Improving interfacial, mechanical and tribological properties of alumina coatings on Al alloy by plasma arc heat-treatment of substrate

Energy Technology Data Exchange (ETDEWEB)

Hou, Guoliang [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); An, Yulong, E-mail: csuayl@sohu.com [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Zhao, Xiaoqin; Zhou, Huidi [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Chen, Jianmin, E-mail: chenjm@licp.cas.cn [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Li, Shuangjian; Liu, Xia; Deng, Wen [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); University of Chinese Academy of Sciences, Beijing 100049 (China)

2017-07-31

Highlights: • Columnar δ-Al{sub 2}O{sub 3} induces epitaxial growth of γ-Al{sub 2}O{sub 3} grains in coating after PA-HT. • Epitaxial growth greatly enhances interfacial bonding of Al{sub 2}O{sub 3} coating on Al alloy. • Penetration of Al{sub 2}O{sub 3} droplets into Al alloy increases interfacial anchorage force. • Crystal structure of the alumina coatings can be refined after PA-HT of substrate. • Mechanical and tribological properties of the coatings are improved after PA-HT. - Abstract: Plasma sprayed ceramic coatings can be used to improve the mechanical properties and wear resistance of aluminum alloys, but there are still some challenges to effectively increase their interfacial adhesion. Thus we conducted plasma arc-heat treatment (PA-HT) of Al alloy substrate before plasma spraying, hoping to tune the microstructure of Al{sub 2}O{sub 3} coatings and improve their interfacial strength as well as mechanical and tribological properties. The influences of PA-HT on the microstructure of alumina coatings were analyzed by X-ray diffraction, transmission electron microscopy and scanning electron microscopy, while its effect on mechanical and tribological properties were evaluated by a nano-indentation tester and a friction and wear tester. Results demonstrate that a few columnar δ-Al{sub 2}O{sub 3} generated on substrate surface after PA-HT at 200–250 °C can induce the epitaxial growth of γ-Al{sub 2}O{sub 3} grains in Al{sub 2}O{sub 3} coatings, thereby enhancing their interfacial bonding. Besides, elevating substrate temperature can help alumina droplets to melt into the interior of substrate and eliminate holes at the interface, finally increasing the interfacial anchorage force. More importantly, no interfacial holes can allow the heat of droplets to be rapidly transmitted to substrate, which is beneficial to yield smaller crystals in coatings and greatly enhance their strength, hardness and wear resistance.

The influence of prior ageing on microstructure, tensile properties and hot hardness of alloy 800HT

International Nuclear Information System (INIS)

El-Magd, E.

1996-01-01

For high temperature applications especially in the construction of equipment, carbide strengthened steels are widely used because of their good mechanical properties and relatively low cost. These materials undergo microstructural changes under such service conditions which contribute greatly to the strength properties and thus play an important role in equipment design considerations. The influence of a prior thermal ageing on the tensile strength values and the hot hardness of the austenitic iron base alloy, Alloy 800HT, is examined in this work. It was therefore necessary to carry out tensile and hot hardness tests with the solution treated and overaged material at ranges between room temperature and 900 . The microstructural changes are investigated using lightmicroscopy, SEM and TEM. The changes of the material properties with thermal pretreatment conditions is studied and discussed in the context of the determined microstructural development. (orig.) [de

Development of Preliminary HT9 Cladding Tube for Sodium-cooled Fast Reactor (SFR)

International Nuclear Information System (INIS)

Kim, Jun Hwan; Baek, Jong Hyuk; Heo, Hyeong Min; Park, Sang Gyu; Kim, Sung Ho; Lee, Chan Bock

2013-01-01

To achieve manufacturing technology of the fuel cladding tube in order to keep pace with the predetermined schedule in developing SFR fuel, KAERI has launched in developing fuel cladding tube in cooperation with a domestic steelmaking company. After fabricating medium-sized 1.1 ton HT9 ingot, followed by the multiple processes of hot and cold working, preliminary samples of HT9 seamless cladding tube having 7.4mm in outer diameter, 0.56mm in thickness, and 3m in length were fabricated. The objective of this study is to summarize the brief development status of the HT9 cladding tubes. Mechanical properties like axial tension, biaxial burst, pressurized creep and sodium compatibility of the cladding tubes were carried out to set up the performance evaluation technology to test the prototype FMS cladding tube which is going to be manufactured in next stage. As a part of developing fuel cladding for the Sodium-cooled Fast Reactor (SFR), preliminary HT9 cladding tube was fabricated in cooperation with a domestic steelmaking company. Microstructure as well as mechanical tests like axial tensile test, biaxial burst test, and pressurized creep test of the fuel cladding were carried out. Performance of the domestic HT9 tube was revealed to be similar in the previously fabricated foreign HT9 tube. Further prototype FMS cladding tube is going to be manufactured in next year based on this experience. Various test items like mechanical test, sodium compatibility test, microstructural analysis, basic property, cladding performance under transient situation, and performance under ion and neutron irradiation are going be performed in the future to set up the relevant technology for the licensing of the SFR cladding tube

Mechanical Stimulation of the HT7 Acupuncture Point to Reduce Ethanol Self-Administration in Rats

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Suk-Yun Kang

2017-01-01

Full Text Available Background. Alcoholism, which is a disabling addiction disorder, is a major public health problem worldwide. The present study was designed to determine whether the application of acupuncture at the Shenmen (HT7 point suppresses voluntary alcohol consumption in addicted rats and whether this suppressive effect is potentiated by the administration of naltrexone. Methods. Rats were initially trained to self-administer a sucrose solution by operating a lever. A mechanical acupuncture instrument (MAI for objective mechanical stimulation was used on rats whose baseline response had been determined. In addition, the effect of HT7 acupuncture on beta-endorphin concentration and ethanol intake via naltrexone were investigated in different groups. Results. We found that ethanol intake and beta-endorphin level in rats being treated with the MAI at the HT7 point reduced significantly. The treatment of naltrexone at high doses reduced the ethanol intake and low-dose injection of naltrexone in conjunction with the MAI also suppressed ethanol intake. Conclusions. The results of the current study indicate that using the MAI at the HT7 point effectively reduces ethanol consumption in rats. Furthermore, the coadministration of the MAI and a low dose of naltrexone can produce some more potent reducing effect of ethanol intake than can acupuncture alone.

5-HT causes splanchnic venodilation.

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Seitz, Bridget M; Orer, Hakan S; Krieger-Burke, Teresa; Darios, Emma S; Thompson, Janice M; Fink, Gregory D; Watts, Stephanie W

2017-09-01

Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT 7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT 7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT 1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT 7 receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT 7 receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT 7 receptor. Male Sprague-Dawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 μg·kg -1 ·min -1 ) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 ± 1.9; portal vein, 17.7 ± 1.8; and abdominal inferior vena cava, 46.9 ± 8.0) while arterial pressure was decreased (~13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT 7 receptor-dependent splanchnic venous dilation associated with a fall in blood pressure. NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT 7 receptor, an in vitro observation (venorelaxation) with in vivo events

From Chemotherapy-Induced Emesis to Neuroprotection: Therapeutic Opportunities for 5-HT3 Receptor Antagonists.

Science.gov (United States)

Fakhfouri, Gohar; Mousavizadeh, Kazem; Mehr, Sharam Ejtemaei; Dehpour, Ahmad Reza; Zirak, Mohammad Reza; Ghia, Jean-Eric; Rahimian, Reza

2015-12-01

5-HT3 receptor antagonists are extensively used as efficacious agents in counteracting chemotherapy-induced emesis. Recent investigations have shed light on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some studies have reported neuroprotective properties for the 5-HT3 receptor antagonists in vitro and in vivo. When administered to Aβ-challenged rat cortical neurons, 5-HT3 receptor antagonists substantially abated apoptosis, elevation of cytosolic Ca(2), glutamate release, reactive oxygen species (ROS) generation, and caspase-3 activity. In addition, in vivo studies show that 5-HT3 receptor antagonists possess, alongside their anti-emetic effects, notable immunomodulatory properties in CNS. We found that pretreatment with tropisetron significantly improved neurological deficits and diminished leukocyte transmigration into the brain, TNF-α level, and brain infarction in a murine model of embolic stroke. Our recent investigation revealed that tropisetron protects against Aβ-induced neurotoxicity in vivo through both 5-HT3 receptor-dependent and -independent pathways. Tropisetron, in vitro, was found to be an efficacious inhibitor of the signaling pathway leading to the activation of pro-inflammatory NF-κB, a transcription factor pivotal to the upregulation of several neuroinflammatory mediators in brain. This mini review summarizes novel evidence concerning effects of 5-HT3 antagonists and their possible mechanisms of action in ameliorating neurodegenerative diseases including Alzheimer, multiple sclerosis, and stroke. Further, we discuss some newly synthesized 5-HT3 receptor antagonists with dual properties of 5-HT3 receptor blockade/alpha-7 nicotinic receptor activator and their potential in management of memory impairment. Since 5-HT3 receptor antagonists possess a large therapeutic window, they can constitute a scaffold for design and synthesis of new neuroprotective medications.

The effects of manipulation of presynaptic 5-HT nerve terminals of postsynaptic 5-HT1 and 5-HT2 binding sites of the rat brain

International Nuclear Information System (INIS)

Hall, H.; Wedel, I.

1985-01-01

The effects of long-term treatment of rats with alaproclate and amiflamine on the number and kinetics of 5-HT 1 and 5-HT 2 binding sites were investigated using in vitro receptor binding techniques. Some other studies have reported down-regulatory effects of alaproclate and amiflamine on 5-HT 2 binding sites in certain regions of the rat forebrain, but no such effects could be detected in the present study. Induction of a high-affinity binding site for 3 H-5-HT after long-term antidepressant treatment, as has been reported elsewhere, was not obtained in the present study. The results are compared to the effects obtained by treatment of rats with para-chloroamphetamine (PCA), which depletes the presynaptic neurons of monoamines. These different types of treatment do not cause any change in the binding properties of the specific 5-HT binding sites. It is thus concluded that such manipulations of the presynaptic 5-HT neurons do not affect the postsynaptic 5-HT 1 and 5-HT 2 binding sites. (Author)

The role of 5-HT(1A) receptors in learning and memory.

Science.gov (United States)

Ogren, Sven Ove; Eriksson, Therese M; Elvander-Tottie, Elin; D'Addario, Claudio; Ekström, Joanna C; Svenningsson, Per; Meister, Björn; Kehr, Jan; Stiedl, Oliver

2008-12-16

The ascending serotonin (5-HT) neurons innervate the cerebral cortex, hippocampus, septum and amygdala, all representing brain regions associated with various domains of cognition. The 5-HT innervation is diffuse and extensively arborized with few synaptic contacts, which indicates that 5-HT can affect a large number of neurons in a paracrine mode. Serotonin signaling is mediated by 14 receptor subtypes with different functional and transductional properties. The 5-HT(1A) subtype is of particular interest, since it is one of the main mediators of the action of 5-HT. Moreover, the 5-HT(1A) receptor regulates the activity of 5-HT neurons via autoreceptors, and it regulates the function of several neurotransmitter systems via postsynaptic receptors (heteroreceptors). This review assesses the pharmacological and genetic evidence that implicates the 5-HT(1A) receptor in learning and memory. The 5-HT(1A) receptors are in the position to influence the activity of glutamatergic, cholinergic and possibly GABAergic neurons in the cerebral cortex, hippocampus and in the septohippocampal projection, thereby affecting declarative and non-declarative memory functions. Moreover, the 5-HT(1A) receptor regulates several transduction mechanisms such as kinases and immediate early genes implicated in memory formation. Based on studies in rodents the stimulation of 5-HT(1A) receptors generally produces learning impairments by interfering with memory-encoding mechanisms. In contrast, antagonists of 5-HT(1A) receptors facilitate certain types of memory by enhancing hippocampal/cortical cholinergic and/or glutamatergic neurotransmission. Some data also support a potential role for the 5-HT(1A) receptor in memory consolidation. Available results also implicate the 5-HT(1A) receptor in the retrieval of aversive or emotional memories, supporting an involvement in reconsolidation. The contribution of 5-HT(1A) receptors in cognitive impairments in various psychiatric disorders is still

Photoelectric Properties of Silicon Nanocrystals/P3HT Bulk-Heterojunction Ordered in Titanium Dioxide Nanotube Arrays

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Švrček Vladimir

2009-01-01

Full Text Available Abstract A silicon nanocrystals (Si-ncs conjugated-polymer-based bulk-heterojunction represents a promising approach for low-cost hybrid solar cells. In this contribution, the bulk-heterojunction is based on Si-ncs prepared by electrochemical etching and poly(3-hexylthiophene (P3HT polymer. Photoelectric properties in parallel and vertical device-like configuration were investigated. Electronic interaction between the polymer and surfactant-free Si-ncs is achieved. Temperature-dependent photoluminescence and transport properties were studied and the ratio between the photo- and dark-conductivity of 1.7 was achieved at ambient conditions. Furthermore the porous titanium dioxide (TiO2 nanotubes’ template was used for vertical order of photosensitive Si-ncs/P3HT-based blend. The anodization of titanium foil in ethylene glycol-based electrolyte containing fluoride ions and subsequent thermal annealing were used to prepare anatase TiO2nanotube arrays. The arrays with nanotube inner diameter of 90 and 50 nm were used for vertical ordering of the Si-ncs/P3HT bulk-heterojunction.

Structure-properties relationships in melt reprocessed PLA/hydrotalcites nanocomposites

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R. Scaffaro

2017-07-01

Full Text Available In this work the effect of multiple reprocessing was studied on molecular structure, morphology and properties of poly(lactic acid/hydrotalcites (PLA/HT nanocomposites compared to neat PLA. In addition, the influence of two different kinds of HT – organically modified (OM-HT and unmodified (U-HT – was evaluated. Thermo-mechanical degradation was induced by means of five subsequent extrusion cycles. The performance of the recycled materials was investigated by mechanical and rheological tests, differential scanning calorimetry (DSC, intrinsic viscosity measurements and SEM observation. The results indicated that the best morphology was achieved in the systems incorporating OM-HT. On increasing the extrusion reprocessing cycles, the properties showed behavior due to two opposite effects: i chain scission due to thermo-mechanical degradation and ii filler dispersion effect resulting from multiple processing. In particular, at low reprocessing cycles, both tensile and rheological properties seem to be mainly affected by HT dispersion, especially when OM-HT was added. After five reprocessing cycles, on the contrary, chain scission, i.e. thermo-mechanical degradation, dominated. As regards the effect of the presence of organic modifier in HT, the results indicated that this variable apparently did not affect the macroscopic performance of the nanocomposites, especially at high reprocessing cycles.

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

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Malgorzata S. Martin-Gronert

2016-04-01

Full Text Available Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC peptides within the arcuate nucleus of the hypothalamus (ARC. We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus of in utero growth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist.

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.

Science.gov (United States)

Martin-Gronert, Malgorzata S; Stocker, Claire J; Wargent, Edward T; Cripps, Roselle L; Garfield, Alastair S; Jovanovic, Zorica; D'Agostino, Giuseppe; Yeo, Giles S H; Cawthorne, Michael A; Arch, Jonathan R S; Heisler, Lora K; Ozanne, Susan E

2016-04-01

Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist. © 2016. Published by The Company of Biologists Ltd.

Mechanisms underlying apoptosis-inducing effects of Kaempferol in HT-29 human colon cancer cells.

Science.gov (United States)

Lee, Hyun Sook; Cho, Han Jin; Yu, Rina; Lee, Ki Won; Chun, Hyang Sook; Park, Jung Han Yoon

2014-02-17

We previously noted that kaempferol, a flavonol present in vegetables and fruits, reduced cell cycle progression of HT-29 cells. To examine whether kaempferol induces apoptosis of HT-29 cells and to explore the underlying molecular mechanisms, cells were treated with various concentrations (0-60 μmol/L) of kaempferol and analyzed by Hoechst staining, Annexin V staining, JC-1 labeling of the mitochondria, immunoprecipitation, in vitro kinase assays, Western blot analyses, and caspase-8 assays. Kaempferol increased chromatin condensation, DNA fragmentation and the number of early apoptotic cells in HT-29 cells in a dose-dependent manner. In addition, kaempferol increased the levels of cleaved caspase-9, caspase-3 and caspase-7 as well as those of cleaved poly (ADP-ribose) polymerase. Moreover, it increased mitochondrial membrane permeability and cytosolic cytochrome c concentrations. Further, kaempferol decreased the levels of Bcl-xL proteins, but increased those of Bik. It also induced a reduction in Akt activation and Akt activity and an increase in mitochondrial Bad. Additionally, kaempferol increased the levels of membrane-bound FAS ligand, decreased those of uncleaved caspase-8 and intact Bid and increased caspase-8 activity. These results indicate that kaempferol induces the apoptosis of HT-29 cells via events associated with the activation of cell surface death receptors and the mitochondrial pathway.

Improving interfacial, mechanical and tribological properties of alumina coatings on Al alloy by plasma arc heat-treatment of substrate

Science.gov (United States)

Hou, Guoliang; An, Yulong; Zhao, Xiaoqin; Zhou, Huidi; Chen, Jianmin; Li, Shuangjian; Liu, Xia; Deng, Wen

2017-07-01

Plasma sprayed ceramic coatings can be used to improve the mechanical properties and wear resistance of aluminum alloys, but there are still some challenges to effectively increase their interfacial adhesion. Thus we conducted plasma arc-heat treatment (PA-HT) of Al alloy substrate before plasma spraying, hoping to tune the microstructure of Al2O3 coatings and improve their interfacial strength as well as mechanical and tribological properties. The influences of PA-HT on the microstructure of alumina coatings were analyzed by X-ray diffraction, transmission electron microscopy and scanning electron microscopy, while its effect on mechanical and tribological properties were evaluated by a nano-indentation tester and a friction and wear tester. Results demonstrate that a few columnar δ-Al2O3 generated on substrate surface after PA-HT at 200-250 °C can induce the epitaxial growth of γ-Al2O3 grains in Al2O3 coatings, thereby enhancing their interfacial bonding. Besides, elevating substrate temperature can help alumina droplets to melt into the interior of substrate and eliminate holes at the interface, finally increasing the interfacial anchorage force. More importantly, no interfacial holes can allow the heat of droplets to be rapidly transmitted to substrate, which is beneficial to yield smaller crystals in coatings and greatly enhance their strength, hardness and wear resistance.

New Insights into the Mechanisms of Photodegradation/Stabilization of P3HT:PCBM Active Layers Using Poly(3-hexyl-d13-Thiophene)

DEFF Research Database (Denmark)

Tournebize, Aurelien; Bussiere, Pierre-Olivier; Rivaton, Agnes

2013-01-01

species involved in the chain radical oxidation of P3HT is a key characteristic in the underlying mechanism. The results obtained in this work advance the understanding of active layer stability and will help improve the design of long lifetime organic solar cells thanks to the use of cutoff filter......The photo-oxidation mechanism of thin-film blends based on poly(3-hexylthiophene):phenyl-C-61-butyric acid methyl ester (P3HT:PCBM) upon irradiation with ultraviolet-visible light (UV-Vis) was studied. The use of deuterated P3HT, i.e., poly(3-hexyl-d(13)-thiophene) (P3HdT), permitted discrimination...

The role of the serotonin receptor subtypes 5-HT1A and 5-HT7 and its interaction in emotional learning and memory

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Oliver eStiedl

2015-08-01

Full Text Available Serotonin (5-hydroxytryptamine, 5-HT is a multifunctional neurotransmitter innervating cortical and limbic areas involved in cognition and emotional regulation. Dysregulation of serotonergic transmission is associated with emotional and cognitive deficits in psychiatric patients and animal models. Drugs targeting the 5-HT system are widely used to treat mood disorders and anxiety-like behaviors. Among the fourteen 5-HT receptor (5-HTR subtypes, the 5-HT1AR and 5-HT7R are associated with the development of anxiety, depression and cognitive function linked to mechanisms of emotional learning and memory. In rodents fear conditioning and passive avoidance (PA are associative learning paradigms to study emotional memory. This review assesses the role of 5-HT1AR and 5-HT7R as well as their interplay at the molecular, neurochemical and behavioral level. Activation of postsynaptic 5-HT1ARs impairs emotional memory through attenuation of neuronal activity, whereas presynaptic 5-HT1AR activation reduces 5-HT release and exerts pro-cognitive effects on PA retention. Antagonism of the 5-HT1AR facilitates memory retention possibly via 5-HT7R activation and evidence is provided that 5HT7R can facilitate emotional memory upon reduced 5-HT1AR transmission. These findings highlight the differential role of these 5-HTRs in cognitive/emotional domains of behavior. Moreover, the results indicate that tonic and phasic 5-HT release can exert different and potentially opposing effects on emotional memory, depending on the states of 5-HT1ARs and 5-HT7Rs and their interaction. Consequently, individual differences due to genetic and/or epigenetic mechanisms play an essential role for the responsiveness to drug treatment, e.g., by SSRIs which increase intrasynaptic 5-HT levels thereby activating multiple pre- and postsynaptic 5-HTR subtypes.

Fluoxetine-induced inhibition of synaptosomal [3H]5-HT release: Possible Ca2+-channel inhibition

International Nuclear Information System (INIS)

Stauderman, K.A.; Gandhi, V.C.; Jones, D.J.

1992-01-01

Fluoxetine, a selective 5-Ht uptake inhibitor, inhibited 15 mM K + -induced [ 3 H]5-HT release from rat spinal cord and cortical synaptosomes at concentrations > 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K + used to depolarize the synaptosomes and the concentration of external Ca 2+ . Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [ 3 H]5-HT release induced by the Ca 2+ -ionophore A 23187 or Ca 2+ -independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K + -induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca 2+ channels and Ca 2+ entry

Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor modulation

DEFF Research Database (Denmark)

Jensen, Jesper Bornø; du Jardin, Kristian Gaarn; Song, Dekun

2014-01-01

Depressed patients suffer from cognitive dysfunction, including memory deficits. Acute serotonin (5-HT) depletion impairs memory and mood in vulnerable patients. The investigational multimodal acting antidepressant vortioxetine is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor...... depletion impaired memory performance in rats through one or more of its receptor activities....... partial agonist, 5-HT1A receptor agonist and 5-HT transporter (SERT) inhibitor that enhances memory in normal rats in novel object recognition (NOR) and conditioned fear (Mørk et al., 2013). We hypothesized that vortioxetine's 5-HT receptor mechanisms are involved in its memory effects, and therefore...

MDMA self-administration fails to alter the behavioral response to 5-HT(1A) and 5-HT(1B) agonists.

Science.gov (United States)

Aronsen, Dane; Schenk, Susan

2016-04-01

Regular use of the street drug, ecstasy, produces a number of cognitive and behavioral deficits. One possible mechanism for these deficits is functional changes in serotonin (5-HT) receptors as a consequence of prolonged 3,4 methylenedioxymethamphetamine (MDMA)-produced 5-HT release. Of particular interest are the 5-HT(1A) and 5-HT(1B) receptor subtypes since they have been implicated in several of the behaviors that have been shown to be impacted in ecstasy users and in animals exposed to MDMA. This study aimed to determine the effect of extensive MDMA self-administration on behavioral responses to the 5-HT(1A) agonist, 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT), and the 5-HT(1B/1A) agonist, RU 24969. Male Sprague-Dawley rats self-administered a total of 350 mg/kg MDMA, or vehicle, over 20-58 daily self-administration sessions. Two days after the last self-administration session, the hyperactive response to 8-OH-DPAT (0.03-1.0 mg/kg) or the adipsic response to RU 24969 (0.3-3.0 mg/kg) were assessed. 8-OH-DPAT dose dependently increased horizontal activity, but this response was not altered by MDMA self-administration. The dose-response curve for RU 24969-produced adipsia was also not altered by MDMA self-administration. Cognitive and behavioral deficits produced by repeated exposure to MDMA self-administration are not likely due to alterations in 5-HT(1A) or 5-HT(1B) receptor mechanisms.

Converging evidence for central 5-HT effects in acute tryptophan depletion

DEFF Research Database (Denmark)

Crockett, Molly; Clark, Luke; Roiser, Jonathan

2012-01-01

the validity of ATD.2 Although we agree that ATD's effects on 5-HT activity at the molecular level need further clarification, van Donkelaar et al.2 goes too far in challenging whether ATD exerts its effects through serotonergic mechanisms. There is strong evidence that ATD reduces brain 5-HT and disrupts......Acute tryptophan depletion (ATD), a dietary technique for manipulating brain serotonin (5-HT) function, has advanced our understanding of 5-HT mechanisms in the etiology and treatment of depression and other affective disorders.1 A recent review article in Molecular Psychiatry questioned...

Correlation between the morphology and photo-physical properties of P3HT: fullerene blends

CSIR Research Space (South Africa)

Motaung, DE

2010-01-01

Full Text Available -induced charge transfer, well-known for blends of P3HT with fullerenes, was evidenced in blends of P3HT:C60 (1:1 wt ratio) by a strong partially quenching of the P3HT luminescence. The ESR measurements allowed one to quantify the charge transfer between P3HT...

Haliotis tuberculata hemocyanin (HtH): analysis of oligomeric stability of HtH1 and HtH2, and comparison with keyhole limpet hemocyanin KLH1 and KLH2.

Science.gov (United States)

Harris, J R; Scheffler, D; Gebauer, W; Lehnert, R; Markl, J

2000-12-01

The multimeric/higher oligomeric states of the two isoforms of Haliotis tuberculata hemocyanin (HtH1 and HtH2) have been assessed by transmission electron microscopy (TEM) of negatively stained specimens, for comparison with previously published structural data from keyhole limpet hemocyanin (KLH1 and KLH2) [see Harris, J.R., Gebauer, W., Guderian, F.U., Markl, J., 1997a. Keyhole limpet hemocyanin (KLH), I: Reassociation from Immucothel followed by separation of KLH1 and KLH2. Micron, 28, 31-41; Harris, J.R., Gebauer, W., Söhngen, S.M., Nermut, M.V., Markl, J., 1997b. Keyhole limpet hemocyanin (KLH). II: Characteristic reassociation properties of purified KLH1 and KLH2. Micron, 28, 43-56; Harris, J.R., Gebauer, W., Adrian, M., Markl, J., 1998. Keyhole limpet hemocyanin (KLH): Slow in vitro reassociation of KLH1 and KLH2 from Immucothel. Micron, 29, 329-339]. In purified samples of both HtH isoforms, the hollow cylindrical ca 8MDa didecamer predominates together with a small number of decamers, but tri- and longer multidecamers are detectable only in the HtH2. The stability of the two HtH isoforms under varying ionic conditions have been monitored, thereby enabling conditions for the production of stable decamers to be established. The ability of these decamers to reform multimers in the presence of 10 and 100mM concentrations of calcium and magnesium ions in Tris-HCl buffer (pH 7.4), and also of individual HtH1 and HtH2 subunits (produced by pH 9.6 dissociation in glycine-NaOH buffer), to reassociate in the presence of calcium and magnesium ions, has been assessed. For the HtH1 decamers, the predominant multimeric product is the didecamer at 10 and 100mM calcium and magnesium concentrations, whereas for the HtH2 decamers, large numbers of multidecamers are produced, with the reaction proceeding more completely at the higher calcium and magnesium concentration. With the HtH1 subunit, reassociation in the presence of 10 and 100mM calcium and magnesium ions yielded

Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional brain-derived neurotrophic factor knock-out mice

DEFF Research Database (Denmark)

Klein, A B; Santini, M A; Aznar, S

2010-01-01

Changes in brain-derived neurotrophic factor (BDNF) expression have been implicated in the etiology of psychiatric disorders. To investigate pathological mechanisms elicited by perturbed BDNF signaling, we examined mutant mice with central depletion of BDNF (BDNF(2L/2LCk-cre)). A severe impairment...... specific for the serotonin 2A receptor (5-HT(2A)R) in prefrontal cortex was described previously in these mice. This is of much interest, as 5-HT(2A)Rs have been linked to neuropsychiatric disorders and anxiety-related behavior. Here we further characterized the serotonin receptor alterations triggered...... was decreased in hippocampus of BDNF mutants, but unchanged in frontal cortex. Molecular analysis indicated corresponding changes in 5-HT(2A) and 5-HT(1A) mRNA expression but normal 5-HT(2C) content in these brain regions in BDNF(2L/2LCk-cre) mice. We investigated whether the reduction in frontal 5-HT(2A...

The pharmacology of TD-8954, a potent and selective 5-HT4 receptor agonist with gastrointestinal prokinetic properties

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David T Beattie

2011-05-01

Full Text Available This study evaluated the in vitro and in vivo pharmacological properties of TD-8954, a potent and selective 5-HT4 receptor agonist. TD-8954 had high affinity (pKi = 9.4 for human recombinant 5-HT4(c (h5-HT4(c receptors, and selectivity (> 2,000-fold over all other 5-HT receptors and non-5-HT receptors, ion channels, enzymes and transporters tested (n = 78. TD-8954 produced an elevation of cAMP in HEK-293 cells expressing the h5-HT4(c receptor (pEC50 = 9.3, and contracted the guinea pig colonic longitudinal muscle/myenteric plexus (LMMP preparation (pEC50 = 8.6. TD-8954 had moderate intrinsic activity (IA in the in vitro assays. In conscious guinea pigs, subcutaneous (s.c. administration of TD 8954 (0.03 - 3 mg/kg increased the colonic transit of carmine red dye, reducing the time taken for its excretion. Following intraduodenal (i.d. dosing to anesthetized rats, TD 8954 (0.03 - 10 mg/kg evoked a dose-dependent relaxation of the esophagus. Following oral administration to conscious dogs, TD 8954 (10 and 30 µg/kg produced an increase in contractility of the antrum, duodenum and jejunum. In a single ascending oral dose study in healthy human subjects, TD-8954 (0.1 - 20 mg increased bowel movement frequency and reduced the time to first stool. It is concluded that TD-8954 is a potent and selective 5-HT4 receptor agonist in vitro, with robust in vivo stimulatory activity in the gastrointestinal (GI tract of guinea pigs, rats, dogs and humans. TD-8954 may have clinical utility in patients with disorders of reduced GI motility.

Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity

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Darya V. Bazovkina

2015-01-01

Full Text Available In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK-212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors.

5-HT in the enteric nervous system: gut function and neuropharmacology.

Science.gov (United States)

McLean, Peter G; Borman, Richard A; Lee, Kevin

2007-01-01

In recent times, the perception of functional gastrointestinal disorders such as irritable bowel syndrome (IBS) has shifted fundamentally. Such disorders are now thought of as serious diseases characterized by perturbations in the neuronal regulation of gastrointestinal function. The concept of visceral hypersensitivity, the characterization of neuronal networks in the 'brain-gut axis' and the identification of several novel 5-HT-mediated mechanisms have contributed to this shift. Here, we review how some of the more promising of these new mechanisms (e.g. those involving 5-HT transporters and the 5-HT(2B), 5-HT(7) and putative 5-HT(1p) receptors) might lead to a range of second-generation therapies that could revolutionize the treatment of functional gastrointestinal disorders, particularly IBS.

In vitro assessment of the agonist properties of the novel 5-HT1A receptor ligand, CUMI-101 (MMP), in rat brain tissue

International Nuclear Information System (INIS)

Hendry, Nicola; Christie, Isabel; Rabiner, Eugenii Alfredovich; Laruelle, Marc; Watson, Jeannette

2011-01-01

Introduction: Development of agonist positron emission tomography (PET) radioligands for the 5-HT neurotransmitter system is an important target to enable the understanding of human 5-HT function in vivo. [ 11 C]CUMI-101, proposed as the first 5-HT 1A receptor agonist PET ligand, has been reported to behave as a potent 5-HT 1A agonist in a cellular system stably expressing human recombinant 5-HT 1A receptors. In this study, we investigate the agonist properties of CUMI-101 in rat brain tissue. Methods: [ 35 S]-GTPγS binding studies were used to determine receptor function in HEK (human embryonic kidney) 293 cells transfected with human recombinant 5-HT 1A receptors and in rat cortex and rat hippocampal tissue, following administration of CUMI-101 and standard 5-HT1A antagonists (5-HT, 5-CT and 8-OH-DPAT). Results: CUMI-101 behaved as an agonist at human recombinant 5-HT 1A receptors (pEC 50 9.2). However, CUMI-101 did not show agonist activity in either rat cortex or hippocampus at concentrations up to 10 μM. In these tissues, CUMI-behaved as an antagonist with pK B s of 9.2 and 9.3, respectively. Conclusions: Our studies demonstrate that as opposed to its behavior in human recombinant system, in rat brain tissue CUMI-101 behaves as a potent 5-HT 1A receptor antagonist.

A Pharmacological Analysis of an Associative Learning Task: 5-HT1 to 5-HT7 Receptor Subtypes Function on a Pavlovian/Instrumental Autoshaped Memory

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Meneses, Alfredo

2003-01-01

Recent studies using both invertebrates and mammals have revealed that endogenous serotonin (5-hydroxytryptamine [5-HT]) modulates plasticity processes, including learning and memory. However, little is currently known about the mechanisms, loci, or time window of the actions of 5-HT. The aim of this review is to discuss some recent results on the effects of systemic administration of selective agonists and antagonists of 5-HT on associative learning in a Pavlovian/instrumental autoshaping (P/I-A) task in rats. The results indicate that pharmacological manipulation of 5-HT1-7 receptors or 5-HT reuptake sites might modulate memory consolidation, which is consistent with the emerging notion that 5-HT plays a key role in memory formation. PMID:14557609

Effects of 5-HT on memory and the hippocampus: model and data.

NARCIS (Netherlands)

Meeter, M.; Talamini, L.M.; Schmitt, J.A.J.; Riedel, W.J.

2006-01-01

5-Hydroxytryptamine (5-HT) transmission has been implicated in memory and in depression. Both 5-HT depletion and specific 5-HT agonists lower memory performance, while depression is also associated with memory deficits. The precise neuropharmacology and neural mechanisms underlying these effects are

The effect of anneal, solar irradiation and humidity on the adhesion/cohesion properties of P3HT:PCBM based inverted polymer solar cells

KAUST Repository

Dupont, Stephanie R.

2012-06-01

We use a thin-film adhesion technique that enables us to precisely measure the energy required to separate adjacent layers in OPV cells. We demonstrate the presence of weak interfaces in prototypical inverted polymer solar cells, either prepared by spin, spray or slot-die coating, including flexible and non flexible solar cells. In all cases, we observed adhesive failure at P3HT:PCBM/PEDOT:PSS interface, indicating the intrinsic material dependence of this mechanism. The impact of temperature, solar irradiation and humidity on the adhesion and cohesion properties of this particular interface is discussed. First, we have found that post-deposition annealing increases the adhesion significantly. Annealing changes the morphology in the photoactive layer and consequently alters the chemical properties at the interface. Second, solar irradiation on fully encapsulated solar cells has no damaging but in contrast an enhancing effect on the adhesion properties, due to the heat generated from IR radiation. Finally, the synergetic effect of stress and an environmental species like moisture greatly accelerates the decohesion rate in the weak hygroscopic PEDOT:PSS layer. This results in a loss of mechanical integrity and device performance. The insight into the mechanisms of delamination and decohesion yields general guidelines for the design of more reliable organic electronic devices. © 2012 IEEE.

Effects of Heat Input on the Mechanical and Metallurgical Characteristics of Tig Welded Incoloy 800Ht Joints

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Kumar S. Arun

2017-09-01

Full Text Available This study focuses on the effect of heat input on the quality characteristics of tungsten inert arc gas welded incoloy 800HT joints using inconel-82 filler wire. Butt welding was done on specimens with four different heat inputs by varying the process parameters like welding current and speed. The result indicated that higher heat input levels has led to the formation of coarser grain structure, reduced mechanical properties and sensitization issues on the weldments. The formation of titanium nitrides provided resistance to fracture and increased the tensile strength of the joints at high temperatures. Further aging was done on the welded sample at a temperature of 750°C for 500 hours and the metallographic result showed formation of carbides along the grain boundaries in a chain of discrete and globular form which increased the hardness of the material. The formation of spinel NiCr2O4 provided oxidation resistance to the material during elevated temperature service.

Degree of phase separation effects on the charge transfer properties of P3HT:Graphene nanocomposites

International Nuclear Information System (INIS)

Bkakri, R.; Kusmartseva, O.E.; Kusmartsev, F.V.; Song, M.; Bouazizi, A.

2015-01-01

Graphene layers were introduced into the matrix of regioregular poly (3-hexylthiophene-2, 5-diyl) (RR-P3HT) via solution processing in the perspective of the development of organic nanocomposites with high P3HT/Graphene interfaces areas for efficient charge transfer process. P3HT and graphene act as electrons donor and electrons acceptor materials, respectively. Spatial Fourier Transforms (FFT) and power spectral density (PSD) analysis of the AFM images show that the phase separation decreases with increasing the graphene weight ratio in the P3HT matrix. The Raman spectra of the P3HT:Graphene nanocomposites shows that the G-band of graphene shifts to low frequencies with progressive addition of graphene which proves that there is an interaction between the nanowires of P3HT and the graphene layers. We suggest that the shift of the G-band is due to electrons transfer from P3HT to graphene. The quenching of the photoluminescence (PL) intensity of P3HT with addition of graphene proves also that an electrons transfer process occurred at the P3HT/Graphene interfaces. - Highlights: • Graphene layers are elaborated from expandable graphite oxide. • The effects of the graphene doping level on the charge transfer process were studied. • The phase separation process decreases with increasing the graphene content in the P3HT matrix. • Quenching of the PL intensity is due to electrons transfer from P3HT to graphene

Superior photoelectrochemical properties of ZnO nanorods/poly(3-hexylthiophene) hybrid photoanodes

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Majumder, T.; Hmar, J. J. L.; Dhar, S.; Mondal, S. P.

2017-06-01

Photoelectrochemical properties of ZnO nanorods (ZnO NRs) and poly(3-hexylthiophene) (P3HT) polymer hybrid photoanodes have been studied. The hybrid photoanodes demonstrated higher photoconversion efficiency, incident photon to current conversion efficiency (IPCE) and lower interfacial resistance compared to pristine ZnO nanorods and P3HT based electrodes. The origin of superior photoelectrochemical properties of ZnO/P3HT photoanodes has been explained using carrier transport mechanism at semiconductor/electrolyte junction. The stability of ZnO NRs/P3HT photoanode has been demonstrated.

Helium-induced weld degradation of HT-9 steel

International Nuclear Information System (INIS)

Wang, Chin-An; Chin, B.A.; Lin, Hua T.; Grossbeck, M.L.

1992-01-01

Helium-bearing Sandvik HT-9 ferritic steel was tested for weldability to simulate the welding of structural components of a fusion reactor after irradiation. Helium was introduced into HT-9 steel to 0.3 and 1 atomic parts per million (appm) by tritium doping and decay. Autogenous single pass full penetration welds were produced using the gas tungsten arc (GTA) welding process under laterally constrained conditions. Macroscopic examination showed no sign of any weld defect in HT-9 steel containing 0.3 appm helium. However, intergranular micro cracks were observed in the HAZ of HT-9 steel containing 1 appm helium. The microcracking was attributed to helium bubble growth at grain boundaries under the influence of high stresses and temperatures that were present during welding. Mechanical test results showed that both yield strength (YS) and ultimate tensile strength (UTS) decreased with increasing temperature, while the total elongation increased with increasing temperature for all control and helium-bearing HT-9 steels

P3HT:PCBM-based organic solar cells : Optimisation of active layer nanostructure and interface properties

Science.gov (United States)

Kadem, Burak Yahya

[61]BM, PC[70]BM and PC[71]BM) and the active layers were processed using the optimum solvent as well as optimum film's thickness.These PCBM derivatives have different lower unoccupied molecular level (LUMO) and different higher occupied molecular level (HOMO) positions, which subsequently influence the PV parameters of the OSCs such as the device open circuit voltage (V[oc]) and its built-in potential (V[bi]). P3HT:PC61BM-based blend has exhibited the highest device performance with PCE reaching 4.2%. Using the above mentioned optimum parameters, the P3HT:PCBM-based devices have been subjected to post-deposition annealing at different temperatures in the range 100-180°C. Efficient device performance was ascribed to P3HT:PCBM layers being subjected to post-deposition heat treatment at 140°C with PCE=5.5%. Device stability as a result of post-deposition heat treatment has also been shown to improve with PCE degrading by about 38% after 55 days.The use of interfacial layer is found to play a key part in modifying the solar cell performance; using electron transport layer (ETL) such as aluminium tris(8-hydroxyquinoline) (Alq3) as a solution processable layer has contributed in increasing PCE to 4.25%, while, using PEDOT:PSS as a hole transport layer (HTL) doped with metal salts has significantly contributed in increasing PCE to reach 6.82% in device when PEDOT:PSS was doped with LiCl aqueous solution. Stability study for the device based on HTL has shown degradation in the PCE from 6.82% to around 1% over 96 days. Using ETL and HTL simultaneously in a complete device has shown a further enhanced PCE reaching 7%. In a further study, doping the P3HT:PCBM with the novel ZnPc hybrids (SWCNTs and reduced graphene oxide (rGO) are covalently and non-covalently functionalised to ZnPc) with the weight ratio of (1:0.01) has significantly altered the solar cell device properties. The best performance is based on P3HT:PCBM blended with ZnPc-SWCNTs-co bonded as a ternary active

Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

DEFF Research Database (Denmark)

Paterson, Louise M; Tyacke, Robin J; Nutt, David J

2010-01-01

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron......, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors and the serotonin reuptake transporter...... have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made...

The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

Science.gov (United States)

Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

2009-09-01

Experimental spinal cord injury. To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

Refining the Role of 5-HT in Postnatal Development of Brain Circuits

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Anne Teissier

2017-05-01

Full Text Available Changing serotonin (5-hydroxytryptamine, 5-HT brain levels during critical periods in development has long-lasting effects on brain function, particularly on later anxiety/depression-related behaviors in adulthood. A large part of the known developmental effects of 5-HT occur during critical periods of postnatal life, when activity-dependent mechanisms remodel neural circuits. This was first demonstrated for the maturation of sensory brain maps in the barrel cortex and the visual system. More recently this has been extended to the 5-HT raphe circuits themselves and to limbic circuits. Recent studies overviewed here used new genetic models in mice and rats and combined physiological and structural approaches to provide new insights on the cellular and molecular mechanisms controlled by 5-HT during late stages of neural circuit maturation in the raphe projections, the somatosensory cortex and the visual system. Similar mechanisms appear to be also involved in the maturation of limbic circuits such as prefrontal circuits. The latter are of particular relevance to understand the impact of transient 5-HT dysfunction during postnatal life on psychiatric illnesses and emotional disorders in adult life.

Investigation of the mechanisms underlying the hypophagic effects of the 5-HT and noradrenaline reuptake inhibitor, sibutramine, in the rat

Science.gov (United States)

Jackson, Helen C; Bearham, M Clair; Hutchins, Lisa J; Mazurkiewicz, Sarah E; Needham, Andrew M; Heal, David J

1997-01-01

Sibutramine is a novel 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin- noradrenaline reuptake inhibitor, SNRI) which is currently being developed as a treatment for obesity. Sibutramine has been shown to decrease food intake in the rat. In this study we have used a variety of monoamine receptor antagonists to examine the pharmacological mechanisms underlying sibutramine-induced hypophagia. Individually-housed male Sprague-Dawley rats were maintained on reversed phase lighting with free access to food and water. Drugs were administered at 09 h 00 min and food intake was monitored over the following 8 h dark period. Sibutramine (10 mg kg−1, p.o.) produced a significant decrease in food intake during the 8 h following drug administration. This hypophagic response was fully antagonized by the α1-adrenoceptor antagonist, prazosin (0.3 and 1 mg kg−1, i.p.), and partially antagonized by the β1-adrenoceptor antagonist, metoprolol (3 and 10 mg kg−1, i.p.) and the 5-HT receptor antagonists, metergoline (non-selective; 0.3 mg kg−1, i.p.); ritanserin (5-HT2A/2C; 0.1 and 0.5 mg kg−1, i.p.) and SB200646 (5-HT2B/2C; 20 and 40 mg kg−1, p.o.). By contrast, the α2-adrenoceptor antagonist, RX821002 (0.3 and 1 mg kg−1, i.p.) and the β2-adrenoceptor antagonist, ICI 118,551 (3 and 10 mg kg−1, i.p.) did not reduce the decrease in food intake induced by sibutramine. These results demonstrate that β1-adrenoceptors, 5-HT2A/2C-receptors and particularly α1-adrenoceptors, are involved in the effects of sibutramine on food intake and are consistent with the hypothesis that sibutramine-induced hypophagia is related to its ability to inhibit the reuptake of both noradrenaline and 5-HT, with the subsequent activation of a variety of noradrenaline and 5-HT receptor systems. PMID:9283694

Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

Science.gov (United States)

Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

2014-01-03

Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

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Xavier Viñals

2015-07-01

Full Text Available Activation of cannabinoid CB1 receptors (CB1R by delta9-tetrahydrocannabinol (THC produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

Science.gov (United States)

Viñals, Xavier; Moreno, Estefanía; Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I; McCormick, Peter J; Maldonado, Rafael; Robledo, Patricia

2015-07-01

Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Influences mass concentration of P3HT and PCBM to application of organic solar cells

International Nuclear Information System (INIS)

Supriyanto, A.; Maya; Iriani, Y.; Ramelan, A. H.; Nurosyid, F; Rosa, E. S.

2016-01-01

Poly (3-hexylthiophene) (P3HT) and [6, 6] -phenyl-C61-butyric acid methyl ester (PCBM) are used for the organic solar cell applications. P3HT and PCBM act as donors and acceptors, respectively. In this study the efficiency of the P3HT: PCBM organic solar cells as function of the mass concentration of the blend P3HT: PCBM with 1, 2, 8, 16 mg/ml. Deposition P3HT:PCBM film using spin coating with a rotary speed of 2500 rpm for 10 seconds. Optical properties of absorption spectra characteristic using a UV-Visible Spectrometer Lambda 25 and electrical properties of I-V characteristic using Keithley 2602 instrument. The results of absoption spectra for P3HT:PCBM within different mass concentration obtained 500-600 nm wavelengths. The Energy-gap obtained about 1.9eV. The organic solar cells device performance were investigated using I-V cahractyeristic. For mass concentration of 1, 2, 8 and 16 mg/ml P3HT:PCBM were obtained 0.5×10 -3 %, 2.2×10 -3 %, 5.9×10 -3 %, and 6.1×10 -3 % efficiency of organics solar cells respectively. (paper)

Inverse agonist and neutral antagonist actions of synthetic compounds at an insect 5-HT1 receptor.

Science.gov (United States)

Troppmann, B; Balfanz, S; Baumann, A; Blenau, W

2010-04-01

5-Hydroxytryptamine (5-HT) has been shown to control and modulate many physiological and behavioural functions in insects. In this study, we report the cloning and pharmacological properties of a 5-HT(1) receptor of an insect model for neurobiology, physiology and pharmacology. A cDNA encoding for the Periplaneta americana 5-HT(1) receptor was amplified from brain cDNA. The receptor was stably expressed in HEK 293 cells, and the functional and pharmacological properties were determined in cAMP assays. Receptor distribution was investigated by RT-PCR and by immunocytochemistry using an affinity-purified polyclonal antiserum. The P. americana 5-HT(1) receptor (Pea5-HT(1)) shares pronounced sequence and functional similarity with mammalian 5-HT(1) receptors. Activation with 5-HT reduced adenylyl cyclase activity in a dose-dependent manner. Pea5-HT(1) was expressed as a constitutively active receptor with methiothepin acting as a neutral antagonist, and WAY 100635 as an inverse agonist. Receptor mRNA was present in various tissues including brain, salivary glands and midgut. Receptor-specific antibodies showed that the native protein was expressed in a glycosylated form in membrane samples of brain and salivary glands. This study marks the first pharmacological identification of an inverse agonist and a neutral antagonist at an insect 5-HT(1) receptor. The results presented here should facilitate further analyses of 5-HT(1) receptors in mediating central and peripheral effects of 5-HT in insects.

Mechanosensory Signaling in Enterochromaffin Cells and 5-HT Release: Potential Implications for Gut Inflammation

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Andromeda Linan Rico

2016-12-01

Full Text Available Enterochromaffin cells (EC synthesize 95% of the body 5-HT and release 5-HT in response to mechanical or chemical stimulation. EC cell 5-HT has physiological effects on gut motility, secretion and visceral sensation. Abnormal regulation of 5-HT occurs in gastrointestinal disorders and Inflammatory Bowel Diseases (IBD where 5-HT may represent a key player in the pathogenesis of intestinal inflammation. The focus of this review is on mechanism(s involved in EC cell ‘mechanosensation’ and critical gaps in our knowledge for future research. Much of our knowledge and concepts are from a human BON cell model of EC, although more recent work has included other cell lines, native EC cells from mouse and human and intact mucosa. EC cells are ‘mechanosensors’ that respond to physical forces generated during peristaltic activity by translating the mechanical stimulus (MS into an intracellular biochemical response leading to 5-HT and ATP release. The emerging picture of mechanosensation includes Piezo 2 channels, caveolin-rich microdomains and tight regulation of 5-HT release by purines. The ‘purinergic hypothesis’ is that MS releases purines to act in an autocrine / paracrine manner to activate excitatory (P2Y1, P2Y4, P2Y6, A2A/A2B or inhibitory (P2Y12, A1, A3 receptors to regulate 5-HT release. MS activates a P2Y1/Gαq/PLC/IP3-IP3R/SERCA Ca2+signaling pathway, an A2A/A2B–Gs/AC/cAMP-PKA signaling pathway, an ATP-gated P2X3 channel, and an inhibitory P2Y12 -Gi/o/AC-cAMP pathway. In human IBD, P2X3 is down regulated and A2B is up regulated in EC cells, but the pathophysiological consequences of abnormal mechanosensory or purinergic 5-HT signaling remain unknown. EC cell mechanosensation remains poorly understood.

Electrical and Thermo-Mechanical properties of Irradiated Clay Nanoparticle/SBR Composites

International Nuclear Information System (INIS)

Ata, M.M.E.M.

2011-01-01

Polymer-Composites incorporating metal, semiconductors, Carbon black, nano materials and Clay materials have been widely used and studied as multifunctional materials with inherent polymer properties. Polymer-clay nano composites show remarkable property improvement when compared to conventionally scaled composites. For designing new materials with desirable, predicted properties, a better understanding of structure-property relationships is necessary. In this work, we employ dielectric relaxation spectroscopy (DRS) to investigate molecular mobility in relation to morphology in styrene butadiene rubber-SBR (treated and untreated) nano composites. In addition to the investigation of dipolar processes, special attention is paid here to the investigation of conductivity effects and mechanical as well as thermo-mechanical properties. From the stress-strain characteristics, one found that, all the compositions showed a tensile strength higher than the virgin rubber. By increasing the filler loading, the tensile strength of the prepared composites increases. The elongation at break for treated and untreated clay filed composites increases with an increase in filer loading up to 10 p hr and then followed by a decrease up to 15 p hr. The cross linking density, υ increases with both treated and untreated clay contents and treated samples have higher increasing rate of υ values than untreated one. To elucidate the tensile behavior of the test samples. The Ht model is tested by using non-Gaussian chain statistics, which give a good fitting with the experimental data.

Identification of Selective Inhibitors of the Plasmodium falciparum Hexose Transporter PfHT by Screening Focused Libraries of Anti-Malarial Compounds.

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Diana Ortiz

Full Text Available Development of resistance against current antimalarial drugs necessitates the search for novel drugs that interact with different targets and have distinct mechanisms of action. Malaria parasites depend upon high levels of glucose uptake followed by inefficient metabolic utilization via the glycolytic pathway, and the Plasmodium falciparum hexose transporter PfHT, which mediates uptake of glucose, has thus been recognized as a promising drug target. This transporter is highly divergent from mammalian hexose transporters, and it appears to be a permease that is essential for parasite viability in intra-erythrocytic, mosquito, and liver stages of the parasite life cycle. An assay was developed that is appropriate for high throughput screening against PfHT based upon heterologous expression of PfHT in Leishmania mexicana parasites that are null mutants for their endogenous hexose transporters. Screening of two focused libraries of antimalarial compounds identified two such compounds that are high potency selective inhibitors of PfHT compared to human GLUT1. Additionally, 7 other compounds were identified that are lower potency and lower specificity PfHT inhibitors but might nonetheless serve as starting points for identification of analogs with more selective properties. These results further support the potential of PfHT as a novel drug target.

