviewed. The texts of these biographically-focussed interviews allowed me to work not only on an ethnographical history of migration but also to gain insights into peoples’ experiences, and over and above that, to learn what kind of stories and techniques of storytelling emigration creates. The book focuses on a comparatively wide time frame of sixty years (Boenisch- Brednich 2001. This makes it possible to analyse very different periods of migration and groups of migrants, contrasting social categories as well as exploring differences in education, milieu, age and gender. Furthermore, it becomes obvious that although all migrants were leaving Germany and arriving in New Zealand, they experienced what were in effect very different countries through time – different Germanys, different New Zealands. To work out the changing reasons for migrating (work migration, refuge, global lifestyle, etc. inside western societies is a major theme the book is aiming for. A second approach is to investigate migration from the perspective of focussing on everyday life, an investigation on the basis of personal experiences, such as “work, housing, food, celebrations, social life”. A special focus is set on the analysing of “mental narratives” as key stories, examples, comparatives etc. The central questions of this project were: What kind of strategies do people use to cope with a major changes in their biography, as constituted by emigration? What does integration really mean and how does it work for different groups? What

  19. Seasonal Survival Probabilities Suggest Low Migration Mortality in Migrating Bats

    Giavi, Simone; Moretti, Marco; Bontadina, Fabio; Zambelli, Nicola; Schaub, Michael

    2014-01-01

    Migration is adaptive if survival benefits are larger than costs of residency. Many aspects of bat migration ecology such as migratory costs, stopover site use and fidelity are largely unknown. Since many migrating bats are endangered, such information is urgently needed to promote conservation. We selected the migrating Leisler's bat (Nyctalus leisleri) as model species and collected capture-recapture data in southern Switzerland year round during 6 years. We estimated seasonal survival and ...

  20. Migration Turnover Rates in Mountain States Counties

    Israelsen, William J.; Israelsen, L. Dwight; Israelsen, Ryan D.

    2006-01-01

    Studies of migration typically examine migration between countries, or, in the United States, migration between states. Recently, there have been several studies done on the determinants of migration at the county level. The current study introduces a new concept into the migration literature: the migration turnover rate (MTR). The migration turnover rate is similar to an employee turnover rate in that it measures the turnover through in-migration and out-migration of the population of an are...

  1. Migration Turnover Rates in United States Counties

    Israelsen, L. Dwight; Israelsen, Ryan D.; Israelsen, William J.

    2006-01-01

    Studies of migration typically examine migration between countries, or, in the United States, migration between states. Recently, there have been several studies done on the determinants of migration at the county level. The current study introduces a new concept into the migration literature: the migration turnover rate (MTR). The migration turnover rate is similar to an employee turnover rate in that it measures the turnover through in-migration and out-migration of the population of an are...

  2. Globalization, Migration and Development

    George, Susan

    2002-01-01

    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

  3. The International Organization for Migration in Global Migration Governance

    Poulsen, Sofie Havn; Andersen, Lise

    2011-01-01

    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.

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

    Akansha Singh

    2010-05-01

    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.

  5. Radionuclide migration studies in soil

    In this work a brief description about retention and migration parameters of radionuclides in soil, including main methods to determine the distribution coefficient (K) are given. Some of several factors that can act on the migration are also mentioned. (author)

  6. International Migration and Real Wages

    Reza Oladi; Hamid Beladi

    2007-01-01

    We provide an analysis of the impact of migration on the skilled- unskilled wage gap. In particular, we show the possibility of a rise in the wage gap following the migration of skilled (unskilled ) labor.

  7. Altruism and International Labour Migration

    Damien Gaumont; Alice Mesnard

    1999-01-01

    This paper investigates the effect of altruism on the pattern of labour migration in a two-country overlapping generations model. We show that differences in degrees of altruism across countries lead to bilateral migration flows. Starting from the autarkic steady-state equilibrium, restrictions on labour migration are relaxed. In temporary post-migration equilibrium factor prices are equal across countries. We then characterize the unique stable steady-state equilibrium: both countries are po...

  8. The definition of illegal migration

    DZHANSARAYEVA RIMA YERENATOVNA; MALIKOVA SHOLPAN BALTABEKOVNA

    2015-01-01

    The article analyzes the definitions of illegal migration. In theory, there is no consensus on the concept of illegal immigration. In the scientific revolution applied the concept of “illegal migration”, “illegal immigration”, “migration of the crime” and “criminal migration”. Crime and illegal migration, although they have common features, are different concepts. For the concept of illegal immigration is characterized by violation of migration laws. For the concept of mandatory criminal migr...

  9. Trade, Aid, Remittances and Migration

    Akkoyunlu, Sule

    2009-01-01

    I investigated whether migration is interrelated with trade, aid and remittances so that any policies that consider trade, aid and remittances also affect the decision to migrate. We developed and estimated an empirical model of Turkish migration to Germany and tested the model for the 1969-2004, using the cointegration technique. A single cointegrating vector is found among the gross migration inflows and the following explanatory variables: the relative income ratio between Germany and Turk...

  10. Abelian modules

    S. Halıcıoğlu; Harmanci, A.; GÜNGÖROĞLU, G.; N. Agayev

    2009-01-01

    In this note, we introduce abelian modules as a generalization of abelian rings. Let R be an arbitrary ring with identity. A module M is called abelian if, for any m Î M and any a Î R, any idempotent e Î R, mae=mea. We prove that every reduced module, every symmetric module, every semicommutative module and every Armendariz module is abelian. For an abelian ring R, we show that the module MR is abelian iff M[x]R[x] is abelian. We produce an example to show that M[x, α] need not be abe...