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Sample records for at1 receptor supports

  1. AT1 receptors as mechanosensors.

    Science.gov (United States)

    Mederos y Schnitzler, Michael; Storch, Ursula; Gudermann, Thomas

    2011-04-01

    G-protein-coupled receptors are appreciated as central components of neurohormonal signaling. Recently, it turned out that they may also play a role in mechanotransduction. The angiotensin II AT(1) receptor was the first G-protein-coupled receptor claimed to be a mechanosensor. In the meantime, several other G(q/11)-coupled receptors were found to be sensitive to mechanical stimuli. Furthermore, there is first evidence to support the concept that G(i/o)-coupled receptors are susceptible to mechanical stimulation as well. Mechanical receptor activation appears to be agonist-independent and is initiated by a conformational change of the receptor protein discernible from agonist-bound conformations. Mechanically induced receptor activation plays a physiological role for myogenic vasoconstriction and is involved in the pathogenesis of cardiac hypertrophy. PMID:21147033

  2. The human angiotensin AT(1) receptor supports G protein-independent extracellular signal-regulated kinase 1/2 activation and cellular proliferation

    DEFF Research Database (Denmark)

    Hansen, Jakob Lerche; Aplin, Mark; Hansen, Jonas Tind; Christensen, Gitte Lund; Bonde, Marie Mi; Schneider, Mikael; Haunsø, Stig; Schiffer, Hans H; Burstein, Ethan S; Weiner, David M; Sheikh, Søren P

    AT(1) receptor signalling is illustrated by the common use of angiotensin AT(1) receptor-inverse agonists in clinical practice. It is well established that rodent orthologues of the angiotensin AT(1) receptor can selectively signal through G protein-dependent and -independent mechanisms in......(1) receptor actions. However, it is currently unknown whether the human angiotensin AT(1) receptor can signal through G protein-independent mechanisms - and if so, what the physiological impact of such signalling is. We have performed a detailed pharmacological analysis of the human angiotensin AT(1......) receptor using a battery of angiotensin analogues and registered drugs targeting this receptor. We show that the human angiotensin AT(1) receptor signals directly through G protein-independent pathways and supports NIH3T3 cellular proliferation. The realization of G protein-independent signalling by the...

  3. Cerebral ischemia enhances vascular angiotensin AT1 receptor-mediated contraction in rats

    DEFF Research Database (Denmark)

    Stenman, Emelie; Edvinsson, Lars

    2004-01-01

    MCA occlusion (P<0.05). The angiotensin II type 1 (AT1) receptor antagonists candesartan and losartan abolished the enhanced responses to angiotensin II (P<0.05), whereas the AT2 receptor antagonist PD123319 had no effect. The amount of AT1 receptor mRNA was lower in the occluded MCAs compared with....... These results support a role for AT1 receptors in cerebral ischemia, and we think that AT1 receptors might be a future therapeutic target in ischemic stroke....

  4. Cerebrovascular angiotensin AT1 receptor regulation in cerebral ischemia

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2008-01-01

    The mechanism behind the positive response to the inhibition of the angiotensin II receptor AT(1) in conjunction with stroke is elusive. Here we demonstrate that cerebrovascular AT(1) receptors show increased expression (upregulation) after cerebral ischemia via enhanced translation. This enhanced...

  5. Increased angiotensin II AT(1) receptor expression in paraventricular nucleus and hypothalamic-pituitary-adrenal axis stimulation in AT(2) receptor gene disrupted mice.

    Science.gov (United States)

    Armando, Inés; Terrón, José A; Falcón-Neri, Alicia; Takeshi, Ito; Häuser, Walter; Inagami, Tadashi; Saavedra, Juan M