The natural triterpene maslinic acid induces apoptosis in HT29 colon cancer cells by a JNK-p53-dependent mechanism

International Nuclear Information System (INIS)

Reyes-Zurita, Fernando J; Pachón-Peña, Gisela; Lizárraga, Daneida; Rufino-Palomares, Eva E; Cascante, Marta; Lupiáñez, José A

2011-01-01

Maslinic acid, a pentacyclic triterpene found in the protective wax-like coating of the leaves and fruit of Olea europaea L., is a promising agent for the prevention of colon cancer. We have shown elsewhere that maslinic acid inhibits cell proliferation to a significant extent and activates mitochondrial apoptosis in colon cancer cells. In our latest work we have investigated further this compound's apoptotic molecular mechanism. We used HT29 adenocarcinoma cells. Changes genotoxicity were analyzed by single-cell gel electrophoresis (comet assay). The cell cycle was determined by flow cytometry. Finally, changes in protein expression were examined by western blotting. Student's t-test was used for statistical comparison. HT29 cells treated with maslinic acid showed significant increases in genotoxicity and cell-cycle arrest during the G0/G1 phase after 72 hours' treatment and an apoptotic sub-G0/G1 peak after 96 hours. Nevertheless, the molecular mechanism for this cytotoxic effect of maslinic acid has never been properly explored. We show here that the anti-tumoral activity of maslinic acid might proceed via p53-mediated apoptosis by acting upon the main signaling components that lead to an increase in p53 activity and the induction of the rest of the factors that participate in the apoptotic pathway. We found that in HT29 cells maslinic acid activated the expression of c-Jun NH2-terminal kinase (JNK), thus inducing p53. Treatment of tumor cells with maslinic acid also resulted in an increase in the expression of Bid and Bax, repression of Bcl-2, release of cytochrome-c and an increase in the expression of caspases -9, -3, and -7. Moreover, maslinic acid produced belated caspase-8 activity, thus amplifying the initial mitochondrial apoptotic signaling. All these results suggest that maslinic acid induces apoptosis in human HT29 colon-cancer cells through the JNK-Bid-mediated mitochondrial apoptotic pathway via the activation of p53. Thus we propose

Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

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Bianchi, M; Moser, C; Lazzarini, C; Vecchiato, E; Crespi, F

2002-03-01

Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the

Chemical durability and degradation mechanisms of HT9 based alloy waste forms with variable Zr content

Energy Technology Data Exchange (ETDEWEB)

Olson, L. N. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2015-10-30

In Corrosion studies were undertaken on alloy waste forms that can result from advanced electrometallurgical processing techniques to better classify their durability and degradation mechanisms. The waste forms were based on the RAW3-(URe) composition, consisting primarily of HT9 steel and other elemental additions to simulate nuclear fuel reprocessing byproducts. The solution conditions of the corrosion studies were taken from an electrochemical testing protocol, and meant to simulate conditions in a repository. The alloys durability was examined in alkaline and acidic brines.

HT oxidation activity of soil irradiated with gamma radiation

International Nuclear Information System (INIS)

Momoshima, Noriyuki; Tjahaja, P.I.; Takashima, Yoshimasa

1992-01-01

The HT oxidation activity was examined for soils irradiated with 60 Co γ-rays at various doses. The HT oxidation rate decreased with increase of initial H 2 concentration, indicating a similar oxidation mechanism between HT and H 2 . Irradiated soils showed decrease of oxidation activity with dose suggests that HT and H 2 oxidation activities were affected by sterilization with γ-rays. The decline of the oxidation activity with dose was analyzed by a composite of two components with different radiosensitivity and they were considered to be activities of soil microorganisms and abiotic soil enzymes. The oxidation activity due to soil microorganisms would be important at low dose range and more radioresistant abiotic soil enzymes would be responsible for the oxidation activity observed at more than several kGy. In non-irradiated soil about half of the oxidation activity was considered resulting from abiotic soil enzymes. (author)

Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

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Paterson, Louise M; Tyacke, Robin J; Nutt, David J; Knudsen, Gitte M

2010-01-01

Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron emission tomography, but has not yet been adequately extended to other neurotransmitter systems. This review focuses on how the technique has been applied to the study of the 5-hydroxytryptamine (5-HT) system. The principles behind visualising fluctuations in neurotransmitters are introduced, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT1A, 5-HT2A, and 5-HT4 receptors and the serotonin reuptake transporter have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made as to how the selection of targets, radiotracers, challenge paradigms, and experimental design might be optimised to improve our chances of successfully imaging endogenous neurotransmitters in the future. PMID:20664611

An assessment of the effects of serotonin 6 (5-HT6) receptor antagonists in rodent models of learning.

Science.gov (United States)

Lindner, Mark D; Hodges, Donald B; Hogan, John B; Orie, Anitra F; Corsa, Jason A; Barten, Donna M; Polson, Craig; Robertson, Barbara J; Guss, Valerie L; Gillman, Kevin W; Starrett, John E; Gribkoff, Valentin K

2003-11-01

Antagonists of serotonin 6 (5-HT6) receptors have been reported to enhance cognition in animal models of learning, although this finding has not been universal. We have assessed the therapeutic potential of the specific 5-HT6 receptor antagonists 4-amino-N-(2,6-bis-methylamino-pyrimidin-4-yl)-benzenesulfonamide (Ro 04-6790) and 5-chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfonamide (SB-271046) in rodent models of cognitive function. Although mice express the 5-HT6 receptor and the function of this receptor has been investigated in mice, all reports of activity with 5-HT6 receptor antagonists have used rat models. In the present study, receptor binding revealed that the pharmacological properties of the mouse receptor are different from the rat and human receptor: Ro 04-6790 does not bind to the mouse 5-HT6 receptor, so all in vivo testing included in the present report was conducted in rats. We replicated previous reports that 5-HT6 receptor antagonists produce a stretching syndrome previously shown to be mediated through cholinergic mechanisms, but Ro 04-6790 and SB-271046 failed to attenuate scopolamine-induced deficits in a test of contextual fear conditioning. We also failed to replicate the significant effects reported previously in both an autoshaping task and in a version of the Morris water maze. The results of our experiments are not consistent with previous reports that suggested that 5-HT6 antagonists might have therapeutic potential for cognitive disorders.

Molecular design of new P3HT derivatives: Adjusting electronic energy levels for blends with PCBM

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Oliveira, Eliezer Fernando [UNESP – Univ Estadual Paulista, POSMAT – Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, Bauru, SP (Brazil); Lavarda, Francisco Carlos, E-mail: lavarda@fc.unesp.br [UNESP – Univ Estadual Paulista, POSMAT – Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, Bauru, SP (Brazil); Faculdade de Ciências, UNESP – Univ Estadual Paulista, Departamento de Física, Av. Eng. Luiz Edmundo Carrijo Coube, 14-01, 17033-360 Bauru, SP (Brazil)

2014-12-15

An intensive search is underway for new materials to make more efficient organic solar cells through improvements in thin film morphology, transport properties, and adjustments to the energy of frontier electronic levels. The use of chemical modifications capable of modifying the electronic properties of materials already known is an interesting approach, as it can, in principle, provide a more adequate adjustment of the frontier electronic levels while preserving properties such as solubility. Based on this idea, we performed a theoretical study of poly(3-hexylthiophene) (P3HT) and 13 new derivatives obtained by substitution with electron acceptor and donor groups, in order to understand how the energy levels of the frontier orbitals are modified. The results show that it is possible to deduce the modification of the electronic levels in accordance with the substituent's acceptor/donor character. We also evaluated how the substituents influence the open circuit voltage and the exciton binding energy. - Highlights: • Prediction of P3HT derivatives properties for bulk-heterojunction solar cells. • Correlating substituent properties with electronic levels of P3HT derivatives. • Fluorinated P3HT improves open circuit voltage and stability.

Analysis of Current HT9 Creep Correlations and Modification

International Nuclear Information System (INIS)

Lee, Cheol Min; Sohn, Dongseong; Cheon, Jin Sik

2014-01-01

It has high thermal conductivity, high mechanical strength and low irradiation induced swelling. However high temperature creep of HT9 has always been a life limiting factor. Above 600 .deg. C, the dislocation density in HT9 is decreased and the M 23 C 6 precipitates coarsen, these processes are accelerated if there is irradiation. Finally microstructural changes at high temperature lead to lower creep strength and large creep strain. For HT9 to be used as a future cladding, creep behavior of the HT9 should be predicted accurately based on the physical understanding of the creep phenomenon. Most of the creep correlations are composed of irradiation creep and thermal creep terms. However, it is certain that in-pile thermal creep and out-of-pile thermal creep are different because of the microstructure changes induced from neutron irradiation. To explain creep behavior more accurately, thermal creep contributions other than neutron irradiation should be discriminated in a creep correlation. To perform this work, existing HT9 creep correlations are analyzed, and the results are used to develop more accurate thermal creep correlation. Then, the differences between in-pile thermal creep and out-of-pile thermal creep are examined

Quantitative Analysis of the Molecular Dynamics of P3HT:PCBM Bulk Heterojunction.

Science.gov (United States)

Guilbert, Anne A Y; Zbiri, Mohamed; Dunbar, Alan D F; Nelson, Jenny

2017-09-28

The optoelectronic properties of blends of conjugated polymers and small molecules are likely to be affected by the molecular dynamics of the active layer components. We study the dynamics of regioregular poly(3-hexylthiophene) (P3HT):phenyl-C61-butyric acid methyl ester (PCBM) blends using molecular dynamics (MD) simulation on time scales up to 50 ns and in a temperature range of 250-360 K. First, we compare the MD results with quasi-elastic neutron-scattering (QENS) measurements. Experiment and simulation give evidence of the vitrification of P3HT upon blending and the plasticization of PCBM by P3HT. Second, we reconstruct the QENS signal based on the independent simulations of the three phases constituting the complex microstructure of such blends. Finally, we found that P3HT chains tend to wrap around PCBM molecules in the amorphous mixture of P3HT and PCBM; this molecular interaction between P3HT and PCBM is likely to be responsible for the observed frustration of P3HT, the plasticization of PCBM, and the partial miscibility of P3HT and PCBM.

Fabrication of P3HT/gold nanoparticle LB films by P3HT templating Langmuir monolayer

International Nuclear Information System (INIS)

Chen, Liang-Huei; Hsu, Wen-Ping; Chan, Han-Wen; Lee, Yuh-Lang

2014-01-01

Highlights: • Addition of ODA into the P3HT monolayer can significantly improve the dispersion ability of P3HT molecules. • The adsorption ability of the P3HT monolayer to the dispersed AuNPs can also be enhanced by the presence of ODA. - Abstract: Regioregular poly(3-hexyl thiophene) (rr-P3HT) and mixed P3HT/octadecyl amine (ODA) were used as template monolayers to adsorb the gold nanoparticles (AuNPs) dispersed in subphase. The behaviors of P3HT and P3HT/ODA monolayers were investigated by surface pressure area per molecule (π–A) isotherms, transmission electron microscopy (TEM) and atomic force microscopy (AFM). The experimental results show that P3HT does not form a homogeneous film and tends to aggregate at the air/water interface. Meanwhile, the amount of AuNPs adsorbed by the P3HT monolayers is low, attributable to the weak interaction between AuNPs and P3HT. By introduction of ODA molecules into the P3HT monolayer, the spreading of P3HT molecules at the air/water interface is improved and the aggregation of P3HT is significantly inhibited. A nearly uniform and homogeneously mixed P3HT/ODA monolayer can be obtained when 50% of ODA is introduced. It is also found that the introduction of ODA can significantly increase the adsorption of AuNPs. For the mixed monolayer with low ratio of ODA (P3HT/ODA = 1/0.2), a higher concentration of adsorbed AuNPs was observed on the corresponding monolayer. However, when the ODA/P3HT ratio increases to 1/1, the AuNPs tend to form three-dimensional (3D) aggregates and the AuNPs cannot distribute well as a homogeneous monolayer. This result is ascribed to the increasing hydrophobicity of the adsorbed AuNPs because of capping of more ODA molecules

Effect of Microwave Radiation on the Synthesis of Poly(3-hexylthiophene and the Subsequent Photovoltaic Performance of CdS/P3HT Solar Cells

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C. H. García-Escobar

2016-01-01

Full Text Available Poly(3-hexylthiophene (P3HT is a semiconductor polymer that has been proved to be a good electron donor in organic or hybrid solar cells. In this work, a detailed study of P3HT synthesis in CH2Cl2 solvent by oxidative method with and without MW assistance has been conducted. Effects of synthesis process parameters on the physical properties of P3HT products and their application in hybrid CdS/P3HT photovoltaic devices were studied. It is observed that the use of MW as well as the reaction time affected the reaction yield and properties of the polymer products. It was found that, by the traditional method (without MW, the maximum yield and the properties of the polymer products were similar after 2 h or 24 h of synthesis. The optimal reaction time with MW for P3HT polymerization in CH2Cl2 solvent was 1 h, and the obtained P3HT product showed similar or better properties than those P3HT polymers synthesized by the traditional method in the same solvent. The effect of using MW during the synthesis was to increase yield and crystal size of P3HT. Larger energy conversion efficiency of ITO/CdS/P3HT/CP-Au devices was obtained when the P3HT product had higher molecular weight and head/tail-head/tail (HT-HT triad contents.

Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

Science.gov (United States)

Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M

2016-03-31

The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

Neuroprotective Properties of Compounds Extracted from Dianthus superbus L. against Glutamate-induced Cell Death in HT22 Cells.

Science.gov (United States)

Yun, Bo-Ra; Yang, Hye Jin; Weon, Jin Bae; Lee, Jiwoo; Eom, Min Rye; Ma, Choong Je

2016-01-01

Dianthus superbus L. has been used in Chinese herbal medicine as a diuretic and anti-inflammatory agent. In this study, we isolated ten bioactive compounds from D. superbus and evaluated their neuroprotective activity against glutamate-induced cell death in the hippocampal neuronal HT22 cells. New compound, (E)-methyl-4-hydroxy-4-(8a-methyl-3-oxodecahydronaphthalen-4a-yl) (1) and, nine known compounds, diosmetin-7-O (2'',6''-di-O-α-L-rhamnopyranosyl)-β-D-glucopyranoside (2), 4-hydroxy-3-methoxy-pentyl ester benzenepropanoic acid (3), vanillic acid (4), 4-hydroxy-benzeneacetic acid (5), 4-methoxybenzeneacetic acid (6), (E)-4-methoxycinnamic acid (7), 3-methoxy-4-hydroxyphenylethanol (8), hydroferulic acid (9), and methyl hydroferulate (10), were isolated by bioactivity-guided separation. Structures of the isolated compounds were identified on the basis of (1)H nuclear magnetic resonance (NMR), (13)C NMR, and two-dimensional NMR spectra, while their neuroprotective properties were evaluated by performing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. D. superbus extract had a neuroprotective effect and isolated 10 compounds. Among the compounds, compounds 5 and 6 effectively protected HT22 cells against glutamate toxicity. In conclusion, the extract of D. superbus and compounds isolated from it exhibited neuroprotective properties, suggesting therapeutic potential for applications in neurotoxic diseases. D. superbus extract significantly protected on glutamate-induced cell death in HT22 cellsNew compound, (E)-methyl-4-hydroxy-4-(8a-methyl-3-oxodecahydronaphthalen-4a-yl) (1) and, nine known compounds, diosmetin-7-O(2'',6''-di-O-α-L-rhamnopyranosyl)-β-D-glucopyranoside (2), 4-hydroxy-3-methoxy-pentyl ester benzenepropanoic acid (3), vanillic acid (4), 4-hydroxy-benzeneacetic acid (5), 4-methoxybenzeneacetic acid (6), (E)-4-methoxycinnamic acid (7), 3-methoxy-4-hydroxyphenylethanol (8), hydroferulic acid (9), and methyl hydroferulate (10

Luffa echinata Roxb. Induces Human Colon Cancer Cell (HT-29 Death by Triggering the Mitochondrial Apoptosis Pathway

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Yan Yu

2012-05-01

Full Text Available The antiproliferative properties and cell death mechanism induced by the extract of the fruits of Luffa echinata Roxb. (LER were investigated. The methanolic extract of LER inhibited the proliferation of human colon cancer cells (HT-29 in both dose-dependent and time-dependent manners and caused a significant increase in the population of apoptotic cells. In addition, obvious shrinkage and destruction of the monolayer were observed in LER-treated cells, but not in untreated cells. Analysis of the cell cycle after treatment of HT-29 cells with various concentrations indicated that LER extracts inhibited the cellular proliferation of HT-29 cells via G2/M phase arrest of the cell cycle. The Reactive oxygen species (ROS level determination revealed that LER extracts induced apoptotic cell death via ROS generation. In addition, LER treatment led to a rapid drop in mitochondrial membrane potential (MMP as a decrease in fluorescence. The transcripts of several apoptosis-related genes were investigated by RT-PCR analysis. The caspase-3 transcripts of HT-29 cells significantly accumulated and the level of Bcl-XL mRNA was decreased after treatment with LER extract. Furthermore, the ratio of mitochondria-dependent apoptosis genes (Bax and Bcl-2 was sharply increased from 1.6 to 54.1. These experiments suggest that LER has anticancer properties via inducing the apoptosis in colon cancer cells, which provided the impetus for further studies on the therapeutic potential of LER against human colon carcinoma.

Preparation and characterization of Sr-Ti-hardystonite (Sr-Ti-HT nanocomposite for bone repair application

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Hossein Mohammadi

2015-07-01

Full Text Available Objective(s: Hardystonite (HT is Zn-modified silicate bioceramics with promising results for bone tissue regeneration. However, HT possesses no obvious apatite formation. Thus, in this study we incorporated Sr and Ti into HT to prepare Sr-Ti-hardystonite (Sr-Ti-HT nanocomposite and evaluated its in vitro bioactivity with the purpose of developing a more bioactive bone substitute material. Materials and methods:The HT and Sr-Ti-HT were prepared by mechanical milling and subsequent heat treatment. Calcium oxide (CaO, zinc oxide (ZnO and silicon dioxide (SiO2 (all from Merck were mixed with molar ratio of 2:1:2. The mixture of powders mixture was then milled in a planetary ball mill for 20 h. In the milling run, the ball-to-powder weight ratio was 10:1 and the rotational speed was 200 rpm. After synthesis of HT, 3% nanotitanium dioxide (TiO2, Degussa and 3% strontium carbonate (SrCO3, Merck were added to HT and then the mixture was ball milled and calcined at 1150°C for 6 h. Simultaneous thermal analysis (STA, X-ray diffraction (XRD, Transmission electron microscopy (TEM and Fourier transform infra-red spectroscopy (FT-IR performed to characterize the powders. Results:XRD and FT-IR confirmed the crystal phase and silicate structure of HT and TEM images demonstrated the nanostructure of powders. Further, Sr-Ti-HT induced apatite formation and showed a higher human mesenchymal stem cell (hMSCs adhesion and proliferation compared to HT. Conclusion:Our study revealed that Sr-Ti-HT with a nanostructured crystal structure of 50 nm, can be prepared by mechanical activation to use as biomaterials for orthopedic applications.

HTO/HT discriminating samplers constructed for the french experiment on the environmental behaviour of HT

International Nuclear Information System (INIS)

Ogram, G.L.

1988-12-01

The French Experiment on Environmental Tritium Behaviour was a field experiment carried out to determine the rate of formation of atmospheric HTO from a release of HT to the natural environment. The Canadian Fusion Fuels Technology Project and Ontario Hydro contributed to the project by supplying HTO/HT-discriminating, atmospheric tritium samplers. Each sampler consisted of a molecular-sieve trap to capture HTO followed by a Pd-impregnated molecular-sieve trap to oxidise and collect HT from the same air stream. This method was selected as it provided high sensitivity over short sampling periods and was convenient for field use. Laboratory tests indicated that this system measured HT concentrations reliably, but only achieved limited discrimination between HT and HTO at HTO/HT concentration ratios below 10 -2 to 10 -3 . Small cold traps were therefore operated during the French experiment in addition to the molecular-sieve samplers exhibited much improved discrimination in the field (approaching 10 4 ), possibly due to higher sampling flow rates than used in the laboratory. These results demonstrate that care should be taken in using desiccant-based, HTO/HT-discriminating samplers when the HT concentration is much higher than HTO concentration, and suggest the need to systematically characterize and perhaps improve the performance of discriminating samplers at low HTO/HT ratios

Thermal conductivity and thermal expansion of stainless steels D9 and HT9

International Nuclear Information System (INIS)

Leibowitz, L.; Blomquist, R.A.

1988-01-01

Renewed interest in the use of metallic fuels in liquid-metal fast breeder reactors has prompted study of the thermodynamic and transport properties of its materials. Two stainless steels are of particular interest because of their good performance under irradiation. These are D9, an austenitic steel, and HT9, a ferritic steel. Thermal conductivity and thermal expansion data for these alloys are of particular interest in assessing in-reactor behavior. Because literature data were inadequate, measurements of these two properties for the two steels were performed and are reported to 1200 K. Of particular interest is the influence on these properties of a phase transition in HT9

Optical properties of P3HT:tributylphosphine oxide-capped CdSe nanocomposites

Energy Technology Data Exchange (ETDEWEB)

Benchaabane, A. [Faculte des Sciences d' Amiens, Laboratoire de Physique de la Matiere Condensee, Amiens (France); Universite Tunis El-Manar, Laboratoire de Materiaux avances et phenomenes quantiques, Faculte des Sciences de Tunis El Manar, Tunis (Tunisia); Universite Arabe des Sciences, Ecole Superieure d' Ingenieurs et des Etudes Technologiques, Tunis (Tunisia); Ben Hamed, Z.; Kouki, F.; Bouchriha, H. [Universite Tunis El-Manar, Laboratoire de Materiaux avances et phenomenes quantiques, Faculte des Sciences de Tunis El Manar, Tunis (Tunisia); Lahmar, A.; Zellama, K.; Zeinert, A. [Faculte des Sciences d' Amiens, Laboratoire de Physique de la Matiere Condensee, Amiens (France); Sanhoury, M.A. [Laboratoire de Chimie Organique Structurale, Synthese et Etudes Physicochimiques, Tunis (Tunisia)

2016-08-15

The optical properties of nanocomposite layers prepared by incorporation of tributylphosphine oxide (TBPO)-capped CdSe nanocrystals (NCs) in a P3HT polymer matrix are studied using different nanocrystal concentrations. Reflection spectra analyzed through Kim oscillator model lead to the determination of optical constants such as refractive index n, extinction coefficient k, dielectric permittivity ε and absorption coefficient α. Using the common Cauchy, Drude-Lorentz, Tauc and single-effective-oscillator theoretical models, we have determined the values of static refractive index n{sub s} and permittivity ε{sub s}, plasma frequency ω{sub p}, carrier density N, optical band gap E{sub g} and oscillator and dispersion energies E{sub 0} and E{sub d}, respectively. It is found that TBPO-capped CdSe NCs concentration affects the optoelectronic parameters of the nanocomposite thin films. Moreover, the disorder of this hybrid system is also studied by the determination of Urbach energy, which increases with TBPO-capped CdSe concentration. (orig.)

Antidepressant activity: contribution of brain microdialysis in knock-out mice to the understanding of BDNF/5-HT transporter/5-HT autoreceptor interactions

Directory of Open Access Journals (Sweden)

Alain M Gardier

2013-08-01

Full Text Available Why antidepressants vary in terms of efficacy is currently unclear. Despite the leadership of Selective serotonin reuptake inhibitors (SSRIs in the treatment of depression, the precise neurobiological mechanisms involved in their therapeutic action are poorly understood. A better knowledge of molecular interactions between monoaminergic system, pre- and post-synaptic partners, brain neuronal circuits and regions involved may help to overcome limitations of current treatments and to identify new therapeutic targets. Intracerebral in vivo microdialysis (ICM already provided important information about the brain mechanism of action of antidepressants first in anesthetized rats in the early 90s, and since then in conscious wild-type or knockout mice. The principle of ICM is based on the balance between release of neurotransmitters (e.g., monoamines, and re-uptake by selective transporters (e.g., SERT for serotonin 5-HT. Complementary to electrophysiology, this technique reflects presynaptic monoamines release and intrasynaptic events corresponding to ≈ 80% of whole brain tissue content. The inhibitory role of serotonergic autoreceptors infers that they limit somatodendritic and nerve terminal 5-HT release. It has been proposed that activation of 5-HT1A and 5-HT1B receptor sub-types limit the antidepressant-like activity of Selective Serotonin Reuptake Inhibitors (SSRI. This hypothesis is based partially on results obtained in ICM experiments performed in naïve, non-stressed Rodents. The present review will first remind the principle and methodology of ICM performed in mice. The crucial need of developing animal models that display anxiety and depression-like behaviors, neurochemical and brain morphological phenotypes reminiscent of these mood disorders in Human, will be underlined. Recently developed genetic mouse models have been generated to independently manipulate 5-HT1A auto and hetero-receptors and ICM helped to clarify the role of the

Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: role of 5HT(1A) and CB2 receptors.

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Pazos, M Ruth; Mohammed, Nagat; Lafuente, Hector; Santos, Martin; Martínez-Pinilla, Eva; Moreno, Estefania; Valdizan, Elsa; Romero, Julián; Pazos, Angel; Franco, Rafael; Hillard, Cecilia J; Alvarez, Francisco J; Martínez-Orgado, Jose

2013-08-01

The mechanisms underlying the neuroprotective effects of cannabidiol (CBD) were studied in vivo using a hypoxic-ischemic (HI) brain injury model in newborn pigs. One- to two-day-old piglets were exposed to HI for 30 min by interrupting carotid blood flow and reducing the fraction of inspired oxygen to 10%. Thirty minutes after HI, the piglets were treated with vehicle (HV) or 1 mg/kg CBD, alone (HC) or in combination with 1 mg/kg of a CB₂ receptor antagonist (AM630) or a serotonin 5HT(1A) receptor antagonist (WAY100635). HI decreased the number of viable neurons and affected the amplitude-integrated EEG background activity as well as different prognostic proton-magnetic-resonance-spectroscopy (H(±)-MRS)-detectable biomarkers (lactate/N-acetylaspartate and N-acetylaspartate/choline ratios). HI brain damage was also associated with increases in excitotoxicity (increased glutamate/N-acetylaspartate ratio), oxidative stress (decreased glutathione/creatine ratio and increased protein carbonylation) and inflammation (increased brain IL-1 levels). CBD administration after HI prevented all these alterations, although this CBD-mediated neuroprotection was reversed by co-administration of either WAY100635 or AM630, suggesting the involvement of CB₂ and 5HT(1A) receptors. The involvement of CB₂ receptors was not dependent on a CBD-mediated increase in endocannabinoids. Finally, bioluminescence resonance energy transfer studies indicated that CB₂ and 5HT(1A) receptors may form heteromers in living HEK-293T cells. In conclusion, our findings demonstrate that CBD exerts robust neuroprotective effects in vivo in HI piglets, modulating excitotoxicity, oxidative stress and inflammation, and that both CB₂ and 5HT(1A) receptors are implicated in these effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preliminary evaluation of microstructure and mechanical properties on low activation ferritic steels

International Nuclear Information System (INIS)

Hsu, C.Y.; Lechtenberg, T.A.

1985-01-01

Radioactive waste disposal has become a primary concern for the selection of materials for the structural components for fusion reactors. One way to minimize this potential environmental problem is to use structural materials in which the induced radioactivity decays quickly to levels that allow for near-surface disposal under 10CFR61 rules. The primary objective of this work is to develop low activation ferritic steels that exhibit mechanical and physical properties approximately equivalent to the HT-9 and 9Cr-1Mo steels, but which only contain elements that would permit near-surface disposal under 10CFR61 after exposure to fusion neutrons. A preliminary evaluation of the microstructure and mechanical properties of a 9Cr-2.5W-0.3V-0.15C (GA3X) low activation ferritic steel has been performed. An optimum heat treatment condition has been defined for GA3X steel. The properties and microstructure of the quenched and tempered specimens were characterized via hardness measurement and optical metallographic observation. The hot-microhardness and ductility parameter measurements were used to estimate the tensile properties at elevated temperatures. The estimated tensile strengths of GA3X steel at elevated temperatures are comparable to both 9Cr-1Mo and the modified 9Cr-1Mo steels. These preliminary results are encouraging in that they suggest that suitable low activation alloys can be successfully produced in this ferritic alloy class

Acetylation/deacetylation reactions of T-2, acetyl T-2, HT-2, and acetyl HT-2 toxins in bovine rumen fluid in vitro

International Nuclear Information System (INIS)

Munger, C.E.; Ivie, G.W.; Christopher, R.J.; Hammock, B.D.; Phillips, T.D.

1987-01-01

A tritiated preparation of the trichothecene mycotoxin, T-2 toxin, underwent both acetylation and deacetylation reactions when incubated with bovine rumen fluid in vitro. Products from incubations of T-2 in rumen fluid included acetyl T-2, HT-2, and acetyl HT-2. Direct studies with tritiated samples of each of these metabolites confirmed their relatively facile interconversion in the rumen. Studies with [ 3 H]HT-2 under conditions of inhibited esterase activity (added diisopropyl fluorophosphate) showed that acetylation is preferred at C-3 vs. C-4. Studies with [ 3 H]acetyl T-2 indicated that deacetylation similarly occurs with greater rapidity at C-3. There were no indications that ester hydrolysis of these trichothecenes occurred at C-8 or C-15 or that they were subjected to epoxide reduction reactions. These data suggest that acetylation of T-2 and other trichothecenes in the rumen in situ may ultimately result in the absorption of more lipophilic metabolites whose toxicological and residual properties are at present unknown

Enhancement of cortical extracellular 5-HT by 5-HT1A and 5-HT2C receptor blockade restores the antidepressant-like effect of citalopram in non-responder mice.

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Calcagno, Eleonora; Guzzetti, Sara; Canetta, Alessandro; Fracasso, Claudia; Caccia, Silvio; Cervo, Luigi; Invernizzi, Roberto W

2009-07-01

We recently found that the response of DBA/2 mice to SSRIs in the forced swim test (FST) was impaired and they also had a smaller basal and citalopram-stimulated increase in brain extracellular serotonin (5-HT) than 'responder' strains. We employed intracerebral microdialysis, FST and selective antagonists of 5-HT1A and 5-HT2C receptors to investigate whether enhancing the increase in extracellular 5-HT reinstated the anti-immobility effect of citalopram in the FST. WAY 100635 (0.3 mg/kg s.c.) or SB 242084 (1 mg/kg s.c.), respectively a selective 5-HT1A and 5-HT2C receptor antagonist, raised the effect of citalopram (5 mg/kg) on extracellular 5-HT in the medial prefrontal cortex of DBA/2N mice (citalopram alone 5.2+/-0.3 fmol/20 microl, WAY 100635+citalopram 9.9+/-2.1 fmol/20 microl, SB 242084+ citalopram 7.6+/-1.0 fmol/20 microl) to the level reached in 'responder' mice given citalopram alone. The 5-HT receptor antagonists had no effect on the citalopram-induced increase in extracellular 5-HT in the dorsal hippocampus. The combination of citalopram with WAY 100635 or SB 242084 significantly reduced immobility time in DBA/2N mice that otherwise did not respond to either drug singly. Brain levels of citalopram in mice given citalopram alone or with 5-HT antagonists did not significantly differ. The results confirm that impaired 5-HT transmission accounts for the lack of effect of citalopram in the FST and suggest that enhancing the effect of SSRIs on extracellular 5-HT, through selective blockade of 5-HT1A and 5-HT2C receptors, could be a useful strategy to restore the response in treatment-resistant depression.

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

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Meneses, Alfredo

2002-05-01

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

The inhibition of cholera toxin-induced 5-HT release by the 5-HT3 receptor antagonist, granisetron, in the rat

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Turvill, J L; Connor, P; Farthing, M J G

2000-01-01

The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the pathophysiology of cholera. 5-HT released from enterochromaffin cells after cholera toxin exposure is thought to activate non-neuronally (5-HT2 dependent) and neuronally (5-HT3 dependent) mediated water and electrolyte secretion. CT-secretion can be reduced by preventing the release of 5-HT. Enterochromaffin cells possess numerous receptors that, under basal conditions, modulate 5-HT release. These include basolateral 5-HT3 receptors, the activation of which is known to enhance 5-HT release. Until now, 5-HT3 receptor antagonists (e.g. granisetron) have been thought to inhibit cholera toxin-induced fluid secretion by blockading 5-HT3 receptors on secretory enteric neurones. Instead we postulated that they act by inhibiting cholera toxin-induced enterochromaffin cell degranulation. Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 μg kg−1, lidoocaine 6 mg kg−1 or saline, were instilled with a supramaximal dose of cholera toxin or saline. Net fluid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal fluid 5-HT levels were determined by HPLC with fluorimetric detection. Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell activity. Both lidocaine and granisetron inhibited fluid secretion. However, granisetron alone, and proportionately, reduced 5-HT release. The simultaneous inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT release from enterochromaffin cells is potentiated by endogenous 5-HT3 receptors. The accentuated 5-HT release promotes cholera toxin-induced fluid secretion. PMID:10882387

Design and Discovery of Functionally Selective Serotonin 2C (5-HT2C) Receptor Agonists.

Science.gov (United States)

Cheng, Jianjun; McCorvy, John D; Giguere, Patrick M; Zhu, Hu; Kenakin, Terry; Roth, Bryan L; Kozikowski, Alan P

2016-11-10

On the basis of the structural similarity of our previous 5-HT 2C agonists with the melatonin receptor agonist tasimelteon and the putative biological cross-talk between serotonergic and melatonergic systems, a series of new (2,3-dihydro)benzofuran-based compounds were designed and synthesized. The compounds were evaluated for their selectivity toward 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors in the calcium flux assay with the ultimate goal to generate selective 5-HT 2C agonists. Selected compounds were studied for their functional selectivity by comparing their transduction efficiency at the G protein signaling pathway versus β-arrestin recruitment. The most functionally selective compound (+)-7e produced weak β-arrestin recruitment and also demonstrated less receptor desensitization compared to serotonin in both calcium flux and phosphoinositide (PI) hydrolysis assays. We report for the first time that selective 5-HT 2C agonists possessing weak β-arrestin recruitment can produce distinct receptor desensitization properties.

Psychopharmacology of 5-HT1A receptors

International Nuclear Information System (INIS)

Cowen, Philip J.

2000-01-01

Serotonin 1A (5-HT 1A ) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT 1A receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT 1A receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT 1A receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT 1A receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT 1A receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT 1A autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT 1A receptor antagonists

Study of charge transport in composite blend of P3HT and PCBM

Science.gov (United States)

Kumar, Manoj; Kumar, Sunil; Upadhyaya, Aditi; Yadav, Anjali; Gupta, Saral K.; Singh, Amarjeet

2018-05-01

Poly (3-hexylthiophene-2,5diyl) (P3HT) as donor and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) as acceptor are mostly used as active medium in polymeric electronic device. In this paper we have prepare the P3HT - PCBM based bulk hetero junction thin films by spin coating technique. The charge transport properties of P3HT:PCBM blends are investigated by the current-voltage measurements using Ag as an electron injecting electrode and ITO as a hole injecting contact. The current density v/s voltage relationships are analyzed in the backdrop of Schottky and Space charge limited current model.

Both exogenous 5-HT and endogenous 5-HT, released by fluoxetine, enhance distension evoked propulsion in guinea-pig ileum in vitro

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Rachel M Gwynne

2014-09-01

Full Text Available The roles of 5-HT3 and 5-HT4 receptors in the modulation of intestinal propulsion by luminal application of 5-HT and augmentation of endogenous 5-HT effects were studied in segments of guinea-pig ileum in vitro. Persistent propulsive contractions evoked by saline distension were examined using a modified Trendelenburg method. When 5-HT (30 nM, fluoxetine (selective serotonin reuptake inhibitor; 1 nM, 2-methyl-5-HT (5-HT3 receptor agonist; 1 mM or RS 67506 (5-HT4 receptor agonist, 1 µM was infused into the lumen, the pressure needed to initiate persistent propulsive activity fell significantly. A specific 5-HT4 receptor antagonist, SB 207266 (10 nM in lumen, abolished the effects of 5-HT, fluoxetine, and RS 67506, but not those of 2-methyl-5-HT. Granisetron (5-HT3 receptor antagonist; 1 µM in lumen abolished the effect of 5-HT, fluoxetine, RS 67506 and 2-methyl-5-HT. The NK3 receptor antagonist SR 142801 (100 nM in lumen blocked the effects of 5-HT, fluoxetine and 2-methyl-5-HT. SB 207266, granisetron and SR 142801 had no effect by themselves. Higher concentrations of fluoxetine (100 nM and 300 nM and RS 67506 (3 µM and 10 µM had no effect on the distension threshold for propulsive contractions. These results indicate that luminal application of exogenous 5-HT, or increased release of endogenous mucosal 5-HT above basal levels, acts to lower the threshold for propulsive contractions in the guinea-pig ileum via activation of 5-HT3 and 5-HT4 receptors and the release of tachykinins. The results further indicate that basal release of 5-HT is insufficient to alter the threshold for propulsive motor activity.

What would 5-HT do? Regional diversity of 5-HT1 receptor modulation of primary afferent neurotransmission

OpenAIRE

Connor, Mark

2012-01-01

5-HT (serotonin) is a significant modulator of sensory input to the CNS, but the only analgesics that selectively target G-protein-coupled 5-HT receptors are highly specific for treatment of headache. Two recent papers in BJP shed light on this puzzling situation by showing that primary afferent neurotransmission to the superficial layers of the spinal and trigeminal dorsal is inhibited by different subtypes of the 5-HT1 receptor – 5-HT1B(and 1D) in the trigeminal dorsal horn and 5-HT1A in th...

Study on the Property Change of Rhizoma Coptidis and Its Ginger Juice Processed Products Based on 5-Ht Level and Brain Tissues Morphology of Rats

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Zhong, Lingyun; Tong, Hengli; Lv, Mu; Deng, Yufen

2017-09-01

According to the theory of traditional Chinese Medicine (TCM), all Chinese materia medica need to be processed using Pao zhi which is a processing technology before being used in clinic. Ginger juice, made from dried or fresh ginger, is one of the main TCM processing accessories and always used to help change some Chinese materia medica’s properties for its warm or hot nature. The purpose of this paper is to discuss the influence of ginger juice on Rhizoma Coptidis (RC) by determining 5-hydroxytryptamine (5-HT) content and observing morphological changes in the harns tissue of rats. Raw Rhizoma Coptidis (RRC), fresh ginger juice processed Rhizoma Coptidis (FGJPRC), dried juice processed Rhizoma Coptidis (DGJPRC), dried ginger juice (DGJ) and fresh ginger juice (FGJ) were prepared using appropriate methods. Immunohistochemical staining was used to observe the distribution of 5-HT and fluorescence spectrophotometry was applied to determine 5-hydroxytryptamine content in the brain tissue of rats. 5 - HT in brain tissue of the rats of RRC group was distributed most densely, with the highest content. Compared to the blank group, RRC and different ginger processed RC groups could lead to increasing content of 5-HT in rat encephalon, and significant differences in RRC. Compared with the RRC, the 5-HT content in rat encephalon in DGJPRC, FGJPRC, FGJ and DGJ groups reduced, and DGJPRC, FGJPRC groups showed significant difference, FGJ and DGJ groups showed extreme significant differences. The research showed that processing with hot, warm accessories would moderate the cold nature of RC. The cold and hot nature of Traditional Chinese Materia Medica could be expressed by the difference of 5-HT contents and morphological changes of rats’ brain tissue. Simultaneously, the research showed the different excipient of ginger juice would have different effects on the processing of RC.

Acetylation/deacetylation reactions of T-2, acetyl T-2, HT-2, and acetyl HT-2 toxins in bovine rumen fluid in vitro

Energy Technology Data Exchange (ETDEWEB)

Munger, C.E.; Ivie, G.W.; Christopher, R.J.; Hammock, B.D.; Phillips, T.D.

A tritiated preparation of the trichothecene mycotoxin, T-2 toxin, underwent both acetylation and deacetylation reactions when incubated with bovine rumen fluid in vitro. Products from incubations of T-2 in rumen fluid included acetyl T-2, HT-2, and acetyl HT-2. Direct studies with tritiated samples of each of these metabolites confirmed their relatively facile interconversion in the rumen. Studies with (/sup 3/H)HT-2 under conditions of inhibited esterase activity (added diisopropyl fluorophosphate) showed that acetylation is preferred at C-3 vs. C-4. Studies with (/sup 3/H)acetyl T-2 indicated that deacetylation similarly occurs with greater rapidity at C-3. There were no indications that ester hydrolysis of these trichothecenes occurred at C-8 or C-15 or that they were subjected to epoxide reduction reactions. These data suggest that acetylation of T-2 and other trichothecenes in the rumen in situ may ultimately result in the absorption of more lipophilic metabolites whose toxicological and residual properties are at present unknown.

Interaction of cruciferin-based nanoparticles with Caco-2 cells and Caco-2/HT29-MTX co-cultures.

Science.gov (United States)

Akbari, Ali; Lavasanifar, Afsaneh; Wu, Jianping

2017-12-01

The objective of this work was to assess the potential of Cruciferin/Calcium (Cru/Ca) and Cruciferin/Chitosan (Cru/Cs) nanoparticles for oral drug delivery. For this purpose, Cru/Ca and Cru/Cs nanoparticles were developed through cold gelation of Cruciferin, a major canola protein, and in interaction with calcium and chitosan, respectively. The extent and rate of particle uptake in Caco-2 cells and Caco-2/HT29 co-culture was then evaluated by fluorescence spectroscopy as well as flow cytometry. Through pre-incubation of Caco-2 cell monolayer with specific endocytosis inhibitors, the mechanism of cell uptake was investigated. Our results showed that the uptake of negatively-charged Cru/Ca particles to be ∼3 times higher than positively-charged Cru/Cs ones by Caco-2 cells. Presence of mucus secreted by HT29 cells in their co-culture with Caco-2 had negligible influence on the uptake and transport of both particles. In contrast to Cru/Ca particles which were dissociated in the simulated gastrointestinal conditions, digestion of Cru/Cs particles resulted in 6- and 2-fold increase in the cellular uptake and transport of encapsulated coumarin in the latter particles, respectively. While the presence of mucus in Caco-2/HT29 co-culture caused 40-50% decrease of cellular uptake and transport for coumarin encapsulated in digested Cru/Cs particles, it had no significant effect on the cell uptake and transport of coumarin associated with Cru/Ca particles after digestion. Energy-dependent mechanisms were the dominant mechanism for uptake of both undigested and digested particles. Therefore, in Caco-2/HT29 co-culture which closely simulated intestinal epithelial cells, undigested Cru/Ca and Cru/Cs particles had the ability to penetrate mucus layers, while digested Cru/Cs particles showed mucoadhesive property, and digested Cru/Ca particles were dissociated. Our results points to a potential for cruciferin based nanoparticles for oral drug delivery. The long-term objective of

h5-HT(1B) receptor-mediated constitutive Galphai3-protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5-HT.

Science.gov (United States)

Newman-Tancredi, Adrian; Cussac, Didier; Marini, Laetitia; Touzard, Manuelle; Millan, Mark J

2003-03-01

) activation and leads to protean agonist properties of 5-HT: that is a switch to inhibition of Galpha(i3).

Effect of multiple austenitizing treatments on HT-9 steels

International Nuclear Information System (INIS)

Emigh, R.A.

1985-12-01

The effect of multiple austenitizing treatments on the toughness of an Fe-12Cr-1.0Mo-0.5W-0.3V (HT-9) steel was studied. The resulting microstructures were characterized by their mechanical properties, precipitated carbide distribution, and fracture surface appearance. It was proposed that multiple transformations would refine the martensite structure and improve toughness. Optical and scanning electron microscopic observations revealed that the martensite packet structure was somewhat refined by a second austenite transformation. Transmission electron microscopy studies of carbon extraction replicas showed that this multiple step treatment had eliminated grain boundary carbide films seen in single treated specimens on prior austenite grain boundaries. The 0.2% yield strength, tensile strength, and elongation were relatively unchanged, but the toughness measured by fatigue pre-cracked Charpy impact tests increased for the multiple step specimens

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding

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Mc Mahon, Brenda; MacDonald Fisher, Patrick; Jensen, Peter Steen; Svarer, Claus; Moos Knudsen, Gitte

2016-01-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [11C]SB207145 for quantification of brain 5-HT4R binding. The Buss–Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. PMID:26772668

Synthesis and pharmacological evaluation of a new series of radiolabeled ligands for 5-HT7 receptor PET neuroimaging

International Nuclear Information System (INIS)

Colomb, Julie; Becker, Guillaume; Forcellini, Elsa; Meyer, Sandra; Buisson, Lauriane; Zimmer, Luc; Billard, Thierry

2014-01-01

Introduction: The brain serotonin-7 receptor (5-HT 7 ) is the most recently discovered serotonin receptor. It is targeted by several drug-candidates in psychopharmacology and neuropharmacology. In these fields, positron emission tomography (PET) is a molecular imaging modality offering great promise for accelerating the development process from preclinical discovery to clinical phases. We recently described fluorinated 5-HT 7 radioligands, inspired by the structure of SB269970, the prototypical 5-HT 7 antagonist. Although these results were promising, it appeared that the radiotracer-candidates suffered, among other drawbacks, from too low a 5-HT 7 receptor affinity. Methods: In the present study, seven structural analogs of SB269970 were synthesized using design strategies aiming to improve their radiopharmacological properties. Their 5-HT 7 binding properties were investigated by cellular functional assay. The nitro-precursors of the analogs were radiolabeled by [ 18 F-]nucleophilic substitution, and in vitro autoradiography was performed in rat brain, followed by in vivo microPET. Result: The chemical and radiochemical purity of the fluorine radiotracers was > 99% with specific activity in the 40–129 GBq/μmol range. The seven derivatives presented heterogeneous binding affinities toward 5-HT 7 and 5-HT 1A receptors. While [ 18 F]2F3P3 had promising characteristics in vitro, it showed poor brain penetration in vivo, partially reversed after pharmacological inhibition of P-glycoprotein. Conclusions: These results indicated that, while chemical modification of these series improved several radiotracer-candidates in terms of 5-HT 7 receptor affinity and specificity toward 5-HT 1A receptors, other physicochemical modulations would be required in order to increase brain penetration

Function and distribution of 5-HT2 receptors in the honeybee (Apis mellifera.

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Markus Thamm

Full Text Available BACKGROUND: Serotonin plays a pivotal role in regulating and modulating physiological and behavioral processes in both vertebrates and invertebrates. In the honeybee (Apis mellifera, serotonin has been implicated in division of labor, visual processing, and learning processes. Here, we present the cloning, heterologous expression, and detailed functional and pharmacological characterization of two honeybee 5-HT2 receptors. METHODS: Honeybee 5-HT2 receptor cDNAs were amplified from brain cDNA. Recombinant cell lines were established constitutively expressing receptor variants. Pharmacological properties of the receptors were investigated by Ca(2+ imaging experiments. Quantitative PCR was applied to explore the expression patterns of receptor mRNAs. RESULTS: The honeybee 5-HT2 receptor class consists of two subtypes, Am5-HT2α and Am5-HT2β. Each receptor gene also gives rise to alternatively spliced mRNAs that possibly code for truncated receptors. Only activation of the full-length receptors with serotonin caused an increase in the intracellular Ca(2+ concentration. The effect was mimicked by the agonists 5-methoxytryptamine and 8-OH-DPAT at low micromolar concentrations. Receptor activities were blocked by established 5-HT receptor antagonists such as clozapine, methiothepin, or mianserin. High transcript numbers were detected in exocrine glands suggesting that 5-HT2 receptors participate in secretory processes in the honeybee. CONCLUSIONS: This study marks the first molecular and pharmacological characterization of two 5-HT2 receptor subtypes in the same insect species. The results presented should facilitate further attempts to unravel central and peripheral effects of serotonin mediated by these receptors.

Function and distribution of 5-HT2 receptors in the honeybee (Apis mellifera).

Science.gov (United States)

Thamm, Markus; Rolke, Daniel; Jordan, Nadine; Balfanz, Sabine; Schiffer, Christian; Baumann, Arnd; Blenau, Wolfgang

2013-01-01

Serotonin plays a pivotal role in regulating and modulating physiological and behavioral processes in both vertebrates and invertebrates. In the honeybee (Apis mellifera), serotonin has been implicated in division of labor, visual processing, and learning processes. Here, we present the cloning, heterologous expression, and detailed functional and pharmacological characterization of two honeybee 5-HT2 receptors. Honeybee 5-HT2 receptor cDNAs were amplified from brain cDNA. Recombinant cell lines were established constitutively expressing receptor variants. Pharmacological properties of the receptors were investigated by Ca(2+) imaging experiments. Quantitative PCR was applied to explore the expression patterns of receptor mRNAs. The honeybee 5-HT2 receptor class consists of two subtypes, Am5-HT2α and Am5-HT2β. Each receptor gene also gives rise to alternatively spliced mRNAs that possibly code for truncated receptors. Only activation of the full-length receptors with serotonin caused an increase in the intracellular Ca(2+) concentration. The effect was mimicked by the agonists 5-methoxytryptamine and 8-OH-DPAT at low micromolar concentrations. Receptor activities were blocked by established 5-HT receptor antagonists such as clozapine, methiothepin, or mianserin. High transcript numbers were detected in exocrine glands suggesting that 5-HT2 receptors participate in secretory processes in the honeybee. This study marks the first molecular and pharmacological characterization of two 5-HT2 receptor subtypes in the same insect species. The results presented should facilitate further attempts to unravel central and peripheral effects of serotonin mediated by these receptors.

Probing Structural Changes in Poly(3-hexylthiophene) (P3HT) During Electrochemical Oxidation with In Situ X-ray Scattering

Science.gov (United States)

Thelen, Jacob L.; Patel, Shrayesh N.; Javier, Anna E.; Balsara, Nitash P.

2014-03-01

Mixtures of poly(3-hexylthiophene)-b-poly(ethylene oxide) (P3HT-b-PEO) block copolymer and lithium bis(trifluromethanesulfonyl) imide (LiTFSI) salt can microphase separate into electron (P3HT) and ion (PEO/LiTFSI) conducting domains. P3HT is a semicrystalline polymer with intrinsically semiconducting electronic properties. Electrochemical oxidation (doping) of the P3HT block provides the P3HT-b-PEO/LiTFSI mixtures with electronic conductivity suitable for lithium battery operation. Due to the presence of the solid-state electrolyte (PEO/LiTFSI) in intimate contact with the microphase separated P3HT domains, electrochemical oxidation of P3HT can be performed entirely in the solid state; therefore, P3HT-b-PEO/LiTFSI provides a unique opportunity to study the structural changes in P3HT induced by oxidation. We use in situ x-ray scattering techniques to probe structural changes in P3HT during electrochemical oxidation and correlate these changes with previously observed enhancements in electron mobility. Supported by the Joint Center for Energy Storage Research (JCESR).

Blockade of the high-affinity noradrenaline transporter (NET) by the selective 5-HT reuptake inhibitor escitalopram: an in vivo microdialysis study in mice

Science.gov (United States)

Nguyen, Hai T; Guiard, Bruno P; Bacq, Alexandre; David, Denis J; David, Indira; Quesseveur, Gaël; Gautron, Sophie; Sanchez, Connie; Gardier, Alain M

2013-01-01

BACKGROUND AND PURPOSE Escitalopram, the S(+)-enantiomer of citalopram is the most selective 5-HT reuptake inhibitor approved. Although all 5-HT selective reuptake inhibitors (SSRIs) increase extracellular levels of 5-HT ([5-HT]ext). some also enhance, to a lesser extent, extracellular levels of noradrenaline ([NA]ext). However, the mechanisms by which SSRIs activate noradrenergic transmission in the brain remain to be determined. EXPERIMENTAL APPROACH This study examined the effects of escitalopram, on both [5-HT]ext and [NA]ext in the frontal cortex (FCx) of freely moving wild-type (WT) and mutant mice lacking the 5-HT transporter (SERT−/−) by using intracerebral microdialysis. We explored the possibilities that escitalopram enhances [NA]ext, either by a direct mechanism involving the inhibition of the low- or high-affinity noradrenaline transporters, or by an indirect mechanism promoted by [5-HT]ext elevation. The forced swim test (FST) was used to investigate whether enhancing cortical [5-HT]ext and/or [NA]ext affected the antidepressant-like activity of escitalopram. KEY RESULTS In WT mice, a single systemic administration of escitalopram produced a significant increase in cortical [5-HT]ext and [NA]ext. As expected, escitalopram failed to increase cortical [5-HT]ext in SERT−/− mice, whereas its neurochemical effects on [NA]ext persisted in these mutants. In WT mice subjected to the FST, escitalopram increased swimming parameters without affecting climbing behaviour. Finally, escitalopram, at relevant concentrations, failed to inhibit cortical noradrenaline and 5-HT uptake mediated by low-affinity monoamine transporters. CONCLUSIONS AND IMPLICATIONS These experiments suggest that escitalopram enhances, although moderately, cortical [NA]extin vivo by a direct mechanism involving the inhibition of the high-affinity noradrenaline transporter (NET). PMID:22233336

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding

DEFF Research Database (Denmark)

da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald

2016-01-01

of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145......Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels...... for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well...

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding.

Science.gov (United States)

da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald; Jensen, Peter Steen; Svarer, Claus; Knudsen, Gitte Moos

2016-04-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145 for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

h5-HT1B receptor-mediated constitutive Gαi3-protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5-HT

Science.gov (United States)

Newman-Tancredi, Adrian; Cussac, Didier; Marini, Laetitia; Touzard, Manuelle; Millan, Mark J

2003-01-01

Serotonin 5-HT1B receptors couple to G-proteins of the Gi/o family. However, their activation of specific G-protein subtypes is poorly characterised. Using an innovative antibody capture/guanosine-5′-0-(3-[35S]thio)-triphosphate ([35S]GTPγS) binding strategy, we characterised Gαi3 subunit activation by h5-HT1B receptors stably expressed in Chinese hamster ovary (CHO) cells. The agonists, 5-HT, alniditan and BMS181,101, stimulated Gαi3, whereas methiothepin and SB224,289 behaved as inverse agonists. The selective 5-HT1B receptor ligand, S18127, modestly stimulated Gαi3 and reversed the actions of both 5-HT and methiothepin. S18127 (1 μM) also produced parallel, dextral shifts of the 5-HT and methiothepin isotherms. Isotopic dilution experiments ([35S]GTPγS versus GTPγS) revealed high-affinity [35S]GTPγS binding to Gαi3 subunits in the absence of receptor ligands indicating constitutive activity. High-affinity [35S]GTPγS binding was increased 2.8-fold by 5-HT with an increase in the affinity of GTPγS for Gαi3 subunits. In contrast, methiothepin halved the number of high-affinity binding sites and decreased their affinity. h5-HT1B receptor-mediated Gαi3 subunit activation was dependent on the concentration of NaCl. At 300 mM, 5-HT stimulated [35S]GTPγS binding, basal Gαi3 activation was low and methiothepin was inactive. In contrast, at 10 mM NaCl, basal activity was enhanced and the inverse agonist activity of methiothepin was accentuated. Under these conditions, 5-HT decreased Gαi3 activation. In conclusion, at h5-HT1B receptors expressed in CHO cells: (i) inverse agonist induced inhibition of Gαi3, and its reversal by S18127, reveals constitutive activation of this Gα subunit; (ii) constitutive Gαi3 activation can be quantified by isotopic dilution [35S]GTPγS binding and (iii) decreasing NaCl concentrations enhances Gαi3 activation and leads to protean agonist properties of 5-HT: that is a switch to inhibition of Gαi3. PMID:12684263

Pet imaging of human pituitary 5-HT2 receptors with F-18 setoperone

Energy Technology Data Exchange (ETDEWEB)

Fischman, A.J.; Bonab, A.A.; Babich, J.W. [Massachusetts General Hospital, Boston, MA (United States)] [and others

1995-05-01

Serotonin (5-HT) receptors play an important role in the regulation of pituitary function. In particular, 5HT agonists stimulate ACTH, {beta}-endorphin, prolactin and growth hormone secretion but inhibit TSH release. 5-HT binding sites have been identified by autoradiographic studies of rat and human pituitary. In the present investigation, we used PET with F-18 setoperone to image 5-HT2 receptors in normal humans. Setoperone, a piperidine derivative with potent 5-HT2 receptor blocking properties was labelled with F-18 by nucleophilic substitution on the nitro derivative. After HPLC purification, specific activity was between 10,000 and 15,000 mCi/{mu} mole and radiochemical purity was >98%. Six healthy male volunteers were injected with 5-7 mCi of F-18. Setoperone and serial PET images and arterial blood samples were collected over 2 hrs. Specific binding to 5-HT2 receptors in the frontal cortex (FC), striatum (ST) and pituitary (P) was quantitated using the cerebellum (C) as reference. The tracer showed clear retention in FC, ST and P (known to contain a high density of 5-HT2 receptors) relative to C (known to be devoid of 5-HT2 receptors). In all subjects, FC/C, ST/C and P/C ratios increased during the first hr. and remained stable thereafter. For FC and ST, the ratios reached similar values; 3.92{plus_minus}0.73 and 3.53{plus_minus}0.32. For pituitary, a significantly higher ratio, was measured at all times; 6.53{plus_minus}1.82 (p<0.01). These results indicate that F-18 setoperone is an effective PET radiopharmaceutical for imaging 5-HT2 receptors in the human pituitary. Future applications of this agent could provide important new insights into neuroendocrine function.

Psychopharmacology of 5-HT{sub 1A} receptors

Energy Technology Data Exchange (ETDEWEB)

Cowen, Philip J

2000-07-01

Serotonin{sub 1A} (5-HT{sub 1A}) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT{sub 1A} receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT{sub 1A} receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT{sub 1A} receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT{sub 1A} receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT{sub 1A} receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT{sub 1A} autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT{sub 1A} receptor antagonists.

Effect of high hydrogen content on metallurgical and mechanical properties of zirconium alloy claddings after heat-treatment at high temperature

International Nuclear Information System (INIS)

Turque, Isabelle

2016-01-01

Under hypothetical loss-of-coolant accident conditions, fuel cladding tubes made of zirconium alloys can be exposed to steam at high temperature (HT, up 1200 C) before being cooled and then quenched in water. In some conditions, after burst occurrence the cladding can rapidly absorb a significant amount of hydrogen (secondary hydriding), up to 3000 wt.ppm locally, during steam exposition at HT. The study deals with the effect, poorly studied up to date, of high contents of hydrogen on the metallurgical and mechanical properties of two zirconium alloys, Zircaloy-4 and M5, during and after cooling from high temperatures, at which zirconium is in its β phase. A specific facility was developed to homogeneously charge in hydrogen up to ∼ 3000 wt.ppm cladding tube samples of several centimeters in length. Phase transformations, chemical element partitioning and hydrogen precipitation during cooling from the β temperature domain of zirconium were studied by using several techniques, for the materials containing up to ∼ 3000 wt.ppm of hydrogen in average: in-situ neutron diffraction upon cooling from 700 C, X-ray diffraction, μ-ERDA, EPMA and electron microscopy in particular. The results were compared to thermodynamic predictions. In order to study the effect of high hydrogen contents on the mechanical behavior of the (prior-)μ phase of zirconium, axial tensile tests were performed at various temperatures between 20 and 700 C upon cooling from the β temperature domain, on samples with mean hydrogen contents up to ∼ 3000 wt.ppm. The results show that metallurgical and mechanical properties of the (prior-)β phase of zirconium alloys strongly depend on temperature and hydrogen content. (author) [fr

Temperature-dependent structural properties of P3HT films

Energy Technology Data Exchange (ETDEWEB)

Grigorian, S; Joshi, S; Pietsch, U, E-mail: grigorian@physik.uni-siegen.de [Institute of Physics, University Siegen, Walter Flex Strasse 3, D-57068, Siegen (Germany)

2010-11-15

Structural investigations of spin coated and drop cast poly(3-hexylthiophene) P3HT films have been performed under x-ray grazing incidence geometry. Drop cast films revealed to be highly oriented and crystalline and only slightly modify with the temperature. In contrast, spin coated films provided random orientational distribution of nanocrystallites and undergo significant morphological and structural changes during annealing. Interestingly, spin coated films of low and high molecular weight fractions behavior differently as a function of temperature. Crystalline domains of the low molecular weight fractions have been decreased, and, in contrast, we found an improvement of crystallinity of high molecular weight fraction with increase of the temperature.

Temperature-dependent structural properties of P3HT films

International Nuclear Information System (INIS)

Grigorian, S; Joshi, S; Pietsch, U

2010-01-01

Structural investigations of spin coated and drop cast poly(3-hexylthiophene) P3HT films have been performed under x-ray grazing incidence geometry. Drop cast films revealed to be highly oriented and crystalline and only slightly modify with the temperature. In contrast, spin coated films provided random orientational distribution of nanocrystallites and undergo significant morphological and structural changes during annealing. Interestingly, spin coated films of low and high molecular weight fractions behavior differently as a function of temperature. Crystalline domains of the low molecular weight fractions have been decreased, and, in contrast, we found an improvement of crystallinity of high molecular weight fraction with increase of the temperature.

Metabolism and apoptotic properties of elevated ceramide in HT29(rev) cells

NARCIS (Netherlands)

Veldman, R J; Klappe, K; Hoekstra, D; Kok, J W

1998-01-01

Ceramide (Cer) has been implicated in the regulation of apoptosis. In this study, we elevated cellular Cer levels in human colon-carcinoma (HT29(rev)) cells by incubating the cells in the presence of bacterial sphingomyelinase (bSMase) or, alternatively, in the presence of C2-Cer, a short-chain

Adaptation of antenna profiles for control of MR guided hyperthermia (HT) in a hybrid MR-HT system

International Nuclear Information System (INIS)

Weihrauch, Mirko; Wust, Peter; Weiser, Martin; Nadobny, Jacek; Eisenhardt, Steffen; Budach, Volker; Gellermann, Johanna

2007-01-01

A combined numerical-experimental iterative procedure, based on the Gauss-Newton algorithm, has been developed for control of magnetic resonance (MR)-guided hyperthermia (HT) applications in a hybrid MR-HT system BSD 2000 3D-MRI. In this MR-HT system, composed of a 3-D HT applicator Sigma-Eye placed inside a tunnel-type MR tomograph Siemens MAGNETOM Symphony (1.5 T), the temperature rise due to the HT radiation can be measured on-line in three dimensions by use of the proton resonance frequency shift (PRFS) method. The basic idea of our iterative procedure is the improvement of the system's characterization by a step-by-step modification of the theoretical HT antenna profiles (electric fields radiated by single antennas). The adaptation of antenna profiles is efficient if the initial estimates are radiation fields calculated from a good a priori electromagnetic model. Throughout the iterative procedure, the calculated antenna fields (FDTD) are step-by-step modified by comparing the calculated and experimental data, the latter obtained using the PRFS method. The procedure has been experimentally tested on homogeneous and inhomogeneous phantoms. It is shown that only few comparison steps are necessary for obtaining a dramatic improvement of the general predictability and quality of the specific absorption rate (SAR) inside the MR-HT hybrid system

Mechanical properties of martensitic alloy AISI 422

International Nuclear Information System (INIS)

Huang, F.H.; Hu, W.L.; Hamilton, M.L.

1992-09-01

HT9 is a martensitic stainless steel that has been considered for structural applications in liquid metal reactors (LMRs) as well as in fusion reactors. AISI 422 is a commercially available martensitic stainless steel that closely resembles HT9, and was studied briefly under the auspices of the US LMR program. Previously unpublished tensile, fracture toughness and charpy impact data on AISI 422 were reexamined for potential insights into the consequences of the compositional differences between the two alloys, particularly with respect to current questions concerning the origin of the radiation-induced embrittlement observed in HT9. 8 refs, 8 figs

Differences in the effects of 5-HT1A receptor agonists on forced swimming behavior and brain 5-HT metabolism between low and high aggressive mice

NARCIS (Netherlands)

Veenema, AH; Cremers, TIFH; Jongsma, ME; Steenbergen, PJ; de Boer, SF; Koolhaas, JM; Jongsma, Minke E.

Rationale: Male wild house- mice genetically selected for long attack latency ( LAL) and short attack latency ( SAL) differ in structural and functional properties of postsynaptic serotonergic- 1A ( 5- HT1A) receptors. These mouse lines also show divergent behavioral responses in the forced swimming

Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and early postnatal lethality.

Directory of Open Access Journals (Sweden)

Jacobus J Dudok

Full Text Available The serotonin (5-HT system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival.

Thermal-induced changes on the properties of spin-coated P3HT:C60 thin films for solar cell applications

CSIR Research Space (South Africa)

Motaung, DE

2009-09-01

Full Text Available on the properties of spin- coated P3HT:C60 thin films for solar cell applications David E. Motaung1, 2, Gerald F. Malgas1,*, Christopher J. Arendse1, Sipho E. Mavundla1, 3 Clive J. Oliphant 1, 2 and Dirk Knoesen2 1National Centre for Nano...-structured Materials, Council for Scientific Industrial Research, P. O. Box 395, Pretoria, 0001, South Africa 2Deparment of Physics, University of the Western Cape, Private Bag X17, Bellville, 7535, South Africa 3Deparment of Chemistry, University of the Western...

Fabrication and characterization of inverted organic solar cells using shuttle cock-type metal phthalocyanine and PCBM:P3HT

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Atsushi, E-mail: suzuki@mat.usp.ac.jp; Furukawa, Ryo, E-mail: suzuki@mat.usp.ac.jp; Akiyama, Tsuyoshi, E-mail: suzuki@mat.usp.ac.jp; Oku, Takeo, E-mail: suzuki@mat.usp.ac.jp [Department of Materials Science, The University of Shiga Prefecture 2500 Hassaka, Hikone, Shiga 522-8533 (Japan)

2015-02-27

Inverted organic solar cells using shuttle cock-type phthalocyanine, semiconducting polymer and fullerenes were fabricated and characterized. Photovoltaic and optical properties of the solar cells with inverted structures were investigated by optical absorption, current density-voltage characteristics. The photovoltaic properties of the tandem organic solar cell using titanyl phthalocyanine, vanadyl phthalocyanine, poly(3-hexylthiophene) (P3HT) and [6, 6]-phenyl C{sub 61}-butyric acid methyl ester (PCBM) were improved. Effect of annealing and solvent treatment on surface morphologies of the active layer was investigated. The photovoltaic mechanisms, energy levels and band gap of active layers were discussed for improvement of the photovoltaic performance.

Fabrication and characterization of inverted organic solar cells using shuttle cock-type metal phthalocyanine and PCBM:P3HT

International Nuclear Information System (INIS)

Suzuki, Atsushi; Furukawa, Ryo; Akiyama, Tsuyoshi; Oku, Takeo

2015-01-01

Inverted organic solar cells using shuttle cock-type phthalocyanine, semiconducting polymer and fullerenes were fabricated and characterized. Photovoltaic and optical properties of the solar cells with inverted structures were investigated by optical absorption, current density-voltage characteristics. The photovoltaic properties of the tandem organic solar cell using titanyl phthalocyanine, vanadyl phthalocyanine, poly(3-hexylthiophene) (P3HT) and [6, 6]-phenyl C 61 -butyric acid methyl ester (PCBM) were improved. Effect of annealing and solvent treatment on surface morphologies of the active layer was investigated. The photovoltaic mechanisms, energy levels and band gap of active layers were discussed for improvement of the photovoltaic performance

Fabrication of a P3HT-ZnO Nanowires Gas Sensor Detecting Ammonia Gas

Directory of Open Access Journals (Sweden)

Chin-Guo Kuo

2017-12-01

Full Text Available In this study, an organic-inorganic semiconductor gas sensor was fabricated to detect ammonia gas. An inorganic semiconductor was a zinc oxide (ZnO nanowire array produced by atomic layer deposition (ALD while an organic material was a p-type semiconductor, poly(3-hexylthiophene (P3HT. P3HT was suitable for the gas sensing application due to its high hole mobility, good stability, and good electrical conductivity. In this work, P3HT was coated on the zinc oxide nanowires by the spin coating to form an organic-inorganic heterogeneous interface of the gas sensor for detecting ammonia gas. The thicknesses of the P3HT were around 462 nm, 397 nm, and 277 nm when the speeds of the spin coating were 4000 rpm, 5000 rpm, and 6000 rpm, respectively. The electrical properties and sensing characteristics of the gas sensing device at room temperature were evaluated by Hall effect measurement and the sensitivity of detecting ammonia gas. The results of Hall effect measurement for the P3HT-ZnO nanowires semiconductor with 462 nm P3HT film showed that the carrier concentration and the mobility were 2.7 × 1019 cm−3 and 24.7 cm2∙V−1∙s−1 respectively. The gas sensing device prepared by the P3HT-ZnO nanowires semiconductor had better sensitivity than the device composed of the ZnO film and P3HT film. Additionally, this gas sensing device could reach a maximum sensitivity around 11.58 per ppm.

PHP-HT (VitaResc Biotech).

Science.gov (United States)

Baldwin, A; Wiley, E

2001-04-01

VitaResc (formerly Apex) is developing PHP-HT, pyridoxalated hemoglobin polyoxyethylene conjugate, for the potential treatment of nitric oxide-induced shock (characterized by hypotension), associated with various etiologies, initially in septic shock. A phase I safety study and an initial phase I/II patient trial for NO-induced shock have been completed, and VitaResc has enrolled patients in three of five planned cohorts in a continuation of these trials to include a protocol of continuous infusion and dose escalation [330680,349187,390918]. The results from the dose escalation trials are expected to provide the basis for a randomized, controlled phase II/III pivotal trial of PHP-HT [390918]. VitaResc has licensed PHP-HT exclusively from Ajinomoto for all indications, worldwide, except Japan [275263]. Ajinomoto originally developed the human derived and chemically modified hemoglobin preparation as a blood substitute, but no development has been reported by the company since 1997 [275277,303577]. The other potential indications of PHP-HT include shock associated with burns, pancreatitis, hemodialysis and cytokine therapies [275277]. VitaResc expects the annual market potential of PHP-HT to exceed 1 billion dollars [330680].

The 5-HT1A Receptor and the Stimulus Effects of LSD in the Rat

Science.gov (United States)

Reissig, C.J.; Eckler, J.R.; Rabin, R.A.; Winter, J.C.

2005-01-01

Rationale It has been suggested that the 5-HT1A receptor plays a significant modulatory role in the stimulus effects of the indoleamine hallucinogen lysergic acid diethylamide (LSD). Objectives The present study sought to characterize the effects of several compounds with known affinity for the 5-HT1A receptor on the discriminative stimulus effects of LSD. Methods 12 Male F-344 rats were trained in a two-lever, fixed ratio10, food reinforced task with LSD (0.1 mg/kg; IP; 15 min pretreatment) as a discriminative stimulus. Combination and substitution tests with the 5-HT1A agonists, 8-OH-DPAT, buspirone, gepirone, and ipsapirone, with LSD-induced stimulus control were then performed. The effects of these 5-HT1A ligands were also tested in the presence of the selective 5-HT1A receptor antagonist, WAY-100,635 (0.3 mg/kg; SC; 30 min. pretreatment). Results In combination tests stimulus control by LSD was increased by all 5-HT1A receptor ligands with agonist properties. Similarly, in tests of antagonism, the increase in drug-appropriate responding caused by stimulation of the 5-HT1A receptor was abolished by administration of WAY-100,635. Conclusions These data, obtained using a drug discrimination model of the hallucinogenic effects of LSD, provide support for the hypothesis that the 5-HT1A receptor has a significant modulatory role in the stimulus effects of LSD. PMID:16025319

Serotonin 5-HT3 and 5-HT4 ligands: an update of medicinal chemistry research in the last few years.

Science.gov (United States)

Modica, M N; Pittalà, V; Romeo, G; Salerno, L; Siracusa, M A

2010-01-01

The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) is one of the most studied neurotransmitters in the central nervous system. It acts through the activation of at least fourteen 5-HT receptor subtypes. Over the last two decades, high attention was devoted to the 5-HT(3) and 5-HT(4) receptors due to their colocalization in the gastrointestinal tract and because their ligands are useful in the treatment of intestinal serotonergic system dysfunctions. The focus of this review is to discuss the literature concerning recent advances on 5-HT(3)R and 5-HT(4)R ligands and their structure-activity relationships from a medicinal chemistry perspective. During the last few years, new and significant progresses have been made in the field of novel potent and selective ligands, mixed ligands, agonists, partial agonists, and antagonists, and a number of patents have been filed. Furthermore several ligands targeting the 5-HT(3)R and 5-HT(4)R have been proposed for novel therapeutic indications such as the treatment of various psychiatric disorders.

Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.

Science.gov (United States)

Peñas-Cazorla, Raúl; Vilaró, M Teresa

2015-11-01

Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.

[On the role of selective silencer Freud-1 in the regulation of the brain 5-HT(1A) receptor gene expression].

Science.gov (United States)

Naumenko, V S; Osipova, D V; Tsybko, A S

2010-01-01

Selective 5-HT(1A) receptor silencer (Freud-1) is known to be one of the main factors for transcriptional regulation of brain serotonin 5-HT(1A) receptor. However, there is a lack of data on implication of Freud-1 in the mechanisms underlying genetically determined and experimentally altered 5-HT(1A) receptor system state in vivo. In the present study we have found a difference in the 5-HT(1A) gene expression in the midbrain of AKR and CBA inbred mouse strains. At the same time no distinction in Freud-1 expression was observed. We have revealed 90.3% of homology between mouse and rat 5-HT(1A) receptor DRE-element, whereas there was no difference in DRE-element sequence between AKR and CBA mice. This indicates the absence of differences in Freud-1 binding site in these mouse strains. In the model of 5-HT(1A) receptor desensitization produced by chronic 5-HT(1A) receptor agonist administration, a significant reduction of 5-HT(1A) receptor gene expression together with considerable increase of Freud-1 expression were found. These data allow us to conclude that the selective silencer of 5-HT(1A) receptor, Freud-1, is involved in the compensatory mechanisms that modulate the functional state of brain serotonin system, although it is not the only factor for 5-HT(1A) receptor transcriptional regulation.

Familial Risk for Major Depression is Associated with Lower Striatal 5-HT4 Receptor Binding

DEFF Research Database (Denmark)

Madsen, Karine; Torstensen, Eva; Holst, Klaus K

2014-01-01

was to determine whether familial risk for MDD is associated with cerebral 5-HT4 receptor binding as measured with [(11)C]SB207145 brain PET imaging. Familial risk is the most potent risk factor of MDD. METHODS: We studied 57 healthy individuals (mean age 36 yrs, range 20-86; 21 women), 26 of which had first......-degree relatives treated for MDD. RESULTS: We found that having a family history of MDD was associated with lower striatal 5-HT4 receptor binding (p = 0.038; in individuals below 40 years, p = 0.013). Further, we found evidence for a "risk-dose effect" on 5-HT4 receptor binding, since the number of first......-degree relatives with a history of MDD binding correlated negatively with 5-HT4 receptor binding in both the striatum (p = 0.001) and limbic regions (p = 0.012). CONCLUSIONS: Our data suggest that the 5-HT4 receptor is involved in the neurobiological mechanism underlying familial risk for depression...

A Molecular-Scale Understanding of Cohesion and Fracture in P3HT:Fullerene Blends

KAUST Repository

Tummala, Naga Rajesh; Bruner, Christopher; Risko, Chad; Bredas, Jean-Luc; Dauskardt, Reinhold H.

2015-01-01

mechanical flexibility, reliability, and lifetime. Here, the molecular mechanism for the initiation of cohesive failure in bulk heterojunction (BHJ) OPV active layers derived from the semiconducting polymer poly-(3-hexylthiophene) [P3HT] and two mono

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

International Nuclear Information System (INIS)

Chi, Yan; Liu, Xin-Guang; Wang, Hua-Hong; Li, Jun-Xia; Li, Yi-Xuan

2012-01-01

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT 4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT 4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT 4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg −1 ·day −1 , days 36-42), tegaserod (1 mg·kg −1 ·day −1 , day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT 4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT 4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

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Chi Yan

2012-10-01

Full Text Available Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05 and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05. Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42, tegaserod (1 mg·kg-1·day-1, day 43, or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01 but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654. These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT(2A) receptor agonist DOI

DEFF Research Database (Denmark)

Santini, Martin A; Balu, Darrick T; Puhl, Matthew D

2014-01-01

Both the serotonin and glutamate systems have been implicated in the pathophysiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. Psychedelic drugs act through the serotonin 2A receptor (5-HT2AR), and elicit a head-twitch response (HTR) in mice, which directly...... correlates to 5-HT2AR activation and is absent in 5-HT2AR knockout mice. The precise mechanism of this response remains unclear, but both an intrinsic cortico-cortical pathway and a thalamo-cortical pathway involving glutamate release have been proposed. Here, we used a genetic model of NMDAR hypofunction......RNA. These altered functional responses in SRKO mice were not associated with changes in cortical or hippocampal 5-HT levels or in 5-HT2AR and metabotropic glutamate-2 receptor (mGluR2) mRNA and protein expression. Together, these findings suggest that D-serine-dependent NMDAR activity is involved in mediating...

Changes of Serotonin (5-HT), 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression,Myocardial Infarction and Myocardial Infarction Co-exist with Depression

Institute of Scientific and Technical Information of China (English)

Mei-Yan Liu; Yah-Ping Ren; Wan-Lin Wei; Guo-Xiang Tian; Guo Li

2015-01-01

Background:To evaluate whether serotonin (5-HT),5-HT2A receptor (5-HT2AR),and 5-HT transporter (serotonin transporter [SERT]) are associated with different disease states of depression,myocardial infarction (MI) and MI co-exist with depression in Sprague-Dawley rats.Methods:After established the animal model of four groups include control,depression,MI and MI with depression,we measured 5-HT,5-HT2AR and SERT from serum and platelet lysate.Results:The serum concentration of 5-HT in depression rats decreased significantly compared with the control group (303.25 ± 9.99 vs.352.98 ± 13.73;P =0.000),while that in MI group increased (381.78 ± 14.17 vs.352.98 ± 13.73;P =0.000).However,the depression + MI group had no change compared with control group (360.62 ± 11.40 vs.352.98 ± 13.73;P =0.036).The changes of the platelet concentration of 5-HT in the depression,MI,and depression + MI group were different from that of serum.The levels of 5-HT in above three groups were lower than that in the control group (380.40 ± 17.90,387.75 ± 22.28,246.40 ± 18.99 vs.500.29 ± 20.91;P =0.000).The platelet lysate concentration of 5-HT2AR increased in depression group,MI group,and depression + MI group compared with the control group (370.75 ± 14.75,393.47 ± 15.73,446.66 ± 18.86 vs.273.66 ± 16.90;P =0.000).The serum and platelet concentration of SERT in the depression group,MI group and depression + MI group were all increased compared with the control group (527.51 ± 28.32,602.02 ± 23.32,734.76 ± 29.59 vs.490.56 ± 16.90;P =0.047,P =0.000,P =0.000 in each and 906.38 ± 51.84,897.33 ± 60.34,1030.17 ± 58.73 vs.708.62 ± 51.15;P =0.000 in each).Conclusions:The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression.Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.

Modulation by calcineurin of 5-HT3 receptor function in NG108-15 neuroblastoma x glioma cells

NARCIS (Netherlands)

Boddeke, HWGM; Meigel, [No Value; Boeijinga, P; Arbuckle, J; Docherty, RJ

1 We have investigated the mechanism of regulation of 5-HT3 receptor channel sensitivity in voltage-clamped (-80 mV) NG108-15 neuroblastoma cells. 2 The 5-HT-induced inward current activated rapidly. The fast onset was followed by a biphasic decay which was characterized by two time constants,

Modulation by calcineurin of 5-HT3receptor function in NG108-15 neuroblastoma x glioma cells

NARCIS (Netherlands)

Boddeke, H.W.G.M.; Meigel, I.; Boeijinga, P.; Arbuckle, J.; Docherty, R.J.

1996-01-01

1. We have investigated the mechanism of regulation of 5-HT3receptor channel sensitivity in voltage-clamped (-80 mV) NG108-15 neuroblastoma cells. 2. The 5-HT-induced inward current activated rapidly. The fast onset was followed by a biphasic decay which was characterized by two time constants,

5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors.

Science.gov (United States)

Eriksson, Therese M; Holst, Sarah; Stan, Tiberiu L; Hager, Torben; Sjögren, Benita; Ogren, Sven Öve; Svenningsson, Per; Stiedl, Oliver

2012-11-01

This study utilized pharmacological manipulations to analyze the role of direct and indirect activation of 5-HT(7) receptors (5-HT(7)Rs) in passive avoidance learning by assessing emotional memory in male C57BL/6J mice. Additionally, 5-HT(7)R binding affinity and 5-HT(7)R-mediated protein phosphorylation of downstream signaling targets were determined. Elevation of 5-HT by the selective serotonin reuptake inhibitor (SSRI) fluoxetine had no effect by itself, but facilitated emotional memory performance when combined with the 5-HT(1A)R antagonist NAD-299. This facilitation was blocked by the selective 5-HT(7)R antagonist SB269970, revealing excitatory effects of the SSRI via 5-HT(7)Rs. The enhanced memory retention by NAD-299 was blocked by SB269970, indicating that reduced activation of 5-HT(1A)Rs results in enhanced 5-HT stimulation of 5-HT(7)Rs. The putative 5-HT(7)R agonists LP-44 when administered systemically and AS19 when administered both systemically and into the dorsal hippocampus failed to facilitate memory. This finding is consistent with the low efficacy of LP-44 and AS19 to stimulate protein phosphorylation of 5-HT(7)R-activated signaling cascades. In contrast, increasing doses of the dual 5-HT(1A)R/5-HT(7)R agonist 8-OH-DPAT impaired memory, while co-administration with NAD-299 facilitated of emotional memory in a dose-dependent manner. This facilitation was blocked by SB269970 indicating 5-HT(7)R activation by 8-OH-DPAT. Dorsohippocampal infusion of 8-OH-DPAT impaired passive avoidance retention through hippocampal 5-HT(1A)R activation, while 5-HT(7)Rs appear to facilitate memory processes in a broader cortico-limbic network and not the hippocampus alone. Copyright © 2012 Elsevier Ltd. All rights reserved.

Molecular and pharmacological characterization of serotonin 5-HT2α and 5-HT7 receptors in the salivary glands of the blowfly Calliphora vicina.

Science.gov (United States)

Röser, Claudia; Jordan, Nadine; Balfanz, Sabine; Baumann, Arnd; Walz, Bernd; Baumann, Otto; Blenau, Wolfgang

2012-01-01

Secretion in blowfly (Calliphora vicina) salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT), which activates both inositol 1,4,5-trisphosphate (InsP(3))/Ca(2+) and cyclic adenosine 3',5'-monophosphate (cAMP) signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7) that share high similarity with mammalian 5-HT(2) and 5-HT(7) receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+)] in a dose-dependent manner (EC(50) = 24 nM). In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP](i) (EC(50) = 4 nM). We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT(2α) or Cv5-HT(7) in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM) activates only the Cv5-HT(2α) receptor, 5-carboxamidotryptamine (300 nM) activates only the Cv5-HT(7) receptor, and clozapine (1 µM) antagonizes the effects of 5-HT via Cv5-HT(7) in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca(2+)- and cAMP-signalling cascades.

Molecular and pharmacological characterization of serotonin 5-HT2α and 5-HT7 receptors in the salivary glands of the blowfly Calliphora vicina.

Directory of Open Access Journals (Sweden)

Claudia Röser

Full Text Available Secretion in blowfly (Calliphora vicina salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT, which activates both inositol 1,4,5-trisphosphate (InsP(3/Ca(2+ and cyclic adenosine 3',5'-monophosphate (cAMP signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7 that share high similarity with mammalian 5-HT(2 and 5-HT(7 receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+] in a dose-dependent manner (EC(50 = 24 nM. In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP](i (EC(50 = 4 nM. We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT(2α or Cv5-HT(7 in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM activates only the Cv5-HT(2α receptor, 5-carboxamidotryptamine (300 nM activates only the Cv5-HT(7 receptor, and clozapine (1 µM antagonizes the effects of 5-HT via Cv5-HT(7 in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca(2+- and cAMP-signalling cascades.

Characterization of the binding of 3H-norzimeldine, a 5-HT uptake inhibitor, to rat brain homogenates

International Nuclear Information System (INIS)

Hall, H.

1984-01-01

The binding of radiolabelled norzimeldine, a potent selective 5-HT reuptake inhibitor, to rat brain homogenates is described. 3 H-Norzimeldine binds to a site with high affinity (Ksub(D) = 10.5 nM) in a saturable manner (Bsub(max) = 15.4 pmol/g wet weight in the cerebral cortex). The number of binding sites in the various regions of the brain parallels the capacity of the 5-HT reuptake mechanism. Drugs that inhibit the reuptake of 5-HT are also potent inhibitors of the 3 H-norzimeldine binding, as are the tricyclic antidepressants, which are non-specific inhibitors of the noradrenaline and the 5-HT reuptake. Lesioning experiments using DSP4 (a NA neurotoxin) and p-chloroamphetamine (a 5-HT neurotoxin) suggest that the binding site is located on the presynaptic 5-HT nerve terminal, although a small component of the binding may be to noradrenergic uptake sites as well.(author)

5HT-1A receptors and anxiety-like behaviours: studies in rats with constitutionally upregulated/downregulated serotonin transporter.

Science.gov (United States)

Bordukalo-Niksic, Tatjana; Mokrovic, Gordana; Stefulj, Jasminka; Zivin, Marko; Jernej, Branimir; Cicin-Sain, Lipa

2010-12-01

Altered activity of brain serotonergic (5HT) system has been implicated in a wide range of behaviours and behavioural disorders, including anxiety. Functioning of 5HT-1A receptor has been suggested as a modulator of emotional balance in both, normal and pathological forms of anxiety. Here, we studied serotonergic modulation of anxiety-like behaviour using a genetic rat model with constitutional differences in 5HT homeostasis, named Wistar-Zagreb 5HT (WZ-5HT) rats. The model, consisting of high-5HT and low-5HT sublines, was developed by selective breeding of animals for extreme activities of peripheral (platelet) 5HT transporter, but selection process had affected also central 5HT homeostasis, as evidenced from neurochemical and behavioural studies. Anxiety-like behaviour in WZ-5HT rats was evaluated by two commonly used paradigms: open field and elevated-plus maze. The involvement of 5HT-1A receptors in behavioural response was assessed by measuring mRNA expression in cell bodies (raphe nuclei) and projection regions (frontal cortex, hippocampus) by use of RT-PCR and in situ hybridization, and by measuring functionality of cortical 5HT-1A receptors by use of [(3)H]8-OH-DPAT radioligand binding. Animals from the high-5HT subline exhibit increased anxiety-like behaviour and decreased exploratory activity when exposed to novel environment. No measurable differences in constitutional (baseline) functionality or expression of 5HT-1A receptors between sublines were found. The results support contribution of increased serotonergic functioning to the anxiety-like behaviour. They also validate the high-5HT subline of WZ-5HT rats as a potential model to study mechanisms of anxiety, especially of its nonpathological form, while the low-5HT subline may be useful to model sensation seeking phenotype. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster

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Wolfgang Blenau

2017-05-01

Full Text Available Serotonin (5-hydroxytryptamine, 5-HT is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects and deuterostomes (e.g., mammals. In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster, a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT1A, Dm5-HT1B, and Dm5-HT7 couple to cAMP signaling cascades, the Dm5-HT2A receptor leads to Ca2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT2B receptor. Knowledge about this receptor’s pharmacological properties is very limited. This is quite surprising because Dm5-HT2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT2B’s pharmacology, we evaluated the receptor’s response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT2B signaling in vitro and in vivo.

Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster.

Science.gov (United States)

Blenau, Wolfgang; Daniel, Stöppler; Balfanz, Sabine; Thamm, Markus; Baumann, Arnd

2017-01-01

Serotonin (5-hydroxytryptamine, 5-HT) is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects) and deuterostomes (e.g., mammals). In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster , a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT 1A , Dm5-HT 1B , and Dm5-HT 7 couple to cAMP signaling cascades, the Dm5-HT 2A receptor leads to Ca 2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT 2B receptor. Knowledge about this receptor's pharmacological properties is very limited. This is quite surprising because Dm5-HT 2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT 2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT 2B 's pharmacology, we evaluated the receptor's response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT 2B signaling in vitro and in vivo .

Functional expression of 5-HT{sub 2A} receptor in osteoblastic MC3T3-E1 cells

Energy Technology Data Exchange (ETDEWEB)

Hirai, Takao; Kaneshige, Kota; Kurosaki, Teruko [Department of Molecular Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-cho, Fukuyama, Hiroshima 729-0292 (Japan); Nishio, Hiroaki, E-mail: nishio@fupharm.fukuyama-u.ac.jp [Department of Molecular Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-cho, Fukuyama, Hiroshima 729-0292 (Japan)

2010-05-28

In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT{sub 2} receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT{sub 2A} and 5-HT{sub 2C} receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT{sub 2A} receptor specific antagonist. Moreover, both DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT{sub 2A} receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells.

Morphology and interdiffusion control to improve adhesion and cohesion properties in inverted polymer solar cells

KAUST Repository

Dupont, Stephanie R.

2015-01-01

© 2014 Elsevier B.V. All rights reserved. The role of pre-electrode deposition annealing on the morphology and the fracture properties of polymer solar cells is discussed. We found an increase in adhesion at the weak P3HT:PCBM/PEDOT:PSS interface with annealing temperature, caused by increased interdiffusion between the organic layers. The formation of micrometer sized PCBM crystallites, which occurs with annealing above the crystallization temperature of PCBM, initially weakened the P3HT:PCBM layer itself. Further annealing improved the cohesion, due to a pull-out toughening mechanism of the growing PCBM clusters. Understanding how the morphology, tuned by annealing, affects the adhesive and cohesive properties in these organic films is essential for the mechanical integrity of OPV devices.

Insulating process for HT-7U central solenoid model coils

International Nuclear Information System (INIS)

Cui Yimin; Pan Wanjiang; Wu Songtao; Wan Yuanxi

2003-01-01

The HT-7U superconducting Tokamak is a whole superconducting magnetically confined fusion device. The insulating system of its central solenoid coils is critical to its properties. In this paper the forming of the insulating system and the vacuum-pressure-impregnating (VPI) are introduced, and the whole insulating process is verified under the super-conducting experiment condition

Adaptive Control of Dorsal Raphe by 5-HT4 in the Prefrontal Cortex Prevents Persistent Hypophagia following Stress

Directory of Open Access Journals (Sweden)

Alexandra Jean

2017-10-01

Full Text Available Transient reduced food intake (hypophagia following high stress could have beneficial effects on longevity, but paradoxically, hypophagia can persist and become anorexia-like behavior. The neural underpinnings of stress-induced hypophagia and the mechanisms by which the brain prevents the transition from transient to persistent hypophagia remain undetermined. In this study, we report the involvement of a network governing goal-directed behavior (decision. This network consists of the ascending serotonergic inputs from the dorsal raphe nucleus (DR to the medial prefrontal cortex (mPFC. Specifically, adult restoration of serotonin 4 receptor (5-HT4R expression in the mPFC rescues hypophagia and specific molecular changes related to depression resistance in the DR (5-HT release elevation, 5-HT1A receptor, and 5-HT transporter reductions of stressed 5-HT4R knockout mice. The adult mPFC-5-HT4R knockdown mimics the null phenotypes. When mPFC-5-HT4Rs are overexpressed and DR-5-HT1ARs are blocked in the DR, hypophagia following stress persists, suggesting an antidepressant action of early anorexia.

Adaptive Control of Dorsal Raphe by 5-HT4 in the Prefrontal Cortex Prevents Persistent Hypophagia following Stress.

Science.gov (United States)

Jean, Alexandra; Laurent, Laetitia; Delaunay, Sabira; Doly, Stéphane; Dusticier, Nicole; Linden, David; Neve, Rachael; Maroteaux, Luc; Nieoullon, André; Compan, Valérie

2017-10-24

Transient reduced food intake (hypophagia) following high stress could have beneficial effects on longevity, but paradoxically, hypophagia can persist and become anorexia-like behavior. The neural underpinnings of stress-induced hypophagia and the mechanisms by which the brain prevents the transition from transient to persistent hypophagia remain undetermined. In this study, we report the involvement of a network governing goal-directed behavior (decision). This network consists of the ascending serotonergic inputs from the dorsal raphe nucleus (DR) to the medial prefrontal cortex (mPFC). Specifically, adult restoration of serotonin 4 receptor (5-HT 4 R) expression in the mPFC rescues hypophagia and specific molecular changes related to depression resistance in the DR (5-HT release elevation, 5-HT 1A receptor, and 5-HT transporter reductions) of stressed 5-HT 4 R knockout mice. The adult mPFC-5-HT 4 R knockdown mimics the null phenotypes. When mPFC-5-HT 4 Rs are overexpressed and DR-5-HT1ARs are blocked in the DR, hypophagia following stress persists, suggesting an antidepressant action of early anorexia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Excitons dynamics of 1-chloronaphthalene added P3HT:PC{sub 61}BM solar cells

Energy Technology Data Exchange (ETDEWEB)

Fan, Xing [Key Laboratory of Luminescence and Optical Information, Beijing Jiaotong University, Ministry of Education, Beijing 100044 (China); Institute of Optoelectronics Technology, Beijing Jiaotong University, Beijing 100044 (China); Zhao, Suling, E-mail: slzhao@bjtu.edu.cn [Key Laboratory of Luminescence and Optical Information, Beijing Jiaotong University, Ministry of Education, Beijing 100044 (China); Institute of Optoelectronics Technology, Beijing Jiaotong University, Beijing 100044 (China); Huang, Qingyu; Yang, Qianqian; Gong, Wei; Xu, Zheng [Key Laboratory of Luminescence and Optical Information, Beijing Jiaotong University, Ministry of Education, Beijing 100044 (China); Institute of Optoelectronics Technology, Beijing Jiaotong University, Beijing 100044 (China)

2014-08-01

The charge photogeneration and recombination are comprehensively investigated in blend films based on poly(3-hexylthiophene) (P3HT) as an electron donor and [6,6]-phenyl-C 61-butyric acid methyl ester (PC{sub 61}BM) as an electron accepter. Transient absorption spectroscopy (TAS) together with absorption, photoluminescence (PL) are used respectively to measure optical properties of these blend films. In this paper, we demonstrate that solvent additive 1-chloronaphthalene (CN) has a unique influence on improving the performance of P3HT:PC{sub 61}BM heterojunction solar cell. It is observed that the absorption of additive-added blends has a higher intensity and is red-shifted than that of the P3HT:PC{sub 61}BM blend. The PL intensity increases which suggest that the conjugation length increases or the domain size of P3HT increases. Large domains with serious phase separation influence the interface area between P3HT and PC{sub 61}BM. Excitons are generated in both the P3HT phase and the PC{sub 61}BM phase. In all the film blends with or without additive, strongly bound interfacial CT states are formed by a large fraction of the excitons indicating geminate recombination may occur. It is demonstrated that in the blend with CN added the enhanced fraction of CT states comes from the more crystalline P3HT phases and the slower CT states and mobile charges decay indicates reduced recombination losses from early time recombination. - Highlights: • 1-chloronaphthalene(CN) can enhance the efficiency of P3HT:PCBM Solar Cells from charge photogeneration and recombination. • The enhanced fraction of CT states with CN added comes from the more crystalline P3HT phases and the slower CT states. • Mobile charges decay of blend with CN added indicates reduced recombination losses from early time recombination.

Time-course of 5-HT(6) receptor mRNA expression during memory consolidation and amnesia.

Science.gov (United States)

Huerta-Rivas, A; Pérez-García, G; González-Espinosa, C; Meneses, A

2010-01-01

Growing evidence indicates that antagonists of the 5-hydroxytryptamine (serotonin) receptor(6) (5-HT(6)) improve memory and reverse amnesia although the mechanisms involved are poorly understood. Hence, in this paper RT-PCR was used to evaluate changes in mRNA expression of 5-HT(6) receptor in trained and untrained rats treated with the 5-HT(6) receptor antagonist SB-399885 and amnesic drugs scopolamine or dizocilpine. Changes in mRNA expression of 5-HT(6) receptor were investigated at different times in prefrontal cortex, hippocampus and striatum. Data indicated that memory in the Pavlovian/instrumental autoshaping task was a progressive process associated to reduced mRNA expression of 5-HT(6) receptor in the three structures examined. SB-399885 improved long-term memory at 48h, while the muscarinic receptor antagonist scopolamine or the non-competitive NMDA receptor antagonist dizocilpine impaired it at 24h. Autoshaping training and treatment with SB-399885 increased 5-HT(6) receptor mRNA expression in (maximum increase) prefrontal cortex and striatum, 24 or 48h. The scopolamine-induced amnesia suppressed 5-HT(6) receptor mRNA expression while the dizocilpine-induced amnesia did not modify 5-HT(6) receptor mRNA expression. SB-399885 and scopolamine or dizocilpine were able to reestablish memory and 5-HT(6) receptor mRNA expression. These data confirmed previous memory evidence and of more interest is the observation that training, SB-399885 and amnesic drugs modulated 5-HT(6) receptor mRNA expression in prefrontal cortex, hippocampus and striatum. Further investigation in different memory tasks, times and amnesia models together with more complex control groups might provide further clues. Copyright 2009 Elsevier Inc. All rights reserved.

Interplay of Nanoscale, Hybrid P3HT/ZTO Interface on Optoelectronics and Photovoltaic Cells.

Science.gov (United States)

Lai, Jian-Jhong; Li, Yu-Hsun; Feng, Bo-Rui; Tang, Shiow-Jing; Jian, Wen-Bin; Fu, Chuan-Min; Chen, Jiun-Tai; Wang, Xu; Lee, Pooi See

2017-09-27

Photovoltaic effects in poly(3-hexylthiophene-2,5-diyl) (P3HT) have attracted much attention recently. Here, natively p-type doped P3HT nanofibers and n-type doped zinc tin oxide (ZTO) nanowires are used for making not only field-effect transistors (FETs) but also p-n nanoscale diodes. The hybrid P3HT/ZTO p-n heterojunction shows applications in many directions, and it also facilitates the investigation of photoelectrons and photovoltaic effects on the nanoscale. As for applications, the heterojunction device shows a simultaneously high on/off ratio of n- and p-type FETs, gatable p-n junction diodes, tristate buffer devices, gatable photodetectors, and gatable solar cells. On the other hand, P3HT nanofibers are taken as a photoactive layer and the role played by the p-n heterojunction in the photoelectric and photovoltaic effects is investigated. It is found that the hybrid P3HT/ZTO p-n heterojunction assists in increasing photocurrents and enhancing photovoltaic effects. Through the controllable gating of the heterojunction, we can discuss the background mechanisms of photocurrent generation and photovoltaic energy harvesting.

Electrophysical properties, synaptic transmission and neuromodulation in serotonergic caudal raphe neurons.

Science.gov (United States)

Li, Y W; Bayliss, D A

1998-06-01

1. We studied electrophysiological properties, synaptic transmission and modulation by 5-hydroxytryptamine (5-HT) of caudal raphe neurons using whole-cell recording in a neonatal rat brain slice preparation; recorded neurons were identified as serotonergic by post-hoc immunohistochemical detection of tryptophan hydroxylase, the 5-HT-synthesizing enzyme. 2. Serotonergic neurons fired spontaneously (approximately 1 Hz), with maximal steady state firing rates of < 4 Hz. 5-Hydroxytryptamine caused hyperpolarization and cessation of spike activity in these neurons by activating inwardly rectifying K+ conductance via somatodendritic 5-HT1A receptors. 3. Unitary glutamatergic excitatory post-synaptic potentials (EPSP) and currents (EPSC) were evoked in serotonergic neurons by local electrical stimulation. Evoked EPSC were potently inhibited by 5-HT, an effect mediated by presynaptic 5-HT1B receptors. 4. In conclusion, serotonergic caudal raphe neurons are spontaneously active in vitro; they receive prominent glutamatergic synaptic inputs. 5-Hydroxytryptamine regulates serotonergic neuronal activity of the caudal raphe by decreasing spontaneous activity via somatodendritic 5-HT1A receptors and by inhibiting excitatory synaptic transmission onto these neurons via presynaptic 5-HT1B receptors. These local modulatory mechanisms provide multiple levels of feedback autoregulation of serotonergic raphe neurons by 5-HT.

Characterization of the binding of /sup 3/H-norzimeldine, a 5-HT uptake inhibitor, to rat brain homogenates

Energy Technology Data Exchange (ETDEWEB)

Hall, H. (Department of Biochemical Neuropharmacology, Research and Development Laboratories, Astra Laekemedel, Soedertaelje, Sweden)

1984-01-01

The binding of radiolabelled norzimeldine, a potent selective 5-HT reuptake inhibitor, to rat brain homogenates is described. /sup 3/H-Norzimeldine binds to a site with high affinity (Ksub(D) = 10.5 nM) in a saturable manner (Bsub(max) = 15.4 pmol/g wet weight in the cerebral cortex). The number of binding sites in the various regions of the brain parallels the capacity of the 5-HT reuptake mechanism. Drugs that inhibit the reuptake of 5-HT are also potent inhibitors of the /sup 3/H-norzimeldine binding, as are the tricyclic antidepressants, which are non-specific inhibitors of the noradrenaline and the 5-HT reuptake. Lesioning experiments using DSP4 (a NA neurotoxin) and p-chloroamphetamine (a 5-HT neurotoxin) suggest that the binding site is located on the presynaptic 5-HT nerve terminal, although a small component of the binding may be to noradrenergic uptake sites as well.

Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task.

Science.gov (United States)

Meneses, Alfredo

2004-12-06

There is an important debate regarding the functional role of the 5-HT(1A) and 5-HT(7) receptor in memory systems. Hence, the objective of this paper is to investigate the function of serotonin (5-hydroxytryptamine, 5-HT) in memory consolidation, utilising an autoshaping Pavlovian/instrumental learning test. Specific antagonists at 5-HT(1A) (WAY 100635) and 5-HT(7) (SB-269970 or DR 4004) receptors administered i.p. or s.c.) after training, significantly decreased the improvement of performance produced by the 5-HT(1A/7) agonist 8-OH-DPAT to levels lower than controls'. These same antagonists attenuated the decreased level of performance produced by mCPP, although they decrease the performance levels after p-chloroamphetamine (PCA) lesion of the 5-HT system, which has no effect on its own on the conditioned response. Moreover, SB-269970 or DR 4004 reversed amnesia induced by scopolamine and dizocilpine. These data confirm a role for 5-HT(1A) and 5-HT(7) receptors in memory formation and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals. These findings support a potential role for both 5-HT(1A) and 5-HT(7) receptors in the pathophysiology and/or treatment of schizophrenia, cognitive deficits and the mechanism of action of atypical antipsychotic drugs.

Novel 5-HT6 receptor antagonists/D2 receptor partial agonists targeting behavioral and psychological symptoms of dementia.

Science.gov (United States)

Kołaczkowski, Marcin; Marcinkowska, Monika; Bucki, Adam; Śniecikowska, Joanna; Pawłowski, Maciej; Kazek, Grzegorz; Siwek, Agata; Jastrzębska-Więsek, Magdalena; Partyka, Anna; Wasik, Anna; Wesołowska, Anna; Mierzejewski, Paweł; Bienkowski, Przemyslaw

2015-03-06

We describe a novel class of designed multiple ligands (DMLs) combining serotonin 5-HT6 receptor (5-HT6R) antagonism with dopamine D2 receptor (D2R) partial agonism. Prototype hybrid molecules were designed using docking to receptor homology models. Diverse pharmacophore moieties yielded 3 series of hybrids with varying in vitro properties at 5-HT6R and D2R, and at M1 receptor and hERG channel antitargets. 4-(piperazin-1-yl)-1H-indole derivatives showed highest antagonist potency at 5-HT6R, with 7-butoxy-3,4-dihydroquinolin-2(1H)-one and 2-propoxybenzamide derivatives having promising D2R partial agonism. 2-(3-(4-(1-(phenylsulfonyl)-1H-indol-4-yl)piperazin-1-yl)propoxy)benzamide (47) exhibited nanomolar affinity at both 5-HT6R and D2R and was evaluated in rat models. It displayed potent antidepressant-like and anxiolytic-like activity in the Porsolt and Vogel tests, respectively, more pronounced than that of a reference selective 5-HT6R antagonist or D2R partial agonist. In addition, 47 also showed antidepressant-like activity (Porsolt's test) and anxiolytic-like activity (open field test) in aged (>18-month old) rats. In operant conditioning tests, 47 enhanced responding for sweet reward in the saccharin self-administration test, consistent with anti-anhedonic properties. Further, 47 facilitated extinction of non-reinforced responding for sweet reward, suggesting potential procognitive activity. Taken together, these studies suggest that DMLs combining 5-HT6R antagonism and D2R partial agonism may successfully target affective disorders in patients from different age groups without a risk of cognitive deficits. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Implication of 5-HT(2B) receptors in the serotonin syndrome.

Science.gov (United States)

Diaz, Silvina Laura; Maroteaux, Luc

2011-09-01

The serotonin (5-HT) syndrome occurs in humans after antidepressant overdose or combination of drugs inducing a massive increase in extracellular 5-HT. Several 5-HT receptors are known to participate in this syndrome in humans and animal models. The 5-HT(2B) receptor has been proposed as a positive modulator of serotonergic activity, but whether it is involved in 5-HT syndrome has not yet been studied. We analyzed here, a putative role of 5-HT(2B) receptors in this disorder by forced swimming test (FST) and behavioral assessment in the open field. In FST, genetic (5-HT(2B)(-/-) mice) or pharmacological (antagonist RS127445 at 0.5 mg/kg) ablation of 5-HT(2B) receptors facilitated selective 5-HT reuptake inhibitors (SSRI)-induced increase of immobility time as well as expression of other symptoms related to 5-HT syndrome like hind limb abduction and Straub tail. Increase in immobility was also developed in FST by both wild type (WT) and 5-HT(2B)(-/-) mice after the administration of 5-HT(1A), 5-HT(2A) or 5-HT(2C) receptor agonists, 8-OH-DPAT (5 mg/kg), DOI (1 mg/kg), or WAY161503 (5 mg/kg), respectively. In contrast, the 5-HT(2B) receptor agonist BW723C86 (3 mg/kg) or 5-HT(1B) receptor agonist CGS12066A (2 mg/kg) decreased immobility time in both genotypes. The 5-HT syndrome induced by fluoxetine at high doses was blocked in WT and 5-HT(2B)(-/-) mice by administration of 5-HT(1A) and 5-HT(2C) receptor antagonists (WAY100635 0.5 mg/kg and SB242084 0.5 mg/kg) but not by the 5-HT(2A) receptor antagonist MDL100907 (1 mg/kg). By behavioral assessment, we confirmed that 5-HT(2B)(-/-) mice were more prone to develop 5-HT syndrome symptoms after administration of high dose of SSRIs or the 5-HT precursor 5-Hydroxytryptophan, 5-HTP, even if increases in 5-HT plasma levels were similar in both genotypes. This evidence suggests that the presence of 5-HT(2B) receptors hinders acute 5-HT toxicity once high levels of 5-HT are attained. Therefore, differential agonism

GPR30 is necessary for estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the rat hypothalamus.

Science.gov (United States)

McAllister, C E; Creech, R D; Kimball, P A; Muma, N A; Li, Q

2012-08-01

Estrogen therapy used in combination with selective serotonin reuptake inhibitor (SSRI) treatment improves SSRI efficacy for the treatment of mood disorders. Desensitization of serotonin 1A (5-HT(1A)) receptors, which takes one to two weeks to develop in animals, is necessary for SSRI therapeutic efficacy. Estradiol modifies 5-HT(1A) receptor signaling and induces a partial desensitization in the paraventricular nucleus (PVN) of the rat within two days, but the mechanisms underlying this effect are currently unknown. The purpose of this study was to identify the estrogen receptor necessary for estradiol-induced 5-HT(1A) receptor desensitization. We previously showed that estrogen receptor β is not necessary for 5-HT(1A) receptor desensitization and that selective activation of estrogen receptor GPR30 mimics the effects of estradiol in rat PVN. Here, we used a recombinant adenovirus containing GPR30 siRNAs to decrease GPR30 expression in the PVN. Reduction of GPR30 prevented estradiol-induced desensitization of 5-HT(1A) receptor as measured by hormonal responses to the selective 5-HT(1A) receptor agonist, (+)8-OH-DPAT. To determine the possible mechanisms underlying these effects, we investigated protein and mRNA levels of 5-HT(1A) receptor signaling components including 5-HT(1A) receptor, Gαz, and RGSz1. We found that two days of estradiol increased protein and mRNA expression of RGSz1, and decreased 5-HT(1A) receptor protein but increased 5-HT(1A) mRNA; GPR30 knockdown prevented the estradiol-induced changes in 5-HT(1A) receptor protein in the PVN. Taken together, these data demonstrate that GPR30 is necessary for estradiol-induced changes in the 5-HT(1A) receptor signaling pathway and desensitization of 5-HT(1A) receptor signaling. Copyright © 2012 Elsevier Ltd. All rights reserved.

Role of grain boundary engineering in the SCC behavior of ferritic-martensitic alloy HT-9

International Nuclear Information System (INIS)

Gupta, G.; Ampornrat, P.; Ren, X.; Sridharan, K.; Allen, T.R.; Was, G.S.

2007-01-01

This paper focuses on the role of grain boundary engineering (GBE) in stress corrosion cracking (SCC) of ferritic-martensitic (F-M) alloy HT-9 in supercritical water (SCW) at 400 deg. C and 500 deg. C. Constant extension rate tensile (CERT) tests were conducted on HT-9 in as-received (AR) and coincident site lattice enhanced (CSLE) condition. Both unirradiated and irradiated specimens (irradiated with 2 MeV protons at 400 deg. C and 500 deg. C to a dose of 7 dpa) were tested. Ferritic-martensitic steel HT-9 exhibited intergranular stress corrosion cracking when subjected to CERT tests in an environment of supercritical water at 400 deg. C and 500 deg. C and also in an inert environment of argon at 500 deg. C. CSL-enhancement reduces grain boundary carbide coarsening and cracking susceptibility in both the unirradiated and irradiated condition. Irradiation enhanced coarsening of grain boundary carbides and cracking susceptibility of HT-9 for both the AR and CSLE conditions. Intergranular (IG) cracking of HT-9 results likely from fracture of IG carbides and seems consistent with the mechanism that coarser carbides worsen cracking susceptibility. Oxidation in combination with wedging stresses is the likely cause of the observed environmental enhancement of high temperature IG cracking in HT-9

Martensite and bainite in steels: transformation mechanism and mechanical properties

International Nuclear Information System (INIS)

Bhadeshia, H.K.D.H.

1997-01-01

Many essential properties of iron alloys depend on what actually happens when one allotropic form gives way to another, i.e. on the mechanism of phase change. The dependence of the mechanical properties on the atomic mechanism by which bainite and martensite grow is the focus of this paper. The discussion is illustrated in the context of some common engineering design parameters, and with a brief example of the inverse problem in which the mechanism may be a function of the mechanical properties. (orig.)

Receptor⁻Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment.

Science.gov (United States)

Borroto-Escuela, Dasiel O; Narváez, Manuel; Ambrogini, Patrizia; Ferraro, Luca; Brito, Ismel; Romero-Fernandez, Wilber; Andrade-Talavera, Yuniesky; Flores-Burgess, Antonio; Millon, Carmelo; Gago, Belen; Narvaez, Jose Angel; Odagaki, Yuji; Palkovits, Miklos; Diaz-Cabiale, Zaida; Fuxe, Kjell

2018-06-03

Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term "heteroreceptor complexes" was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A⁻FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A⁻FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL) rats). Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A⁻5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1⁻15) was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1⁻GalR2⁻5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression.

Receptor–Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment

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Dasiel O. Borroto-Escuela

2018-06-01

Full Text Available Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term “heteroreceptor complexes” was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A–FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A–FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL rats. Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A–5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1–15 was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1–GalR2–5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression.

(+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist

International Nuclear Information System (INIS)

Burris, K.D.; Breeding, M.; Sanders-Bush, E.

1991-01-01

Activation of central serotonin 5HT2 receptors is believed to be the primary mechanism whereby lysergic acid diethylamide (LSD) and other hallucinogens induce psychoactive effects. This hypothesis is based on extensive radioligand binding and electrophysiological and behavioral studies in laboratory animals. However, the pharmacological profiles of 5HT2 and 5HT1C receptors are similar, making it difficult to distinguish between effects due to activation of one or the other receptor. For this reason, it was of interest to investigate the interaction of LSD with 5HT1C receptors. Agonist-stimulated phosphoinositide hydrolysis in rat choroid plexus was used as a direct measure of 5HT1C receptor activation. (+)LSD potently stimulated phosphoinositide hydrolysis in intact choroid plexus and in cultures of choroid plexus epithelial cells, with EC50 values of 9 and 26 nM, respectively. The effect of (+)LSD in both systems was blocked by 5HT receptor antagonists with an order of activity consistent with interaction at 5HT1C receptors. Neither (+)-2-bromo-LSD nor lisuride, two nonhallucinogenic congeners of LSD, were able to stimulate 5HT1C receptors in cultured cells or intact choroid plexus. In contrast, lisuride, like (+)LSD, is a partial agonist at 5HT2 receptors in cerebral cortex slices and in NIH 3T3 cells transfected with 5HT2 receptor cDNA. The present finding that (+)LSD, but not its nonhallucinogenic congeners, is a 5HT1C receptor agonist suggests a possible role for these receptors in mediating the psychoactive effects of LSD

Optimizing P3HT/PCBM/MWCNT films for increased stability in polymer bulk heterojunction solar cells

International Nuclear Information System (INIS)

Singh, Vinamrita; Arora, Swati; Arora, Manoj; Sharma, Vishal; Tandon, R.P.

2014-01-01

The effect of multi-walled carbon nanotubes on the properties of P3HT:PCBM based solar cells has been studied. The concentration of MWCNT was optimized at 0.2% and the concentration of P3HT:PCBM was increased from 20mg/ml to 30mg/ml to obtain highest efficiency. An increase in charge carrier mobility was also observed, which is attributed to high charge transport properties of MWCNT. The active layer was optically stable with respect to absorption, whereas the emission spectra revealed an increase in charge recombination with time. The solar cells doped with MWCNT exhibited increased stability as compared to undoped cells. - Highlights: • MWCNT doped P3HT:PCBM based solar cells are optimized for increased efficiency. • Degradation studies showed that MWCNT stabilizes the cell performance. • Mobility and basic device characteristics decreased with time. • Photoluminescence studies with time showed an increase in charge recombination. • Degradation for devices kept in air is faster as compared to the samples in vacuum

Optimizing P3HT/PCBM/MWCNT films for increased stability in polymer bulk heterojunction solar cells

Energy Technology Data Exchange (ETDEWEB)

Singh, Vinamrita [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India); Arora, Swati, E-mail: drswatia@yahoo.com [Department of Physics, Zakir Husain Delhi College, University of Delhi, Delhi 110002 (India); Arora, Manoj [Department of Physics, Ramjas College, University of Delhi, Delhi 110007 (India); Sharma, Vishal; Tandon, R.P. [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India)

2014-08-22

The effect of multi-walled carbon nanotubes on the properties of P3HT:PCBM based solar cells has been studied. The concentration of MWCNT was optimized at 0.2% and the concentration of P3HT:PCBM was increased from 20mg/ml to 30mg/ml to obtain highest efficiency. An increase in charge carrier mobility was also observed, which is attributed to high charge transport properties of MWCNT. The active layer was optically stable with respect to absorption, whereas the emission spectra revealed an increase in charge recombination with time. The solar cells doped with MWCNT exhibited increased stability as compared to undoped cells. - Highlights: • MWCNT doped P3HT:PCBM based solar cells are optimized for increased efficiency. • Degradation studies showed that MWCNT stabilizes the cell performance. • Mobility and basic device characteristics decreased with time. • Photoluminescence studies with time showed an increase in charge recombination. • Degradation for devices kept in air is faster as compared to the samples in vacuum.

Computer modelling of HT gas metabolism in humans

International Nuclear Information System (INIS)

Peterman, B.F.

1982-01-01

A mathematical model was developed to simulate the metabolism of HT gas in humans. The rate constants of the model were estimated by fitting the calculated curves to the experimental data by Pinson and Langham in 1957. The calculations suggest that the oxidation of HT gas (which probably occurs as a result of the enzymatic action of hydrogenase present in bacteria of human gut) occurs at a relatively low rate with a half-time of 10-12 hours. The inclusion of the dose due to the production of the HT oxidation product (HTO) in the soft tissues lowers the value of derived air concentration by about 50%. Furthermore the relationship between the concentration of HTO in urine and the dose to the lung from HT in the air in lungs is linear after short HT exposures, and hence HTO concentrations in urine can be used to estimate the upper limits on the lung dose from HT exposures. (author)

The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors.

Science.gov (United States)

De Gregorio, Danilo; Posa, Luca; Ochoa-Sanchez, Rafael; McLaughlin, Ryan; Maione, Sabatino; Comai, Stefano; Gobbi, Gabriella

2016-11-01

d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT 1 and 5-HT 2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity, compared these effects to those produced on 5-HT neurons in the dorsal raphe nucleus (DRN), and attempted to identify the mechanism of action mediating the effects of LSD on VTA DA neurons. LSD, at low doses (5-20μg/kg, i.v.) induced a significant decrease of DRN 5-HT firing activity through 5-HT 2A and D 2 receptors. At these low doses, LSD did not alter VTA DA neuronal activity. On the contrary, at higher doses (30-120μg/kg, i.v.), LSD dose-dependently decreased VTA DA firing activity. The depletion of 5-HT with p-chlorophenylalanine did not modulate the effects of LSD on DA firing activity. The inhibitory effects of LSD on VTA DA firing activity were prevented by the D 2 receptor antagonist haloperidol (50μg/kg, i.v.) and by the 5-HT 1A receptor antagonist WAY-100,635 (500μg/kg, i.v.). Notably, pretreatment with the trace amine-associate receptor 1 (TAAR 1 ) antagonist EPPTB (5mg/kg, i.v.) blocked the inhibitory effect of LSD on VTA DA neurons. These results suggest that LSD at high doses strongly affects DA mesolimbic neuronal activity in a 5-HT independent manner and with a pleiotropic mechanism of action involving 5-HT 1A, D 2 and TAAR 1 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Research on investment casting of TiAl alloy agitator treated by HIP and HT

Directory of Open Access Journals (Sweden)

LI Zhen-xi

2007-05-01

Full Text Available Using TiAl alloy to substitute superalloy is a hot topic in aeroengine industry because of its low density,high elevated temperature strength, and anti-oxidization ability. In this research, Ti-47.5AL-2Cr-2Nb-0.2B alloy was used as the test material. By applying a combination process of ceramic shell mold and core making, vacuum arc melting and centrifugal pouring, and heat isostatic pressing (HIP and heat treatment (HT etc., the TiAl vortex agitator casting for aeroengine was successfully made. This paper introduced key techniques in making the TiAl vortex agitator with investment casting process, provided some experimental results including mechanical properties and machinability, and explained some concerns that could affect applications of TiAl castings.

Increased hypothalamic 5-HT2A receptor gene expression and effects of pharmacologic 5-HT2A receptor inactivation in obese Ay mice

International Nuclear Information System (INIS)

Nonogaki, Katsunori; Nozue, Kana; Oka, Yoshitomo

2006-01-01

Serotonin (5-hydroxytryptamine; 5-HT) 2A receptors contribute to the effects of 5-HT on platelet aggregation and vascular smooth muscle cell proliferation, and are reportedly involved in decreases in plasma levels of adiponectin, an adipokine, in diabetic subjects. Here, we report that systemic administration of sarpogrelate, a 5-HT2A receptor antagonist, suppressed appetite and increased hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript, corticotropin releasing hormone, 5-HT2C, and 5-HT1B receptor gene expression. A y mice, which have ectopic expression of the agouti protein, significantly increased hypothalamic 5-HT2A receptor gene expression in association with obesity compared with wild-type mice matched for age. Systemic administration of sarpogrelate suppressed overfeeding, body weight gain, and hyperglycemia in obese A y mice, whereas it did not increase plasma adiponectin levels. These results suggest that obesity increases hypothalamic 5-HT2A receptor gene expression, and pharmacologic inactivation of 5-HT2A receptors inhibits overfeeding and obesity in A y mice, but did not increase plasma adiponectin levels

Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production.

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Bhattarai, Yogesh; Schmidt, Bradley A; Linden, David R; Larson, Eric D; Grover, Madhusudan; Beyder, Arthur; Farrugia, Gianrico; Kashyap, Purna C

2017-07-01

Serotonin [5-hydroxytryptamine (5-HT)], an important neurotransmitter and a paracrine messenger in the gastrointestinal tract, regulates intestinal secretion by its action primarily on 5-HT 3 and 5-HT 4 receptors. Recent studies highlight the role of gut microbiota in 5-HT biosynthesis. In this study, we determine whether human-derived gut microbiota affects host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age-matched Swiss Webster germ-free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice. 5-HT evoked a significantly greater increase in short-circuit current (Δ I sc ) in GF compared with HM mice. Additionally, 5-HT 3 receptor mRNA and protein expression was significantly higher in GF compared with HM mice. Ondansetron, a 5-HT 3 receptor antagonist, inhibited 5-HT-evoked Δ I sc in GF mice but not in HM mice. Furthermore, a 5-HT 3 receptor-selective agonist, 2-methyl-5-hydroxytryptamine hydrochloride, evoked a significantly higher Δ I sc in GF compared with HM mice. Immunohistochemistry in 5-HT 3A -green fluorescent protein mice localized 5-HT 3 receptor expression to enterochromaffin cells in addition to nerve fibers. The significant difference in 5-HT-evoked Δ I sc between GF and HM mice persisted in the presence of tetrodotoxin (TTX) but was lost after ondansetron application in the presence of TTX. Application of acetate (10 mM) significantly lowered 5-HT 3 receptor mRNA in GF mouse colonoids. We conclude that host secretory response to 5-HT may be modulated by gut microbiota regulation of 5-HT 3 receptor expression via acetate production. Epithelial 5-HT 3 receptor may function as a mediator of gut microbiota-driven change in intestinal secretion. NEW & NOTEWORTHY We found that gut microbiota alters serotonin (5-HT)-evoked intestinal secretion in a 5-HT 3 receptor-dependent mechanism and gut microbiota metabolite acetate alters 5-HT 3 receptor expression in

Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

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Nilgun Gurbuz

Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D-mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

Directory of Open Access Journals (Sweden)

Nilgun Gurbuz

Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D- mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

In the search for a lead structure among series of potent and selective hydantoin 5-HT7 R agents: The drug-likeness in vitro study.

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Latacz, Gniewomir; Lubelska, Annamaria; Jastrzębska-Więsek, Magdalena; Partyka, Anna; Sobiło, Andrzej; Olejarz, Agnieszka; Kucwaj-Brysz, Katarzyna; Satała, Grzegorz; Bojarski, Andrzej J; Wesołowska, Anna; Kieć-Kononowicz, Katarzyna; Handzlik, Jadwiga

2017-12-01

Since the year 1993, when 5-HT 7 receptor (5-HT 7 R) was discovered, there is no selective 5-HT 7 R ligand introduced to the pharmaceutical market. One out of the main reasons disqualifying the 5-HT 7 R ligands is weak drugability properties, including metabolic instability or low permeability. This study is focused on the search of a lead compound by "drug-likeness" estimation of the first series of selective and potent 5-HT 7 R ligands among 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-aryl-piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione derivatives (11-16). The most important drugability parameters, i.e., permeability, metabolic stability, and safety, have been evaluated. The main metabolic pathways were determined. The forced swim test (FST) in mice was performed as a primary in vivo assay for compound 13 and the reference 2. The experiments showed promising drug-like properties for all ligands, with special attention to the benzhydryl (diphenylmethyl) derivative 13. The studies have also indicated in vivo activity of the compound 13 that was observed as a significant and specific antidepressant-like activity in the FST. Taking into account the beneficial properties of 13, i.e., good drug-like parameters, the significant antagonistic action, high selectivity to 5-HT 7 R, and its in vivo antidepressant-like activity, the compound should be considered as a new lead in the search for drugs acting on CNS via 5-HT 7 receptor. © 2017 John Wiley & Sons A/S.

Antistress Effects of Rosa rugosa Thunb. on Total Sleep Deprivation-Induced Anxiety-Like Behavior and Cognitive Dysfunction in Rat: Possible Mechanism of Action of 5-HT6 Receptor Antagonist.

Science.gov (United States)

Na, Ju-Ryun; Oh, Dool-Ri; Han, SeulHee; Kim, Yu-Jin; Choi, EunJin; Bae, Donghyuck; Oh, Dong Hwan; Lee, Yoo-Hyun; Kim, Sunoh; Jun, Woojin

2016-09-01

Our previous results suggest that the Rosa rugosa Thunb. (family Rosaceae) alleviates endurance exercise-induced stress by decreasing oxidative stress levels. This study aimed to screen and identify the physiological antistress effects of an extract of R. rugosa (RO) on sleep deprivation-induced anxiety-like behavior and cognitive tests (in vivo) and tested for hippocampal CORT and monoamine levels (ex vivo), corticosterone (CORT)-induced injury, N-methyl-d-aspartate (NMDA) receptor, and serotonin 6 (5-hydroxytryptamine 6, 5-HT6) receptor activities (in vitro) in search of active principles and underlying mechanisms of action. We confirmed the antistress effects of RO in a sleep-deprived stress model in rat and explored the underlying mechanisms of its action. In conclusion, an R. rugosa extract showed efficacy and potential for use as an antistress therapy to treat sleep deprivation through its antagonism of the 5-HT6 receptor and resulting inhibition of cAMP activity.

Do dorsal raphe 5-HT neurons encode "beneficialness"?

Science.gov (United States)

Luo, Minmin; Li, Yi; Zhong, Weixin

2016-11-01

The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) affects numerous behavioral and physiological processes. Drugs that alter 5-HT signaling treat several major psychiatric disorders and may lead to widespread abuse. The dorsal raphe nucleus (DRN) in the midbrain provides a majority of 5-HT for the forebrain. The importance of 5-HT signaling propels the search for a general theoretical framework under which the diverse functions of the DRN 5-HT neurons can be interpreted and additional therapeutic solutions may be developed. However, experimental data so far support several seeming irreconcilable theories, suggesting that 5-HT neurons mediate behavioral inhibition, aversive processing, or reward signaling. Here, we review recent progresses and propose that DRN 5-HT neurons encode "beneficialness" - how beneficial the current environmental context represents for an individual. Specifically, we speculate that the activity of these neurons reflects the possible net benefit of the current context as determined by p·R-C, in which p indicates reward probability, R the reward value, and C the cost. Through the widespread projections of these neurons to the forebrain, the beneficialness signal may reconfigure neural circuits to bias perception, boost positive emotions, and switch behavioral choices. The "beneficialness" hypothesis can explain many conflicting observations, and at the same time raises new questions. We suggest additional experiments that will help elucidate the exact computational functions of the DRN 5-HT neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat.

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Nair, Sunila G; Gudelsky, Gary A

2004-09-15

The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

Effect of the 5-HT{sub 4} receptor and serotonin transporter on visceral hypersensitivity in rats

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Chi, Yan; Liu, Xin-Guang; Wang, Hua-Hong; Li, Jun-Xia; Li, Yi-Xuan [Department of Gastroenterology, Peking University First Hospital, Beijing (China)

2012-07-27

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT{sub 4} receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT{sub 4} receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT{sub 4} receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg{sup −1}·day{sup −1}, days 36-42), tegaserod (1 mg·kg{sup −1}·day{sup −1}, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT{sub 4} receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT{sub 4} receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT

Effects of Constant Flickering Light on Refractive Status, 5-HT and 5-HT2A Receptor in Guinea Pigs.

Science.gov (United States)

Li, Bing; Luo, Xiumei; Li, Tao; Zheng, Changyue; Ji, Shunmei; Ma, Yuanyuan; Zhang, Shuangshuang; Zhou, Xiaodong

2016-01-01

To investigate the effects of constant flickering light on refractive development, the role of serotonin (i.e.5-hydroxytryptamine, 5-HT)and 5-HT2A receptor in myopia induced by flickering light in guinea pigs. Forty-five guinea pigs were randomly divided into three groups: control, form deprivation myopia (FDM) and flickering light induced myopia (FLM) groups(n = 15 for each group). The right eyes of the FDM group were covered with semitransparent hemispherical plastic shells serving as eye diffusers. Guinea pigs in FLM group were raised with illumination of a duty cycle of 50% at a flash frequency of 0.5Hz. The refractive status, axial length (AL), corneal radius of curvature(CRC) were measured by streak retinoscope, A-scan ultrasonography and keratometer, respectively. Ultramicroscopy images were taken by electron microscopy. The concentrations of 5-HTin the retina, vitreous body and retinal pigment epithelium (RPE) were assessed by high performance liquid chromatography, the retinal 5-HT2A receptor expression was evaluated by immunohistofluorescence and western blot. The refraction of FDM and FLM eyes became myopic from some time point (the 4th week and the 6th week, respectively) in the course of the experiment, which was indicated by significantly decreased refraction and longer AL when compared with the controls (plight could cause progressive myopia in guinea pigs. 5-HT and 5-HT2A receptor increased both in form deprivation myopia and flickering light induced myopia, indicating that 5-HT possibly involved in myopic development via binding to5-HT2A receptor.

5HT(1A) and 5HT(1B) receptors of medial prefrontal cortex modulate anxiogenic-like behaviors in rats.

Science.gov (United States)

Solati, Jalal; Salari, Ali-Akbar; Bakhtiari, Amir

2011-10-31

Medial prefrontal cortex (MPFC) is one of the brain regions which play an important role in emotional behaviors. The purpose of the present study was to evaluate the role of 5HT(1A) and 5HT(1B) receptors of the MPFC in modulation of anxiety behaviors in rats. The elevated plus maze (EPM) which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used. Bilateral intra-MPFC administration of 5HT(1A) receptor agonist, 8-OH-DPAT (5, 10, and 50 ng/rat) decreased the percentages of open arm time (OAT%) and open arm entries (OAE%), indicating an anxiogenic response. Moreover, administration of 5HT(1A) receptor antagonist, NAN-190 (0.25, 0.5, and 1 μg/rat) significantly increased OAT% and OAE%. Pre-treatment administration of NAN-190 (0.5 μg/rat), which was injected into the MPFC, reversed the anxiogenic effects of 8-OH-DPAT (5, 10, and 50 ng/rat). Intra-MPFC microinjection of 5HT(1B) receptor agonist, CGS-12066A (0.25, 0.5, and 1 μg/rat) significantly decreased OAT% and OAE%, without any change in locomotor activity, indicating an anxiogenic effect. However, injection of 5HT(1B) receptor antagonist, SB-224289 (0.5, 1, and 2 μg/rat) into the MPFC showed no significant effect. In conclusion, these findings suggest that 5HT(1A) and 5HT(1B) receptors of the MPFC region modulate anxiogenic-like behaviors in rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Activation of 5-HT7 receptors reverses NMDA-R-dependent LTD by activating PKA in medial vestibular neurons.

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Li, Yan-Hai; Han, Lei; Wu, Kenneth Lap Kei; Chan, Ying-Shing

2017-09-01

The medial vestibular nucleus (MVN) is a major output station for neurons that project to the vestibulo-spinal pathway. MVN neurons show capacity for long-term depression (LTD) during the juvenile period. We investigated LTD of MVN neurons using whole-cell patch-clamp recordings. High frequency stimulation (HFS) robustly induced LTD in 90% of type B neurons in the MVN, while only 10% of type A neurons were responsive, indicating that type B neurons are the major contributors to LTD in the MVN. The neuromodulator serotonin (5-HT) is known to modulate LTD in neural circuits of the cerebral cortex and the hippocampus. We therefore aim to determine the action of 5-HT on the LTD of type B MVN neurons and elucidate the relevant 5-HT receptor subtypes responsible for its action. Using specific agonists and antagonists of 5-HT receptors, we found that selective activation of 5-HT 7 receptor in type B neurons in the MVN of juvenile (P13-16) rats completely abolished NMDA-receptor-mediated LTD in a protein kinase A (PKA)-dependent manner. Our finding that 5-HT restricts plasticity of type B MVN neurons via 5-HT 7 receptors offers a mechanism whereby vestibular tuning contributes to the maturation of the vestibulo-spinal circuit and highlights the role of 5-HT in postural control. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of hydrothermal treatment temperature on the properties of sewage sludge derived solid fuel

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Mi Yan

2015-10-01

Full Text Available High moisture content along with poor dewaterability are the main challenges for sewage sludge treatment and utilization. In this study, the effect of hydrothermal treatment at various temperature (120-200 ˚C on the properties of sewage sludge derived solid fuel was investigated in the terms of mechanical dewatering character, drying character, calorific value and heavy metal distribution. Hydrothermal treatment (HT followed by dewatering process significantly reduced moisture content and improved calorific value of sewage sludge with the optimum condition obtained at 140˚C. No significant alteration of drying characteristic was produced by HT. Heavy metal enrichment in solid particle was found after HT that highlighted the importance of further study regarding heavy metal behavior during combustion. However, it also implied the potential application of HT on sewage sludge for heavy metal removal from wastewater.

Antioxidant and ACE-inhibitory activities of hemp (Cannabis sativa L.) protein hydrolysates produced by the proteases AFP, HT, Pro-G, actinidin and zingibain.

Science.gov (United States)

Teh, Sue-Siang; Bekhit, Alaa El-Din A; Carne, Alan; Birch, John

2016-07-15

Hemp protein isolates (HPIs) were hydrolysed by proteases (AFP, HT, ProG, actinidin and zingibain). The enzymatic hydrolysis of HPIs was evaluated through the degree of hydrolysis and SDS-PAGE profiles. The bioactive properties of the resultant hydrolysates (HPHs) were accessed through ORAC, DPPḢ scavenging and ACE-inhibitory activities. The physical properties of the resultant HPHs were evaluated for their particle sizes, zeta potential and surface hydrophobicity. HT had the highest rate of caseinolytic activity at the lowest concentration (0.1 mg mL(-1)) compared to other proteases that required concentration of 100 mg mL(-1) to achieve their maximum rate of caseinolytic activity. This led to the highest degree of hydrolysis of HPIs by HT in the SDS-PAGE profiles. Among all proteases and substrates, HT resulted in the highest bioactivities (ORAC, DPPḢ scavenging and ACE-inhibitory activities) generated from alkali extracted HPI in the shortest time (2 h) compared to the other protease preparations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deletion of Munc18-1 in 5-HT Neurons Results in Rapid Degeneration of the 5-HT System and Early Postnatal Lethality

NARCIS (Netherlands)

Dudok, J.J.; Groffen, A.J.A.; Toonen, R.F.G.; Verhage, M.

2011-01-01

The serotonin (5-HT) system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT)

Effect of acute and chronic tramadol on [3H]-5-HT uptake in rat cortical synaptosomes

OpenAIRE

Giusti, Pietro; Buriani, Alessandro; Cima, Lorenzo; Lipartiti, Maria

1997-01-01

Tramadol hydrochloride is a centrally acting opioid analgesic, the efficacy and potency of which is only five to ten times lower than that of morphine. Opioid, as well as non-opioid mechanisms, may participate in the analgesic activity of tramadol.[3H]-5-hydroxytryptamine (5-HT) uptake in rat isolated cortical synaptosomes was studied in the presence of tramadol, desipramine, fluoxetine, methadone and morphine. Methadone and tramadol inhibited synaptosomal [3H]-5-HT uptake with apparent Kis o...

Influence of the introduction and formation of artificial pinning centers on the transport properties of nanostructured Nb{sub 3}Sn superconducting wires

Energy Technology Data Exchange (ETDEWEB)

Da Silva, L B S; Rodrigues, C A; Bormio-Nunes, C; Oliveira, N F Jr; Rodrigues, D Jr, E-mail: lucas_sarno@ppgem.eel.usp.b, E-mail: durval@demar.eel.usp.b [Superconductivity Group, Department of Materials Engineering (DEMAR) Escola de Engenharia de Lorena (EEL), Universidade de Sao Paulo - USP Polo Urbo-Industrial, Gleba AI-6 - PO Box 116 - Lorena, SP (Brazil)

2009-05-01

The formation of nanostructures projected to act as pinning centers is presented as a highly promising technique for the transport properties optimization of superconductors. However, due to the necessity of nanometric dimensions of these pinning centers, the heat treatment (HT) profiles must be carefully analyzed. The present work describes a methodology to optimize the HT profiles in respect to diffusion, reaction and formation of the superconducting phases. After the HT, samples were removed for micro structural characterization. Measurements of transport properties were performed to analyze the influence of the introduction of artificial pinning centers (APC) on the superconducting phase and to find the flux pinning mechanism acting in these wires. Fitting the volumetric pinning force vs. applied magnetic field (F{sub p} vs. mu{sub o}H) curves of transport properties, we could determine the type and influence of flux pinning mechanism acting in the global behavior of the samples. It was concluded that the maximum current densities were obtained when normal phases (due to the introduction of the APCs) are the most efficient pinning centers in the global behavior of the samples. The use of HT with profile 220{sup 0}C/100h+575{sup 0}C/50h+650{sup 0}C/100h was found as the best treatment for these nanostructured superconducting wires.

Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

Science.gov (United States)

Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

2011-11-01

Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.

Science.gov (United States)

De Gregorio, Danilo; Comai, Stefano; Posa, Luca; Gobbi, Gabriella

2016-11-23

d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles' reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD's mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT 2A receptor as a partial agonist and 5-HT 1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D₂, Trace Amine Associate receptor 1 (TAAR₁) and 5-HT 2A . More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR₁ receptors.

Review article: the many potential roles of intestinal serotonin (5-hydroxytryptamine, 5-HT) signalling in inflammatory bowel disease.

Science.gov (United States)

Coates, M D; Tekin, I; Vrana, K E; Mawe, G M

2017-09-01

Serotonin (5-hydroxytryptamine, 5-HT) is an important mediator of every major gut-related function. Recent investigations also suggest that 5-HT can influence the development and severity of inflammation within the gut, particularly in the setting of inflammatory bowel disease (IBD). To review the roles that the intestinal serotonin signalling system plays in gut function, with a specific focus on IBD. We reviewed manuscripts from 1952 to 2017 that investigated and discussed roles for 5-HT signalling in gastrointestinal function and IBD, as well as the influence of inflammation on 5-HT signalling elements within the gut. Inflammation appears to affect every major element of intestinal 5-HT signalling, including 5-HT synthesis, release, receptor expression and reuptake capacity. Importantly, many studies (most utilising animal models) also demonstrate that modulation of selective serotonergic receptors (via agonism of 5-HT 4 R and antagonism of 5-HT 3 R) or 5-HT signal termination (via serotonin reuptake inhibitors) can alter the likelihood and severity of intestinal inflammation and/or its complicating symptoms. However, there are few human studies that have studied these relationships in a targeted manner. Insights discussed in this review have strong potential to lead to new diagnostic and therapeutic tools to improve the management of IBD and other related disorders. Specifically, strategies that focus on modifying the activity of selective serotonin receptors and reuptake transporters in the gut could be effective for controlling disease activity and/or its associated symptoms. Further studies in humans are required, however, to more completely understand the pathophysiological mechanisms underlying the roles of 5-HT in this setting. © 2017 John Wiley & Sons Ltd.

Mechanical properties of rock at high temperatures

International Nuclear Information System (INIS)

Kinoshita, Naoto; Abe, Tohru; Wakabayashi, Naruki; Ishida, Tsuyoshi.

1997-01-01

The laboratory tests have been performed in order to investigate the effects of temperature up to 300degC and pressure up to 30 MPa on the mechanical properties of three types of rocks, Inada granite, Sanjoume andesite and Oya tuff. The experimental results indicated that the significant differences in temperature dependence of mechanical properties exist between the three rocks, because of the difference of the factors which determine the mechanical properties of the rocks. The effect of temperature on the mechanical properties for the rocks is lower than that of pressure and water content. Temperature dependence of the mechanical properties is reduced by increase in pressure in the range of pressure and temperature investigated in this paper. (author)

Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

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Kim, Sojin; Jin, Zhenhua; Lee, Goeun [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Park, Yong Seek; Park, Cheung-Seog [Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Jin, Young-Ho, E-mail: jinyh@khu.ac.kr [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)

2015-01-02

Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

Role of Molecular Weight on the Mechanical Device Properties of Organic Polymer Solar Cells

KAUST Repository

Bruner, Christopher

2014-02-11

For semiconducting polymers, such as regioregular poly(3-hexylthiophene-2, 5-diyl) (rr-P3HT), the molecular weight has been correlated to charge carrier field-effect mobilities, surface morphology, and gelation rates in solution and therefore has important implications for long-Term reliability, manufacturing, and future applications of electronic organic thin films. In this work, we show that the molecular weight rr-P3HT in organic solar cells can also significantly change the internal cohesion of the photoactive layer using micromechanical testing techniques. Cohesive values ranged from ∼0.5 to ∼17 J m -2, following the general trend of greater cohesion with increasing molecular weight. Using nanodynamic mechanical analysis, we attribute the increase in cohesion to increased plasticity which helps dissipate the applied energy. Finally, we correlate photovoltaic efficiency with cohesion to assess the device physics pertinent to optimizing device reliability. This research elucidates the fundamental parameters which affect both the mechanical stability and efficiency of polymer solar cells. © 2014 American Chemical Society.

Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling.

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Buchborn, Tobias; Schröder, Helmut; Höllt, Volker; Grecksch, Gisela

2014-06-01

A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; from these, only the hippocampal decrease in 5-HT2 related [(35)S]-GTP-gamma-S binding is normalised by LSD. Importantly, the sham-operated rats do not profit from LSD, and exhibit reduced hippocampal 5-HT2 signalling. As behavioural deficits after bulbectomy respond to agents classified as antidepressants only, we conclude that the effect of LSD in this model can be considered antidepressant-like, and discuss it in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling. © The Author(s) 2014.

Geoditin A Induces Oxidative Stress and Apoptosis on Human Colon HT29 Cells

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Wing-Keung Liu

2010-01-01

Full Text Available Geoditin A, an isomalabaricane triterpene isolated from the marine sponge Geodia japonica, has been demonstrated to dissipate mitochondrial membrane potential, activate caspase 3, decrease cytoplasmic proliferating cell nuclear antigen (PCNA, and induce apoptosis of leukemia cells, but the underlying mechanism remains unclear [1]. In this study, we found fragmentation of Golgi structure, suppression of transferrin receptor expression, production of oxidants, and DNA fragmentation in human colon cancer HT29 cells after treatment with geoditin A for 24 h. This apoptosis was not abrogated by chelation of intracellular iron with salicylaldehyde isonicotinoyl hydrazone (SIH, but suppressed by N-acetylcysteine (NAC, a thiol antioxidant and GSH precursor, indicating that the cytotoxic effect of geoditin A is likely mediated by a NAC-inhibitable oxidative stress. Our results provide a better understanding of the apoptotic properties and chemotherapeutical potential of this marine triterpene.

Estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus is independent of estrogen receptor-beta.

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Rossi, Dania V; Dai, Ying; Thomas, Peter; Carrasco, Gonzalo A; DonCarlos, Lydia L; Muma, Nancy A; Li, Qian

2010-08-01

Estradiol regulates serotonin 1A (5-HT(1A)) receptor signaling. Since desensitization of 5-HT(1A) receptors may be an underlying mechanism by which selective serotonin reuptake inhibitors (SSRIs) mediate their therapeutic effects and combining estradiol with SSRIs enhances the efficacy of the SSRIs, it is important to determine which estrogen receptors are capable of desensitizating 5-HT(1A) receptor function. We previously demonstrated that selective activation of the estrogen receptor, GPR30, desensitizes 5-HT(1A) receptor signaling in rat hypothalamic paraventricular nucleus (PVN). However, since estrogen receptor-beta (ERbeta), is highly expressed in the PVN, we investigated the role of ERbeta in estradiol-induced desensitization of 5-HT(1A) receptor signaling. We first showed that a selective ERbeta agonist, diarylpropionitrile (DPN) has a 100-fold lower binding affinity than estradiol for GPR30. Administration of DPN did not desensitize 5-HT(1A) receptor signaling in rat PVN as demonstrated by agonist-stimulated hormone release. Second, we used a recombinant adenovirus containing ERbeta siRNAs to decrease ERbeta expression in the PVN. Reductions in ERbeta did not alter the estradiol-induced desensitization of 5-HT(1A) receptor signaling in oxytocin cells. In contrast, in animals with reduced ERbeta, estradiol administration, instead of producing desensitization, augmented the ACTH response to a 5-HT(1A) agonist. Combined with the results from the DPN treatment experiments, desensitization of 5-HT(1A) receptor signaling does not appear to be mediated by ERbeta in oxytocin cells, but that ERbeta, together with GPR30, may play a complex role in central regulation of 5-HT(1A)-mediated ACTH release. Determining the mechanisms by which estrogens induce desensitization may aid in the development of better treatments for mood disorders. Copyright 2010 Elsevier Ltd. All rights reserved.

Barrier Performance of CVD Graphene Films Using a Facile P3HT Thin Film Optical Transmission Test

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Srinivasa Kartik Nemani

2018-01-01

Full Text Available The barrier performance of CVD graphene films was determined using a poly(3-hexylthiophene (P3HT thin film optical transmission test. P3HT is a semiconducting polymer that photo-oxidatively degrades upon exposure to oxygen and light. The polymer is stable under ambient conditions and indoor lighting, enabling P3HT films to be deposited and encapsulated in air. P3HT’s stability under ambient conditions makes it desirable for an initial evaluation of barrier materials as a complimentary screening method in combination with conventional barrier tests. The P3HT test was used to demonstrate improved barrier performance for polymer substrates after addition of CVD graphene films. A layer-by-layer transfer method was utilized to enhance the barrier performance of monolayer graphene. Another set of absorption measurements were conducted to demonstrate the barrier performance of graphene and the degradation mechanism of graphene/P3HT over multiple wavelengths from 400 to 800 nm. The absorption spectra for graphene/polymer composite were simulated by solving Fresnel equations. The simulation results were found to be in good agreement with the measured absorption spectra. The P3HT degradation results qualitatively indicate the potential of graphene films as a possible candidate for medium performance barriers.

Growth and adhesion to HT-29 cells inhibition of Gram-negatives by Bifidobacterium longum BB536 e Lactobacillus rhamnosus HN001 alone and in combination.

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Inturri, R; Stivala, A; Furneri, P M; Blandino, G

2016-12-01

The aim of this study was to test the inhibitory effect of supernatants of broth cultures of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001, both individually and in combination, against Gram-negative strains (uropathogens, enteropathogens and a reference strain). Moreover, in vitro protection of B. longum BB536 and L. rhamnosus HN001, both individually and in combination, against pathogen adhesion to HT-29 cell line, was investigated. The inhibitory activity was performed by the agar diffusion test and in vitro antagonistic activity against pathogen adhesion to human epithelial intestinal HT-29 cells was performed using standardized culture techniques. The study showed that B. longum BB536 and L. rhamnosus HN001, individually and in combination have inhibitory activity against the majority of the Gram negative strains tested. Furthermore, the results showed that both probiotic strains have a good capacity to inhibit pathogenic adhesion to HT-29 cells. Moreover, the ability of B. longum BB536 and L. rhamnosus HN001 to inhibit pathogenic adhesion increased when they were used in combination. The combination of B. longum BB536 and L. rhamnosus HN001 showed inhibitory activity against Gram-negatives and an improved ability to reduce their adhesion properties and to compete with them. The simultaneous presence of the two-probiotic strains could promote competitive mechanisms able to reduce the adhesion properties of pathogen strains and have an important ecological role within the highly competitive environment of the human gut.

Discerning apical and basolateral properties of HT-29/B6 and IPEC-J2 cell layers by impedance spectroscopy, mathematical modeling and machine learning.

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Thomas Schmid

Full Text Available Quantifying changes in partial resistances of epithelial barriers in vitro is a challenging and time-consuming task in physiology and pathophysiology. Here, we demonstrate that electrical properties of epithelial barriers can be estimated reliably by combining impedance spectroscopy measurements, mathematical modeling and machine learning algorithms. Conventional impedance spectroscopy is often used to estimate epithelial capacitance as well as epithelial and subepithelial resistance. Based on this, the more refined two-path impedance spectroscopy makes it possible to further distinguish transcellular and paracellular resistances. In a next step, transcellular properties may be further divided into their apical and basolateral components. The accuracy of these derived values, however, strongly depends on the accuracy of the initial estimates. To obtain adequate accuracy in estimating subepithelial and epithelial resistance, artificial neural networks were trained to estimate these parameters from model impedance spectra. Spectra that reflect behavior of either HT-29/B6 or IPEC-J2 cells as well as the data scatter intrinsic to the used experimental setup were created computationally. To prove the proposed approach, reliability of the estimations was assessed with both modeled and measured impedance spectra. Transcellular and paracellular resistances obtained by such neural network-enhanced two-path impedance spectroscopy are shown to be sufficiently reliable to derive the underlying apical and basolateral resistances and capacitances. As an exemplary perturbation of pathophysiological importance, the effect of forskolin on the apical resistance of HT-29/B6 cells was quantified.

The love of a lifetime: 5-HT in the cardiovascular system.

Science.gov (United States)

Watts, Stephanie W

2009-02-01

Serotonin [5-hydroxytryptamine (5-HT)] is an amine made from the essential amino acid tryptophan. 5-HT serves numerous functions in the body, including mood, satiety, and gastrointestinal function. Less understood is the role 5-HT plays in the cardiovascular system, although 5-HT receptors have been localized to every important cardiovascular organ and 5-HT-induced changes in physiological function attributed to activation of these receptors. This manuscript relates a few scientific stories that test the idea that 5-HT is important to the control of normal vascular tone, more so in the hypertensive condition. Currently, our laboratory is faced with two different lines of experimentation from which one could draw vastly different conclusions as to the ability of 5-HT to modify endogenous vascular tone and blood pressure. Studies point to 5-HT being important in maintaining high blood pressure, but other studies solidly support the ability of 5-HT to reduce elevated blood pressure. This work underscores that our knowledge of the functions of 5-HT in the cardiovascular system is significantly incomplete. As such, this field is an exciting one in which to be, because there are superb questions to be asked.

Environmental HTO/HT sampler development

International Nuclear Information System (INIS)

Workman, W.J.G.; Brown, R.M.; Wood, M.J.

1992-12-01

Tests of retention by several drying agents of HTO from an air stream containing HT have been performed. Two batches of Molecular Sieve (MS) 4A retained up to 1.3% of HT passed through them in contrast to material tested in 1986, when retention was -4 . Retention of 10 -5 to 10 -6 was observed for DRIERITE (anhydrous calcium sulphate) and Silica Gel. DRIERITE is preferred over Silica Gel as a desiccant in an air sampler for environmental HTO/HT, because it is much easier to decontaminate for reuse. An improved air sampler has been designed, 2 units constructed and components procured for 3 more. The air sampler may be line or battery operated, accommodates up to four 120 g drier or oxidizer traps, and will pump up to 4 L/min for up to 24 hours on battery power. It is build into a rugged aluminum case and weighs approximately 11 kg overall, facilitating deployment in the field

Environmental HTO/HT sampler development

International Nuclear Information System (INIS)

Workman, W.J.G.; Brown, R.M.; Wood, M.J.

1994-01-01

Tests of retention by several drying agents of HTO from an air stream containing HT have been performed. Two batches of Molecular Sieve (MS) 4A retained up to 1.3% of HT passed through them, in contrast to material tested in 1986, when retention was -4 . Retention of 10 -5 to 10 -6 was observed for DRIERITE (anhydrous calcium sulphate) and Silica Gel. DRIERITE is preferred over Silica Gel as a desiccant in an air sampler for environmental HTO/HT, because it is much easier to decontaminate for reuse. An improved air sampler has been designed, 2 units constructed and components procured for 3 more. The air sampler may be line or battery operated, accommodates up to four 120 g drier or oxidizer traps, and will pump up to 4 L/min for up to 24 hours on battery power. It is built into a rugged aluminum case and weighs approximately 11 kg overall, facilitating deployment in the field. (author). 5 refs., 2 tabs., 4 figs

The reconstruction of HT-7 superconducting tokamak and the present status of HT-7U project

International Nuclear Information System (INIS)

Weng, P.D.

2000-01-01

The first Chinese superconducting tokamak HT-7 was reconstructed from T-7. The main purposes of reconstruction are to improve the accessibility of the device and to provide a possibility of long pulse operation with high performance. The reconstruction has been done successfully. The HT-7U project has been approved and funded as a National Project, the engineering design and R and D are on the way. (author)

The effects of inorganic lead on the spontaneous and potassium-evoked release of 3H-5-HT from rat cortical synaptosome interaction with calcium

International Nuclear Information System (INIS)

Oudar, P.; Caillard, L.; Fillion, G.

1989-01-01

Interaction of lead with the serotonergic system has been studied in vitro in rat brain synaptosomal fraction prepared from cortical tissue. Synaptosomes were loaded with 3 H-5-HT and spontaneous and K + -evoked release of the amine was examined in the presence and the absence of calcium. It was shown that lead itself induced the release of 3 H-5-HT (EC50=27 μM). This effect decreased (40%) in the presence of calcium without modification of the EC50. Moreover, lead markedly inhibited the K + -evoked release of 3 H-5-HT observed in the presence of calcium. This effect was obtained either in the presence of lead or using synaptosomes pretreated with lead and washed. These results indicate that lead interferes with neuronal 5-HT release by mechanism(s) involving calcium. (author)

Changes of Serotonin (5-HT, 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression, Myocardial Infarction and Myocardial Infarction Co-exist with Depression

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Mei-Yan Liu

2015-01-01

Conclusions: The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression. Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.

125I-BH-8-MeO-N-PAT, a new ligand for studying 5-HT1A receptors in the central nervous system

International Nuclear Information System (INIS)

Ponchant, M.; Beaucourt, J.P.; Vanhove, A.

1988-01-01

Specific radioactive ligands are needed for studying the pharmacological properties and the regional distribution of the different classes of 5-HT 1 receptors within the central nervous system. We describe here the synthesis and some characteristics of the first iodinated specific ligand of 5-HT 1A receptors. Like its parent compound, the agonist 8-hydroxy-2-(di-n-propylamino)tetralin or 8-OH-DPAT, [ 125 I]-BH-8-MeO-N-PAT, exhibits a high affinity and excellent selectivity for 5-HT 1A sites. Its high specific radioactivity makes this ligand a useful tool for studying 5-HT 1A receptors in membranes and sections of the rat brain [fr

Effects of chronic treatment with escitalopram or citalopram on extracellular 5-HT in the prefrontal cortex of rats: role of 5-HT1A receptors

Science.gov (United States)

Ceglia, I; Acconcia, S; Fracasso, C; Colovic, M; Caccia, S; Invernizzi, R W

2004-01-01

Microdialysis was used to study the acute and chronic effects of escitalopram (S-citalopram; ESCIT) and chronic citalopram (CIT), together with the 5-HT1A receptor antagonist WAY100,635 (N-[2-[methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride) and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on extracellular 5-hydroxytryptamine (5-HT) levels in the rat prefrontal cortex. Extracellular 5-HT rose to 234 and 298% of basal values after subcutaneous (s.c.) acute doses of 0.15 and 0.63 mg kg−1 ESCIT. No further increase was observed at 2.5 mg kg−1 ESCIT (290%). The effect of 13-day s.c. infusion of 10 mg kg−1day−1 ESCIT on extracellular 5-HT (422% of baseline) was greater than after 2 days (257% of baseline), whereas exposure to ESCIT was similar. In contrast, the increase in extracellular 5-HT induced by the infusion of CIT for 2 (306%) and 13 days (302%) was similar. However, brain and plasma levels of S-citalopram in rats infused with CIT for 13 days were lower than after 2 days. Acute treatment with 2.5 mg kg−1 ESCIT or 5 mg kg−1 CIT raised extracellular 5-HT by 243 and 276%, respectively, in rats given chronic vehicle but had no effect in rats given ESCIT (10 mg kg−1 day−1) or CIT (20 mg kg−1 day−1) for 2 or 13 days, suggesting that the infused doses had maximally increased extracellular 5-HT. WAY100,635 (0.1 mg kg−1 s.c.) increased extracellular 5-HT levels by 168, 174 and 169% of prechallenge values in rats infused with vehicle or ESCIT for 2 or 13 days, respectively. WAY100,635 enhanced extracellular 5-HT levels to 226, 153 and 164% of prechallenge values in rats infused with vehicle or CIT for 2 and 13 days, respectively. 8-OH-DPAT (0.025 mg kg−1) reduced extracellular 5-HT by 54% in control rats, but had no effect in those given ESCIT and CIT for 13 days. This series of experiments led to the conclusion that chronic treatment with ESCIT desensitizes the 5-HT1A

Synthesis of a highly dispersed CuO catalyst on CoAl-HT for the epoxidation of styrene.

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Hu, Rui; Yang, Pengfei; Pan, Yongning; Li, Yunpeng; He, Yufei; Feng, Junting; Li, Dianqing

2017-10-10

A highly dispersed CuO catalyst was prepared by the deposition-precipitation method and evaluated for the catalytic epoxidation of styrene with tert-butyl hydroperoxide (TBHP) as the oxidant under solvent acetonitrile conditions. Compared with MgAl hydrotalcite (MgAl-HT)-, MgO-, TiO 2 -, C-, and MCM-22-supported catalysts, CuO/CoAl-HT exhibited preferable activity and selectivity towards styrene oxide (72% selectivity at 99.5% styrene conversion) due to its high dispersion of CuO and surface area of Cu. The improved dispersion of CuO/CoAl-HT could be ascribed to the nature of HT support, especially the synergistic effect of acidic and basic sites on the surface, which facilitated the formation of highly dispersed CuO species. A structure-performance relationship study indicated that copper(ii) in CuO was the active site for the epoxidation and oxidation of styrene, and that Cu II of rich electronic density favored the improvement of selectivity of styrene oxide. Based on these results, a reaction mechanism was proposed. Moreover, the preferred catalytic performance of CuO/CoAl-HT could be maintained in five reused cycles.

Anorexigen-induced pulmonary hypertension and the serotonin (5-HT hypothesis: lessons for the future in pathogenesis

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Adnot Serge

2002-01-01

Full Text Available Abstract Epidemiological studies have established that fenfluramine, D-fenfluramine, and aminorex, but not other appetite suppressants, increase the risk of primary pulmonary hypertension (PH. One current hypothesis suggests that fenfluramine-like medications may act through interactions with the serotonin (5-hydroxytryptamine [5-HT] transporter (5-HTT located on pulmonary artery smooth muscle cells and responsible for the mitogenic action of 5-HT. Anorexigens may contribute to PH by boosting 5-HT levels in the bloodstream, directly stimulating smooth muscle cell growth, or altering 5-HTT expression. We suggest that individuals with a high basal level of 5-HTT expression related to the presence of the long 5-HTT gene promoter variant may be particularly susceptible to one or more of these potential mechanisms of appetite-suppressant-related PH.

The 5HT(1A) receptor ligand, S15535, antagonises G-protein activation: a [35S]GTPgammaS and [3H]S15535 autoradiography study.

Science.gov (United States)

Newman-Tancredi, A; Rivet, J; Chaput, C; Touzard, M; Verrièle, L; Millan, M J

1999-11-19

4-(Benzodioxan-5-yl)1-(indan-2-yl)piperazine (S15535) is a highly selective ligand at 5-HT(1A) receptors. The present study compared its autoradiographic labelling of rat brain sections with its functional actions, visualised by guanylyl-5'-[gamma-thio]-triphosphate ([35S]GTPgammaS) autoradiography, which affords a measure of G-protein activation. [3H]S15535 binding was highest in hippocampus, frontal cortex, entorhinal cortex, lateral septum, interpeduncular nucleus and dorsal raphe, consistent with specific labelling of 5-HT(1A) receptors. In functional studies, S15535 (10 microM) did not markedly stimulate G-protein activation in any brain region, but abolished the activation induced by the selective 5-HT(1A) agonist, (+)-8-hydroxy-dipropyl-aminotetralin ((+)-8-OH-DPAT, 1 microM), in structures enriched in [3H]S15535 labelling. S15535 did not block 5-HT-stimulated activation in caudate nucleus or substantia nigra, regions where (+)-8-OH-DPAT was ineffective and [3H]S15535 binding was absent. Interestingly, S15535 attenuated (+)-8-OH-DPAT and 5-HT-stimulated G-protein activation in dorsal raphe, a region in which S15535 is known to exhibit agonist properties in vivo [Lejeune, F., Millan, M.J., 1998. Induction of burst firing in ventral tegmental area dopaminergic neurons by activation of serotonin (5-HT)(1A) receptors: WAY100,635-reversible actions of the highly selective ligands, flesinoxan and S15535. Synapse 30, 172-180.]. The present data show that (i) [3H]S15535 labels pre- and post-synaptic populations of 5-HT(1A) sites in rat brain sections, (ii) S15535 exhibits antagonist properties at post-synaptic 5-HT(1A) receptors in corticolimbic regions, and (iii) S15535 also attenuates agonist-stimulated G-protein activation at raphe-localised 5-HT(1A) receptors.

Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.

Science.gov (United States)

Gianotti, Massimo; Botta, Maurizio; Brough, Stephen; Carletti, Renzo; Castiglioni, Emiliano; Corti, Corrado; Dal-Cin, Michele; Delle Fratte, Sonia; Korajac, Denana; Lovric, Marija; Merlo, Giancarlo; Mesic, Milan; Pavone, Francesca; Piccoli, Laura; Rast, Slavko; Roscic, Maja; Sava, Anna; Smehil, Mario; Stasi, Luigi; Togninelli, Andrea; Wigglesworth, Mark J

2010-11-11

Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.

Repeated 7-Day Treatment with the 5-HT2C Agonist Lorcaserin or the 5-HT2A Antagonist Pimavanserin Alone or in Combination Fails to Reduce Cocaine vs Food Choice in Male Rhesus Monkeys.

Science.gov (United States)

Banks, Matthew L; Negus, S Stevens

2017-04-01

Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin (5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT 2C agonist lorcaserin (0.1-1.0 mg/kg per day, intramuscular; 0.032-0.1 mg/kg/h, intravenous) or the 5-HT 2A inverse agonist/antagonist pimavanserin (0.32-10 mg/kg per day, intramuscular) attenuated cocaine reinforcement under a concurrent 'choice' schedule of cocaine and food availability in rhesus monkeys. During saline treatment, cocaine maintained a dose-dependent increase in cocaine vs food choice. Repeated pimavanserin (3.2 mg/kg per day) treatments significantly increased small unit cocaine dose choice. Larger lorcaserin (1.0 mg/kg per day and 0.1 mg/kg/h) and pimavanserin (10 mg/kg per day) doses primarily decreased rates of operant behavior. Coadministration of ineffective lorcaserin (0.1 mg/kg per day) and pimavanserin (0.32 mg/kg per day) doses also failed to significantly alter cocaine choice. These results suggest that neither 5-HT 2C receptor activation nor 5-HT 2A receptor blockade are sufficient to produce a therapeutic-like decrease in cocaine choice and a complementary increase in food choice. Overall, these results do not support the clinical utility of 5-HT 2C agonists and 5-HT 2A inverse agonists/antagonists alone or in combination as candidate anti-cocaine use disorder pharmacotherapies.

Structural characterisation of Arquad 2HT-75 organobentonites: Surface charge characteristics and environmental application

Energy Technology Data Exchange (ETDEWEB)

Sarkar, Binoy; Megharaj, Mallavarapu; Xi, Yunfei [CERAR - Centre for Environmental Risk Assessment and Remediation, Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); CRC CARE - Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, P.O. Box 486, Salisbury, SA 5106 (Australia); Naidu, Ravi, E-mail: ravi.naidu@crccare.com [CERAR - Centre for Environmental Risk Assessment and Remediation, Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); CRC CARE - Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, P.O. Box 486, Salisbury, SA 5106 (Australia)

2011-11-15

Highlights: {yields} Arquad 2HT-75 is comparatively less toxic and inexpensive surfactant. {yields} Increasing Arquad 2HT-75 loadings give rise to various organobentonite structures. {yields} The organobentonites produce positive zeta potential at TOC contents above 28.1%. {yields} Zeta potential values decrease with increasing suspension pH. {yields} Multiple mechanisms of partitioning, physio-sorption and chemisorption control adsorption. - Abstract: Organoclays are increasingly being used to remediate both contaminated soils and waste water. The present study was attempted to elucidate the structural evolution of bentonite based organoclays prepared from a commercially available, low-cost alkyl ammonium surfactant Arquad 2HT-75. XRD, FTIR, SEM and zeta potential measurement were used to characterise the organoclays. In particular, the relationship between surface charge characteristics of the organoclays and their ability to remediate organic contaminants such as phenol and p-nitrophenol was investigated. The investigation revealed that the arrangement and conformation of surfactant molecules in the bentonite became more regular, ordered and solid-like as of Arquad 2HT-75 loading increased. This also led to the formation of a positive zeta potential on the surface of organobentonites prepared with 3.57:1 and 4.75:1 surfactant-clay (w/w) ratio. The zeta potential values decreased with increasing pH of the suspension. The adsorption data of phenol and p-nitrophenol were best fitted to Freundlich isotherm model. The adsorption was controlled by multiple mechanisms of partitioning, physico-sorption and chemisorption. The outcomes of this study are useful for the synthesis of low cost organobentonite adsorbents for the remediation of ionisable organic contaminants such as phenol and p-nitrophenol from waste water.

Chronic alcohol abuse in men alters bone mechanical properties by affecting both tissue mechanical properties and microarchitectural parameters.

Science.gov (United States)

Cruel, M; Granke, M; Bosser, C; Audran, M; Hoc, T

2017-06-01

Alcohol-induced secondary osteoporosis in men has been characterized by higher fracture prevalence and a modification of bone microarchitecture. Chronic alcohol consumption impairs bone cell activity and results in an increased fragility. A few studies highlighted effects of heavy alcohol consumption on some microarchitectural parameters of trabecular bone. But to date and to our knowledge, micro- and macro-mechanical properties of bone of alcoholic subjects have not been investigated. In the present study, mechanical properties and microarchitecture of trabecular bone samples from the iliac crest of alcoholic male patients (n=15) were analyzed and compared to a control group (n=8). Nanoindentation tests were performed to determine the tissue's micromechanical properties, micro-computed tomography was used to measure microarchitectural parameters, and numerical simulations provided the apparent mechanical properties of the samples. Compared to controls, bone tissue from alcoholic patients exhibited an increase of micromechanical properties at tissue scale, a significant decrease of apparent mechanical properties at sample scale, and significant changes in several microarchitectural parameters. In particular, a crucial role of structure model index (SMI) on mechanical properties was identified. 3D microarchitectural parameters are at least as important as bone volume fraction to predict bone fracture risk in the case of alcoholic patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Recombinant HT{sub m4} gene, protein and assays

Science.gov (United States)

Lim, B.; Adra, C.N.; Lelias, J.M.

1996-09-03

The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs.

Biological reduction of hexavalent chromium and mechanism analysis of detoxification by enterobacter sp. HT1 isolated from tannery effluents, Mongolia

Directory of Open Access Journals (Sweden)

N Marjangul

2014-12-01

Full Text Available Enterobacter sp. HT1, Cr (VI resistant bacterial strain was isolated from the wastewater sample of the tannery in Mongolia. Batch experiments on hexavalent chromium removal was carried out at 10, 20, and 30 mg/L of Cr (VI added as potassium dichromate (K2Cr2O7, at pH 7 and temperature of 30 °C using pure culture of Enterobacter sp. HT1 as inoculum.  The isolated HT1 is capable of reduction nearly 100% of Cr (VI resulting in the decrease of Cr (VI from 10 to 0.2 mg/L within 20 hours. When the concentration of Cr (VI increased to 20 and 30mg/L, almost complete reduction of Cr (VI could achieve after 72 and 96 hours, respectively.DOI: http://doi.dx.org/10.5564/mjc.v15i0.322 Mongolian Journal of Chemistry 15 (41, 2014, p47-52

Transient failure behavior of HT9

International Nuclear Information System (INIS)

Huang, F.H.

1994-07-01

Alloy HT9 has-been chosen as candidate materials for fast and fusion reactor applications because the.material exhibits excellent resistance to void swelling. However, ferritic alloys are known to undergo a ductile-brittle transition as the test temperature is decreased. This inherent problem has limited their applications to reactor component materials subjected to low neutron exposures. Despite the ductile-brittle transition problem, results show that the materials exhibit superior resistance to fracture under very high neutron fluences at irradiation temperatures above 380C. Results also show that the transient behavior for HT9 cladding specimens taken from the fuel column region and cladding taken from outside the fuel column or unirradiated cladding are the same. HT9 cladding maintained its transient strength with irradiation to a fluence of 9 x 10 22 n/cm 2 (E > 0.1 MeV)

d-Lysergic Acid Diethylamide (LSD as a Model of Psychosis: Mechanism of Action and Pharmacology

Directory of Open Access Journals (Sweden)

Danilo De Gregorio

2016-11-01

Full Text Available d-Lysergic Acid Diethylamide (LSD is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’ reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2, Trace Amine Associate receptor 1 (TAAR1 and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA mechanism or acting on TAAR1 receptors.

P3HT-graphene bilayer electrode for Schottky junction photodetectors

Science.gov (United States)

Aydın, H.; Kalkan, S. B.; Varlikli, C.; Çelebi, C.

2018-04-01

We have investigated the effect of a poly (3-hexylthiophene-2.5-diyl)(P3HT)-graphene bilayer electrode on the photoresponsivity characteristics of Si-based Schottky photodetectors. P3HT, which is known to be an electron donor and absorb light in the visible spectrum, was placed on CVD grown graphene by dip-coating method. The results of the UV-vis and Raman spectroscopy measurements have been evaluated to confirm the optical and electronic modification of graphene by the P3HT thin film. Current-voltage measurements of graphene/Si and P3HT-graphene/Si revealed rectification behavior confirming a Schottky junction formation at the graphene/Si interface. Time-resolved photocurrent spectroscopy measurements showed the devices had excellent durability and a fast response speed. We found that the maximum spectral photoresponsivity of the P3HT-graphene/Si photodetector increased more than three orders of magnitude compared to that of the bare graphene/Si photodetector. The observed increment in the photoresponsivity of the P3HT-graphene/Si samples was attributed to the charge transfer doping from P3HT to graphene within the spectral range between near-ultraviolet and near-infrared. Furthermore, the P3HT-graphene electrode was found to improve the specific detectivity and noise equivalent power of graphene/Si photodetectors. The obtained results showed that the P3HT-graphene bilayer electrodes significantly improved the photoresponsivity characteristics of our samples and thus can be used as a functional component in Si-based optoelectronic device applications.

Real-time observations of mechanical stimulus-induced enhancements of mechanical properties in osteoblast cells

International Nuclear Information System (INIS)

Zhang Xu; Liu Xiaoli; Sun Jialun; He Shuojie; Lee, Imshik; Pak, Hyuk Kyu

2008-01-01

Osteoblast, playing a key role in the pathophysiology of osteoporosis, is one of the mechanical stress sensitive cells. The effects of mechanical load-induced changes of mechanical properties in osteoblast cells were studied at real-time. Osteoblasts obtained from young Wister rats were exposed to mechanical loads in different frequencies and resting intervals generated by atomic force microscopy (AFM) probe tip and simultaneously measured the changes of the mechanical properties by AFM. The enhancement of the mechanical properties was observed and quantified by the increment of the apparent Young's modulus, E * . The observed mechanical property depended on the frequency of applied tapping loads. For the resting interval is 50 s, the mechanical load-induced enhancement of E * -values disappears. It seems that the enhanced mechanical property was recover able under no additional mechanical stimulus

Study of Incoloy 800HT alloy tested by heat-cycling

International Nuclear Information System (INIS)

Velciu, L.; Meleg, T.; Pantiru, M.; Petrescu, D.; Voicu, F.

2016-01-01

This paper investigated Incoloy 800HT (UNS N08811) alloy after some heat-cycling tests. The study continues prior tests realized in INR Pitesti concerning utilization of some nickel-based alloys in the heat exchangers and steam generators construction. The thermal-cycling consist in a successive series of heating and cooling with some rates in a range temperature. Technical parameters of thermal cycling: 50 & 200 cycles, 25 °C/minute heating-cooling rate, temperature range 450-1000°C, and argon working medium. The analysis consisted in metallographic examination (microstructure), Vickers microhardness, and traction tests. The average grain size was determined by linear interception method (ASTM E-112). The micro hardness was calculated by the relationship of the device technical book. On the Strength-Deformation diagrams were obtained: tensile strength and elongation. The tested samples were compared with the ''as received'' material. The results showed a good metallographic and mechanical behaviour of Incoloy 800HT at these thermal-cycling tests. (authors)

Anti-dyskinetic mechanisms of amantadine and dextromethorphan in the 6-OHDA rat model of Parkinson's disease: role of NMDA vs. 5-HT1A receptors.

Science.gov (United States)

Paquette, Melanie A; Martinez, Alex A; Macheda, Teresa; Meshul, Charles K; Johnson, Steven W; Berger, S Paul; Giuffrida, Andrea

2012-11-01

Amantadine and dextromethorphan suppress levodopa (L-DOPA)-induced dyskinesia (LID) in patients with Parkinson's disease (PD) and abnormal involuntary movements (AIMs) in the unilateral 6-hydroxydopamine (6-OHDA) rat model. These effects have been attributed to N-methyl-d-aspartate (NMDA) antagonism. However, amantadine and dextromethorphan are also thought to block serotonin (5-HT) uptake and cause 5-HT overflow, leading to stimulation of 5-HT(1A) receptors, which has been shown to reduce LID. We undertook a study in 6-OHDA rats to determine whether the anti-dyskinetic effects of these two compounds are mediated by NMDA antagonism and/or 5-HT(1A) agonism. In addition, we assessed the sensorimotor effects of these drugs using the Vibrissae-Stimulated Forelimb Placement and Cylinder tests. Our data show that the AIM-suppressing effect of amantadine was not affected by the 5-HT(1A) antagonist WAY-100635, but was partially reversed by the NMDA agonist d-cycloserine. Conversely, the AIM-suppressing effect of dextromethorphan was prevented by WAY-100635 but not by d-cycloserine. Neither amantadine nor dextromethorphan affected the therapeutic effects of L-DOPA in sensorimotor tests. We conclude that the anti-dyskinetic effect of amantadine is partially dependent on NMDA antagonism, while dextromethorphan suppresses AIMs via indirect 5-HT(1A) agonism. Combined with previous work from our group, our results support the investigation of 5-HT(1A) agonists as pharmacotherapies for LID in PD patients. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Spinal 5-HT7 Receptors and Protein Kinase A Constrain Intermittent Hypoxia-Induced Phrenic Long-term Facilitation

Science.gov (United States)

Hoffman, M.S.; Mitchell, G.S.

2013-01-01

Phrenic long-term facilitation (pLTF) is a form of serotonin-dependent respiratory plasticity induced by acute intermittent hypoxia (AIH). pLTF requires spinal Gq protein-coupled serotonin-2 receptor (5-HT2) activation, new synthesis of brain-derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, TrkB. Intrathecal injections of selective agonists for Gs protein-coupled receptors (adenosine 2A and serotonin-7; 5-HT7) also induce long-lasting phrenic motor facilitation via TrkB “trans-activation.” Since serotonin release near phrenic motor neurons may activate multiple serotonin receptor subtypes, we tested the hypothesis that 5-HT7 receptor activation contributes to AIH-induced pLTF. A selective 5-HT7 receptor antagonist (SB-269970, 5mM, 12μl) was administered intrathecally at C4 to anesthetized, vagotomized and ventilated rats prior to AIH (3, 5-min episodes, 11% O2). Contrary to predictions, pLTF was greater in SB-269970 treated versus control rats (80±11% vs 45±6% 60 min post-AIH; p<0.05). Hypoglossal LTF was unaffected by spinal 5-HT7 receptor inhibition, suggesting that drug effects were localized to the spinal cord. Since 5-HT7 receptors are coupled to protein kinase A (PKA), we tested the hypothesis that PKA inhibits AIH-induced pLTF. Similar to 5-HT7 receptor inhibition, spinal PKA inhibition (KT-5720, 100μM, 15μl) enhanced pLTF (99±15% 60 min post-AIH; p<0.05). Conversely, PKA activation (8-br-cAMP, 100μM, 15μl) blunted pLTF versus control rats (16±5% vs 45±6% 60 min post-AIH; p<0.05). These findings suggest a novel mechanism whereby spinal Gs protein-coupled 5-HT7 receptors constrain AIH-induced pLTF via PKA activity. PMID:23850591

The Fabrication of Bulk Heterojunction P3HT: PCBM Organic Photovoltaics

Science.gov (United States)

Darwis, D.; Sesa, E.; Farhamza, D.; Iqbal

2018-05-01

Bulk heterojunction Organic photovoltaic (OPV) devices are gaining a lot of interest due to their potential for ease of processing and lower manufacturing cost sustainable energy generation. In consequence, the number of studies into the properties and characteristics of organic solar cell devices has been increased to improving their power conversion. A further advancement over past decade has shown that improved efficiency could be obtained by mixed of poly(3 - hexylthiophene) (P3HT) and [1] – phenyl - C61-butyric acid methyl ester (PCBM) as an active layer. A series of optimizations of this P3HT: PCBM blends, such as the mixture ratio variation, the annealing treatments, and solvent treatment, have been emerged to improve the efficiency of the OPV. As a result, significant improvements were achieved. Here, we report the fabrication heterojunction devices of 2.9 % efficiency. This result has been achieved using the configuration of a typical heterojunction solar cell modules consists of layered glass/ITO/PEDOT: PSS/active layer/cathode interlayer

Distribution of serotonin 5-HT1A-binding sites in the brainstem and the hypothalamus, and their roles in 5-HT-induced sleep and ingestive behaviors in rock pigeons (Columba livia).

Science.gov (United States)

Dos Santos, Tiago Souza; Krüger, Jéssica; Melleu, Fernando Falkenburger; Herold, Christina; Zilles, Karl; Poli, Anicleto; Güntürkün, Onur; Marino-Neto, José

2015-12-15

Serotonin 1A receptors (5-HT1ARs), which are widely distributed in the mammalian brain, participate in cognitive and emotional functions. In birds, 5-HT1ARs are expressed in prosencephalic areas involved in visual and cognitive functions. Diverse evidence supports 5-HT1AR-mediated 5-HT-induced ingestive and sleep behaviors in birds. Here, we describe the distribution of 5-HT1ARs in the hypothalamus and brainstem of birds, analyze their potential roles in sleep and ingestive behaviors, and attempt to determine the involvement of auto-/hetero-5-HT1ARs in these behaviors. In 6 pigeons, the anatomical distribution of [(3)H]8-OH-DPAT binding in the rostral brainstem and hypothalamus was examined. Ingestive/sleep behaviors were recorded (1h) in 16 pigeons pretreated with MM77 (a heterosynaptic 5-HT1AR antagonist; 23 or 69 nmol) for 20 min, followed by intracerebroventricular ICV injection of 5-HT (N:8; 150 nmol), 8-OH-DPAT (DPAT, a 5-HT1A,7R agonist, 30 nmol N:8) or vehicle. 5-HT- and DPAT-induced sleep and ingestive behaviors, brainstem 5-HT neuronal density and brain 5-HT content were examined in 12 pigeons, pretreated by ICV with the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (N:6/group). The distribution of brainstem and diencephalic c-Fos immunoreactivity after ICV injection of 5-HT, DPAT or vehicle (N:5/group) into birds provided with or denied access to water is also described. 5-HT1ARs are concentrated in the brainstem 5-HTergic areas and throughout the periventricular hypothalamus, preoptic nuclei and circumventricular organs. 5-HT and DPAT produced a complex c-Fos expression pattern in the 5-HT1AR-enriched preoptic hypothalamus and the circumventricular organs, which are related to drinking and sleep regulation, but modestly affected c-Fos expression in 5-HTergic neurons. The 5-HT-induced ingestivebehaviors and the 5-HT- and DPAT-induced sleep behaviors were reduced by MM77 pretreatment. 5,7-DHT increased sleep per se, decreased tryptophan

Phthalate SHEDS-HT runs

Data.gov (United States)

U.S. Environmental Protection Agency — Inputs and outputs for SHEDS-HT runs of DiNP, DEHP, DBP. This dataset is associated with the following publication: Moreau, M., J. Leonard, K. Phillips, J. Campbell,...

Improvement of ketamine-induced social withdrawal in rats: the role of 5-HT7 receptors.

Science.gov (United States)

Hołuj, Małgorzata; Popik, Piotr; Nikiforuk, Agnieszka

2015-12-01

Social withdrawal, one of the core negative symptoms of schizophrenia, can be modelled in the social interaction (SI) test in rats using N-methyl-D-aspartate receptor glutamate receptor antagonists. We have recently shown that amisulpride, an antipsychotic with a high affinity for serotonin 5-HT7 receptors, reversed ketamine-induced SI deficits in rats. The aim of the present study was to further elucidate the potential involvement of 5-HT7 receptors in the prosocial action of amisulpride. Acute administration of amisulpride (3 mg/kg) and SB-269970 (1 mg/kg), a 5-HT7 receptor antagonist, reversed ketamine-induced social withdrawal, whereas sulpiride (20 or 30 mg/kg) and haloperidol (0.2 mg/kg) were ineffective. The 5-HT7 receptor agonist AS19 (10 mg/kg) abolished the prosocial efficacy of amisulpride (3 mg/kg). The coadministration of an inactive dose of SB-269970 (0.2 mg/kg) showed the prosocial effects of inactive doses of amisulpride (1 mg/kg) and sulpiride (20 mg/kg). The anxiolytic chlordiazepoxide (2.5 mg/kg) and the antidepressant fluoxetine (2.5 mg/kg) were ineffective in reversing ketamine-induced SI deficits. The present study suggests that the antagonism of 5-HT7 receptors may contribute towards the mechanisms underlying the prosocial action of amisulpride. These results may have therapeutic implications for the treatment of negative symptoms in schizophrenia and other disorders characterized by social withdrawal.

Selected mechanical properties of modified beech wood

Directory of Open Access Journals (Sweden)

Jiří Holan

2008-01-01

Full Text Available This thesis deals with an examination of mechanical properties of ammonia treated beach wood with a trademark Lignamon. For determination mechanical properties were used procedures especially based on ČSN. From the results is noticeable increased density of wood by 22% in comparison with untreated beach wood, which makes considerable increase of the most mechanical wood properties. Considering failure strength was raised by 32% and modulus of elasticity was raised at average about 46%.

Anti-dyskinetic mechanisms of amantadine and dextromethorphan in the 6-OHDA rat model of Parkinson’s disease: role of NMDA vs. 5-HT1A receptors

Science.gov (United States)

Paquette, Melanie A.; Martinez, Alex A.; Macheda, Teresa; Meshul, Charles K.; Johnson, Steven W.; Berger, S. Paul; Giuffrida, Andrea

2013-01-01

Amantadine and dextromethorphan suppress levodopa (L-DOPA)-induced dyskinesia (LID) in patients with Parkinson’s disease (PD) and abnormal involuntary movements (AIMs) in the unilateral 6-hydroxydopamine (6-OHDA) rat model. These effects have been attributed to N-methyl-d-aspartate (NMDA) antagonism. However, amantadine and dextromethorphan are also thought to block serotonin (5-HT) uptake and cause 5-HT overflow, leading to stimulation of 5-HT1A receptors, which has been shown to reduce LID. We undertook a study in 6-OHDA rats to determine whether the anti-dyskinetic effects of these two compounds are mediated by NMDA antagonism and/or 5-HT1A agonism. In addition, we assessed the sensorimotor effects of these drugs using the Vibrissae-Stimulated Forelimb Placement and Cylinder tests. Our data show that the AIM-suppressing effect of amantadine was not affected by the 5-HT1A antagonist WAY-100635, but was partially reversed by the NMDA agonist d-cycloserine. Conversely, the AIM-suppressing effect of dextromethorphan was prevented by WAY-100635 but not by d-cycloserine. Neither amantadine nor dextromethorphan affected the therapeutic effects of L-DOPA in sensorimotor tests. We conclude that the anti-dyskinetic effect of amantadine is partially dependent on NMDA antagonism, while dextromethorphan suppresses AIMs via indirect 5-HT1A agonism. Combined with previous work from our group, our results support the investigation of 5-HT1A agonists as pharmacotherapies for LID in PD patients. PMID:22861201

BDNF downregulates 5-HT(2A) receptor protein levels in hippocampal cultures

DEFF Research Database (Denmark)

Trajkovska, V; Santini, M A; Marcussen, Anders Bue

2009-01-01

Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT(2A)) have been related to depression pathology. Specific 5-HT(2A) receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT(2A) receptor level. Here we show a direct effect of BDNF...... on 5-HT(2A) receptor protein levels in primary hippocampal neuronal and mature hippocampal organotypic cultures exposed to different BDNF concentrations for either 1, 3, 5 or 7 days. In vivo effects of BDNF on hippocampal 5-HT(2A) receptor levels were further corroborated in (BDNF +/-) mice...... with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50ng/mL BDNF resulted in downregulation of 5-HT(2A), but not of 5-HT(1A), receptor protein levels. The BDNF-associated downregulation of 5-HT(2A) receptor levels was also observed in mature hippocampal organotypic cultures...

The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat.

Science.gov (United States)

Dawson, Patrick; Opacka-Juffry, Jolanta; Moffatt, James D; Daniju, Yusuf; Dutta, Neelakshi; Ramsey, John; Davidson, Colin

2014-01-03

5-APB, commonly marketed as 'benzofury' is a new psychoactive substance and erstwhile 'legal high' which has been implicated in 10 recent drug-related deaths in the UK. This drug was available on the internet and in 'head shops' and was one of the most commonly sold legal highs up until its recent UK temporary ban (UK Home Office). Despite its prominence, very little is known about its pharmacology. This study was undertaken to examine the pharmacology of 5-APB in vitro. We hypothesised that 5-APB would activate the dopamine and 5-HT systems which may underlie its putative stimulant and hallucinogenic effects. Autoradiographic studies showed that 5-APB displaced both [(125)I] RTI-121 and [(3)H] ketanserin from rat brain tissue suggesting affinity at the dopamine transporter and 5-HT2 receptor sites respectively. Voltammetric studies in rat accumbens brain slices revealed that 5-APB slowed dopamine reuptake, and at high concentrations caused reverse transport of dopamine. 5-APB also caused vasoconstriction of rat aorta, an effect antagonised by the 5-HT2A receptor antagonist ketanserin, and caused contraction of rat stomach fundus, which was reversed by the 5-HT2B receptor antagonist RS-127445. These data show that 5-APB interacts with the dopamine transporter and is an agonist at the 5-HT2A and 5-HT2B receptors in the rat. Thus 5-APB's pharmacology is consistent with it having both stimulant and hallucinogenic properties. In addition, 5-APB's activity at the 5-HT2B receptor may cause cardiotoxicity. © 2013.

Microstructures and mechanical properties of aging materials

International Nuclear Information System (INIS)

Liaw, P.K.; Viswanathan, R.; Murty, K.L.; Simonen, E.P.; Frear, D.

1993-01-01

This book contains a collection of papers presented at the symposium on ''Microstructures and Mechanical Properties of Aging Materials,'' that was held in Chicago, IL. November 2-5, 1992 in conjunction with the Fall Meeting of The Minerals, Metals and Materials Society (TMS). The subjects of interest in the symposium included: (1) mechanisms of microstructural degradation, (2) effects of microstructural degradation on mechanical behavior, (3) development of life prediction methodology for in-service structural and electronic components, (4) experimental techniques to monitor degradation of microstructures and mechanical properties, and (5) effects of environment on microstructural degradation and mechanical properties. Individual papers have been processed separately for inclusion in the appropriate data bases

Differential involvement of 5-HT(1A) and 5-HT(1B/1D) receptors in human interferon-alpha-induced immobility in the mouse forced swimming test.

Science.gov (United States)

Zhang, Hongmei; Wang, Wei; Jiang, Zhenzhou; Shang, Jing; Zhang, Luyong

2010-01-01

Although Interferon-alpha (IFN-alpha, CAS 9008-11-1) is a powerful drug in treating several viral infections and certain tumors, a considerable amount of neuropsychiatric side-effects such as depression and anxiety are an unavoidable consequence. Combination with the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine (CAS 56296-78-7) significantly improved the situation. However, the potential 5-HT(1A) receptor- and 5-HT(1B) receptor-signals involved in the antidepressant effects are still unclear. The effects of 5-HT(1A) receptor- and 5-HT(1B) receptor signals were analyzed by using the mouse forced swimming test (FST), a predictive test of antidepressant-like action. The present results indicated that (1) fluoxetine (administrated intragastrically, 30 mg/kg; not subactive dose: 15 mg/kg) significantly reduced IFN-alpha-induced increase of the immobility time in the forced swimming test; (2) 5-HT(1A) receptor- and 5-HT(1B) receptor ligands alone or in combination had no effects on IFN-alpha-induced increase of the immobility time in the FST; (3) surprisingly, WAY 100635 (5-HT(1A) receptor antagonist, 634908-75-1) and 8-OH-DPAT(5-HT(1A) receptor agonist, CAS 78950-78-4) markedly enhanced the antidepressant effect of fluoxetine at the subactive dose (15 mg/kg, i. g.) on the IFN-alpha-treated mice in the FST. Further investigations showed that fluoxetine combined with WAY 100635 and 8-OH-DPAT failed to produce antidepressant effects in the FST. (4) Co-application of CGS 12066A (5-HT(1B) receptor agonist, CAS 109028-09-3) or GR 127935 (5-HT(1B/1D) receptor antagonist, CAS 148642-42-6) with fluoxetine had no synergistic effects on the IFN-alpha-induced increase of immobility time in FST. (5) Interestingly, co-administration of GR 127935, WAY 100635 and fluoxetine significantly reduced the IFN-alpha-induced increase in immobility time of FST, being more effective than co-administration of WAY 100635 and fluoxetine. All results suggest that (1) compared to

Influence of hot rolling and high speed hydrostatic extrusion on the microstructure and mechanical properties of an ODS RAF steel

Energy Technology Data Exchange (ETDEWEB)

Oksiuta, Z., E-mail: oksiuta@pb.edu.pl [Bialystok Technical University, Faculty of Mechanical Engineering, Wiejska 45c, 15-352 Bialystok (Poland); Lewandowska, M.; Kurzydlowski, K.J. [Warsaw University of Technology, Faculty of Materials Science and Engineering, Woloska 141, 02-504 Warsaw (Poland); Baluc, N. [Ecole Polytechnique Federale de Lausanne (EPFL), Centre de Recherches en Physique des Plasmas, Association Euratom-Confederation Suisse, 5232 Villigen PSI (Switzerland)

2011-02-15

An argon gas atomized, pre-alloyed Fe-14Cr-2W-0.3Ti (wt.%) reduced activation ferritic (RAF) steel powder was mechanically alloyed with 0.3wt.% Y{sub 2}O{sub 3} nano-particles in an attritor ball mill and consolidated by hot isostatic pressing at 1150 {sup o}C under a pressure of 200 MPa for 3 h. In the aim to improve its mechanical properties the ODS steel was then submitted to a thermo-mechanical treatment (TMT): hot rolling (HR) at 850 deg. C or high speed hydrostatic extrusion (HSHE) at 900 deg. C, followed by heat treatment (HT). Transmission electron microscopy (TEM) observations of the ODS alloys after TMT and heat treatment revealed the presence of elongated grains in the longitudinal direction, with an average width of 8 {mu}m and an average length of 75 {mu}m, and equiaxed grains, a few microns in diameter, in the transverse direction. Two populations of oxide particles were observed by TEM: large Ti-Al-O particles, up to 250 nm in diameter, usually located at the grain boundaries and small Y-Ti-O nanoclusters, about 2.5 nm in diameter, uniformly distributed in the matrix. Charpy impact tests revealed that the HSHE material exhibits a larger upper shelf energy (5.8 J) than the HR material (2.9 J). The ductile-to-brittle transition temperature of both alloys is relatively high, in the range of 55-72 deg. C. Tensile mechanical properties of both ODS alloys were found satisfactory over the full range of investigated temperatures (23-750 deg. C). The HSHE material exhibits better tensile strength and ductility than the HR material. These results indicate that HSHE can be considered as a promising TMT method for improving the mechanical properties of ODS RAF steels.

Synergies Between ' and Cavity Formation in HT-9 Following High Dose Neutron Irradiation

Energy Technology Data Exchange (ETDEWEB)

Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Parish, Chad M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Saleh, Tarik A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Eftink, Benjamin P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-06-01

Candidate cladding materials for advanced nuclear power reactors including fast reactor designs require materials capable of withstanding high dose neutron irradiation at elevated temperatures. One candidate material, HT-9, through various research programs have demonstrated the ability to withstand significant swelling and other radiation-induced degradation mechanisms in the high dose regime (>50 displacements per atom, dpa) at elevated temperatures (>300 C). Here, high efficiency multi-dimensional scanning transmission electron microscopy (STEM) acquisition with the aid of a three-dimensional (3D) reconstruction and modeling technique is used to probe the microstructural features that contribute to the exceptional swelling resistance of HT-9. In particular, the synergies between ' and fine-scale and moderate-scale cavity formation is investigated.

A Passive Diffusion Sampler for HT- and HTO-in-Air

International Nuclear Information System (INIS)

Surette, R.A.; Nunes, J.C.

2005-01-01

Fusion research and tritium removal facilities potentially handle large inventories of tritium gas (HT). If any HT is released into the workplace, a fraction may be converted to tritiated water vapour (HTO). A convenient method to determine the activity concentration of each species is necessary to assess the potential hazard since the radiological hazard of HTO is more than 10 4 that due to HT. Passive samplers for measuring tritiated water vapour (HTO) have been shown to be suitable for use indoors and outdoors. These simple samplers consist of a standard 20-mL liquid scintillation vial with a diffusion orifice that determines the sampling rate.The total tritium samplers described herein are passive or diffusion samplers that contain a small amount of AECL-proprietary wet-proofed catalyst fixed to the underside of the sampling heads to allow conversion of the HT to HTO that is subsequently collected in the sink, (HTO), in the bottom of the sampler. After an appropriate sampling time, liquid scintillation cocktail is added to the vial and the activity collected determined by liquid scintillation analysis. When used in conjunction with the conventional HTO passive sampler the difference between the total and HTO samplers can be used to determine the HT fraction ((HT+HTO) - HTO HT). The sampling rates for the modified diffusion sampler were measured to be 4.6 and 8.1 L/d for HTO and HT, respectively. For a fifteen-minute sampling period, passive samplers can be used to measure tritium activity concentrations from 37 kBq/m 3 to 115 MBq/m 3

Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience.

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Pokorny, Thomas; Preller, Katrin H; Kraehenmann, Rainer; Vollenweider, Franz X

2016-04-01

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (ppsilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study.

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Newman-Tancredi, A; Gavaudan, S; Conte, C; Chaput, C; Touzard, M; Verrièle, L; Audinot, V; Millan, M J

1998-08-21

' antipsychotic agents displayed antagonist properties at h5-HT1A sites with generally much lower affinity than at hD2 dopamine receptors. It is suggested that agonist activity at 5-HT1A receptors may be of utility for certain antipsychotic agents.

On-line Measurement of Boiler Tube Corrosion Rates using Dedicated EMAT (HT-EMAT) Phase 1

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Borggreen, Kjeld (SydTek AB, Malmoe (Sweden))

2009-06-15

The project includes development of prototype HT-EMAT (High Temperature Electro Magnetic Acoustic Transducer) probes and testing of these in laboratory environment at high temperatures. The following results were obtained: Standard Alnico (Al-Ni-Co-Fe) magnets are sufficiently strong to drive a HT-EMAT probe in the magnetostrictive mode at temperatures up to 550 deg C. With a standard (diam)20 x 40 mm Alnico magnet, the number of turns in the coil using a 0.25 mm wire should be 25 - 30 to give optimum response and highest accuracy. The velocity of shear type sound waves in metals varies linearly with temperature in the interval considered. The prototype HT-EMAT only needs to be calibrated at room temperature, which is a simple procedure. If the temperature dependence of the velocity of the sound waves in steels is taking into account, the prototype probe gives excellent results at temperatures up to 550 deg C. The coil and the connection wire should preferably have a high electric conductivity to minimize damping, skin effects, and impedance mismatch, and also a high oxidation resistance. Pure copper and fine silver are the candidate materials for the HT-EMAT. Deposition of magnetostrictive layers on steel surfaces has been resolved. Magnetite seems as the only useful material until further. Thin layers of natural grown magnetite can be made by long term heat treatments. Thicker layers of artificial magnetite can be made by thermal spraying. Most of the reduction in efficiency of the HT-EMAT probe at high temperatures may be explained by the thermal dependence of the magnetostrictive constant for magnetite. Because the magnetostriction of magnetite disappears at its Curie temperature, the theoretical temperature limit for the HT-EMAT probe is foreseen to be 575 deg C. The prototype HT-EMAT performed well up to 550 deg C both during long time testing and at dynamic testing. The electronic and mechanical stabilities were excellent

Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task.

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Simon R O Nilsson

Full Text Available Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS-, in a T- or Y-maze configuration. This was followed by three conditions; (1 Full reversal, where contingencies reversed; (2 Perseverance, where the previous CS+ became CS- and the previous CS- was replaced by a novel CS+; (3 Learned non-reward, where the previous CS- became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss

Troglitazone induced apoptosis via PPARγ activated POX-induced ROS formation in HT29 cells.

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Wang, Jing; Lv, XiaoWen; Shi, JiePing; Hu, XiaoSong; DU, YuGuo

2011-08-01

In order to investigate the potential mechanisms in troglitazone-induced apoptosis in HT29 cells, the effects of PPARγ and POX-induced ROS were explored. [3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, Annexin V and PI staining using FACS, plasmid transfection, ROS formation detected by DCFH staining, RNA interference, RT-PCR & RT-QPCR, and Western blotting analyses were employed to investigate the apoptotic effect of troglitazone and the potential role of PPARγ pathway and POX-induced ROS formation in HT29 cells. Troglitazone was found to inhibit the growth of HT29 cells by induction of apoptosis. During this process, mitochondria related pathways including ROS formation, POX expression and cytochrome c release increased, which were inhibited by pretreatment with GW9662, a specific antagonist of PPARγ. These results illustrated that POX upregulation and ROS formation in apoptosis induced by troglitazone was modulated in PPARγ-dependent pattern. Furthermore, the inhibition of ROS and apoptosis after POX siRNA used in troglitazone-treated HT29 cells indicated that POX be essential in the ROS formation and PPARγ-dependent apoptosis induced by troglitazone. The findings from this study showed that troglitazone-induced apoptosis was mediated by POX-induced ROS formation, at least partly, via PPARγ activation. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Multi-response optimization of process parameters for TIG welding of Incoloy 800HT by Taguchi grey relational analysis

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Arun Kumar Srirangan

2016-06-01

Full Text Available Incoloy 800HT which was selected as one of the prominent material for fourth generation power plant can exhibit appreciable strength, good resistance to corrosion and oxidation in high temperature environment. This study focuses on the multi-objective optimization using grey relational analysis for Incoloy 800HT welded with tungsten inert arc welding process with N82 filler wire of diameter 1.2 mm. The welding input parameters play a vital role in determining desired weld quality. The experiments were conducted according to L9 orthogonal array. The input parameter chosen were the welding current, Voltage and welding speed. The output response for quality targets chosen were the ultimate tensile strength and yield strength (at room temperature, 750 °C and impact toughness. Grey relational analysis was applied to optimize the input parameters simultaneously considering multiple output variables. The optimal parameters combination was determined as A2B1C2 i.e. welding current at 110 A, voltage at 10 V and welding speed at 1.5 mm/s. ANOVA method was used to assess the significance of factors on the overall quality of the weldment. The output of the mechanical properties for best and least grey relational grade was validated by the metallurgical characteristics:

Mechanical Properties of Composite Materials

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Mitsuhiro Okayasu

2014-10-01

Full Text Available An examination has been made of the mechanical and failure properties of several composite materials, such as a short and a long carbon fiber reinforced plastic (short- and long-CFRP and metal based composite material. The short CFRP materials were used for a recycled CFRP which fabricated by the following process: the CFRP, consisting of epoxy resin with carbon fiber, is injected to a rectangular plate cavity after mixing with acrylonitrile butadiene styrene resin with different weight fractions of CFRP. The fatigue and ultimate tensile strength (UTS increased with increasing CFRP content. These correlations, however, break down, especially for tensile strength, as the CFPR content becomes more than 70%. Influence of sample temperature on the bending strength of the long-CFRP was investigated, and it appears that the strength slightly degreases with increasing the temperature, due to the weakness in the matrix. Broken fiber and pull-out or debonding between the fiber and matrix were related to the main failure of the short- and long-CFRP samples. Mechanical properties of metal based composite materials have been also investigated, where fiber-like high hardness CuAl2 structure is formed in aluminum matrix. Excellent mechanical properties were obtained in this alloy, e.g., the higher strength and the higher ductility, compared tothe same alloy without the fiber-like structure. There are strong anisotropic effects on the mechanical properties due to the fiber-like metal composite in a soft Al based matrix.

Role of N-Arachidonoyl-Serotonin (AA-5-HT in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation

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Eric Murillo-Rodríguez

2017-05-01

Full Text Available The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA and 2-arachidonoylglycerol (2-AG], receptors (CB1 and CB2, enzymes such as [fatty acid amide hydrolase (FAHH and monoacylglycerol lipase (MAGL], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep–wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1, N-arachidonoyl-serotonin (AA-5-HT in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p. injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W and increased slow wave sleep (SWS as well as rapid eye movement sleep (REMS. Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA, norepinephrine (NE, epinephrine (EP, serotonin (5-HT whereas the levels of adenosine (AD were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD or modafinil (MOD during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD. The

Anxiolytic-like effect of inhalation of essential oil from Lavandula officinalis: investigation of changes in 5-HT turnover and involvement of olfactory stimulation.

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Takahashi, Mizuho; Yamanaka, Ayako; Asanuma, Chihiro; Asano, Hiroko; Satou, Tadaaki; Koike, Kazuo

2014-07-01

Essential oil extracted from Lavandula officinalis (LvEO) has a long history of usage in anxiety alleviation with good evidence to support its use. However, findings and information regarding the exact pathway involved and mechanism of action remain inconclusive. Therefore, we aimed to (1) reveal the influence of olfactory stimulation, and (2) determine whether the serotonergic system is involved in the anxiolytic effect of LvEO when it is inhaled. To this end, we first compared the anxiety-related behaviors of normosmic and anosmic mice. LvEO inhalation caused notable elevation in anxiety-related parameters with or without olfactory perception, indicating that olfactory stimulation is not necessarily required for LvEO to be effective. Neurochemical analysis of the serotonin (5-HT) turnover rate, accompanied by EPM testing, was then performed. LvEO significantly increased the striatal and hippocampal levels of 5-HT and decreased turnover rates in accordance with the anxiolytic behavioral changes. These results, together with previous findings, support the hypothesis that serotonergic neurotransmission plays a certain role in the anxiolytic properties of LvEO.

Study of anisotropic mechanical properties for aeronautical PMMA

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Wei Shang

Full Text Available For the properties of polymer are relative to its structure, the main purpose of the present work is to investigate the mechanical properties of the aeronautical PMMA which has been treated by the directional tensile technology. Isodyne images reveal the stress state in directional PMMA. And then, an anisotropic mechanical model is established. Furthermore, all mechanical parameters are measured by the digital image correlation method. Finally, based on the anisotropic mechanical model and mechanical parameters, the FEM numerical simulation and experimental methods are applied to analyze the fracture mechanical properties along different directions.

Autroadiographic characterization of 125I-labeled 2,5-dimethoxy-4-iodophenylisopropylamine (DOI): A phenylisopropylamine derivative labeling both 5HT2 and 5HT1c receptors

International Nuclear Information System (INIS)

Appel, N.M.; Mitchell, W.M.; Garlick, R.K.; Glennon, R.A.; Titeler, M.; De Souza, E.B.

1990-01-01

The best-characterized 5HT 2 radioligands, such as [ 3 H]ketanserin and [ 3 H]spiperone, are antagonists that label both high- and low-affinity states of this receptor. Recently, the radiolabeled phenylisopropylamine hallucinogens DOB and DOI, which are agonists at 5HT 2 receptors, have been demonstrated to label selectively the high-affinity state of brain 5HT 2 receptors. In the present study, the authors determined optimum conditions for autoradiographic visualization of [ 125 I]DOI binding and characterized its pharmacology and guanine nucleotide sensitivity under those conditions. In slide-mounted tissue sections (rat forebrain; two 10 μm sections/slide), (±)[ 125 I]DOI binding was saturable, of high affinity (K D ∼4nM) and displayed a pharmacological profile [R(-)DOI > spiperone > DOB > (±)DOI > ketanserin > S(+)DOI > 5HT > DOM] comparable to that seen in homogenate assays. Consistent with coupling of 5HT 2 receptors to a guanine nucleotide regulatory protein, [ 125 I]DOI binding was inhibited by guanine nucleotides but not by ATP. In autoradiograms, high densities of [ 125 I]DOI binding sites were present in frontal cortex, olfactory tubercle, claustrum, caudate/putamen and mamillary nuclei with lower densities in trigeminal and solitary nuclei. The highest density of [ 125 l]DOI binding was observed in choroid plexus; these binding sites displayed a pharmacological profile characteristic of 5HT 1C receptors. These data suggest that [ 125 I]DOI labels both 5HT 2 and 5HT 1C receptors

Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

Science.gov (United States)

Cadirci, Elif; Halici, Zekai; Bayir, Yasin; Albayrak, Abdulmecit; Karakus, Emre; Polat, Beyzagul; Unal, Deniz; Atamanalp, Sabri S; Aksak, Selina; Gundogdu, Cemal

2013-10-01

Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality. Copyright © 2013 Elsevier GmbH. All rights reserved.

Quantification of 5-HT{sub 1A} receptors in human brain using p-MPPF kinetic modelling and PET

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Sanabria-Bohorquez, S.M.; Veraart, C. [Neural Rehabilitation Engineering Lab., Univ. Catholique de Louvain, Brussels (Belgium); Biver, F.; Damhaut, P.; Wikler, D.; Goldman, S. [PET/Biomedical Cyclotron Unit, Univ. Libre de Bruxelles (Belgium)

2002-01-01

Serotonin-1A (5-HT{sub 1A}) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-[{sup 18}F]fluorobenzamido] ethyl] piperazine (p-MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT{sub 1A} receptors. To test p-MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p-MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p-MPPF and 5-HT{sub 1A} receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT{sub 1A} receptor brain distribution. In conclusion, our results show that p-MPPF is a suitable PET radioligand for 5-HT{sub 1A} receptor human studies. (orig.)

Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase

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Guan Kunliang

2003-06-01

Full Text Available Abstract Background G protein-coupled receptors (GPCRs interact with heterotrimeric GTP-binding proteins (G proteins to modulate acute changes in intracellular messenger levels and ion channel activity. In contrast, long-term changes in cellular growth, proliferation and differentiation are often mediated by tyrosine kinase receptors and certain GPCRs by activation of mitogen-activated protein (MAP kinases. Complex interactions occur between these signaling pathways, but the specific mechanisms of such regulatory events are not well-understood. In particular it is not clear whether GPCRs are modulated by tyrosine kinase receptor-MAP kinase pathways. Results Here we describe tyrosine kinase receptor regulation of a GPCR via MAP kinase. Insulin reduced the activity of the 5-HT2C receptor in choroid plexus cells which was blocked by the MAP kinase kinase (MEK inhibitor, PD 098059. We demonstrate that the inhibitory effect of insulin and insulin-like growth factor type 1 (IGF-1 on the 5-HT2C receptor is dependent on tyrosine kinase, RAS and MAP kinase. The effect may be receptor-specific: insulin had no effect on another GPCR that shares the same G protein signaling pathway as the 5-HT2C receptor. This effect is also direct: activated MAP kinase mimicked the effect of insulin, and removing a putative MAP kinase site from the 5-HT2C receptor abolished the effect of insulin. Conclusion These results show that insulin signaling can inhibit 5-HT2C receptor activity and suggest that MAP kinase may play a direct role in regulating the function of a specific GPCR.

Mechanical Properties of Organic Semiconductors for Stretchable, Highly Flexible, and Mechanically Robust Electronics.

Science.gov (United States)

Root, Samuel E; Savagatrup, Suchol; Printz, Adam D; Rodriquez, Daniel; Lipomi, Darren J

2017-05-10

Mechanical deformability underpins many of the advantages of organic semiconductors. The mechanical properties of these materials are, however, diverse, and the molecular characteristics that permit charge transport can render the materials stiff and brittle. This review is a comprehensive description of the molecular and morphological parameters that govern the mechanical properties of organic semiconductors. Particular attention is paid to ways in which mechanical deformability and electronic performance can coexist. The review begins with a discussion of flexible and stretchable devices of all types, and in particular the unique characteristics of organic semiconductors. It then discusses the mechanical properties most relevant to deformable devices. In particular, it describes how low modulus, good adhesion, and absolute extensibility prior to fracture enable robust performance, along with mechanical "imperceptibility" if worn on the skin. A description of techniques of metrology precedes a discussion of the mechanical properties of three classes of organic semiconductors: π-conjugated polymers, small molecules, and composites. The discussion of each class of materials focuses on molecular structure and how this structure (and postdeposition processing) influences the solid-state packing structure and thus the mechanical properties. The review concludes with applications of organic semiconductor devices in which every component is intrinsically stretchable or highly flexible.

Field studies of HT oxidation and dispersion in the environment

International Nuclear Information System (INIS)

Brown, R.M.; Ogram, G.L.; Spencer, F.S.; Ontario Hydro, Toronto, ON

1988-10-01

A tracer quantity of 3.54 TBq tritiated hydrogen (HT) was released into the atmosphere at a Chalk River, Ontario field site to determine the behaviour of HT in the environment. The primary objective was to establish the oxidation rate of HT to tritiated water (HTO) in air, soil and vegetation compartments. HTO/HT atmospheric concentration ratios observed during the release ranged from 0.14 x 10 -4 at 5 m to 7.0 x 10 -4 at 400 m distance from the release point indicating an effective oxidation rate of about 1.5% h -1 . Gas phase oxidation in the atmosphere would be less than this effective rate. Results confirm that surface soils play the dominant role in converting HT to HTO. Soil HT deposition velocities were between 2.7 x 10 -4 and 11 x 10 -4 m s -1 for an open field of varied composition, and between 3.3 x 10 -4 and 12 x 10 -4 m s -1 for a conifer forest. Soil HTO loss rates were initially 1 to 3 % h -1 averaged over the first 24 h after release. Vegetation tissue-free water tritium (TFWT) resulted from uptake of soil HTO and exchange with atmospheric HTO vapour. Upper limit HT deposition velocities to vegetation measured as TFWT in 5 species were 0.23 x 10 -7 to 6 x 10 -7 m s -1 expressed on a leaf area basis. TFWT loss rates were 5.2 to 8.1 % h -1 from about 12 to 48 h after release with low activity rain and 0.42 to 0.56 % h -1 from about 48 to 335 h. Vegetation organically-bound tritium/TFWT specific activity ratios (Bq g -1 H) were about 0.1 initially, increasing to 16 after 113 days as TFWT specific activity declined more rapidly than that of OBT. The effective HT oxidation rate, deposition velocities and HTO loss rates were in good agreement with a 1986 HT field release and previous laboratory experiments

Pharmacological, neurochemical, and behavioral profile of JB-788, a new 5-HT1A agonist.

Science.gov (United States)

Picard, M; Morisset, S; Cloix, J F; Bizot, J C; Guerin, M; Beneteau, V; Guillaumet, G; Hevor, T K

2010-09-01

A novel pyridine derivative, 8-{4-[(6-methoxy-2,3-dihydro-[1,4]dioxino[2,3-b]pyridine-3-ylmethyl)-amino]-butyl}-8-aza-spiro[4.5]decane-7,9-dione hydrochloride, termed JB-788, was designed to selectively target 5-HT(1A) receptors. In the present study, the pharmacological profile of JB-788 was characterized in vitro using radioligands binding tests and in vivo using neurochemical and behavioural experiments. JB-788 bound tightly to human 5-HT(1A) receptor expressed in human embryonic kidney 293 (HEK-293) cells with a K(i) value of 0.8 nM. Its binding affinity is in the same range as that observed for the (+/-)8-OH-DPAT, a reference 5HT(1A) agonist compound. Notably, JB-788 only bound weakly to 5-HT(1B) or 5-HT(2A) receptors and moreover the drug displayed only weak or indetectable binding to muscarinic, alpha(2), beta(1) and beta(2) adrenergic receptors, or dopaminergic D(1) receptors. JB-788 was found to display substantial binding affinity for dopaminergic D(2) receptors and, to a lesser extend to alpha(1) adrenoreceptors. JB-788 dose-dependently decreased forskolin-induced cAMP accumulation in HEK cells expressing human 5-HT(1A), thus acting as a potent 5-HT(1A) receptor agonist (E(max.) 75%, EC(50) 3.5 nM). JB-788 did not exhibit any D(2) receptor agonism but progressively inhibited the effects of quinpirole, a D(2) receptor agonist, in the cAMP accumulation test with a K(i) value of 250 nM. JB-788 induced a weak change in cAMP levels in mouse brain but, like some antipsychotics, transiently increased glycogen contents in various brain regions. Behavioral effects were investigated in mice using the elevated plus-maze. JB-788 was found to increase the time duration spent by animals in anxiogenic situations. Locomotor hyperactivity induced by methamphetamine in mouse, a model of antipsychotic activity, was dose-dependently inhibited by JB-788. Altogether, these results suggest that JB-788 displays pharmacological properties, which could be of interest in the area

Stochastic modelling in design of mechanical properties of nanometals

International Nuclear Information System (INIS)

Tengen, T.B.; Wejrzanowski, T.; Iwankiewicz, R.; Kurzydlowski, K.J.

2010-01-01

Polycrystalline nanometals are being fabricated through different processing routes and conditions. The consequence is that nanometals having the same mean grain size may have different grain size dispersion and, hence, may have different material properties. This has often led to conflicting reports from both theoretical and experimental findings about the evolutions of the mechanical properties of nanomaterials. The present paper employs stochastic model to study the impact of microstructure evolution during grain growth on the mechanical properties of polycrystalline nanometals. The stochastic model for grain growth and the stochastic model for changes in mechanical properties of nanomaterials are proposed. The model for the mechanical properties developed is tested on aluminium samples.Many salient features of the mechanical properties of the aluminium samples are revealed. The results show that the different mechanisms of grain growth impart different nature of response to the material mechanical properties. The conventional, homologous and anomalous temperature dependences of the yield stress have also been revealed to be due to different nature of interactions of the microstructures during evolution.

Characterization of high temperature tensile and creep–fatigue properties of Alloy 800H for intermediate heat exchanger components of (V)HTRs

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Kolluri, M., E-mail: kolluri@nrg.eu; Pierick, P. ten, E-mail: tenpierick@nrg.eu; Bakker, T., E-mail: t.bakker@nrg.eu

2015-04-01

Highlights: • High temperature tensile, creep–fatigue (C–F) properties of Alloy 800H are studied. • Strength and uniform elongation properties at 800 °C are much lower than RT values. • Strong influence of hold time and Δε{sub tot} on low cycle fatigue life was observed. • The total allowable C–F damage (D) at 800 °C decreases with the decreasing Δε{sub tot}. • Synergetic effect of C–F interactions showed stronger effect at lower Δε{sub tot} values. - Abstract: Alloy 800H is considered as a candidate material for intermediate heat exchanger (IHX) components of (very) high temperature reactors (V)HTRs. Qualification of the this alloy for the aforementioned nuclear applications requires understanding of its high temperature tensile, low-cycle fatigue behavior and creep–fatigue interactions because the IHX components suffer from combined creep–fatigue loadings resulting from thermally induced strain cycles associated with start-up and shutdown cycles. To this end, in this paper, the tensile properties of the Alloy 800H base and tungsten inert gas (TIG) welded materials are studied at three different temperatures, room temperature 21, 700 and 800 °C. Low cycle fatigue (LCF) behavior of the base material is investigated at 800 °C with no-hold time (no-HT) and hold time (HT) to study creep–fatigue interactions. The tensile test results showed substantial differences between the strength and ductility properties of the base and weld materials at all 3 temperatures, however, the trends in temperature dependence of tensile properties are similar for both base and weld materials. LCF studies with no-HT and HT showed a strong influence of HT on the low cycle fatigue life of this alloy illustrating the substantial influence of creep mechanisms at 800 °C. Finally, cumulative values of creep versus fatigue damage fractions are plotted in a creep–fatigue interaction diagram and these results are discussed with respect to the existing bi

Microstructure, mechanical properties, bio-corrosion properties and antibacterial properties of Ti-Ag sintered alloys.

Science.gov (United States)

Chen, Mian; Zhang, Erlin; Zhang, Lan

2016-05-01

In this research, Ag element was selected as an antibacterial agent to develop an antibacterial Ti-Ag alloy by a powder metallurgy. The microstructure, phase constitution, mechanical properties, corrosion resistance and antibacterial properties of the Ti-Ag sintered alloys have been systematically studied by X-ray diffraction (XRD), scanning electron microscope (SEM), compressive test, electrochemical measurements and antibacterial test. The effects of the Ag powder size and the Ag content on the antibacterial property and mechanical property as well as the anticorrosion property have been investigated. The microstructure results have shown that Ti-Ag phase, residual pure Ag and Ti were the mainly phases in Ti-Ag(S75) sintered alloy while Ti2Ag was synthesized in Ti-Ag(S10) sintered alloy. The mechanical test indicated that Ti-Ag sintered alloy showed a much higher hardness and the compressive yield strength than cp-Ti but the mechanical properties were slightly reduced with the increase of Ag content. Electrochemical results showed that Ag powder size had a significant effect on the corrosion resistance of Ti-Ag sintered alloy. Ag content increased the corrosion resistance in a dose dependent way under a homogeneous microstructure. Antibacterial tests have demonstrated that antibacterial Ti-Ag alloy was successfully prepared. It was also shown that the Ag powder particle size and the Ag content influenced the antibacterial activity seriously. The reduction in the Ag powder size was benefit to the improvement in the antibacterial property and the Ag content has to be at least 3wt.% in order to obtain a strong and stable antibacterial activity against Staphylococcus aureus bacteria. The bacterial mechanism was thought to be related to the Ti2Ag and its distribution. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanical properties of ordered alloys

International Nuclear Information System (INIS)

Kroupa, F.

1977-06-01

A survey is given of the metallophysical fundamentals of the mechanical properties of ordered two-phase alloys. Alloys of this type have a superlattice structure in a substitution mixed crystal. Ordering is achieved by slow cooling or by annealing below the critical temperature, during which ordering domains (antiphase domains) are formed. At a high degree of ordering, the dislocations are concentrated to form pairs, so-called super-dislocations. The mechanical properties may be selectively changed by varying different parameters (size of the ordering domains, degree of ordering, energy of the antiphase boundaries) by a special composition and heat treatment.(GSC) [de

Skin mechanical properties and modeling: A review.

Science.gov (United States)

Joodaki, Hamed; Panzer, Matthew B

2018-04-01

The mechanical properties of the skin are important for various applications. Numerous tests have been conducted to characterize the mechanical behavior of this tissue, and this article presents a review on different experimental methods used. A discussion on the general mechanical behavior of the skin, including nonlinearity, viscoelasticity, anisotropy, loading history dependency, failure properties, and aging effects, is presented. Finally, commonly used constitutive models for simulating the mechanical response of skin are discussed in the context of representing the empirically observed behavior.

5-HT7 Receptor Antagonists with an Unprecedented Selectivity Profile.

Science.gov (United States)

Ates, Ali; Burssens, Pierre; Lorthioir, Olivier; Lo Brutto, Patrick; Dehon, Gwenael; Keyaerts, Jean; Coloretti, Francis; Lallemand, Bénédicte; Verbois, Valérie; Gillard, Michel; Vermeiren, Céline

2018-04-23

Selective leads: In this study, we generated a new series of serotonin 5-HT 7 receptor antagonists. Their synthesis, structure-activity relationships, and selectivity profiles are reported. This series includes 5-HT 7 antagonists with unprecedented high selectivity for the 5-HT 7 receptor, setting the stage for lead optimization of drugs acting on a range of neurological targets. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechanical properties of chemically modified portuguese pinewood

OpenAIRE

Lopes, Duarte B; Mai, Carsten; Militz, Holger

2014-01-01

To turn wood into a construction material with enhanced properties, many methods of chemical modification have been developed in the last few decades. In this work, mechanical properties of pine wood were chemically modified, compared and evaluated. Maritime pine wood (Pinus pinaster) was modified with four chemical processes: 1,3-dimethylol-4,5- dihydroxyethyleneurea, N-methylol melamine formaldehyde, tetra-alkoxysilane and wax. The following mechanical properties were assessed experiment...

Prediction of mechanical properties for hexagonal boron nitride nanosheets using molecular mechanics model

Energy Technology Data Exchange (ETDEWEB)

Natsuki, Toshiaki [Shinshu University, Faculty of Textile Science and Technology, Ueda (Japan); Shinshu University, Institute of Carbon Science and Technology, Nagano (Japan); Natsuki, Jun [Shinshu University, Institute of Carbon Science and Technology, Nagano (Japan)

2017-04-15

Mechanical behaviors of nanomaterials are not easy to be evaluated in the laboratory because of their extremely small size and difficulty controlling. Thus, a suitable model for the estimation of the mechanical properties for nanomaterials becomes very important. In this study, the elastic properties of boron nitride (BN) nanosheets, including the elastic modulus, the shear modulus, and the Poisson's ratio, are predicted using a molecular mechanics model. The molecular mechanics force filed is established to directly incorporate the Morse potential function into the constitutive model of nanostructures. According to the molecular mechanics model, the chirality effect of hexagonal BN nanosheets on the elastic modulus is investigated through a closed-form solution. The simulated result shows that BN nanosheets exhibit an isotropic elastic property. The present analysis yields a set of very simple formulas and is able to be served as a good approximation on the mechanical properties for the BN nanosheets. (orig.)

Prediction of mechanical properties for hexagonal boron nitride nanosheets using molecular mechanics model

International Nuclear Information System (INIS)

Natsuki, Toshiaki; Natsuki, Jun

2017-01-01

Mechanical behaviors of nanomaterials are not easy to be evaluated in the laboratory because of their extremely small size and difficulty controlling. Thus, a suitable model for the estimation of the mechanical properties for nanomaterials becomes very important. In this study, the elastic properties of boron nitride (BN) nanosheets, including the elastic modulus, the shear modulus, and the Poisson's ratio, are predicted using a molecular mechanics model. The molecular mechanics force filed is established to directly incorporate the Morse potential function into the constitutive model of nanostructures. According to the molecular mechanics model, the chirality effect of hexagonal BN nanosheets on the elastic modulus is investigated through a closed-form solution. The simulated result shows that BN nanosheets exhibit an isotropic elastic property. The present analysis yields a set of very simple formulas and is able to be served as a good approximation on the mechanical properties for the BN nanosheets. (orig.)

Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice

DEFF Research Database (Denmark)

Licht, Cecilie L; Kirkegaard, Lisbeth; Zueger, Maha

2010-01-01

. The olfactory bulbectomized mice displayed increased activity in the open field test, a characteristic depression-like feature of this model. After bulbectomy, 5-HT(4) receptor binding was increased in the ventral hippocampus (12%) but unchanged in the dorsal hippocampus, frontal and caudal caudate putamen......]citalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR(+/-)) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR(+/-) mice have a deficit in hypothalamic-pituitary-adrenal (HPA) system control....... Among post hoc analyzed regions, there was a 14% decrease in 5-HT(4) receptor binding in the olfactory tubercles. The 5-HTT binding was unchanged in the hippocampus and caudate putamen of bulbectomized mice but post hoc analysis showed small decreases in lateral septum and lateral globus pallidus...

The Canadian experimental HT release of June 10, 1987, US measurements

International Nuclear Information System (INIS)

Jalbert, R.A.; Murphy, C.E.

1988-09-01

In June 1987, an experiment was performed at the Chalk River Nuclear Laboratories in Ontario, Canada, to study the oxidation of elemental tritium (HT) released to the environment. The experiment involved a 30-minute release of 3.54 TBq (95.7 Ci)of HT to the atmosphere at an elevation of one meter. Scientists from six countries participated in the experiment. The air measurements showed HT concentrations downwind of the release in general agreement with classical atmospheric diffusion (Gaussian) up to the maximum distance measured (400 m). The HTO/HT ratios were shown to slowly increase downwind (∼ 4 x 10/sup /minus/5/ at 50 m to almost 10/sup /minus/3/ at 400 m) as conversion of HT took place. After the release, HTO concentrations in the atmosphere remained elevated. Vegetation samples were also taken since the vegetation and associated soil system have been implicated in the oxidation of HT. Freeze-dried water from vegetation samples was found to be low in HTO immediately after the release suggesting a low direct uptake of HTO in air by vegetation. The tritiated water concentration increased during the first day, peaking during the second day (about 15--30 kBq/L of water at 50 m from the source), and decreasing by the end of the second day. This pattern suggests oxidation in the soil followed by plant uptake through sorption of soil water. This was confirmed by measurements taken by other groups at the experiment site. The HTO in vegetation decreased with distance downwind with the same pattern as the HT measured during the release indicating that the oxidation of HT was linearly related to the HT concentration in the atmosphere during the exposure period. An adequate description of the process can be made through the observed phenomenon of HT deposition into the soil with subsequent rapid oxidation by soil bacteria. 30 refs., 10 figs., 4 tabs

Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

Science.gov (United States)

Vidal, Rebeca; Castro, Elena; Pilar-Cuéllar, Fuencisla; Pascual-Brazo, Jesús; Díaz, Alvaro; Rojo, María Luisa; Linge, Raquel; Martín, Alicia; Valdizán, Elsa M; Pazos, Angel

2014-01-01

The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.

The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.

Science.gov (United States)

Larson, Eric D; Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C; Finger, Thomas E

2015-12-02

Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response. Copyright © 2015 the authors 0270-6474/15/3515984-12$15.00/0.

Photoconductance of Bulk Heterojunctions with Tunable Nanomorphology Consisting of P3HT and Naphtalene Diimide Siloxane Oligomers

NARCIS (Netherlands)

Grzegorczyk, W.J.; Ganesan, P.; Savenije, T.J.; Bavel, van S.; Loos, J.; Sudhölter, E.J.R.; Siebbeles, L.D.A.; Zuilhof, H.

2009-01-01

The relation between the morphology, optical, and photoconductive properties of thin-film bulk heterojunctions of poly(3-hexylthiophene) (P3HT) with a series of electron-accepting siloxanes with a different number (x = 2, 4, 5) of pendant naphthalene diimide (NDIS) moieties is reported. All NDIS

Effect of Mechanical Alloying Atmospheres and Oxygen Concentration on Mechanical Properties of ODS Ferritic Steels

International Nuclear Information System (INIS)

Noh, Sanghoon; Choi, Byoungkwon; Han, Changhee; Kim, Kibaik; Kang, Sukhoon; Chun, Youngbum; Kim, Taekyu

2013-01-01

Finely dispersed nano-oxide particles with a high number density in the homogeneous grain matrix are essential to achieve superior mechanical properties at high temperatures, and these unique microstructures can be obtained through the mechanical alloying (MA) and hot consolidation process. The microstructure and mechanical property of ODS steel significantly depends on its powder property and the purity after the MA process. These contents should be carefully controlled to improve the mechanical property at elevated temperature. In particular, appropriate the control of oxygen concentration improves the mechanical property of ODS steel at high temperature. An effective method is to control the mechanical alloying atmosphere by high purity inert gas. In the present study, the effects of mechanical alloying atmospheres and oxygen concentration on the mechanical property of ODS steel were investigated. ODS ferritic alloys were fabricated in various atmospheres, and the HIP process was used to investigate the effects of MA atmospheres and oxygen concentration on the microstructure and mechanical property. ODS ferritic alloys milled in an Ar-H 2 mixture, and He is effective to reduce the excess oxygen concentration. The YH 2 addition made an extremely reduced oxygen concentration by the internal oxygen reduction reaction and resulted in a homogeneous microstructure and superior creep strength

5-HT1A receptor gene silencers Freud-1 and Freud-2 are differently expressed in the brain of rats with genetically determined high level of fear-induced aggression or its absence.

Science.gov (United States)

Kondaurova, Elena M; Ilchibaeva, Tatiana V; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

2016-09-01

Serotonin 5-HT1A receptor is known to play a crucial role in the mechanisms of genetically defined aggression. In its turn, 5-HT1A receptor functional state is under control of multiple factors. Among others, transcriptional factors Freud-1 and Freud-2 are known to be involved in the repression of 5-HT1A receptor gene expression. However, implication of these factors in the regulation of behavior is unclear. Here, we investigated the expression of 5-HT1A receptor and silencers Freud-1 and Freud-2 in the brain of rats selectively bred for 85 generations for either high level of fear-induced aggression or its absence. It was shown that Freud-1 and Freud-2 levels were different in aggressive and nonaggressive animals. Freud-1 protein level was decreased in the hippocampus, whereas Freud-2 protein level was increased in the frontal cortex of highly aggressive rats. There no differences in 5-HT1A receptor gene expression were found in the brains of highly aggressive and nonaggressive rats. However, 5-HT1A receptor protein level was decreased in the midbrain and increased in the hippocampus of highly aggressive rats. These data showed the involvement of Freud-1 and Freud-2 in the regulation of genetically defined fear-induced aggression. However, these silencers do not affect transcription of the 5-HT1A receptor gene in the investigated rats. Our data indicate the implication of posttranscriptional rather than transcriptional regulation of 5-HT1A receptor functional state in the mechanisms of genetically determined aggressive behavior. On the other hand, the implication of other transcriptional regulators for 5-HT1A receptor gene in the mechanisms of genetically defined aggression could be suggested. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanical properties of nuclear waste glasses

International Nuclear Information System (INIS)

Connelly, A.J.; Hand, R.J.; Bingham, P.A.; Hyatt, N.C.

2011-01-01

The mechanical properties of nuclear waste glasses are important as they will determine the degree of cracking that may occur either on cooling or following a handling accident. Recent interest in the vitrification of intermediate level radioactive waste (ILW) as well as high level radioactive waste (HLW) has led to the development of new waste glass compositions that have not previously been characterised. Therefore the mechanical properties, including Young's modulus, Poisson's ratio, hardness, indentation fracture toughness and brittleness of a series of glasses designed to safely incorporate wet ILW have been investigated. The results are presented and compared with the equivalent properties of an inactive simulant of the current UK HLW glass and other nuclear waste glasses from the literature. The higher density glasses tend to have slightly lower hardness and indentation fracture toughness values and slightly higher brittleness values, however, it is shown that the variations in mechanical properties between these different glasses are limited, are well within the range of published values for nuclear waste glasses, and that the surveyed data for all radioactive waste glasses fall within relatively narrow range.

A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients.Points that need more investigation.

Science.gov (United States)

Liontiris, Michael I; Mazokopakis, Elias E

2017-01-01

Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroid disease caused by an interaction between genetic factors and environmental conditions, both of which are yet to be fully understood. The management of HT depends on its clinical manifestations, commonly including diffuse or nodular goiter with euthyroidism, subclinical hypothyroidism and permanent hypothyroidism. However, in most cases of patients with HT, lifelong levothyroxine substitution is required. The additional role of diet for the management of HT is usually overlooked. A literature search regarding the importance and the influence of iodine, selenium, vitamin D and gluten on HT was conducted. In HT careful supplementation of possible deficiencies is recommended for the dietary management of these patients. The use of a diet low in gluten among HT patients with or without celiac disease (CD) is discussed.

Oppositional effects of serotonin receptors 5-HT1a, 2 and 2c in the regulation of adult hippocampal neurogenesis

Directory of Open Access Journals (Sweden)

Friederike Klempin

2010-07-01

Full Text Available Serotonin (5-HT appears to play a major role in controlling adult hippocampal neurogenesis and thereby it is relevant for theories linking failing adult neurogenesis to the pathogenesis of major depression and the mechanisms of action of antidepressants. Serotonergic drugs lack acute effects on adult neurogenesis in many studies, which suggests a surprising long latency phase. Here we report that the selective serotonin reuptake inhibitor fluoxetine, which has no acute effect on precursor cell proliferation, causes the well-described increase in net neurogenesis upon prolonged treatment partly by promoting the survival and maturation of new postmitotic neurons. We hypothesized that this result is the cumulative effect of several 5-HT-dependent events in the course of adult neurogenesis. Thus, we used specific agonists and antagonists to 5-HT1a, 2, and 2c receptor subtypes to analyze their impact on different developmental stages. We found that 5-HT exerts acute and opposing effects on proliferation and survival or differentiation of precursor cells by activating the diverse receptor subtypes on different stages within the neuronal lineage in vivo. This was confirmed in vitro by demonstrating that 5-HT1a receptors are involved in self-renewal of precursor cells, whereas 5-HT2 receptors effect both proliferation and promote neuronal differentiation. We propose that under acute conditions 5-HT2 effects counteract the positive proliferative effect of 5-HT1a receptor activation. However, prolonged 5-HT2c receptor activation fosters an increase in late stage progenitor cells and early postmitotic neurons, leading to a net increase in adult neurogenesis. Our data indicate that serotonin does not show effect latency in the adult dentate gyrus. Rather, the delayed response to serotonergic drugs with respect to endpoints downstream of the immediate receptor activity is largely due to the initially antagonistic and un-balanced action of different 5-HT

The renewed HT-7 plasma control system based on real-time Linux cluster

Energy Technology Data Exchange (ETDEWEB)

Yuan, Q.P., E-mail: qpyuan@ipp.ac.cn [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China); Xiao, B.J.; Zhang, R.R. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei (China); Walker, M.L.; Penaflor, B.G.; Piglowski, D.A.; Johnson, R.D. [General Atomics, DIII-D National Fusion Facility, San Diego, CA (United States)

2012-12-15

Highlights: Black-Right-Pointing-Pointer The hardware and software structure of the new HT-7 plasma control system (HT-7 PCS) is reported. Black-Right-Pointing-Pointer All original systems were integrated in the new HT-7 PCS. And the implementation details of the control algorithms are given in the paper. Black-Right-Pointing-Pointer Different from EAST PCS, the AC operation mode is realized in HT-7 PCS. Black-Right-Pointing-Pointer The experiment results are discussed. Good control performance has been obtained. - Abstract: In order to improve the synchronization, flexibility and expansibility of the plasma control on HT-7, a new plasma control system (HT-7 PCS) was constructed. The HT-7 PCS was based on a real-time Linux cluster with a well-defined, robust and flexible software infrastructure which was adapted from DIII-D PCS. In this paper, the hardware structure and system customization details for HT-7 PCS are reported. The plasma position and current control, plasma density control and off-normal event detection, which were realized in separated systems originally, have been integrated and implemented in such HT-7 PCS. All these control algorithms have been successfully validated in the last several HT-7 experiment campaigns. Good control performance has been achieved and the experiment results are discussed in the paper.

Mechanical and electro-mechanical properties of three-dimensional nanoporous graphene-poly(vinylidene fluoride composites

Directory of Open Access Journals (Sweden)

G. P. Zheng

2016-09-01

Full Text Available Three-dimensional nanoporous graphene monoliths are utilized to prepare graphene-poly(vinylidene fluoride nanocomposites with enhanced mechanical and electro-mechanical properties. Pre-treatment of the polymer (poly(vinylidene fluoride, PVDF with graphene oxides (GOs facilitates the formation of uniform and thin PVDF films with a typical thickness below 100 nm well coated at the graphene nano-sheets. Besides their excellent compressibility, ductility and mechanical strength, the nanoporous graphene-PVDF nanocomposites are found to possess high sensitivity in strain-dependent electrical conductivity. The improved mechanical and electro-mechanical properties are ascribed to the enhanced crystalline β phase in PVDF which possesses piezoelectricity. The mechanical relaxation analyses on the interfaces between graphene and PVDF reveal that the improved mechanical and electro-mechanical properties could result from the interaction between the –C=O groups in the nanoporous graphene and the –CF2 groups in PVDF, which also explains the important role of GOs in the preparation of the graphene-polymer nanocomposites with superior combined mechanical and electro-mechanical properties.

Chronic 5-HT4 receptor agonist treatment restores learning and memory deficits in a neuroendocrine mouse model of anxiety/depression.

Science.gov (United States)

Darcet, Flavie; Gardier, Alain M; David, Denis J; Guilloux, Jean-Philippe

2016-03-11

Cognitive disturbances are often reported as serious invalidating symptoms in patients suffering from major depression disorders (MDD) and are not fully corrected by classical monoaminergic antidepressant drugs. If the role of 5-HT4 receptor agonists as cognitive enhancers is well established in naïve animals or in animal models of cognitive impairment, their cognitive effects in the context of stress need to be examined. Using a mouse model of anxiety/depression (CORT model), we reported that a chronic 5-HT4 agonist treatment (RS67333, 1.5mg/kg/day) restored chronic corticosterone-induced cognitive deficits, including episodic-like, associative and spatial learning and memory impairments. On the contrary, a chronic monoaminergic antidepressant drug treatment with fluoxetine (18mg/kg/day) only partially restored spatial learning and memory deficits and had no effect in the associative/contextual task. These results suggest differential mechanisms underlying cognitive effects of these drugs. Finally, the present study highlights 5-HT4 receptor stimulation as a promising therapeutic mechanism to alleviate cognitive symptoms related to MDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A representative prescription for emotional disease, Ding-Zhi-Xiao-Wan restores 5-HT system deficit through interfering the synthesis and transshipment in chronic mild stress-induced depressive rats.

Science.gov (United States)

Dong, Xian-Zhe; Li, Zhao-Liang; Zheng, Xiao-Li; Mu, Li-Hua; Zhang, Gang-qiang; Liu, Ping

2013-12-12

Ding-Zhi-Xiao-Wan (DZ, also known as Kai-Xin-San) is a famous traditional Chinese medicine used for the treatment of emotional disease. Previously, we have found that in a variety of animal models of depression (such as tail suspension model, model of chronic fatigue and forced swimming model) DZ demonstrated significant antidepressant behavior and promoted the production of 5-hydroxytryptamine (5-HT). However, the mechanisms of 5-HT regulation are still unclear. Therefore, the current study is designed to further investigate the antidepressant effect of DZ by observing its influence on 5-HT synthesis, metabolism, transport and other key links, so as to clarify the molecular mechanism of its 5-HT regulation. Solitary rising combined with the chronic unpredictable mild stress (CMS) was used to establish the rat model of depression. The rats were given DZ for 3 weeks, the behavior change and the following items in hippocampus and prefrontal cortex were detected simultaneously: 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC), monoamine oxidase (MAO) and 5-HT transporter (5-HTT) were observed. Our results showed that treatment with the DZ significantly improved the behavior and simultaneously increased the 5-HT level in the hippocampus, prefrontal cortex tissues and hippocampus extracellular of depressive rats. In future studies revealed that DZ could significantly increase the protein and mRNA expression of the key enzymes TPH during the 5-HT synthesis process in the hippocampus and prefrontal cortex of the depressed rats, and suppress the expression of 5-HTT protein and mRNA at the same time. But it had no effects on MAO-A and MAO-B activities. We believe that antidepressant effect of DZ is caused by the increase of 5-HT synthesis and reduction of 5-HT re-uptake, and eventually increase the content of 5-HT in the brain and the synaptic gaps. © 2013 Published by Elsevier Ireland Ltd.

Impaired social behavior in 5-HT3A receptor knockout mice

Directory of Open Access Journals (Sweden)

Laura A Smit-Rigter

2010-11-01

Full Text Available The 5-HT3 receptor is a ligand-gated ion channel expressed on interneurons throughout the brain. So far, analysis of the 5-HT3A knockout mouse revealed changes in nociceptive processing and a reduction in anxiety related behavior. Recently, it was shown that the 5-HT3 receptor is also expressed on Cajal-Retzius cells which play a key role in cortical development and that knockout mice lacking this receptor showed aberrant growth of the dendritic tree of cortical layer II/III pyramidal neurons. Other mouse models in which serotonergic signaling was disrupted during development showed similar morphological changes in the cortex, and in addition, also deficits in social behavior. Here, we subjected male and female 5-HT3A knockout mice and their non-transgenic littermates to several tests of social behavior. We found that 5-HT3A knockout mice display impaired social communication in the social transmission of food preference task. Interestingly, we showed that in the social interaction test only female 5-HT3A knockout mice spent less time in reciprocal social interaction starting after 5 minutes of testing. Moreover, we observed differences in preference for social novelty for male and female 5-HT3A knockout mice during the social approach test. However, no changes in olfaction, exploratory activity and anxiety were detected. These results indicate that the 5-HT3A knockout mouse displays impaired social behavior with specific changes in males and females, reminiscent to other mouse models in which serotonergic signaling is disturbed in the developing brain.

Effect of juvenile hormone and serotonin (5-HT) on mixis induction of the rotifer Brachionus plicatilis Muller.

Science.gov (United States)

Gallardo; Hagiwara; Snell

2000-09-05

Juvenile hormone (JH) and serotonin (5-HT) were previously shown to enhance mictic (sexual) female production of the rotifer Brachionus plicatilis in batch cultures. To explore the basis of these effects, experiments were conducted on isolated individuals. JH treatment of maternal rotifers with 5 and 50 µgml(-1) (18.8 and 187.7 µM) resulted in significantly higher (P<0.05) mictic female production in the second (F(2)) and third (F(3)) generations. JH treatment was effective even at a lower food concentration of 7x10(5) cellsml(-1), but it was not effective when free ammonia was added at 2.4 and 3.1 µgml(-1). Mictic female production was not increased with exposure to 5-HT up to 50 µgml(-1) (129.1 µM) concentrations. When food level was reduced to 7x10(5) cellsml(-1), however, 5-HT-treated rotifers produced significantly (P<0.05) more mictic females than the control, particularly in F(3) generation. Mictic female production of 5-HT-treated rotifers did not differ from that of the control with or without free ammonia, but the intrinsic rate of natural increase (r) of 5-HT-treated rotifers at 3.1 µgml(-1) free ammonia was significantly higher than the control. These results show that juvenile hormone increases mictic female production under optimum and sub-optimum food levels, whereas 5-HT increases both mictic female production at low food level and population growth rate at high free ammonia concentrations. These compounds could be used to manage rotifer cultures and probe the mechanisms controlling the rotifer life cycle as it switches to mictic reproduction.

Microstructure, mechanical properties, bio-corrosion properties and antibacterial properties of Ti–Ag sintered alloys

Energy Technology Data Exchange (ETDEWEB)

Chen, Mian [Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, Northeastern University, Shenyang 110819 (China); Zhang, Erlin, E-mail: zhangel@atm.neu.edu.cn [Key Lab. for Anisotropy and Texture of Materials, Education Ministry of China, Northeastern University, Shenyang 110819 (China); Zhang, Lan [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China)

2016-05-01

In this research, Ag element was selected as an antibacterial agent to develop an antibacterial Ti–Ag alloy by a powder metallurgy. The microstructure, phase constitution, mechanical properties, corrosion resistance and antibacterial properties of the Ti–Ag sintered alloys have been systematically studied by X-ray diffraction (XRD), scanning electron microscope (SEM), compressive test, electrochemical measurements and antibacterial test. The effects of the Ag powder size and the Ag content on the antibacterial property and mechanical property as well as the anticorrosion property have been investigated. The microstructure results have shown that Ti–Ag phase, residual pure Ag and Ti were the mainly phases in Ti–Ag(S75) sintered alloy while Ti{sub 2}Ag was synthesized in Ti–Ag(S10) sintered alloy. The mechanical test indicated that Ti–Ag sintered alloy showed a much higher hardness and the compressive yield strength than cp-Ti but the mechanical properties were slightly reduced with the increase of Ag content. Electrochemical results showed that Ag powder size had a significant effect on the corrosion resistance of Ti–Ag sintered alloy. Ag content increased the corrosion resistance in a dose dependent way under a homogeneous microstructure. Antibacterial tests have demonstrated that antibacterial Ti–Ag alloy was successfully prepared. It was also shown that the Ag powder particle size and the Ag content influenced the antibacterial activity seriously. The reduction in the Ag powder size was benefit to the improvement in the antibacterial property and the Ag content has to be at least 3 wt.% in order to obtain a strong and stable antibacterial activity against Staphylococcus aureus bacteria. The bacterial mechanism was thought to be related to the Ti{sub 2}Ag and its distribution. - Highlights: • Ti–Ag alloy with up to 99% antibacterial rate was developed by powder metallurgy. • The effects of the Ag powder size and the Ag content on the

Variability of mechanical properties of nuclear pressure vessel steels

International Nuclear Information System (INIS)

Petrequin, P.; Soulat, P.

1980-01-01

Causes of variability of mechanical properties nuclear pressure vessel steels are reviewed and discussed. The effects of product shape and size, processing history and heat treatment are investigated. Some quantitative informations are given on the scatter of mechanical properties of typical pressure vessel components. The necessity of using recommended or standardized properties for comparing mechanical properties before and after irradiation in pin pointed. (orig.) [de

Experimental Analysis of Tensile Mechanical Properties of Sprayed FRP

Directory of Open Access Journals (Sweden)

Zhao Yang

2016-01-01

Full Text Available To study the tensile mechanical properties of sprayed FRP, 13 groups of specimens were tested through uniaxial tensile experiments, being analyzed about stress-strain curve, tensile strength, elastic modulus, breaking elongation, and other mechanical properties. Influencing factors on tensile mechanical properties of sprayed FRP such as fiber type, resin type, fiber volume ratio, fiber length, and composite thickness were studied in the paper too. The results show that both fiber type and resin type have an obvious influence on tensile mechanical properties of sprayed FRP. There will be a specific fiber volume ratio for sprayed FRP to obtain the best tensile mechanical property. The increase of fiber length can lead to better tensile performance, while that of composite thickness results in property degradation. The study can provide reference to popularization and application of sprayed FRP material used in structure reinforcement.

Risk-seeking for losses is associated with 5-HTTLPR, but not with transient changes in 5-HT levels.

Science.gov (United States)

Neukam, Philipp T; Kroemer, Nils B; Deza Araujo, Yacila I; Hellrung, Lydia; Pooseh, Shakoor; Rietschel, Marcella; Witt, Stephanie H; Schwarzenbolz, Uwe; Henle, Thomas; Smolka, Michael N

2018-05-05

Serotonin (5-HT) plays a key role in different aspects of value-based decision-making. A recent framework proposed that tonic 5-HT (together with dopamine, DA) codes future average reward expectations, providing a baseline against which possible choice outcomes are compared to guide decision-making. To test whether high 5-HT levels decrease loss aversion, risk-seeking for gains, and risk-seeking for losses. In a first session, 611 participants were genotyped for 5-HTTLPR and performed a mixed gambles (MGA) task and two probability discounting tasks for gains and losses, respectively (PDG/PDL). Afterwards, a subsample of 105 participants (44 with S/S, 6 with S/L, 55 with L/L genotype) completed the pharmacological study using a crossover design with tryptophan depletion (ATD), loading (ATL), and balanced (BAL) conditions. The same decision constructs were assessed. We found increased risk-seeking for losses in S/S compared to L/L individuals at the first visit (p = 0.002). Neither tryptophan depletion nor loading affected decision-making, nor did we observe an interaction between intervention and 5-HTTLPR genotype. Our data do not support the idea that transient changes of tonic 5-HT affect value-based decision-making. We provide evidence for an association of 5-HTTLPR with risk-seeking for losses, independent of acute 5-HT levels. This indicates that the association of 5-HTTLPR and risk-seeking for losses is mediated via other mechanisms, possibly by differences in the structural development of neural circuits of the 5-HT system during early life phases.

Mechanical properties of the human Achilles tendon, in vivo

DEFF Research Database (Denmark)

Kongsgaard, M; Nielsen, C H; Hegnsvad, S

2011-01-01

Ultrasonography has been widely applied for in vivo measurements of tendon mechanical properties. Assessments of human Achilles tendon mechanical properties have received great interest. Achilles tendon injuries predominantly occur in the tendon region between the Achilles-soleus myotendinous...... junction and Achilles-calcaneus osteotendinous junction i.e. in the free Achilles tendon. However, there has been no adequate ultrasound based method for quantifying the mechanical properties of the free human Achilles tendon. This study aimed to: 1) examine the mechanical properties of the free human...

Mechanical Properties of Moringa ( Moringa oleifera ) Seeds in ...

African Journals Online (AJOL)

Mechanical properties are very important in the design of machines and the analysis of the behaviour of products during agricultural processing. In this research work, the mechanical properties of Moringa were determined as design parameters for the development of an oil expeller for the crop. The properties were the ...

Food mechanical properties and dietary ecology.

Science.gov (United States)

Berthaume, Michael A

2016-01-01

Interdisciplinary research has benefitted the fields of anthropology and engineering for decades: a classic example being the application of material science to the field of feeding biomechanics. However, after decades of research, discordances have developed in how mechanical properties are defined, measured, calculated, and used due to disharmonies between and within fields. This is highlighted by "toughness," or energy release rate, the comparison of incomparable tests (i.e., the scissors and wedge tests), and the comparison of incomparable metrics (i.e., the stress and displacement-limited indices). Furthermore, while material scientists report on a myriad of mechanical properties, it is common for feeding biomechanics studies to report on just one (energy release rate) or two (energy release rate and Young's modulus), which may or may not be the most appropriate for understanding feeding mechanics. Here, I review portions of materials science important to feeding biomechanists, discussing some of the basic assumptions, tests, and measurements. Next, I provide an overview of what is mechanically important during feeding, and discuss the application of mechanical property tests to feeding biomechanics. I also explain how 1) toughness measures gathered with the scissors, wedge, razor, and/or punch and die tests on non-linearly elastic brittle materials are not mechanical properties, 2) scissors and wedge tests are not comparable and 3) the stress and displacement-limited indices are not comparable. Finally, I discuss what data gathered thus far can be best used for, and discuss the future of the field, urging researchers to challenge underlying assumptions in currently used methods to gain a better understanding between primate masticatory morphology and diet. © 2016 Wiley Periodicals, Inc.

Phosphotidylinositol turnover in vascular, uterine, fundal, and tracheal smooth muscle: effect of serotonin (5HT)

International Nuclear Information System (INIS)

Cohen, M.L.; Wittenauer, L.A.

1986-01-01

In brain, platelets, and aorta, 5HT has been reported to increase phosphotidylinositol turnover, an effect linked to 5HT 2 receptors. The authors examined the effect of 5HT on 3 H-inositol-1-phosphate ( 3 H-I-P) in tissues possessing 5HT 2 receptors that mediate contraction to 5HT (rat jugular vein, aorta, uterus and guinea pig trachea) and in a tissue in which contraction to 5HT is not mediated by 5HT 2 receptors (rat stomach fundus). Tissues were incubated (37 0 C, 95% O 2 , 5% CO 2 ) with 3 H-inositol (90 min), washed, LiCl 2 (10 mM) and 5HT added for 90 min, extracted, and 3 H-I-P eluted from a Dowex-1 column. Basal 3 H-I-P was 10-fold higher in the uterus than in the other tissues. 5HT (10 -6 -10 -4 M) increased 3 H-I-P in the jugular vein, aorta, and uterus but not in the trachea or fundus. Maximum increase was greatest in the jugular vein (8-fold) with an ED 50 of 0.4 μM 5HT. The selective 5HT 2 receptor blocker, LY53857 (10 -8 M) antagonized the increase in 3 H-I-P by 5HT in the jugular vein, aorta and uterus. Pargyline (10 -5 M) added to the trachea and fundus did not unmask an effect of 5HT (10 -4 M). These data suggest that (1) the jugular vein produced the most sensitive response to 5HT-induced increases in 3 H-I-P, (2) increases in 3 H-I-P by 5HT in smooth muscle may be linked to 5HT 2 receptors and (3) activation of 5HT 2 receptors as occurred in the trachea will not always increase 3 H-I-P

Low 5-HT1B receptor binding in the migraine brain

DEFF Research Database (Denmark)

Deen, Marie; Hansen, Hanne D; Hougaard, Anders

2018-01-01

Background The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT1B receptor is considered a key player due to the efficacy of 5-HT1B receptor agonists for treatment of migraine attacks. Aim To examine the cerebral 5-HT1B receptor binding....... Patients who reported migraine brain regions involved in pain modulation as regions of interest and applied a latent variable model (LVM) to assess the group effect on binding across these regions. Results Our data...... support a model wherein group status predicts the latent variable ( p = 0.038), with migraine patients having lower 5-HT1B receptor binding across regions compared to controls. Further, in a whole-brain voxel-based analysis, time since last migraine attack correlated positively with 5-HT1B receptor...

Activation of glucocorticoid receptors increases 5-HT2A receptor levels

DEFF Research Database (Denmark)

Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

2009-01-01

an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased......Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker...... of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish...

New Insights into the Molecular Dynamics of P3HT:PCBM Bulk Heterojunction: A Time-of-Flight Quasi-Elastic Neutron Scattering Study.

Science.gov (United States)

Guilbert, Anne A Y; Zbiri, Mohamed; Jenart, Maud V C; Nielsen, Christian B; Nelson, Jenny

2016-06-16

The molecular dynamics of organic semiconductor blend layers are likely to affect the optoelectronic properties and the performance of devices such as solar cells. We study the dynamics (5-50 ps) of the poly(3-hexylthiophene) (P3HT): phenyl-C61-butyric acid methyl ester (PCBM) blend by time-of-flight quasi-elastic neutron scattering, at temperatures in the range 250-360 K, thus spanning the glass transition temperature region of the polymer and the operation temperature of an OPV device. The behavior of the QENS signal provides evidence for the vitrification of P3HT upon blending, especially above the glass transition temperature, and the plasticization of PCBM by P3HT, both dynamics occurring on the picosecond time scale.

Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924.

Science.gov (United States)

Newman-Tancredi, A; Rivet, J-M; Cussac, D; Touzard, M; Chaput, C; Marini, L; Millan, M J

2003-09-01

This study employed [(35)S]guanosine 5'- O-(3-thiotriphosphate) ([(35)S]GTPgammaS) binding to compare the actions of antipsychotic agents known to stimulate cloned, human 5-HT(1A) receptors with those of reference agonists at postsynaptic 5-HT(1A) receptors. In rat hippocampal membranes, the following order of efficacy was observed (maximum efficacy, E(max), values relative to 5-HT=100): (+)8-OH-DPAT (85), flesinoxan (62), eltoprazine (60), S14506 (59), S16924 (48), buspirone (41), S15535 (22), clozapine (22), ziprasidone (21), pindolol (7), p-MPPI (0), WAY100,635 (0), spiperone (0). Despite differences in species and tissue source, the efficacy and potency (pEC(50)) of agonists (with the exception of clozapine) correlated well with those determined previously at human 5-HT(1A) receptors expressed in Chinese hamster ovary (CHO) cells. In contrast, clozapine was more potent at hippocampal membranes. The selective antagonists p-MPPI and WAY100,635 abolished stimulation of binding by (+)8-OH-DPAT, clozapine and S16924 (p-MPPI), indicating that these actions were mediated specifically by 5-HT(1A) receptors. Clozapine and S16924 also attenuated 5-HT- and (+)8-OH-DPAT-stimulated [(35)S]GTPgammaS binding, consistent with partial agonist properties. In [(35)S]GTPgammaS autoradiographic studies, 5-HT-induced stimulation, mediated through 5-HT(1A) receptors, was more potent in the septum (pEC(50) approximately 6.5) than in the dentate gyrus of the hippocampus (pEC(50) approximately 5) suggesting potential differences in coupling efficiency or G protein expression. Though clozapine (30 and 100 microM) did not enhance [(35)S]GTPgammaS labelling in any structure, S16924 (10 micro M) modestly increased [(35)S]GTPgammaS labelling in the dentate gyrus. On the other hand, both these antipsychotic agents attenuated 5-HT (10 microM)-stimulated [(35)S]GTPgammaS binding in the dentate gyrus and septum. In conclusion, clozapine, S16924 and ziprasidone act as partial agonists for G

Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm.

Science.gov (United States)

Meyer, Jeffrey H; McMain, Shelley; Kennedy, Sidney H; Korman, Lorne; Brown, Gregory M; DaSilva, Jean N; Wilson, Alan A; Blak, Thomas; Eynan-Harvey, Rahel; Goulding, Verdell S; Houle, Sylvain; Links, Paul

2003-01-01

Dysfunctional attitudes are negatively biased assumptions and beliefs regarding oneself, the world, and the future. In healthy subjects, increasing serotonin (5-HT) agonism with a single dose of d-fenfluramine lowered dysfunctional attitudes. To investigate whether the converse, a low level of 5-HT agonism, could account for the higher levels of dysfunctional attitudes observed in patients with major depression or with self-injurious behavior, cortex 5-HT(2) receptor binding potential and dysfunctional attitudes were measured in patients with major depressive disorder, patients with a history of self-injurious behavior, and healthy comparison subjects (5-HT(2) receptor density increases during 5-HT depletion). Twenty-nine healthy subjects were recruited to evaluate the effect of d-fenfluramine or of clonidine (control condition) on dysfunctional attitudes. Dysfunctional attitudes were assessed with the Dysfunctional Attitude Scale 1 hour before and 1 hour after drug administration. In a second experiment, dysfunctional attitudes and 5-HT(2) binding potential were measured in 22 patients with a major depressive episode secondary to major depressive disorder, 18 patients with a history of self-injurious behavior occurring outside of a depressive episode, and another 29 age-matched healthy subjects. Cortex 5-HT(2) binding potential was measured with [(18)F]setoperone positron emission tomography. In the first experiment, dysfunctional attitudes decreased after administration of d-fenfluramine. In the second experiment, in the depressed group, dysfunctional attitudes were positively associated with cortex 5-HT(2) binding potential, especially in Brodmann's area 9 (after adjustment for age). Depressed subjects with extremely dysfunctional attitudes had higher 5-HT(2) binding potential, compared to healthy subjects, particularly in Brodmann's area 9. Low levels of 5-HT agonism in the brain cortex may explain the severely pessimistic, dysfunctional attitudes associated

Uniaxial orientation of P3HT film prepared by soft friction transfer method.

Science.gov (United States)

Imanishi, Masayoshi; Kajiya, Daisuke; Koganezawa, Tomoyuki; Saitow, Ken-Ichi

2017-07-11

The realization of room-temperature processes is an important factor in the development of flexible electronic devices composed of organic materials. In addition, a simple and cost-effective process is essential to produce stable working devices and to enhance the performance of a smart material for flexible, wearable, or stretchable-skin devices. Here, we present a soft friction transfer method for producing aligned polymer films; a glass substrate was mechanically brushed with a velvet fabric and poly(3-hexylthiophene) (P3HT) solution was then spin-coated on the substrate. A P3HT film with a uniaxial orientation was obtained in air at room temperature. The orientation factor was 17 times higher than that of a film prepared using a conventional friction transfer technique at a high temperature of 120 °C. In addition, an oriented film with a thickness of 40 nm was easily picked up and transferred to another substrate. The mechanism for orientation of the film was investigated using six experimental methods and theoretical calculation, and was thereby attributed to a chemical process, i.e., cellulose molecules attach to the substrate and act as a template for molecular alignment.

Detailed mapping of serotonin 5-HT1B and 5-HT1D receptor messenger RNA and ligand binding sites in guinea-pig brain and trigeminal ganglion: clues for function

International Nuclear Information System (INIS)

Leysen, J.E.; Schotte, A.; Jurzak, M.; Luyten, W.H.M.L.; Voorn, P.; Bonaventure, P.

1997-01-01

The similar pharmacology of the 5-HT 1B and 5-HT 1D receptors, and the lack of selective compounds sufficiently distinguishing between the two receptor subtypes, have hampered functional studies on these receptors. In order to provide clues for differential functional roles of the two subtypes, we performed a parallel localization study throughout the guinea-pig brain and the trigeminal ganglia by means of quantitative in situ hybridization histochemistry (using [ 35 S]-labelled riboprobes probes for receptor messenger RNA) and receptor autoradiography (using a new radioligand [ 3 H]alniditan).The anatomical patterns of 5-HT 1B and 5-HT 1D receptor messenger RNA were quite different. While 5-HT 1B receptor messenger RNA was abundant throughout the brain (with highest levels in the striatum, nucleus accumbens, olfactory tubercle, cortex, hypothalamus, hippocampal formation, amygdala, thalamus, dorsal raphe and cerebellum), 5-HT 1D receptor messenger RNA exhibited a more restricted pattern; it was found mainly in the olfactory tubercle, entorhinal cortex, dorsal raphe, cerebellum, mesencephalic trigeminal nucleus and in the trigeminal ganglion. The density of 5-HT 1B/1D binding sites (combined) obtained with [ 3 H]alniditan autoradiography was high in the substantia nigra, superior colliculus and globus pallidus, whereas lower levels were detected in the caudate-putamen, hypothalamus, hippocampal formation, amygdala, thalamus and central gray. This distribution pattern was indistinguishable from specific 5-HT 1B receptor labelling in the presence of ketanserin under conditions to occlude 5-HT 1D receptor labelling; hence the latter were below detection level. Relationships between the regional distributions of the receptor messenger RNAs and binding sites and particular neuroanatomical pathways are discussed with respect to possible functional roles of the 5-HT 1B and 5-HT 1D receptors. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

Directory of Open Access Journals (Sweden)

Urszula eSlawinska

2014-08-01

Full Text Available There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-OHDPAT (acting on 5-HT1A/7 receptors and quipazine (acting on 5-HT2 receptors, to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor CPG. Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the locomotor activation.

Blonanserin Ameliorates Phencyclidine-Induced Visual-Recognition Memory Deficits: the Complex Mechanism of Blonanserin Action Involving D3-5-HT2A and D1-NMDA Receptors in the mPFC

Science.gov (United States)

Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

2015-01-01

Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr197 and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser897 by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser896 by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC. PMID:25120077

Review of research on the mechanical properties of the human tooth

Science.gov (United States)

Zhang, Ya-Rong; Du, Wen; Zhou, Xue-Dong; Yu, Hai-Yang

2014-01-01

‘Bronze teeth' reflect the mechanical properties of natural teeth to a certain extent. Their mechanical properties resemble those of a tough metal, and the gradient of these properties lies in the direction from outside to inside. These attributes confer human teeth with effective mastication ability. Understanding the various mechanical properties of human teeth and dental materials is the basis for the development of restorative materials. In this study, the elastic properties, dynamic mechanical properties (visco-elasticity) and fracture mechanical properties of enamel and dentin were reviewed to provide a more thorough understanding of the mechanical properties of human teeth. PMID:24743065

Enhancement of mechanical properties of 123 superconductors

Science.gov (United States)

Balachandran, Uthamalingam

1995-01-01

A composition and method of preparing YBa.sub.2 Cu.sub.3 O.sub.7-x superconductor. Addition of tin oxide containing compounds to YBCO superconductors results in substantial improvement of fracture toughness and other mechanical properties without affect on T.sub.c. About 5-20% additions give rise to substantially improved mechanical properties.

Mechanical Adaptivity as a Process: Implications to New Materials and Material System Design

Science.gov (United States)

2012-08-01

Mfg / Origami HT Thermal Shape Memory PhotoChem- Mechanical Autonomic Chemo-Mechanical Building Blocks Predictive Models...structure Farkas et al. Chaos 5 1995 Bishop et al. JACS, 2005 Controlling oscillations through medium selection and geometry Controlling...Additive Mfg / Origami HT Thermal Shape Memory PhotoChem- Mechanical Autonomic Chemo-Mechanical Building Blocks Predictive Models

Investigation of sawtooth behavior and confinement property with RHF on the HT-6B tokamak

International Nuclear Information System (INIS)

Hao Yuping; Xie Jikang; Li Linzhong

1989-01-01

The experiment results of the resonant helical field (RHF) effects on plasma confinement and sawtooth behavior on the HT-6B Tokamak are presented. The RHF makes decrease of electron thermal conductivity, broadening of temperature profile, increase of plasma density and enhancement of impurity radiation, in meanwhile intensification of sawtooth oscillation (in amplitude, period, rising slope and invert radius) and suppression of m = 2, 3, 4 modes. It is shown that the discharge transforms to a new discharge condition

Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness

Directory of Open Access Journals (Sweden)

Albert Paul R

2011-05-01

Full Text Available Abstract The serotonin-1A (5-HT1A receptor is among the most abundant and widely distributed 5-HT receptors in the brain, but is also expressed on serotonin neurons as an autoreceptor where it plays a critical role in regulating the activity of the entire serotonin system. Over-expression of the 5-HT1A autoreceptor has been implicated in reducing serotonergic neurotransmission, and is associated with major depression and suicide. Extensive characterization of the transcriptional regulation of the 5-HT1A gene (HTR1A using cell culture systems has revealed a GC-rich "housekeeping" promoter that non-selectively drives its expression; this is flanked by a series of upstream repressor elements for REST, Freud-1/CC2D1A and Freud-2/CC2D1B factors that not only restrict its expression to neurons, but may also regulate the level of expression of 5-HT1A receptors in various subsets of neurons, including serotonergic neurons. A separate set of allele-specific factors, including Deaf1, Hes1 and Hes5 repress at the HTR1A C(-1019G (rs6295 polymorphism in serotonergic neurons in culture, as well as in vivo. Pet1, an obligatory enhancer for serotonergic differentiation, has been identified as a potent activator of 5-HT1A autoreceptor expression. Taken together, these results highlight an integrated regulation of 5-HT1A autoreceptors that differs in several aspects from regulation of post-synaptic 5-HT1A receptors, and could be selectively targeted to enhance serotonergic neurotransmission.

Performance of HT9 clad metallic fuel at high temperature

International Nuclear Information System (INIS)

Pahl, R.G.; Lahm, C.E.; Hayes, S.L.

1992-01-01

Steady-state testing of HT9 clad metallic fuel at high temperatures was initiated in EBR-II in November of 1987. At that time U-10 wt. % Zr fuel clad with the low-swelling ferritic/martensitic alloy HT9 was being considered as driver fuel options for both EBR-II and FFTF. The objective of the X447 test described here was to determine the lifetime of HT9 cladding when operated with metallic fuel at beginning of life inside wall temperatures approaching ∼660 degree C. Though stress-temperature design limits for HT9 preclude its use for high burnup applications under these conditions due to excessive thermal creep, the X447 test was carried out to obtain data on high temperature breach phenomena involving metallic fuel since little data existed in that area

Successful treatment with risperidone increases 5-HT 3A receptor gene expression in patients with paranoid schizophrenia - data from a prospective study.

Science.gov (United States)

Chen, Hongying; Fan, Yong; Zhao, Lei; Hao, Yong; Zhou, Xiajun; Guan, Yangtai; Li, Zezhi

2017-09-01

The relationship between peripheral 5-HT3A receptor mRNA level and risperidone efficiency in paranoid schizophrenia patients is still unknown. A total 52 first-episode and drug-naive paranoid schizophrenia patients who were treated with risperidone and 53 matched healthy controls were enrolled. Patients were naturalistically followed up for 8 weeks. Positive and Negative Syndrome Scale (PANSS) was applied to assess symptom severity of the patients at baseline and at the end of 8th week. There was no difference in 5-HT3A receptor mRNA level between paranoid schizophrenia patients and healthy controls at baseline ( p  = .24). Among 47 patients who completed 8-week naturalistic follow-up, 37 were responders to risperidone treatment. 5-HT3A receptor mRNA level of paranoid schizophrenia patients did not change in overall patients after 8-week treatment with risperidone ( p  = .29). However, 5-HT3A receptor mRNA level in responders increased significantly ( p  = .04), but not in nonresponders ( p  = .81). Successful treatment with risperidone increases 5-HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that 5-HT3A receptor may be involved in the mechanism of risperidone effect.

Enhancement of mechanical properties of 123 superconductors

Science.gov (United States)

Balachandran, U.

1995-04-25

A composition and method are disclosed of preparing YBa{sub 2}Cu{sub 3}O{sub 7{minus}x} superconductor. Addition of tin oxide containing compounds to YBCO superconductors results in substantial improvement of fracture toughness and other mechanical properties without affect on T{sub c}. About 5-20% additions give rise to substantially improved mechanical properties.

Central Serotonin-2A (5-HT2A Receptor Dysfunction in Depression and Epilepsy: The Missing Link?

Directory of Open Access Journals (Sweden)

Bruno Pierre Guiard

2015-03-01

Full Text Available 5-Hydroxytryptamine 2A receptors (5-HT2A-Rs are G-protein coupled receptors. In agreement with their location in the brain, they have been implicated not only in various central physiological functions including memory, sleep, nociception, eating and reward behaviors, but also in many neuropsychiatric disorders. Interestingly, a bidirectional link between depression and epilepsy is suspected since patients with depression and especially suicide attempters have an increased seizure risk, while a significant percentage of epileptic patients suffer from depression. Such epidemiological data led us to hypothesize that both pathologies may share common anatomical and neurobiological alteration of the 5-HT2A signaling. After a brief presentation of the pharmacological properties of the 5-HT2A-Rs, this review illustrates how these receptors may directly or indirectly control neuronal excitability in most networks involved in depression and epilepsy through interactions with the monoaminergic, GABAergic and glutamatergic neurotransmissions. It also synthetizes the preclinical and clinical evidence demonstrating the role of these receptors in antidepressant and antiepileptic responses.

Development of the 5-HT2CR-Tango System Combined with an EGFP Reporter Gene.

Science.gov (United States)

Watanabe, Yoshihisa; Tsujimura, Atsushi; Aoki, Miku; Taguchi, Katsutoshi; Tanaka, Masaki

2016-02-01

The serotonin 2C receptor (5-HT2CR) is a G-protein-coupled receptor implicated in emotion, feeding, reward, and cognition. 5-HT2CRs are pharmacological targets for mental disorders and metabolic and reward system abnormalities, as alterations in 5-HT2CR expression, RNA editing, and SNPs are involved in these disturbances. To date, 5-HT2CR activity has mainly been measured by quantifying inositol phosphate production and intracellular Ca(2+) release, but these assays are not suitable for in vivo analysis. Here, we developed a 5-HT2CR-Tango assay system, a novel analysis tool of 5-HT2CR activity based on the G-protein-coupled receptor (GPCR)-arrestin interaction. With desensitization of activated 5-HT2CR by arrestin, this system converts the 5-HT2CR-arrestin interaction into EGFP reporter gene signal via the LexA transcriptional activation system. For validation of our system, we measured activity of two 5-HT2CR RNA-editing isoforms (INI and VGV) in HEK293 cells transfected with EGFP reporter gene. The INI isoform displayed both higher basal- and 5-HT-stimulated activities than the VGV isoform. Moreover, an inhibitory effect of 5-HT2CR antagonist SB242084 was also detected by 5-HT2CR-Tango system. This novel tool is useful for in vitro high-throughput targeted 5-HT2CR drug screening and can be applied to future in vivo brain function studies associated with 5-HT2CRs in transgenic animal models.

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

Science.gov (United States)

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

2012-04-01

The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

Science.gov (United States)

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

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Drew J. Puxty

2017-07-01

Full Text Available Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol, which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg, combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg. Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations. Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.

Linking the HOMO-LUMO gap to torsional disorder in P3HT/PCBM blends

International Nuclear Information System (INIS)

McLeod, John A.; Pitman, Amy L.; Moewes, Alexander; Kurmaev, Ernst Z.; Finkelstein, Larisa D.; Zhidkov, Ivan S.; Savva, Achilleas

2015-01-01

The electronic structure of [6,6]-phenyl C 61 butyric acid methyl ester (PCBM), poly(3-hexylthiophene) (P3HT), and P3HT/PCBM blends is studied using soft X-ray emission and absorption spectroscopy and density functional theory calculations. We find that annealing reduces the HOMO-LUMO gap of P3HT and P3HT/PCBM blends, whereas annealing has little effect on the HOMO-LUMO gap of PCBM. We propose a model connecting torsional disorder in a P3HT polymer to the HOMO-LUMO gap, which suggests that annealing helps to decrease the torsional disorder in the P3HT polymers. Our model is used to predict the characteristic length scales of the flat P3TH polymer segments in P3HT and P3HT/PCBM blends before and after annealing. Our approach may prove useful in characterizing organic photovoltaic devices in situ or even in operando

Optimization of mechanical properties, biocorrosion properties and antibacterial properties of wrought Ti-3Cu alloy by heat treatment

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Mianmian Bao

2018-03-01

Full Text Available Previous study has shown that Ti-3Cu alloy shows good antibacterial properties (>90% antibacterial rate, but the mechanical properties still need to be improved. In this paper, a series of heat-treatment processes were selected to adjust the microstructure in order to optimize the properties of Ti-3Cu alloy. Microstructure, mechanical properties, biocorrosion properties and antibacterial properties of wrought Ti-3Cu alloy at different conditions was systematically investigated by X-ray diffraction, optical microscope, scanning electron microscope, transmission electron microscopy, electrochemical measurements, tensile test, fatigue test and antibacterial test. Heat treatment could significantly improve the mechanical properties, corrosion resistance and antibacterial rate due to the redistribution of copper elements and precipitation of Ti2Cu phase. Solid solution treatment increased the yield strength from 400 to 740 MPa and improved the antibacterial rate from 33% to 65.2% while aging treatment enhanced the yield strength to 800–850 MPa and antibacterial rate (>91.32%. It was demonstrated that homogeneous distribution and fine Ti2Cu phase plays a very important role in mechanical properties, corrosion resistance and antibacterial properties.

Optimization of mechanical properties, biocorrosion properties and antibacterial properties of wrought Ti-3Cu alloy by heat treatment.

Science.gov (United States)

Bao, Mianmian; Liu, Ying; Wang, Xiaoyan; Yang, Lei; Li, Shengyi; Ren, Jing; Qin, Gaowu; Zhang, Erlin

2018-03-01

Previous study has shown that Ti-3Cu alloy shows good antibacterial properties (>90% antibacterial rate), but the mechanical properties still need to be improved. In this paper, a series of heat-treatment processes were selected to adjust the microstructure in order to optimize the properties of Ti-3Cu alloy. Microstructure, mechanical properties, biocorrosion properties and antibacterial properties of wrought Ti-3Cu alloy at different conditions was systematically investigated by X-ray diffraction, optical microscope, scanning electron microscope, transmission electron microscopy, electrochemical measurements, tensile test, fatigue test and antibacterial test. Heat treatment could significantly improve the mechanical properties, corrosion resistance and antibacterial rate due to the redistribution of copper elements and precipitation of Ti 2 Cu phase. Solid solution treatment increased the yield strength from 400 to 740 MPa and improved the antibacterial rate from 33% to 65.2% while aging treatment enhanced the yield strength to 800-850 MPa and antibacterial rate (>91.32%). It was demonstrated that homogeneous distribution and fine Ti 2 Cu phase plays a very important role in mechanical properties, corrosion resistance and antibacterial properties.

Atmospheric HT and HTO: V. distribution and large-scale circulation

International Nuclear Information System (INIS)

Mason, A.S.; Oestlund, H.G.

1979-01-01

The two major chemical forms of atmospheric tritium are water vapour (HTO) and hydrogen gas (HT). These forms have quite different sources, distributions and sinks. The chemical conversion from HT to HTO in the atmosphere proceeds with a characteristic time of 6.5 years. Combined with the radioactive decay, a net lifetime of 4.8 years is estimated for atmospheric HT. HT is released predominately at the surface in mid- to high latitudes in the northern hemisphere. A negative gradient southward has been found from aircraft transects and from sampling at surface stations. After many years of a relatively constant global inventory of 1.1 kg of tritium gas, the HT mixing ratios decreased during 1977, with the sharpest drop at high latitudes. The estimated decline in annual production was 100 g. At the end of 1977, the atmospheric HT burden was 1.0 kg, and the estimated annual release was 200 g. An unknown portion is present as T 2 gas. The effect of T 2 is to decrease the net lifetime to 3.7 years. In the troposphere, the cycle of HTO has been treated exhaustively by others. The stratospheric distribution of HTO has been sampled from aircraft, and found to increase rapidly with height above the troposphere. An annual cycle has been observed, in which the lower stratosphere is depleted during the spring, and replenished by subsidence from higher levels during summer and fall. The effects of a nuclear test by the People's Republic of China in November 1976 have been clearly observed in the stratospheric HTO; however, no HT deposition was found. Presumably, the HTO at higher levels was originally deposited by the large nuclear weapons tests of the 1960s. An estimated 5 kg of tritium are now present in the stratosphere below 19 km. (author)

Relaxation and Conductivity in P3HT/PC71BM Blends As Revealed by Dielectric Spectroscopy

DEFF Research Database (Denmark)

Cui, Jing; Martinez-Tong, Daniel E.; Sanz, Alejandro

2016-01-01

The conduction mechanism and the molecular dynamics on the paradigmatic bulk heterojunction formed by poly(3-hexylthiophene) (P3HT) and phenyl-C-71-butyric acid methyl ester (PC71BM) blends have been characterized by dielectric spectroscopy. The results show that hexyl lateral chains of the polym...

Regulators of G-protein signaling 4: modulation of 5-HT1A-mediated neurotransmitter release in vivo.

Science.gov (United States)

Beyer, Chad E; Ghavami, Afshin; Lin, Qian; Sung, Amy; Rhodes, Kenneth J; Dawson, Lee A; Schechter, Lee E; Young, Kathleen H

2004-10-01

Regulators of G-protein signaling (RGS) play a key role in the signal transduction of G-protein-coupled receptors (GPCRs). Specifically, RGS proteins function as GTPase accelerating proteins (GAPs) to dampen or "negatively regulate" GPCR-mediated signaling. Our group recently showed that RGS4 effectively GAPs Galpha(i)-mediated signaling in CHO cells expressing the serotonin-1A (5-HT(1A)) receptor. However, whether a similar relationship exists in vivo has yet to be identified. In present studies, a replication-deficient herpes simplex virus (HSV) was used to elevate RGS4 mRNA in the rat dorsal raphe nuclei (DRN) while extracellular levels of 5-HT in the striatum were monitored by in vivo microdialysis. Initial experiments conducted with noninfected rats showed that acute administration of 8-OH-DPAT (0.01-0.3 mg/kg, subcutaneous [s.c.]) dose dependently decreased striatal levels of 5-HT, an effect postulated to result from activation of somatodendritic 5-HT(1A) autoreceptors in the DRN. In control rats receiving a single intra-DRN infusion of HSV-LacZ, 8-OH-DPAT (0.03 mg/kg, s.c.) decreased 5-HT levels to an extent similar to that observed in noninfected animals. Conversely, rats infected with HSV-RGS4 in the DRN showed a blunted neurochemical response to 8-OH-DPAT (0.03 mg/kg, s.c.); however, increasing the dose to 0.3 mg/kg reversed this effect. Together, these findings represent the first in vivo evidence demonstrating that RGS4 functions to GAP Galpha(i)-coupled receptors and suggest that drug discovery efforts targeting RGS proteins may represent a novel mechanism to manipulate 5-HT(1A)-mediated neurotransmitter release.

Differential signal pathway activation and 5-HT function: the role of gut enterochromaffin cells as oxygen sensors.

Science.gov (United States)

Haugen, Martin; Dammen, Rikard; Svejda, Bernhard; Gustafsson, Bjorn I; Pfragner, Roswitha; Modlin, Irvin; Kidd, Mark

2012-11-15

The chemomechanosensory function of the gut enterochromaffin (EC) cell enables it to respond to dietary agents and mechanical stretch. We hypothesized that the EC cell, which also sensed alterations in luminal or mucosal oxygen level, was physiologically sensitive to fluctuations in O(2). Given that low oxygen levels induce 5-HT production and secretion through a hypoxia inducible factor 1α (HIF-1α)-dependent pathway, we also hypothesized that increasing O(2) would reduce 5-HT production and secretion. Isolated normal EC cells as well as the well-characterized EC cell model KRJ-I were used to examine HIF signaling (luciferase-assays), hypoxia transcriptional response element (HRE)-mediated transcription (PCR), signaling pathways (Western blot), and 5-HT release (ELISA) during exposure to different oxygen levels. Normal EC cells and KRJ-I cells express HIF-1α, and transient transfection with Renilla luciferase under HRE control identified a hypoxia-mediated pathway in these cells. PCR confirmed activation of HIF-downstream targets, GLUT1, IGF2, and VEGF under reduced O(2) levels (0.5%). Reducing O(2) also elevated 5-HT secretion (2-3.2-fold) as well as protein levels of HIF-1α (1.7-3-fold). Increasing O(2) to 100% inhibited HRE-mediated signaling, transcription, reduced 5-HT secretion, and significantly lowered HIF-1α levels (∼75% of control). NF-κB signaling was also elevated during hypoxia (1.2-1.6-fold), but no significant changes were noted in PKA/cAMP. We concluded that gut EC cells are oxygen responsive, and alterations in O(2) levels differentially activate HIF-1α and tryptophan hydroxylase 1, as well as NF-κB signaling. This results in alterations in 5-HT production and secretion and identifies that the chemomechanosensory role of EC cells extends to oxygen sensing.

Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy

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Paul R Albert

2010-06-01

Full Text Available Major depression is the most common form of mental illness, and is treated with antidepressant compounds that increase serotonin (5-HT neurotransmission. Increased 5-HT1A autoreceptor levels in the raphe nuclei act as a “brake” to inhibit the 5-HT system, leading to depression and resistance to antidepressants. Several 5-HT1A receptor agonists (buspirone, flesinoxan, ipsapirone that preferentially desensitize 5-HT1A autoreceptors have been tested for augmentation of antidepressant drugs with mixed results. One explanation could be the presence of the C(-1019G 5-HT1A promoter polymorphism that prevents gene repression of the 5-HT1A autoreceptor. Furthermore, down-regulation of 5-HT1A autoreceptor expression, not simply desensitization of receptor signaling, appears to be required to enhance and accelerate antidepressant action. The current review focuses on the transcriptional regulators of 5-HT1A autoreceptor expression, their roles in permitting response to 5-HT1A-targeted treatments and their potential as targets for new antidepressant compounds for treatment-resistant depression.

Novel pyridylmethylamines as highly selective 5-HT(1A) superagonists.

Science.gov (United States)

Bollinger, Stefan; Hübner, Harald; Heinemann, Frank W; Meyer, Karsten; Gmeiner, Peter

2010-10-14

To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT(1A) binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT(2), α(1), and α(2)-adrenergic as well as D(1)-D(4) dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT(1A) were examined in vitro employing a GTPγS assay. The investigation guided us to highly selective 5HT(1A) superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT(1A) recognition with a K(i) value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.

Cyclopentadienyl tricarbonyl complexes of 99mTc for the in vivo imaging of the serotonin 5-HT 1a receptor in the brain

International Nuclear Information System (INIS)

Saidi, Mouldi; Trabelsi, Adel; MEKNI, Abdelkader; Kretzschmar, M.; Sefert, S.; Bergmann, R.; Pietzsch, H.-J.

2005-01-01

The present interest in the 5-HT 1a receptor is due to its implicated role in several major neuropsychiatric disorders such as depression, eating disorders and anxiety. For the diagnosis of these pathophysiological processes it is important to have radioligands in hand able to specifically bind on the 5-HT 1a receptor in order to allow brain imaging. due to the optimal radiation properties of 99mTc there is a considerable interest in the development of 99mTc radiopharmaceuticals for imaging serotonergic CNS receptors using single-photon emission tomography (SPET). Here we introduce two cyclopentadienyl technitium tricarbonyl conjugates of piperidine derivatives which show high accumulation of radioactivity in brain areas rich in 5-HT 1a receptors

Structure–mechanics property relationship of waste derived biochars

Energy Technology Data Exchange (ETDEWEB)

Das, Oisik, E-mail: odas566@aucklanduni.ac.nz [Department of Civil and Environmental Engineering, University of Auckland, Auckland 1142 (New Zealand); Sarmah, Ajit K., E-mail: a.sarmah@auckland.ac.nz [Department of Civil and Environmental Engineering, University of Auckland, Auckland 1142 (New Zealand); Bhattacharyya, Debes, E-mail: d.bhattacharyya@auckland.ac.nz [Department of Mechanical Engineering, Center for Advanced Composite Materials, University of Auckland, Auckland 1142 (New Zealand)

2015-12-15

The widespread applications of biochar in agriculture and environmental remediation made the scientific community ignore its mechanical properties. Hence, to examine the scope of biochar's structural applications, its mechanical properties have been investigated in this paper through nanoindentation technique. Seven waste derived biochars, made under different pyrolysis conditions and from diverse feedstocks, were studied via nanoindentation, infrared spectroscopy, X–ray crystallography, thermogravimetry, and electron microscopy. Following this, an attempt was made to correlate the biochars' hardness/modulus with reaction conditions and their chemical properties. The pine wood biochar made at 900 °C and 60 min residence time was found to have the highest hardness and elastic modulus of 4.29 and 25.01 GPa, respectively. It was shown that a combination of higher heat treatment (≥ 500 °C) temperature and longer residence time (~ 60 min) increases the values of hardness and modulus. It was further realized that pyrolysis temperature was a more dominant factor than residence time in determining the final mechanical properties of biochar particles. The degree of aromaticity and crystallinity of the biochar were also correlated with higher values of hardness and modulus. - Highlights: • Characterization was done on waste based biochars which included nanoindentation. • Pine saw dust biochar made at 900 °C for 60 min had highest hardness/modulus. • Combination of temperature/residence time affect biochar's mechanical propertie.s • Aromaticity and crystallinity positively affected biochar's mechanical properties.

Structure–mechanics property relationship of waste derived biochars

International Nuclear Information System (INIS)

Das, Oisik; Sarmah, Ajit K.; Bhattacharyya, Debes

2015-01-01

The widespread applications of biochar in agriculture and environmental remediation made the scientific community ignore its mechanical properties. Hence, to examine the scope of biochar's structural applications, its mechanical properties have been investigated in this paper through nanoindentation technique. Seven waste derived biochars, made under different pyrolysis conditions and from diverse feedstocks, were studied via nanoindentation, infrared spectroscopy, X–ray crystallography, thermogravimetry, and electron microscopy. Following this, an attempt was made to correlate the biochars' hardness/modulus with reaction conditions and their chemical properties. The pine wood biochar made at 900 °C and 60 min residence time was found to have the highest hardness and elastic modulus of 4.29 and 25.01 GPa, respectively. It was shown that a combination of higher heat treatment (≥ 500 °C) temperature and longer residence time (~ 60 min) increases the values of hardness and modulus. It was further realized that pyrolysis temperature was a more dominant factor than residence time in determining the final mechanical properties of biochar particles. The degree of aromaticity and crystallinity of the biochar were also correlated with higher values of hardness and modulus. - Highlights: • Characterization was done on waste based biochars which included nanoindentation. • Pine saw dust biochar made at 900 °C for 60 min had highest hardness/modulus. • Combination of temperature/residence time affect biochar's mechanical propertie.s • Aromaticity and crystallinity positively affected biochar's mechanical properties.

Modification of smoothing in 4253H[T

Science.gov (United States)

Azmi, Nurul Nisa'Khairol; Adam, Mohd Bakri; Shitan, Mahendran; Ali, Norhaslinda Mohd

2017-05-01

Some modified non-linear smoothers particularly 4253H[T] are explained in this paper. The modifications are focused on estimating the middle point of running median for even span by applying the following types of means; geometric, harmonic, quadratic and contraharmonic. The performance of the techniques is assessed by applying it to daily price index of a bank in Malaysia that issues sukuk for funding in Islamic banking and financial business. The results show that 4253H[T] with geometric mean modification is better than others in preserving variation and curve fitting.

Simulations of cloudy hyperspectral infrared radiances using the HT-FRTC, a fast PC-based multipurpose radiative transfer code

Science.gov (United States)

Havemann, S.; Aumann, H. H.; Desouza-Machado, S. G.

2017-12-01

The HT-FRTC uses principal components which cover the spectrum at a very high spectral resolution allowing very fast line-by-line-like, hyperspectral and broadband simulations for satellite-based, airborne and ground-based sensors. Using data from IASI and from the Airborne Research Interferometer Evaluation System (ARIES) on board the FAAM BAE 146 aircraft, variational retrievals in principal component space with HT-FRTC as forward model have demonstrated that valuable information on temperature and humidity profiles and on the cirrus cloud properties can be obtained simultaneously. The NASA/JPL/UMBC cloudy RTM inter-comparison project has been working on a global dataset consisting of 7377 AIRS spectra. Initial simulations with HT-FRTC for this dataset have been promising. A next step taken here is to investigate how sensitive the results are with respect to different assumptions in the cloud modelling. One aspect of this is to study how assumptions about the microphysical and related optical properties of liquid/ice clouds impact the statistics of the agreement between model and observations. The other aspect is about the cloud overlap scheme. Different schemes have been tested (maximum, random, maximum random). As the computational cost increases linearly with the number of cloud columns, it will be investigated if there is an optimal number of columns beyond which there is little additional benefit to be gained. During daytime the high wave number channels of AIRS are affected by solar radiation. With full scattering calculations using a monochromatic version of the Edwards-Slingo radiation code the HT-FRTC can model solar radiation reasonably well, but full scattering calculations are relatively expensive. Pure Chou scaling on the other hand can not properly describe scattering of solar radiation by clouds and requires additional refinements.

Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1

DEFF Research Database (Denmark)

Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila

2015-01-01

have previously found that the atypical antipsychotics clozapine and olanzapine inhibited G protein activation and, surprisingly, induced both internalization and lysosomal degradation of 5-HT7 receptors. Here, we aimed to determine the mechanism of clozapine- and olanzapine-mediated degradation of 5......-HT7 receptors. In the C-terminus of the 5-HT7 receptor, we identified two YXXΦ motifs, LR residues, and a palmitoylated cysteine anchor as potential sites involved in receptor trafficking to lysosomes followed by receptor degradation. Mutating either of these sites inhibited clozapine- and olanzapine...... of clozapine or olanzapine to the 5-HT7 receptor leads to antagonist-mediated lysosomal degradation by exposing key residues in the C-terminal tail that interact with GASP-1....

In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists.

Directory of Open Access Journals (Sweden)

Yaxin Zheng

Full Text Available Kadsura longipedunculata (KL has been widely used for the treatment of insomnia in traditional Chinese medicine. The aim of this study was to explore the mechanism of the sedative and hypnotic effects of KL.The content of KL was evaluated by HPLC-TOF-MS, and a potential target was found and used to construct its 3D structure to screen for potential ligands among the compounds in KL by using bioinformatics analysis, including similarity ensemble approach (SEA docking, homology modeling, molecular docking and ligand-based pharmacophore. The PCPA-induced insomnia rat model was then applied to confirm the potential targets related to the sedative effects of KL by performing the forced swimming test (FST, the tail suspension test (TST and the measurement of target-related proteins using western blotting and immunofluorescence.Bioinformatics analysis showed that most of lignan compounds in KL were optimal ligands for the 5-HT1A receptor (5-HT1AR, and they were found to be potential targets related to sedative effects; the main lignan content of KL extracts was characterized by HPLC-TOF-MS, with 7 proposed lignans detected. Administration of KL could significantly reduce FST and TST immobility time in the PCPA-induced 5HT-depleted insomnia rat model. The expressions of proteins related to the 5-HT1AR pathway were regulated by extracts of KL in a concentration-dependent manner, indicating that extracts of KL had 5-HT1AR agonist-like effects.In silico analysis and experimental validation together demonstrated that lignan extracts from KL can target 5-HT1AR in insomniac rats, which could shed light on its use as a potential 5-HT1AR agonist drug.

Metal Additive Manufacturing: A Review of Mechanical Properties

Science.gov (United States)

Lewandowski, John J.; Seifi, Mohsen

2016-07-01

This article reviews published data on the mechanical properties of additively manufactured metallic materials. The additive manufacturing techniques utilized to generate samples covered in this review include powder bed fusion (e.g., EBM, SLM, DMLS) and directed energy deposition (e.g., LENS, EBF3). Although only a limited number of metallic alloy systems are currently available for additive manufacturing (e.g., Ti-6Al-4V, TiAl, stainless steel, Inconel 625/718, and Al-Si-10Mg), the bulk of the published mechanical properties information has been generated on Ti-6Al-4V. However, summary tables for published mechanical properties and/or key figures are included for each of the alloys listed above, grouped by the additive technique used to generate the data. Published values for mechanical properties obtained from hardness, tension/compression, fracture toughness, fatigue crack growth, and high cycle fatigue are included for as-built, heat-treated, and/or HIP conditions, when available. The effects of test orientation/build direction on properties, when available, are also provided, along with discussion of the potential source(s) (e.g., texture, microstructure changes, defects) of anisotropy in properties. Recommendations for additional work are also provided.

Mechanical properties of fracture zones

International Nuclear Information System (INIS)

Leijon, B.

1993-05-01

Available data on mechanical characteristics of fracture zones are compiled and discussed. The aim is to improve the basis for adequate representation of fracture zones in geomechanical models. The sources of data researched are primarily borehole investigations and case studies in rock engineering, involving observations of fracture zones subjected to artificial load change. Boreholes only yield local information about the components of fracture zones, i.e. intact rock, fractures and various low-strength materials. Difficulties are therefore encountered in evaluating morphological and mechanical properties of fracture zones from borehole data. Although often thought of as macroscopically planar features, available field data consistently show that fracture zones are characterized by geometrical irregularities such as thickness variations, surface undulation and jogs. These irregularities prevail on all scales. As a result, fracture zones are on all scales characterized by large, in-plane variation of strength- and deformational properties. This has important mechanical consequences in terms of non-uniform stress transfer and complex mechanisms of shear deformation. Field evidence for these findings, in particular results from the underground research laboratory in Canada and from studies of induced fault slip in deep mines, is summarized and discussed. 79 refs

Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

Science.gov (United States)

Asante, Curtis O.; Dickenson, Anthony H.

2010-01-01

We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

Mechanical properties of self-curing concrete (SCUC

Directory of Open Access Journals (Sweden)

Magda I. Mousa

2015-12-01

Full Text Available The mechanical properties of concrete containing self-curing agents are investigated in this paper. In this study, two materials were selected as self-curing agents with different amounts, and the addition of silica fume was studied. The self-curing agents were, pre-soaked lightweight aggregate (Leca; 0.0%, 10%, 15%, and 20% of volume of sand; or polyethylene-glycol (Ch.; 1%, 2%, and 3% by weight of cement. To carry out this study the cement content of 300, 400, 500 kg/m3, water/cement ratio of 0.5, 0.4, 0.3 and 0.0%, 15% silica fume of weight of cement as an additive were used in concrete mixes. The mechanical properties were evaluated while the concrete specimens were subjected to air curing regime (in the laboratory environment with 25 °C, 65% R.H. during the experiment. The results show that, the use of self-curing agents in concrete effectively improved the mechanical properties. The concrete used polyethylene-glycol as self-curing agent, attained higher values of mechanical properties than concrete with saturated Leca. In all cases, either 2% Ch. or 15% Leca was the optimum ratio compared with the other ratios. Higher cement content and/or lower water/cement ratio lead(s to more efficient performance of self-curing agents in concrete. Incorporation of silica fume into self-curing concrete mixture enhanced all mechanical properties, not only due to its pozzolanic reaction, but also due to its ability to retain water inside concrete.

The effects of Bifidobacterium breve on immune mediators and proteome of HT29 cells monolayers.

Science.gov (United States)

Sánchez, Borja; González-Rodríguez, Irene; Arboleya, Silvia; López, Patricia; Suárez, Ana; Ruas-Madiedo, Patricia; Margolles, Abelardo; Gueimonde, Miguel

2015-01-01

The use of beneficial microorganisms, the so-called probiotics, to improve human health is gaining popularity. However, not all of the probiotic strains trigger the same responses and they differ in their interaction with the host. In spite of the limited knowledge on mechanisms of action some of the probiotic effects seem to be exerted through maintenance of the gastrointestinal barrier function and modulation of the immune system. In the present work, we have addressed in vitro the response of the intestinal epithelial cell line HT29 to the strain Bifidobacterium breve IPLA20004. In the array of 84 genes involved in inflammation tested, the expression of 12 was modified by the bifidobacteria. The genes of chemokine CXCL6, the chemokine receptor CCR7, and, specially, the complement component C3 were upregulated. Indeed, HT29 cells cocultivated with B. breve produced significantly higher levels of protein C3a. The proteome of HT29 cells showed increased levels of cytokeratin-8 in the presence of B. breve. Altogether, it seems that B. breve IPLA20004 could favor the recruitment of innate immune cells to the mucosa reinforcing, as well as the physical barrier of the intestinal epithelium.

Catabolism of neurotensin by neural (neuroblastoma clone N1E115) and extraneural (HT29) cell lines

International Nuclear Information System (INIS)

Checler, F.; Amar, S.; Kitabgi, P.; Vincent, J.P.

1986-01-01

The mechanisms by which neurotensin (NT) was inactivated by differentiated neuroblastoma and HT29 cells were characterized. In both cell lines, the sites of primary cleavages of NT were Pro7-Arg8, Arg8-Arg9 and Pro10-Tyr11 bonds. The cleavage at the Pro7-Arg8 bond was totally inhibited by N-benzyloxycarbonyl-Prolyl-Prolinal and therefore resulted from the action of proline endopeptidase. This peptidase also contributed in a major way to the cleavage at the Pro10-Tyr11 bond. However the latter breakdown was partly due to an NT-degrading neutral metallopeptidase. Finally, we demonstrated the involvement of a recently purified rat brain soluble metalloendopeptidase at the Arg8-Arg9 site by the use of its specific inhibitor N-[1(R,S)-carboxy-2-Phenylethyl]-alanylalanylphenylalanine-p-amino benzoate. The secondary processing of NT degradation products revealed differences between HT29 and N1E115 cells. Angiotensin converting enzyme was shown to degrade NT1-10 and NT1-7 in N1E115 cells but was not detected in HT29 cells. A post-proline dipeptidyl aminopeptidase activity converted NT9-13 into NT11-13 in HT29 cells but not in N1E115 cells. Finally, bestatin-sensitive aminopeptidases rapidly broke down NT11-13 to Tyr in both cell lines. Models for the inactivation of NT in HT29 and N1E115 cells are proposed and compared to that previously described for purified rat brain synaptic membranes

PVA/Polysaccharides Blended Films: Mechanical Properties

Directory of Open Access Journals (Sweden)

Fábio E. F. Silva

2013-01-01

Full Text Available Blends of polyvinyl alcohol (PVA and angico gum (AG and/or cashew gum (CG were used to produce films by casting method. Morphological and mechanical properties of these films were studied and compared to the properties of a commercial collagen membrane of bovine origin (MBO. The films presented thickness varying from 70 to 140 μm (PVA/AG and 140 to 200 μm (PVA/CG. Macroscopic analysis showed that a PVA/CG film was very similar to MBO regarding the color and transparency. The higher values of tensile strength (TS and elastic modulus (EM were observed in the film. On the other hand, PVA/CG and PVA/CG-AG presented the highest value of percentage of elongation (E%. Pearson’s Correlation Analysis revealed a positive correlation between TS and EM and a negative correlation between E% and EM. The PVA/CG film presented mechanical properties very similar to MBO, with the advantage of a higher E% (11.96 than MBO (2.94. The properties of the PVA blended films depended on the polysaccharide added in the blend, as well as the acid used as a catalyst. However, all produced films presented interesting mechanical characteristics which enables several biotechnological applications.

Effects of combined administration of 5-HT1A and/or 5-HT1B receptor antagonists and paroxetine or fluoxetine in the forced swimming test in rats.

Science.gov (United States)

Tatarczyńska, Ewa; Kłodzińska, Aleksandra; Chojnacka-Wójcik, Ewa

2002-01-01

Clinical data suggest that coadministration of pindolol, a 5-HT1A/5-HT1B/beta-adrenoceptor antagonist, and selective serotonin reuptake inhibitors (SSRIs) may shorten the time of onset of a clinical action and may increase beneficial effects of the therapy of drug-resistant depression. Effects of combined administration of SSRIs and 5-HT receptor ligands are currently evaluated in animal models for the detection of an antidepressant-like activity; however, the obtained results turned out to be inconsistent. The aim of the present study was to investigate effects of a 5-HT1A antagonist (WAY 100635), 5-HT1B antagonists (SB 216641 and GR 127935) or pindolol, given in combination with paroxetine or fluoxetine (SSRIs), in the forced swimming test in rats (Porsolt test). When given alone, paroxetine (10 and 20 mg/kg), fluoxetine (10 and 20 mg/kg), WAY 100635 (0.1 and 1 mg/kg), SB 216641 (2 mg/kg), GR 127935 (10 and 20 mg/kg) and pindolol (4 and 8 mg/kg) did not shorten the immobility time of rats in that test. Interestingly, SB 216641 administered alone at a dose of 4 mg/kg produced a significant reduction of the immobility time in that test. A combination of paroxetine (20 mg/kg) and WAY 100635 or pindolol failed to reveal a significant interaction; on the other hand, when paroxetine was given jointly with SB 216641 (2 mg/kg) or GR 127935 (10 and 20 mg/kg), that combination showed a significant antiimmobility action in the forced swimming test in rats. The active behaviors in that test did not reflect increased general activity because combined administration of both the 5-HT1B antagonists and paroxetine failed to alter the locomotor activity of rats, measured in the open field test. Coadministration of fluoxetine and all the antagonists used did not affect the behavior of rats in the forced swimming test. The obtained results seem to indicate that blockade of 5-HT1B receptors, but not 5-HT1A ones, can facilitate the antidepressant-like effect of paroxetine in the

Mechanical properties of human atherosclerotic intima tissue.

Science.gov (United States)

Akyildiz, Ali C; Speelman, Lambert; Gijsen, Frank J H

2014-03-03

Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Probing cell mechanical properties with microfluidic devices

Science.gov (United States)

Rowat, Amy

2012-02-01

Exploiting flow on the micron-scale is emerging as a method to probe cell mechanical properties with 10-1000x advances in throughput over existing technologies. The mechanical properties of cells and the cell nucleus are implicated in a wide range of biological contexts: for example, the ability of white blood cells to deform is central to immune response; and malignant cells show decreased stiffness compared to benign cells. We recently developed a microfluidic device to probe cell and nucleus mechanical properties: cells are forced to deform through a narrow constrictions in response to an applied pressure; flowing cells through a series of constrictions enables us to probe the ability of hundreds of cells to deform and relax during flow. By tuning the constriction width so it is narrower than the width of the cell nucleus, we can specifically probe the effects of nuclear physical properties on whole cell deformability. We show that the nucleus is the rate-limiting step in cell passage: inducing a change in its shape to a multilobed structure results in cells that transit more quickly; increased levels of lamin A, a nuclear protein that is key for nuclear shape and mechanical stability, impairs the passage of cells through constrictions. We are currently developing a new class of microfluidic devices to simultaneously probe the deformability of hundreds of cell samples in parallel. Using the same soft lithography techniques, membranes are fabricated to have well-defined pore distribution, width, length, and tortuosity. We design the membranes to interface with a multiwell plate, enabling simultaneous measurement of hundreds of different samples. Given the wide spectrum of diseases where altered cell and nucleus mechanical properties are implicated, such a platform has great potential, for example, to screen cells based on their mechanical phenotype against a library of drugs.

In vitro phototoxic potential and photochemical properties of imidazopyridine derivative: a novel 5-HT4 partial agonist.

Science.gov (United States)

Onoue, Satomi; Igarashi, Naoko; Yamauchi, Yukinori; Kojima, Takashi; Murase, Noriaki; Zhou, Yu; Yamada, Shizuo; Tsuda, Yoshiko

2008-10-01

Drug-induced phototoxic skin responses have been recognized as undesirable side effects, and as we previously proposed the determination of reactive oxygen species (ROS) from photo-irradiated compounds can be effective for the prediction of phototoxic potential. In this investigation, we evaluated the photosensitizing properties of imidazopyridine derivative, a novel 5-HT(4) partial agonist, using ROS assay and several analytical/biochemical techniques. Exposure of the compound to simulated sunlight resulted in the significant production of singlet oxygen, which is indicative of its phototoxic potential. In practice, an imidazopyridine derivative under UVA/B light exposure also showed significant photodegradation and even photobiochemical events; peroxidation of fatty acid and genetic damage after DNA-binding, which are considered as causative agents for phototoxic dermatitis. Interestingly, both photodegradation and lipoperoxidation were dramatically attenuated by the addition of radical scavengers, especially singlet oxygen quenchers, suggesting the possible involvement of ROS generation in the phototoxic pathways. In the 3T3 neutral red uptake phototoxicity test, imidazopyridine derivative also showed the phototoxic effect on 3T3 mouse fibroblast cells. These results suggest the phototoxic risk of newly synthesized imidazopyridine derivative and also verify the usefulness of ROS assay for phototoxicity prediction. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

HT-7U superconducting tokamak: Physics design, engineering progress and schedule

International Nuclear Information System (INIS)

Wan Yuanxi

2002-01-01

The superconducting tokamak research program begun in China in ASIPP since 1994. The program is included in existent superconducting tokamak HT-7 and the next new superconducting tokamak HT-7U which is one of national key research projects in China. With the elongation cross-section, divertor and higher plasma parameter the main objectives of HT-7U are widely investigation both of the physics and technology for steady state advanced tokamak as well as the investigation of power and particle handle under steady-state operation condition. The physics and engineering design have been completed and significant progresses on R and D and fabrication have been achieved. HT-7U will begin assembly at 2003 and possible to get first plasma around 2004. (author)

Ebselen has lithium-like effects on central 5-HT2A receptor function.

Science.gov (United States)

Antoniadou, I; Kouskou, M; Arsiwala, T; Singh, N; Vasudevan, S R; Fowler, T; Cadirci, E; Churchill, G C; Sharp, T

2018-02-27

Lithium's antidepressant action may be mediated by inhibition of inositol monophosphatase (IMPase), a key enzyme in G q protein coupled receptor signalling. Recently, the antioxidant agent ebselen was identified as an IMPase inhibitor. Here we investigated both ebselen and lithium in models of the 5-HT 2A receptor, a G q protein coupled receptor implicated in lithium's actions. 5-HT 2A receptor function was modelled in mice by measuring the behavioural (head-twitches) and cortical immediate early gene (IEG; Arc, c-fos and Erg2 mRNA) responses to 5-HT 2A receptor agonist administration. Ebselen and lithium were administered either acutely or chronically prior to assessment of 5-HT 2A receptor function. Given the SSRI augmenting action of lithium and 5-HT 2A antagonists, ebselen was also tested for this action by co-administration with the SSRI citalopram in microdialysis (extracellular 5-HT) experiments. Acute and repeated administration of ebselen inhibited behavioural and IEG responses to the 5-HT 2A receptor agonist DOI. Repeated lithium also inhibited DOI-evoked behavioural and IEG responses. In comparison, a selective IMPase inhibitor (L-690,330) attenuated the behavioural response to DOI whereas glycogen synthase kinase inhibitor (AR-A014418) did not. Finally, ebselen increased regional brain 5-HT synthesis and enhanced the increase in extracellular 5-HT induced by citalopram. The current data demonstrate lithium-mimetic effects of ebselen in different experimental models of 5-HT 2A receptor function, likely mediated by IMPase inhibition. This evidence of lithium-like neuropharmacological effects of ebselen adds further support for the clinical testing of ebselen in mood disorder, including as an antidepressant augmenting agent. This article is protected by copyright. All rights reserved.

Mechanical properties of natural fibre reinforced polymer composites

Indian Academy of Sciences (India)

In the present communication, a study on the synthesis and mechanical properties of new series of green composites involving Hibiscus sabdariffa fibre as a reinforcing material in urea–formaldehyde (UF) resin based polymer matrix has been reported. Static mechanical properties of randomly oriented intimately mixed ...

Mechanical properties of carbon nanotubes

Science.gov (United States)

Salvetat, J.-P.; Bonard, J.-M.; Thomson, N. H.; Kulik, A. J.; Forró, L.; Benoit, W.; Zuppiroli, L.

A variety of outstanding experimental results on the elucidation of the elastic properties of carbon nanotubes are fast appearing. These are based mainly on the techniques of high-resolution transmission electron microscopy (HRTEM) and atomic force microscopy (AFM) to determine the Young's moduli of single-wall nanotube bundles and multi-walled nanotubes, prepared by a number of methods. These results are confirming the theoretical predictions that carbon nanotubes have high strength plus extraordinary flexibility and resilience. As well as summarising the most notable achievements of theory and experiment in the last few years, this paper explains the properties of nanotubes in the wider context of materials science and highlights the contribution of our research group in this rapidly expanding field. A deeper understanding of the relationship between the structural order of the nanotubes and their mechanical properties will be necessary for the development of carbon-nanotube-based composites. Our research to date illustrates a qualitative relationship between the Young's modulus of a nanotube and the amount of disorder in the atomic structure of the walls. Other exciting results indicate that composites will benefit from the exceptional mechanical properties of carbon nanotubes, but that the major outstanding problem of load transfer efficiency must be overcome before suitable engineering materials can be produced.

Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Trung Dung; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland (Australia)

2014-05-05

Based on the characterization by Atomic Force Microscopy, we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young's moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton and the intracellular fluid when the fixed chondrocytes are mainly governed by their intracellular fluid, which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

Subarachnoid hemorrhage-induced upregulation of the 5-HT1B receptor in cerebral arteries in rats

DEFF Research Database (Denmark)

Hansen-Schwartz, Jacob; Hoel, Natalie Løvland; Xu, Cang-Bao

2003-01-01

experimental SAH. METHODS: Experimental SAH was induced in rats by using an autologous prechiasmatic injection of arterial blood. Two days later, the middle cerebral artery (MCA), posterior communicating artery (PCoA), and basilar artery (BA) were harvested and examined functionally with the aid of a sensitive...... RNA coding for the 5-HT1B receptor as determined by quantitative real-time PCR. In the PCoA no upregulation of the 5-HT1B receptor was observed. CONCLUSIONS: Changes in the receptor phenotype in favor of contractile receptors may well represent the end stage in a sequence of events leading from SAH...... to the actual development of cerebral vasospasm. Insight into the mechanism of upregulation may provide new targets for developing specific treatment against cerebral vasospasm....

Chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene expressions/editings and metabolism of glutamate, glucose and glycogen: a potential paradigm shift

Directory of Open Access Journals (Sweden)

Leif eHertz

2015-02-01

Full Text Available It is firmly believed that the mechanism of action of SSRIs in major depression is to inhibit the serotonin transporter, SERT, and increase extracellular concentration of serotonin. However, this undisputed observation does not prove that SERT inhibition is the mechanism, let alone the only mechanism, by which SSRI’s exert their therapeutic effects. It has recently been demonstrated that 5-HT2B receptor stimulation is needed for the antidepressant effect of fluoxetine in vivo. The ability of all 5 currently used SSRIs to stimulate the 5-HT2B receptor equipotentially incultured astrocyteshas been known for several years,and increasing evidence has shown the importance of astrocytes and astrocyte-neuronal interactions for neuroplasticity and complex brain activity. This paper reviews acute and chronic effects of 5-HT2B receptor stimulation in cultured astrocytes and in astrocytes freshly isolated from brains of mice treated with fluoxetine for 14 daystogether with effects ofanti-depressant therapy on turnover of glutamate and GABA and metabolism of glucose and glycogen. It is suggested that these events are causally related to the mechanism of action of SSRIs and of interest for development of newer antidepressant drugs.

BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors

Directory of Open Access Journals (Sweden)

Rui Hao

2017-10-01

Full Text Available Brain-derived neurotrophic factor (BDNF is a key regulator of neuronal plasticity and cognitive functions. BDNF val66met polymorphism, a human single-nucleotide polymorphism (SNP in the pro-domain of BDNF gene, is associated with deficits in activity-dependent BDNF secretion and hippocampus-dependent memory. However, the underlying mechanism remains unclear. Here we show that in the BDNFMet/Met mouse line mimicking the human SNP, BDNF expression in the hippocampus was decreased. There was a reduction in the total number of cells in hippocampal CA1 region, while hippocampal expression of mRNAs for NR2a, 2b, GluR1, 2 and GABAARβ3 subunits were up-regulated. Although basal glutamatergic neurotransmission was unaltered, hippocampal long-term depression (LTD induced by low-frequency stimulation was impaired, which was partially rescued by exogenous application of BDNF. Interestingly, 5-HT3a receptors were down-regulated in the hippocampus of BDNFMet/Met mice, whereas 5-HT2c receptors were up-regulated. Moreover, impaired LTD in BDNFMet/Met mice was reversed by 5-HT3aR agonist. Thus, these observations indicate that BDNF val66met polymorphism changes hippocampal synaptic plasticity via down-regulation of 5-HT3a receptors, which may underlie cognition dysfunction of Met allele carriers.

Dynamic mechanical properties of buffer material

International Nuclear Information System (INIS)

Takaji, Kazuhiko; Taniguchi, Wataru

1999-11-01

The buffer material is expected to maintain its low water permeability, self-sealing properties, radionuclides adsorption and retardation properties, thermal conductivity, chemical buffering properties, overpack supporting properties, stress buffering properties, etc. over a long period of time. Natural clay is mentioned as a material that can relatively satisfy above. Among the kinds of natural clay, bentonite when compacted is superior because (i) it has exceptionally low water permeability and properties to control the movement of water in buffer, (ii) it fills void spaces in the buffer and fractures in the host rock as it swells upon water uptake, (iii) it has the ability to exchange cations and to adsorb cationic radioelements. In order to confirm these functions for the purpose of safety assessment, it is necessary to evaluate buffer properties through laboratory tests and engineering-scale tests, and to make assessments based on the ranges in the data obtained. This report describes the procedures, test conditions, results and examinations on the buffer material of dynamic triaxial tests, measurement of elastic wave velocity and liquefaction tests that aim at getting hold of dynamic mechanical properties. We can get hold of dependency on the shearing strain of the shearing modulus and hysteresis damping constant, the application for the mechanical model etc. by dynamic triaxial tests, the acceptability of maximum shearing modulus obtained from dynamic triaxial tests etc. by measurement of elastic wave velocity and dynamic strength caused by cyclic stress etc. by liquefaction tests. (author)

Serotonergic 5-HT6 Receptor Antagonists: Heterocyclic Chemistry and Potential Therapeutic Significance.

Science.gov (United States)

Bali, Alka; Singh, Shalu

2015-01-01

The serotonin 5-HT(6) receptor (5- HT(6)R) is amongst the recently discovered serotonergic receptors with almost exclusive localization in the brain. Hence, this receptor is fast emerging as a promising target for cognition enhancement in central nervous system (CNS) diseases such as Alzheimer's disease (cognitive function), obesity, schizophrenia and anxiety. The last decade has seen a surge of literature reports on the functional role of this receptor in learning and memory processes and investigations related to the chemistry and pharmacology of 5-HT(6) receptor ligands, especially 5- HT(6) receptor antagonists. Studies show the involvement of multiple neurotransmitter systems in cognitive enhancement by 5-HT(6)R antagonists including cholinergic, glutamatergic, and GABAergic systems. Several of the 5-HT(6)R ligands are indole based agents bearing structural similarity to the endogenous neurotransmitter serotonin. Based on the pharmacophoric models proposed for these agents, drug designing has been carried out incorporating various heterocyclic replacements for the indole nucleus. In this review, we have broadly summarized the medicinal chemistry and current status of this fairly recent class of drugs along with their potential therapeutic applications.

Molecular mechanisms in compatibility and mechanical properties of Polyacrylamide/Polyvinyl alcohol blends.

Science.gov (United States)

Wei, Qinghua; Wang, Yanen; Che, Yu; Yang, Mingming; Li, Xinpei; Zhang, Yingfeng

2017-01-01

The objectives of this study were to develop a computational model based on molecular dynamics technique to investigate the compatibility and mechanical properties of Polyacrylamide (PAM)/Polyvinyl alcohol (PVA) blends. Five simulation models of PAM/PVA with different composition ratios (4/0, 3/1, 2/2, 1/3, 0/4) were constructed and simulated by using molecular dynamics (MD) simulation. The interaction mechanisms of molecular chains in PAM/PVA blend system were elaborated from the aspects of the compatibility, mechanical properties, binding energy and pair correlation function, respectively. The computed values of solubility parameters for PAM and PVA indicate PAM has a good miscibility with PVA. The results of the static mechanical analysis, based on the equilibrium structures of blends with differing component ratios, shows us that the elastic coefficient, engineering modulus, and ductility are increased with the addition of PVA content, which is 4/0 PAM/PVAPVAPVAPVAPVA. Moreover, binding energy results indicate that a stronger interaction exists among PVA molecular chains comparing with PAM molecular chains, which is why the mechanical properties of blend system increasing with the addition of PVA content. Finally, the results of pair correlation functions (PCFs) between polar functional groups and its surrounding hydrogen atoms, indicated they interact with each other mainly by hydrogen bonds, and the strength of three types of polar functional groups has the order of O(-OH)>O(-C=O)>N(-NH 2 ). This further elaborates the root reason why the mechanical properties of blend system increase with the addition of PVA content. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurement of the mechanical properties of layered systems

International Nuclear Information System (INIS)

Blank, E.

2002-01-01

Thin films for integrated electronic circuitry, packaging and small structures in micro-electromechanical systems (MEMS) as well as protective coatings require mechanical testing to control fabrication processes, guarantee product quality and establish data bases for engineering purposes. They generally escape classical materials testing owing to their small size in at least one dimension and their incorporation into larger structures. The fact that material properties change in the micro- and nanometer range when sample dimensions reach the scale of defect structures, implies that sample and probe size become part of the property evaluation process. Although research into the mechanical behaviour of thin films and small structures now is established, the fundamentals of mechanical testing continue to be identified while there is a growing need for methods allowing to measure intrinsic material properties. This lecture will focus on the mechanics of thin film and small volume structures and review recently developed testing techniques for measuring materials properties, particularly indentation, bulge and bend testing. The effect of specimen and probe geometry on property evaluation will be discussed. The use of Raman spectroscopy for residual stress measurement will be illustrated. (Author)

Neuromodulation of reciprocal glutamatergic inhibition between antagonistic motoneurons by 5-hydroxytryptamine (5-HT) in crayfish walking system.

Science.gov (United States)

Pearlstein, E; Clarac, F; Cattaert, D

1998-01-23

In an in vitro preparation of the crayfish thoracic locomotor system, paired intracellular recordings were performed from antagonistic depressor (Dep) and levator (Lev) motoneurons (MNs) that control the second joint of walking legs. Connections between these two groups of MNs consist mainly of inhibitory connections and weak electrotonic synapses. Injection of depolarizing current into a Lev MN results in a hyperpolarization in a Dep MN, and vice versa. This reciprocal glutamatergic inhibition, is not changed in the presence of the sodium channel blocker tetrodotoxin (TTX) and therefore is likely supported by a direct connection between MNs. By contrast, reciprocal inhibition is largely reduced in the presence of 5-hydroxytryptamine (5-HT; 10 microM). Direct micro-application of glutamate pressure-ejected close to an intracellularly recorded MN, evoked an inhibitory response in that MN, accompanied by a decrease of input resistance. These two effects were dramatically reduced in the presence of 5-HT. Thus 5-HT could be involved in mechanisms of dynamic reconfigurations of the neural network controlling leg movements in crayfish.

Stably dispersible P3HT/ZnO nanocomposites with tunable luminescence by in-situ hydrolysis and copolymerization of zinc methacrylate

International Nuclear Information System (INIS)

Zhang Lin; Li Fan; Chen Yiwang; Peng Xiaoming; Zhou Weihua

2010-01-01

In this paper, the copolymer shell with the internal hydrophobic polymethacrylate layer and the external hydrophilic poly(ethylene glycol) methyl ether groups was successfully bonded on the surface of ZnO nanocrystals through a simple sol-gel method, i.e., radical polymerization of zinc methacrylate (Zn(MA) 2 ) and poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) and hydrolysis. The prepared ZnO-poly(methacrylate-co-poly(ethylene glycol) methyl ether methacrylate) (ZnO-PPEGMA) nanocrystals showed good dispersion and smaller particle size, due to the presence of copolymer shell. The optical properties of ZnO-PPEGMA nanocrystals were characterized by ultraviolet-visible (UV-vis) spectroscopy and photoluminescence (PL) spectroscopy. The results indicated that the absorption edge and PL emission in the UV region of ZnO-PPEGMA nanocrystals appeared obvious blue-shift, due to the smaller particle size. Incorporation of ZnO-PPEGMA nanocrystals into poly(3-hexylthiophene) (P3HT) matrix, the dispersion of P3HT/ZnO-PPEGMA nanocomposites was greatly improved and the nanocomposites possessed excellent photoluminescence stability. Meanwhile, it was observed that the PL emission of P3HT/ZnO-PPEGMA nanocomposites was enhanced significantly, due to the presence of copolymer shell and the improvement of compatibility of ZnO-PPEGMA in the P3HT matrix. The results showed that the P3HT/ZnO-PPEGMA nanocomposites could be potential candidates for optical applications.

G-LiHT: Goddard's LiDAR, Hyperspectral and Thermal Airborne Imager

Science.gov (United States)

Cook, Bruce; Corp, Lawrence; Nelson, Ross; Morton, Douglas; Ranson, Kenneth J.; Masek, Jeffrey; Middleton, Elizabeth

2012-01-01

Scientists at NASA's Goddard Space Flight Center have developed an ultra-portable, low-cost, multi-sensor remote sensing system for studying the form and function of terrestrial ecosystems. G-LiHT integrates two LIDARs, a 905 nanometer single beam profiler and 1550 nm scanner, with a narrowband (1.5 nanometers) VNIR imaging spectrometer and a broadband (8-14 micrometers) thermal imager. The small footprint (approximately 12 centimeters) LIDAR data and approximately 1 meter ground resolution imagery are advantageous for high resolution applications such as the delineation of canopy crowns, characterization of canopy gaps, and the identification of sparse, low-stature vegetation, which is difficult to detect from space-based instruments and large-footprint LiDAR. The hyperspectral and thermal imagery can be used to characterize species composition, variations in biophysical variables (e.g., photosynthetic pigments), surface temperature, and responses to environmental stressors (e.g., heat, moisture loss). Additionally, the combination of LIDAR optical, and thermal data from G-LiHT is being used to assess forest health by sensing differences in foliage density, photosynthetic pigments, and transpiration. Low operating costs (approximately $1 ha) have allowed us to evaluate seasonal differences in LiDAR, passive optical and thermal data, which provides insight into year-round observations from space. Canopy characteristics and tree allometry (e.g., crown height:width, canopy:ground reflectance) derived from G-LiHT data are being used to generate realistic scenes for radiative transfer models, which in turn are being used to improve instrument design and ensure continuity between LiDAR instruments. G-LiHT has been installed and tested in aircraft with fuselage viewports and in a custom wing-mounted pod that allows G-LiHT to be flown on any Cessna 206, a common aircraft in use throughout the world. G-LiHT is currently being used for forest biomass and growth estimation

High density operation on the HT-7 superconducting tokamak

International Nuclear Information System (INIS)

Xiang Gao

2000-01-01

The structure of the operation region has been studied in the HT-7 superconducting tokamak, and progress on the extension of the HT-7 ohmic discharge operation region is reported. A density corresponding to 1.2 times the Greenwald limit was achieved by RF boronization. The density limit appears to be connected to the impurity content and the edge parameters, so the best results are obtained with very clean plasmas and peaked electron density profiles. The peaking factors of electron density profiles for different current and line averaged densities were observed. The density behaviour and the fuelling efficiency for gas puffing (20-30%), pellet injection (70-80%) and molecular beam injection (40-50%) were studied. The core crash sawteeth and MHD behaviour, which were induced by an injected pellet, were observed and the events correlated with the change of current profile and reversed magnetic shear. The MARFE phenomena on HT-7 are summarized. The best correlation has been found between the total input ohmic power and the product of the edge line averaged density and Z eff . HT-7 could be easily operated in the high density region MARFE-free using RF boronization. (author)

Importance of M2-M3 loop in governing properties of genistein at the α7 nicotinic acetylcholine receptor inferred from α7/5-HT3A chimera.

Science.gov (United States)

Grønlien, Jens Halvard; Ween, Hilde; Thorin-Hagene, Kirsten; Cassar, Steven; Li, Jinhe; Briggs, Clark A; Gopalakrishnan, Murali; Malysz, John

2010-11-25

Genistein and 5-hydroxyindole (5-HI) potentiate the α7 nicotinic acetylcholine receptor current by primarily increasing peak amplitude, a property of type I α7 positive allosteric modulation. In this study, the effects of these two compounds were investigated at two different α7/5-HT(3) chimeras (chimera 1, comprising of extracellular α7 N-terminus fused to the remainder of 5-HT(3A), and chimera 2 containing an additional α7 encoded M2-M3 loop), and wild-type α7 and 5-HT(3A) receptors. Agonist-evoked responses, examined by expression of the chimeras in Xenopus laevis oocytes or HEK-293 cells, revealed that currents decayed slower and compounds {rank order: N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987)~2-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-5-phenyl-1,3,4-oxadiazole (NS6784)>acetylcholine>choline} were more potent in chimera 2 than chimera 1 or α7 receptors. In chimera 2, genistein and 5-HI potentiated agonist-evoked responses (EC(50): 4-5 μM for genistein and 300-500 μM for 5-HI) and at higher concentrations evoked current directly consistent with ago-allosteric modulation. At chimera 1 and 5-HT(3A) receptors, neither compound directly evoked any current and 5-HI, only at chimera 1, was able to potentiate agonist-evoked responses. Genistein and 5-HI did not inhibit the binding of the α7 agonist [(3)H](1S,4S)-2,2-dimethyl-5-(6-phenylpyridazin-3-yl)-5-aza-2-azoniabicyclo[2.2.1] heptane ([(3)H]A-585539) to rat brain or chimera 2. In summary, this study supports the role of the M2-M3 loop being critical for the positive allosteric effect of genistein, but not 5-HI, and in agonist-evoked response fine-tuning. The identification of distinct α7 receptor modulatory sites offers unique opportunities for developing CNS therapeutics and understanding its pharmacology. Copyright © 2010 Elsevier B.V. All rights reserved.

Lorcaserin and CP-809101 reduce motor impulsivity and reinstatement of food seeking behavior in male rats: Implications for understanding the anti-obesity property of 5-HT2C receptor agonists.

Science.gov (United States)

Higgins, Guy A; Silenieks, Leo B; Altherr, Everett B; MacMillan, Cam; Fletcher, Paul J; Pratt, Wayne E

2016-07-01

The 5-HT2C receptor agonist lorcaserin (Belviq®) has been approved by the FDA for the treatment of obesity. Impulsivity is a contributory feature of some eating disorders. Experiments investigated the effect of lorcaserin and the highly selective 5-HT2C agonist CP-809101 on measures of impulsivity and on reinstatement of food-seeking behaviour, a model of dietary relapse. The effect of both drugs on 22-h deprivation-induced feeding was also examined, as was the effect of prefeeding in each impulsivity test. Lorcaserin (0.3-0.6 mg/kg SC) and CP-809101 (0.6-1 mg/kg SC) reduced premature responding in rats trained on the 5-CSRTT and improved accuracy in a Go-NoGo task by reducing false alarms. At equivalent doses, both drugs also reduced reinstatement for food-seeking behaviour. Neither drug altered impulsive choice measured in a delay-discounting task. Lorcaserin (1-3 mg/kg SC) and CP-809101 (3-6 mg/kg SC) reduced deprivation-induced feeding but only at higher doses. These results suggest that in addition to previously reported effects on satiety and reward, altered impulse control may represent a contributory factor to the anti-obesity property of 5-HT2C receptor agonists. Lorcaserin may promote weight loss by improving adherence to dietary regimens in individuals otherwise prone to relapse and may be beneficial in cases where obesity is associated with eating disorders tied to impulsive traits, such as binge eating disorder.

Paroxetine-induced reduction of sexual incentive motivation in female rats is not modified by 5-HT1B or 5-HT2C antagonists.

Science.gov (United States)

Kaspersen, Helge; Agmo, Anders

2012-03-01

Clinical data show that paroxetine causes sexual dysfunction in a substantial proportion of women taking this compound. This work was conducted to determine whether chronic paroxetine reduces sexual incentive motivation in female rats and whether this compound can modify any aspect of paced mating. The role of the 5-HT(1B) and 5-HT(2C) receptors in any potential effects was also evaluated. Ovariectomized female rats were implanted with osmotic minipumps releasing 10 mg/kg per day of paroxetine or vehicle for 28 days. Tests for sexual incentive motivation and paced mating were performed just before implantation and at regular intervals thereafter. The females were primed with estradiol benzoate (25 μg/rat) and progesterone (1 mg/rat) before each of these tests. On days 25-27 of treatment, the females were injected with the 5-HT(1B) antagonist GR125,743 (5 mg/kg), the 5-HT(2C) antagonist SB206,553 (5 mg/kg) and vehicle in counterbalanced order. Preinjection time was 30 min. Paroxetine reduced sexual incentive motivation on day 20 of treatment without affecting any aspect of paced mating. None of the antagonists modified the inhibitory effect of paroxetine on sexual incentive motivation. In the group chronically treated with vehicle, SB206,553 reduced proceptive behaviors in the paced mating test. No other effect was obtained. The effects of paroxetine seen in female rats are similar to those observed in women, suggesting that disturbances of sexual incentive motivation in rats are predictive of sexual dysfunction in women. The 5-HT(1B) and 5-HT(2C) receptors do not seem to be of any importance for paroxetine's inhibitory effect.

High pressure sintering (HP-HT) of diamond powders with titanium and titanium carbide

International Nuclear Information System (INIS)

Jaworska, L.

1999-01-01

Polycrystalline diamond compacts for cutting tools are mostly manufactured using high pressure sintering (HP-HT). The standard diamond compacts are prepared by diamond powders sintering with metallic binding phase. The first group of metallic binder are metals able to solve carbon - Co, Ni. The second group of metal binders are carbide forming elements - Ti, Cr, W and others. The paper describes high pressure sintering of diamond powder with titanium and nonstoichiometry titanium carbide for cutting tool application. A type of binding phase has the significant influence on microstructure and mechanical properties of diamond compacts. Very homogeneous structure was achieved in case of compacts obtained from metalized diamond where diamond-TiC-diamond connection were predominant. In the case of compacts prepared by mechanical mixing of diamond with titanium powders the obtained structure was nonhomogeneous with titanium carbide clusters. They had more diamond to diamond connections. These compacts compared to the compact made of metallized diamond have greater wear resistance. In the case of the diamond and TiC 0.92 sintering the strong bonding of TiC diamond grains was obtained. The microstructure observations for diamond with 5% wt. Ti and diamond with 5% wt. TiC 0.92 (the initial composition) compacts were performed in transmission microscope. For two type of compacts the strong bonding phase TiC without defects is creating. (author)

Operant learning and differential-reinforcement-of-low-rate 36-s responding in 5-HT1A and 5-HT1B receptor knockout mice.

NARCIS (Netherlands)

Pattij, T.; Broersen, L.M.; Linde, J. van der; Groenink, L.; Gugten, J. van der; Maes, R.A.A.; Olivier, B.

2003-01-01

Previous studies with mice lacking 5-HT(1A) (1AKO) and 5-HT(1B) (1BKO) receptors in hippocampus-dependent learning and memory paradigms, suggest that these receptors play an important role in learning and memory, although their precise role is unclear. In the present study, 1AKO and 1BKO mice were

Modeling the mechanics of cancer: effect of changes in cellular and extra-cellular mechanical properties.

Science.gov (United States)

Katira, Parag; Bonnecaze, Roger T; Zaman, Muhammad H

2013-01-01

Malignant transformation, though primarily driven by genetic mutations in cells, is also accompanied by specific changes in cellular and extra-cellular mechanical properties such as stiffness and adhesivity. As the transformed cells grow into tumors, they interact with their surroundings via physical contacts and the application of forces. These forces can lead to changes in the mechanical regulation of cell fate based on the mechanical properties of the cells and their surrounding environment. A comprehensive understanding of cancer progression requires the study of how specific changes in mechanical properties influences collective cell behavior during tumor growth and metastasis. Here we review some key results from computational models describing the effect of changes in cellular and extra-cellular mechanical properties and identify mechanistic pathways for cancer progression that can be targeted for the prediction, treatment, and prevention of cancer.

Influence of Storage on Briquettes Mechanical Properties

Directory of Open Access Journals (Sweden)

Brožek M.

2014-09-01

Full Text Available The effects of the storage place, placing manner, and storage time on mechanical properties of briquettes made from birch chips were laboratorily tested. A unique methodology developed by the present author enabling a relatively easy assessment of mechanical properties of the briquettes is described. The briquettes properties were evaluated by their density and rupture force determination. From the test results it follows that if the briquettes are stored in a well closed plastic bag, neither the place nor the storage time influence significantly their life time. When stored in a net plastic bag, the briquettes get seriously damaged, namely depending on their storage place and storage time.

Rationally designed synthetic protein hydrogels with predictable mechanical properties.

Science.gov (United States)

Wu, Junhua; Li, Pengfei; Dong, Chenling; Jiang, Heting; Bin Xue; Gao, Xiang; Qin, Meng; Wang, Wei; Bin Chen; Cao, Yi

2018-02-12

Designing synthetic protein hydrogels with tailored mechanical properties similar to naturally occurring tissues is an eternal pursuit in tissue engineering and stem cell and cancer research. However, it remains challenging to correlate the mechanical properties of protein hydrogels with the nanomechanics of individual building blocks. Here we use single-molecule force spectroscopy, protein engineering and theoretical modeling to prove that the mechanical properties of protein hydrogels are predictable based on the mechanical hierarchy of the cross-linkers and the load-bearing modules at the molecular level. These findings provide a framework for rationally designing protein hydrogels with independently tunable elasticity, extensibility, toughness and self-healing. Using this principle, we demonstrate the engineering of self-healable muscle-mimicking hydrogels that can significantly dissipate energy through protein unfolding. We expect that this principle can be generalized for the construction of protein hydrogels with customized mechanical properties for biomedical applications.

Characterization and modelling of the mechanical properties of mineral wool

DEFF Research Database (Denmark)

Chapelle, Lucie

2016-01-01

and as a consequence focus on the mechanical properties of mineral wool has intensified. Also understanding the deformation mechanisms during compression of low density mineral wool is crucial since better thickness recovery after compression will result in significant savings on transport costs. The mechanical...... properties of mineral wool relate closely to the arrangement and characteristics of the fibres inside the material. Because of the complex architecture of mineral wool, the characterization and the understanding of the mechanism of deformations require a new methodology. In this PhD thesis, a methodology...... of the structure on mechanical properties can be explored. The size of the representative volume elements for the prediction of the elastic properties is determined for two types of applied boundary conditions. For sufficiently large volumes, the predicted elastic properties are consistent with results from...

Morphology Effect of Silver Nanostructures on the Performance of a P3HT:Graphene:AgNs-Based Active Layer Obtained via Dip Coating

Directory of Open Access Journals (Sweden)

Alí Gómez-Acosta

2016-01-01

Full Text Available We report the effect of the use of different silver nanostructures (AgNs layers deposited via dip coating onto a poly(3-hexylthiophene (P3HT and solution processable functionalized graphene (SPFGraphene composite film intended to be used as active layer in BHJ devices. SPFGraphene was added to P3HT in a ratio of 1.5 wt%. The best results were achieved when a layer of silver nano-pseudospheres (AgNPSs obtained after 10 immersion cycles was used as coating; in this case the highest light trapping and efficiency percent (η=0.23% were achieved. This means an increase of ~11.3% in comparison with the efficiency of the noncoated P3HT:SPFGraphene composite. Results also indicate that graphene was successfully functionalized in order to obtain appropriate dispersion in P3HT and that such conjugated polymer remained unaltered after the addition of SPFGraphene. Finally, it can be concluded that the electrical properties of the as-synthesized films are dependent on the shape and concentration of the AgNs deposited via dip coating.

Mechanical properties of low dimensional materials

Science.gov (United States)

Saini, Deepika

Recent advances in low dimensional materials (LDMs) have paved the way for unprecedented technological advancements. The drive to reduce the dimensions of electronics has compelled researchers to devise newer techniques to not only synthesize novel materials, but also tailor their properties. Although micro and nanomaterials have shown phenomenal electronic properties, their mechanical robustness and a thorough understanding of their structure-property relationship are critical for their use in practical applications. However, the challenges in probing these mechanical properties dramatically increase as their dimensions shrink, rendering the commonly used techniques inadequate. This dissertation focuses on developing techniques for accurate determination of elastic modulus of LDMs and their mechanical responses under tensile and shear stresses. Fibers with micron-sized diameters continuously undergo tensile and shear deformations through many phases of their processing and applications. Significant attention has been given to their tensile response and their structure-tensile properties relations are well understood, but the same cannot be said about their shear responses or the structure-shear properties. This is partly due to the lack of appropriate instruments that are capable of performing direct shear measurements. In an attempt to fill this void, this dissertation describes the design of an inexpensive tabletop instrument, referred to as the twister, which can measure the shear modulus (G) and other longitudinal shear properties of micron-sized individual fibers. An automated system applies a pre-determined twist to the fiber sample and measures the resulting torque using a sensitive optical detector. The accuracy of the instrument was verified by measuring G for high purity copper and tungsten fibers. Two industrially important fibers, IM7 carbon fiber and KevlarRTM 119, were found to have G = 17 and 2.4 GPa, respectively. In addition to measuring the shear

Vacuum physics analysis of HT-7 superconducting tokamak pump limiter

International Nuclear Information System (INIS)

Hu Jiansheng; Li Chengfu; He Yexi

1998-10-01

The pump limiter is analysed with HT-7 superconducting tokamak parameter and the pump limiter construction. The particle exhaust of the pump limiter can be to achieve about 7.7%. So the pump limiter can be applied in the HT-7 device and will make good affection in plasma discharge

Liaison of 3H 5-HT and adenyl cyclasic activation induced by the 5-HT in preparations of brain glial membranes

International Nuclear Information System (INIS)

Fillion, Gilles; Beaudoin, Dominique; Rousselle, J.-C.; Jacob, Joseph

1980-01-01

Purified glial membrane preparations have been isolated from horse brain striatum. Tritiated 5-HT bound to these membranes with a high affinity (K(D)=10 nM); the corresponding bindings is reversible and appears specific of the serotoninergic structure. In parallel, 5-HT activates an adenylate cyclase with a low affinity (K(D)=1 μM). The sites involved in this binding and in this adenylate cyclase activation appear different from the serotoninergic sites reported in the neuronal membrane preparations [fr

Estimation of Physical Properties for Hydrogen Isotopes Using Aspen Plus Simulator

International Nuclear Information System (INIS)

Cho, Jung Ho; Yun, Sei Hun; Cho, Seung Yon; Chang, Min Ho; Kang, Hyun Goo; Jung, Ki Jung; Kim, Dong Min

2009-01-01

Hydrogen isotopes are H 2 , HD, D 2 , H 2 , HD, D 2 , HT, DT and T 2 . Among the hydrogen isotopes, the physical properties of H2, HD and D+2 are included in the Aspen Plus, however HT, D T and T 2 are not included. In this study, various thermodynamic properties were estimated for six components of isotopes by use of the fixed properties and temperature-dependent properties. To estimate thermodynamic properties, Soave modified Redlich-Kwong equation of state and Aspenplus simulator was used. The results were verified and compared with by PRO/II with PROVISION of Invensys

Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity.

Science.gov (United States)

Calcagno, E; Canetta, A; Guzzetti, S; Cervo, L; Invernizzi, R W

2007-11-01

We used the microdialysis technique to compare basal extracellular serotonin (5-HT) and the response to citalopram in different strains of mice with functionally different allelic forms of tryptophan hydroxylase-2 (TPH-2), the rate-limiting enzyme in brain 5-HT synthesis. DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele of TPH-2 had less dialysate 5-HT in the medial prefrontal cortex and dorsal hippocampus (DH) (20-40% reduction) than C57BL/6J and C57BL/6N mice carrying the 1473C allele. Extracellular 5-HT estimated by the zero-net flux method confirmed the result of conventional microdialysis. Citalopram, 1.25, 5 and 20 mg/kg, dose-dependently raised extracellular 5-HT in the medial prefrontal cortex of C57BL/6J mice, with maximum effect at 5 mg/kg, but had significantly less effect in DBA/2J and BALB/c mice and in the DH of DBA/2J mice. A tryptophan (TRP) load enhanced basal extracellular 5-HT in the medial prefrontal cortex of DBA/2J mice but did not affect citalopram's ability to raise cortical and hippocampal extracellular 5-HT. The impairment of 5-HT synthesis quite likely accounts for the reduction of basal 5-HT and the citalopram-induced rise in mice carrying the mutated enzyme. These findings might explain why DBA/2 and BALB/c mice do not respond to citalopram in the forced swimming test. Although TRP could be a useful strategy to improve the antidepressant effect of citalopram (Cervo et al. 2005), particularly in subjects with low 5-HT synthesis, the contribution of serotonergic and non-serotonergic mechanisms to TRP's effect remains to be elucidated.

Detailed mapping of serotonin 5-HT{sub 1B} and 5-HT{sub 1D} receptor messenger RNA and ligand binding sites in guinea-pig brain and trigeminal ganglion: clues for function

Energy Technology Data Exchange (ETDEWEB)

Leysen, J.E. [Graduate School Neurosciences, Amsterdam (Netherlands); Schotte, A.; Jurzak, M.; Luyten, W.H.M.L. [Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse (Belgium); Voorn, P.; Bonaventure, P. [Graduate School Neurosciences, Amsterdam (Netherlands)

1997-10-17

The similar pharmacology of the 5-HT{sub 1B} and 5-HT{sub 1D} receptors, and the lack of selective compounds sufficiently distinguishing between the two receptor subtypes, have hampered functional studies on these receptors. In order to provide clues for differential functional roles of the two subtypes, we performed a parallel localization study throughout the guinea-pig brain and the trigeminal ganglia by means of quantitative in situ hybridization histochemistry (using [{sup 35}S]-labelled riboprobes probes for receptor messenger RNA) and receptor autoradiography (using a new radioligand [{sup 3}H]alniditan).The anatomical patterns of 5-HT{sub 1B} and 5-HT{sub 1D} receptor messenger RNA were quite different. While 5-HT{sub 1B} receptor messenger RNA was abundant throughout the brain (with highest levels in the striatum, nucleus accumbens, olfactory tubercle, cortex, hypothalamus, hippocampal formation, amygdala, thalamus, dorsal raphe and cerebellum), 5-HT{sub 1D} receptor messenger RNA exhibited a more restricted pattern; it was found mainly in the olfactory tubercle, entorhinal cortex, dorsal raphe, cerebellum, mesencephalic trigeminal nucleus and in the trigeminal ganglion. The density of 5-HT{sub 1B/1D} binding sites (combined) obtained with [{sup 3}H]alniditan autoradiography was high in the substantia nigra, superior colliculus and globus pallidus, whereas lower levels were detected in the caudate-putamen, hypothalamus, hippocampal formation, amygdala, thalamus and central gray. This distribution pattern was indistinguishable from specific 5-HT{sub 1B} receptor labelling in the presence of ketanserin under conditions to occlude 5-HT{sub 1D} receptor labelling; hence the latter were below detection level. Relationships between the regional distributions of the receptor messenger RNAs and binding sites and particular neuroanatomical pathways are discussed with respect to possible functional roles of the 5-HT{sub 1B} and 5-HT{sub 1D} receptors. (Copyright (c

Mechanical properties of additively manufactured octagonal honeycombs

Energy Technology Data Exchange (ETDEWEB)

Hedayati, R., E-mail: rezahedayati@gmail.com [Department of Mechanical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Hafez Ave, Tehran (Iran, Islamic Republic of); Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD Delft (Netherlands); Sadighi, M.; Mohammadi-Aghdam, M. [Department of Mechanical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Hafez Ave, Tehran (Iran, Islamic Republic of); Zadpoor, A.A. [Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD Delft (Netherlands)

2016-12-01

Honeycomb structures have found numerous applications as structural and biomedical materials due to their favourable properties such as low weight, high stiffness, and porosity. Application of additive manufacturing and 3D printing techniques allows for manufacturing of honeycombs with arbitrary shape and wall thickness, opening the way for optimizing the mechanical and physical properties for specific applications. In this study, the mechanical properties of honeycomb structures with a new geometry, called octagonal honeycomb, were investigated using analytical, numerical, and experimental approaches. An additive manufacturing technique, namely fused deposition modelling, was used to fabricate the honeycomb from polylactic acid (PLA). The honeycombs structures were then mechanically tested under compression and the mechanical properties of the structures were determined. In addition, the Euler-Bernoulli and Timoshenko beam theories were used for deriving analytical relationships for elastic modulus, yield stress, Poisson's ratio, and buckling stress of this new design of honeycomb structures. Finite element models were also created to analyse the mechanical behaviour of the honeycombs computationally. The analytical solutions obtained using Timoshenko beam theory were close to computational results in terms of elastic modulus, Poisson's ratio and yield stress, especially for relative densities smaller than 25%. The analytical solutions based on the Timoshenko analytical solution and the computational results were in good agreement with experimental observations. Finally, the elastic properties of the proposed honeycomb structure were compared to those of other honeycomb structures such as square, triangular, hexagonal, mixed, diamond, and Kagome. The octagonal honeycomb showed yield stress and elastic modulus values very close to those of regular hexagonal honeycombs and lower than the other considered honeycombs. - Highlights: • The octagonal

Mechanical properties of organic nanofibers

DEFF Research Database (Denmark)

Kjelstrup-Hansen, Jakob; Hansen, Ole; Rubahn, H.R.

2006-01-01

Intrinsic elastic and inelastic mechanical Properties of individual, self-assembled, quasi-single-crystalline para-hexaphenylene nanofibers supported on substrates with different hydrophobicities are investigated as well as the interplay between the fibers and the underlying substrates. We find...

An immunocapture/scintillation proximity analysis of G alpha q/11 activation by native serotonin (5-HT)2A receptors in rat cortex: blockade by clozapine and mirtazapine.

Science.gov (United States)

Mannoury La Cour, C; Chaput, C; Touzard, M; Millan, M J

2009-02-01

Though transduction mechanisms recruited by heterologously expressed 5-HT(2A) receptors have been extensively studied, their interaction with specific subtypes of G-protein remains to be directly evaluated in cerebral tissue. Herein, as shown by an immunocapture/scintillation proximity analysis, 5-HT, the prototypical 5-HT(2A) agonist, DOI, and Ro60,0175 all enhanced [(35)S]GTPgammaS binding to G alpha q/11 in rat cortex with pEC(50) values of 6.22, 7.24 and 6.35, respectively. No activation of G o or G s/olf was seen at equivalent concentrations of DOI. Stimulation of G alpha q/11 by 5-HT (30 microM) and DOI (30 microM) was abolished by the selective 5-HT(2A) vs. 5-HT(2C)/5-HT(2B) antagonists, ketanserin (pK(B) values of 9.11 and 8.88, respectively) and MDL100,907 (9.82 and 9.68). By contrast, 5-HT-induced [(35)S]GTPgammaS binding to G alpha q/11 was only weakly inhibited by the preferential 5-HT(2C) receptor antagonists, RS102,221 (6.94) and SB242,084 (7.39), and the preferential 5-HT(2B) receptor antagonist, LY266,097 (6.66). The antipsychotic, clozapine, which had marked affinity for 5-HT(2A) receptors, blocked the recruitment of G alpha q/11 by 5-HT and DOI with pK(B) values of 8.54 and 8.14, respectively. Its actions were mimicked by the "atypical" antidepressant and 5-HT(2A) receptor antagonist, mirtazapine, which likewise blocked 5-HT and DOI-induced G alpha q/11 protein activation with pK(B) values of 7.90 and 7.76, respectively. In conclusion, by use of an immunocapture/scintillation proximity strategy, this study shows that native 5-HT(2A) receptors in rat frontal cortex specifically recruit G alpha q/11 and that this action is blocked by clozapine and mirtazapine. Quantification of 5-HT(2A) receptor-mediated G alpha q/11 activation in frontal cortex should prove instructive in characterizing the actions of diverse classes of psychotropic agent. 2008 Wiley-Liss, Inc.

Field studies of HT oxidation and dispersion in the environment. I

International Nuclear Information System (INIS)

Brown, R.M.

1987-01-01

The environmental dispersion and oxidation of a controlled atmospheric release of tritiated hydrogen (HT) was studied in a pilot-scale field experiment. This study was designed to test procedures and obtain preliminary results for planning a more intensive experiment to determine the environmental behaviour of HT with emphasis on the processes leading to the appearance of HTO in the atmosphere, ie., conversion, deposition and resuspension. Field observations led to the following conclusions: 1) no evidence was found for the rapid conversion of HT to HTO in the atmosphere, 2) observations support the hypothesis that the dominant process giving rise to the observed HTO in air was HT oxidation in the soil by microbial action followed by resuspension of HTO, 3) HT deposition velocities to soil ranged between 0.041 cm/s and 0.13 cm/s, consistent with previous chamber measurements, 4) the rate of HTO loss from soil, averaged over 21 days, was less than 1% per hour, and 5) vegetation HTO concentrations initially increased with time then by 48 hours decreased exponentially at a rate similar to soils. These results will be validated and extended by the intensive experiment scheduled for June, 1987

MECHANICAL AND THERMO–MECHANICAL PROPERTIES OF BI-DIRECTIONAL AND SHORT CARBON FIBER REINFORCED EPOXY COMPOSITES

Directory of Open Access Journals (Sweden)

G. AGARWAL

2014-10-01

Full Text Available This paper based on bidirectional and short carbon fiber reinforced epoxy composites reports the effect of fiber loading on physical, mechanical and thermo-mechanical properties respectively. The five different fiber loading, i.e., 10wt. %, 20wt. %, 30wt. %, 40wt. % and 50wt. % were taken for evaluating the above said properties. The physical and mechanical properties, i.e., hardness, tensile strength, flexural strength, inter-laminar shear strength and impact strength are determined to represent the behaviour of composite structures with that of fiber loading. Thermo-mechanical properties of the material are measured with the help of Dynamic Mechanical Analyser to measure the damping capacity of the material that is used to reduce the vibrations. The effect of storage modulus, loss modulus and tan delta with temperature are determined. Finally, Cole–Cole analysis is performed on both bidirectional and short carbon fiber reinforced epoxy composites to distinguish the material properties of either homogeneous or heterogeneous materials. The results show that with the increase in fiber loading the mechanical properties of bidirectional carbon fiber reinforced epoxy composites increases as compared to short carbon fiber reinforced epoxy composites except in case of hardness, short carbon fiber reinforced composites shows better results. Similarly, as far as Loss modulus, storage modulus is concerned bidirectional carbon fiber shows better damping behaviour than short carbon fiber reinforced composites.

Characterization of porosity in support of mechanical property analysis

International Nuclear Information System (INIS)

Price, R.H.; Martin, R.J. III; Boyd, P.J.

1992-01-01

Previous laboratory investigations of tuff have shown that porosity has a dominant, general effect on mechanical properties. As a result, it is very important for the interpretation of mechanical property data that porosity is measured on each sample tested. Porosity alone, however, does not address all of the issues important to mechanical behavior. Variability in size and distribution of pore space produces significantly different mechanical properties. A nondestructive technique for characterizing the internal structure of the sample prior to testing is being developed and the results are being analyzed. The information obtained from this technique can help in both qualitative and quantitative interpretation of test results

Mechanical properties of F82H plates with different thicknesses

Energy Technology Data Exchange (ETDEWEB)

Sakasegawa, Hideo, E-mail: sakasegawa.hideo@jaea.go.jp; Tanigawa, Hiroyasu

2016-11-01

Highlights: • Mass effect, homogeneity, and anisotropy in mechanical properties were studied. • Thickness dependence of tensile property was not observed. • Thickness dependence of Charpy impact property was observed. • Appropriate mechanical properties were obtained using an electric furnace. - Abstract: Fusion DEMO reactor requires over 11,000 tons of reduced activation ferritic/martensitic steel and it is indispensable to develop the manufacturing technology for producing large-scale components of DEMO blanket with appropriate mechanical properties. This is because mechanical properties are generally degraded with increasing production volume. In this work, we focused mechanical properties of F82H–BA12 heat which was melted in a 20 tons electric arc furnace. Plates with difference thicknesses from 18 to 100 mm{sup t} were made from its ingot through forging and hot-rolling followed by heat treatments. Tensile and Charpy impact tests were then performed on plates focusing on their homogeneity and anisotropy. From the result, their homogeneity and anisotropy were not significant. No obvious differences were observed in tensile properties between the plates with different thicknesses. However, Charpy impact property changed with increasing plate thickness, i.e. the ductile brittle transition temperature of a 100 mm{sup t} thick plate was higher than that of the other thinner plates.

Hot spot manifestation in eclipsing dwarf nova HT Cassiopeiae

OpenAIRE

Bakowska, K.; Olech, A.

2014-01-01

We report the detection of the hot spot in light curves of the eclipsing dwarf nova HT Cassiopeiae during its superoutburst in 2010 November. Analysis of eight reconstructed light curves of the hot spot eclipses showed directly that the brightness of the hot spot was changing significantly during the superoutburst. Thereby, detected hot spot manifestation in HT Cas is the newest observational evidence for the EMT model for dwarf novae.

Mechanical properties of self-compacting concrete state-of-the-art report of the RILEM technical committee 228-MPS on mechanical properties of self-compacting concrete

CERN Document Server

Schutter, Geert

2014-01-01

The State-of-the-Art Report of RILEM Technical Committee 228-MPS on Mechanical properties of Self-Compacting Concrete (SCC) summarizes an extensive body of information related to mechanical properties and mechanical behaviour of SCC. Due attention is given to the fact that the composition of SCC varies significantly. A wide range of  mechanical properties are considered, including compressive strength, stress-strain relationship, tensile and flexural strengths, modulus of elasticity, shear strength, effect of elevated temperature, such as fire spalling and residual properties after fire, in-situ properties, creep, shrinkage, bond properties, and structural behaviour. A chapter on fibre-reinforced SCC is included, as well as a chapter on specialty SCC, such as light-weight SCC, heavy-weight SCC, preplaced aggregate SCC, special fibre reinforced SCC, and underwater concrete.

Serotonergic Regulation of Prefrontal Cortical Circuitries Involved in Cognitive Processing: A Review of Individual 5-HT Receptor Mechanisms and Concerted Effects of 5-HT Receptors Exemplified by the Multimodal Antidepressant Vortioxetine.

Science.gov (United States)

Leiser, Steven C; Li, Yan; Pehrson, Alan L; Dale, Elena; Smagin, Gennady; Sanchez, Connie

2015-07-15

It has been known for several decades that serotonergic neurotransmission is a key regulator of cognitive function, mood, and sleep. Yet with the relatively recent discoveries of novel serotonin (5-HT) receptor subtypes, as well as an expanding knowledge of their expression level in certain brain regions and localization on certain cell types, their involvement in cognitive processes is still emerging. Of particular interest are cognitive processes impacted in neuropsychiatric and neurodegenerative disorders. The prefrontal cortex (PFC) is critical to normal cognitive processes, including attention, impulsivity, planning, decision-making, working memory, and learning or recall of learned memories. Furthermore, serotonergic dysregulation within the PFC is implicated in many neuropsychiatric disorders associated with prominent symptoms of cognitive dysfunction. Thus, it is important to better understand the overall makeup of serotonergic receptors in the PFC and on which cell types these receptors mediate their actions. In this Review, we focus on 5-HT receptor expression patterns within the PFC and how they influence cognitive behavior and neurotransmission. We further discuss the net effects of vortioxetine, an antidepressant acting through multiple serotonergic targets given the recent findings that vortioxetine improves cognition by modulating multiple neurotransmitter systems.

Size-dependent mechanical properties of 2D random nanofibre networks

International Nuclear Information System (INIS)

Lu, Zixing; Zhu, Man; Liu, Qiang

2014-01-01

The mechanical properties of nanofibre networks (NFNs) are size dependent with respect to different fibre diameters. In this paper, a continuum model is developed to reveal the size-dependent mechanical properties of 2D random NFNs. Since such size-dependent behaviours are attributed to different micromechanical mechanisms, the surface effects and the strain gradient (SG) effects are, respectively, introduced into the mechanical analysis of NFNs. Meanwhile, a modified fibre network model is proposed, in which the axial, bending and shearing deformations are incorporated. The closed-form expressions of effective modulus and Poisson's ratio are obtained for NFNs. Different from the results predicted by conventional fibre network model, the present model predicts the size-dependent mechanical properties of NFNs. It is found that both surface effects and SG effects have significant influences on the effective mechanical properties. Moreover, the present results show that the shearing deformation of fibre segment is also crucial to precisely evaluate the effective mechanical properties of NFNs. This work mainly aims to provide an insight into the micromechanical mechanisms of NFNs. Besides, this work is also expected to provide a more accurate theoretical model for 2D fibre networks. (paper)

Structure-activity relationships studies on weakly basic N-arylsulfonylindoles with an antagonistic profile in the 5-HT6 receptor

Science.gov (United States)

Mella, Jaime; Villegas, Francisco; Morales-Verdejo, César; Lagos, Carlos F.; Recabarren-Gajardo, Gonzalo

2017-07-01

We recently reported a series of 39 weakly basic N-arylsulfonylindoles as novel 5-HT6 antagonists. Eight of the compounds exhibited moderate to high binding affinities, with 2-(4-(2-Methoxyphenyl)piperazin-1-yl)-1-(1-tosyl-1H-indol-3-yl)ethanol 16 showing the highest binding affinity (pKi = 7.87). Given these encouraging results and as a continuation of our research, we performed an extensive step-by-step search for the best 3D-QSAR model that allows us to rationally propose novel molecules with improved 5-HT6 affinity based on our previously reported series. A comparative molecular similarity indices analysis (CoMSIA) model built on a docking-based alignment was developed, wherein steric, electrostatic, hydrophobic and hydrogen bond properties are correlated with biological activity. The model was validated internally and externally (q2 = 0.721; r2pred = 0.938), and identified the sulfonyl and hydroxyl groups and the piperazine ring among the main regions of the molecules that can be modified to create new 5-HT6 antagonists.

The Effects of Bifidobacterium breve on Immune Mediators and Proteome of HT29 Cells Monolayers

Directory of Open Access Journals (Sweden)

Borja Sánchez

2015-01-01

Full Text Available The use of beneficial microorganisms, the so-called probiotics, to improve human health is gaining popularity. However, not all of the probiotic strains trigger the same responses and they differ in their interaction with the host. In spite of the limited knowledge on mechanisms of action some of the probiotic effects seem to be exerted through maintenance of the gastrointestinal barrier function and modulation of the immune system. In the present work, we have addressed in vitro the response of the intestinal epithelial cell line HT29 to the strain Bifidobacterium breve IPLA20004. In the array of 84 genes involved in inflammation tested, the expression of 12 was modified by the bifidobacteria. The genes of chemokine CXCL6, the chemokine receptor CCR7, and, specially, the complement component C3 were upregulated. Indeed, HT29 cells cocultivated with B. breve produced significantly higher levels of protein C3a. The proteome of HT29 cells showed increased levels of cytokeratin-8 in the presence of B. breve. Altogether, it seems that B. breve IPLA20004 could favor the recruitment of innate immune cells to the mucosa reinforcing, as well as the physical barrier of the intestinal epithelium.

Differential effects of centrally-active antihypertensives on 5-HT1A receptors in rat dorso-lateral septum, rat hippocampus and guinea-pig hippocampus.

Science.gov (United States)

Leishman, D J; Boeijinga, P H; Galvan, M

1994-01-01

1. The electrophysiological responses elicited by 5-hydroxytryptamine1A-(5-HT1A) receptor agonists in rat and guinea-pig CA1 pyramidal neurones and rat dorso-lateral septal neurones were compared in vitro by use of conventional intracellular recording techniques. 2. In the presence of 1 microM tetrodotoxin (TTX), to prevent indirect effects, 5-HT, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT) hyperpolarized the neurones from rat and guinea-pig brain. 3. The hypotensive drug flesinoxan, a selective 5-HT1A receptor agonist, hyperpolarized neurones in all three areas tested; however, another hypotensive agent with high affinity at 5-HT1A-receptors, 5-methyl-urapidil, hyperpolarized only the neurones in rat hippocampus and septum. 4. In guinea-pig hippocampal neurones, 5-methyl-urapidil behaved as a 5-HT1A-receptor antagonist. 5. The relative efficacies (5-HT = 1) of DP-5-CT, 8-OH-DPAT, flesinoxan and 5-methyl-urapidil at the three sites were: rat hippocampus, 1.09, 0.7, 0.5 and 0.24; rat septum, 0.88, 0.69, 0.82 and 0.7; guinea-pig hippocampus, 1.0, 0.69, 0.89 and 0, respectively. 6. It is concluded that the hypotensive agents flesinoxan and 5-methyl-urapidil appear to have different efficacies at 5-HT1A receptors located in different regions of the rodent brain. Whether these regional and species differences arise from receptor plurality or variability in intracellular transduction mechanisms remains to be elucidated.

Adhesion properties of inverted polymer solarcells: Processing and film structure parameters

KAUST Repository

Dupont, Stephanie R.

2013-05-01

We report on the adhesion of weak interfaces in inverted P3HT:PCBM-based polymer solar cells (OPV) with either a conductive polymer, PEDOT:PSS, or a metal oxide, molybdenum trioxide (MoO3), as the hole transport layer. The PEDOT:PSS OPVs were prepared by spin or spray coating on glass substrates, or slot-die coating on flexible PET substrates. In all cases, we observed adhesive failure at the interface between the P3HT:PCBM with PEDOT:PSS layer. The adhesion energy measured for the solar cells made on glass substrates was about 1.8 J/m2, but only 0.5 J/m2 for the roll-to-roll processed flexible solar cells. The adhesion energy was insensitive to the PEDOT:PSS layer thickness in the range of 10-40 nm. A marginal increase in adhesion energy was measured with increased O2 plasma power. Compared to solution processed PEDOT:PSS, we found that thermally evaporated MoO 3 adheres less to the P3HT:PCBM layer, which we attributed to the reduced mixing at the MoO3/P3HT:PCBM interface during the thermal evaporation process. Insights into the mechanisms of delamination and the effect of different material properties and processing parameters yield general guidelines for the design of more reliable organic photovoltaic devices.© 2013 Elsevier B.V. All rights reserved.

Adhesion properties of inverted polymer solarcells: Processing and film structure parameters

KAUST Repository

Dupont, Stephanie R.; Voroshazi, Eszter; Heremans, Paul; Dauskardt, Reinhold H.

2013-01-01

We report on the adhesion of weak interfaces in inverted P3HT:PCBM-based polymer solar cells (OPV) with either a conductive polymer, PEDOT:PSS, or a metal oxide, molybdenum trioxide (MoO3), as the hole transport layer. The PEDOT:PSS OPVs were prepared by spin or spray coating on glass substrates, or slot-die coating on flexible PET substrates. In all cases, we observed adhesive failure at the interface between the P3HT:PCBM with PEDOT:PSS layer. The adhesion energy measured for the solar cells made on glass substrates was about 1.8 J/m2, but only 0.5 J/m2 for the roll-to-roll processed flexible solar cells. The adhesion energy was insensitive to the PEDOT:PSS layer thickness in the range of 10-40 nm. A marginal increase in adhesion energy was measured with increased O2 plasma power. Compared to solution processed PEDOT:PSS, we found that thermally evaporated MoO 3 adheres less to the P3HT:PCBM layer, which we attributed to the reduced mixing at the MoO3/P3HT:PCBM interface during the thermal evaporation process. Insights into the mechanisms of delamination and the effect of different material properties and processing parameters yield general guidelines for the design of more reliable organic photovoltaic devices.© 2013 Elsevier B.V. All rights reserved.

Nanostructured thin films and coatings mechanical properties

CERN Document Server

2010-01-01

The first volume in "The Handbook of Nanostructured Thin Films and Coatings" set, this book concentrates on the mechanical properties, such as hardness, toughness, and adhesion, of thin films and coatings. It discusses processing, properties, and performance and provides a detailed analysis of theories and size effects. The book presents the fundamentals of hard and superhard nanocomposites and heterostructures, assesses fracture toughness and interfacial adhesion strength of thin films and hard nanocomposite coatings, and covers the processing and mechanical properties of hybrid sol-gel-derived nanocomposite coatings. It also uses nanomechanics to optimize coatings for cutting tools and explores various other coatings, such as diamond, metal-containing amorphous carbon nanostructured, and transition metal nitride-based nanolayered multilayer coatings.