    2002-09-01

    Angiotensin II AT(2) receptor gene-disrupted mice have increased blood pressure and response to angiotensin II, behavioral alterations, greater response to stress, and increased adrenal AT(1) receptors. We studied hypothalamic AT(1) receptor binding and mRNA by receptor autoradiography and in situ hybridization, adrenal catecholamines by HPLC, adrenal tyrosine hydroxylase mRNA by in situ hybridization and pituitary and adrenal hormones by RIA in AT(2) receptor-gene disrupted mice and wild-type controls. To confirm the role of adrenal AT(1) receptors, we treated wild-type C57 BL/6J mice with the AT(1) antagonist candesartan for 2 weeks, and measured adrenal hormones, catecholamines and tyrosine hydroxylase mRNA. In the absence of AT(2) receptor transcription, we found increased AT(1) receptor binding in brain areas involved in the regulation of the hypothalamic-pituitary-adrenal axis, the hypothalamic paraventricular nucleus and the median eminence, and increased adrenal catecholamine synthesis as shown by higher adrenomedullary tyrosine hydroxylase mRNA and higher adrenal dopamine, norepinephrine and epinephrine levels when compared to wild-type mice. In addition, in AT(2) receptor gene-disrupted mice there were higher plasma adrenocorticotropin (ACTH) and corticosterone levels and lower adrenal aldosterone content when compared to wild-type controls. Conversely, AT(1) receptor inhibition in CB57 BL/6J mice reduced adrenal tyrosine hydroxylase mRNA and catecholamine content and increased adrenal aldosterone content. These results can help to explain the enhanced response of AT(2) receptor gene-disrupted mice to exogenous angiotensin II, support the hypothesis of cross-talk between AT(1) and AT(2) receptors, indicate that the activity of the hypothalamic-pituitary-adrenal axis parallels the AT(1) receptor expression, and suggest that expression of AT(1) receptors can be dependent on AT(2) receptor expression. Our results provide an explanation for the increased

  6. Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury

    DEFF Research Database (Denmark)

    Hostrup, Anders; Christensen, Gitte Lund; Bentzen, Bo Hjort; Liang, Bo; Aplin, Mark; Grunnet, Morten; Hansen, Jakob Lerche; Jespersen, Thomas

    2012-01-01

    physiological functions of AngII. The AT(1)R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the ß-arrestin biased agonist [SII]AngII on ischemia......-reperfusion injury in rat hearts. Isolated hearts mounted in a Langendorff perfused rat heart preparations showed that preconditioning with [SII]AngII reduced the infarct size induced by global ischemia from 46±8.4% to 22±3.4%. In contrast, neither preconditioning with AngII nor postconditioning with AngII or [SII...

  7. Angiotensin II AT1 receptor blockers as treatments for inflammatory brain disorders

    OpenAIRE

    Saavedra, Juan M.

    2012-01-01

    The effects of brain AngII (angiotensin II) depend on AT1 receptor (AngII type 1 receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT1 receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood–brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurod...

  8. Significance of AT1 receptor independent activation of mineralocorticoid receptor in murine diabetic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Yuji Nagatomo

    Full Text Available BACKGROUND: Diabetes mellitus (DM has deleterious influence on cardiac performance independent of coronary artery disease and hypertension. The objective of the present study was to investigate the role of the renin-angiotensin-aldosterone system, especially angiotensin II type 1a receptor (AT1aR and mineralocorticoid receptor (MR signaling, in left ventricular (LV dysfunction induced by diabetes mellitus (DM. METHODS AND RESULTS: DM was induced by intraperitoneal injection of streptozotocin (200 mg/kg BW in wild-type (WT or AT1aR knockout (KO male mice, and they were bred during 6 or 12 weeks. Some KO mice were administered the MR antagonist eplerenone (100 mg/kg body weight. At 6 weeks, LV diastolic function was impaired in WT-DM, but preserved in KO-DM. At that time point MR mRNA expression was upregulated, NADPH oxidase subunit (p47phox and glutathione peroxidase (GPx1 mRNA expression were upregulated, the staining intensities of LV tissue for 4-hydroxy-2-nonenal was stronger in immunohistochemistry, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL positive cells was increased, Bcl-2 protein expression was significantly downregulated, and the expression of SERCA2a and phosphorylated phospholamban was depressed in WT-DM, while these changes were not seen in KO-DM. At 12 weeks, however, these changes were also noted in KO-DM. Eplerenone arrested those changes. The plasma aldosterone concentration was elevated in WT-DM but not in KO-DM at 6 weeks. It showed 3.7-fold elevation at 12 weeks even in KO-DM, which suggests "aldosterone breakthrough" phenomenon. However, the aldosterone content in LV tissue was unchanged in KO-DM. CONCLUSIONS: DM induced diastolic dysfunction was observed even in KO at 12 weeks, which was ameliorated by minelarocorticoid receptor antagonist, eplerenone. AT1-independent MR activation in the LV might be responsible for the pathogenesis of diabetic cardiomyopathy.

  9. Immunohistochemical Localization of AT1a, AT1b, and AT2 Angiotensin II Receptor Subtypes in the Rat Adrenal, Pituitary, and Brain with a Perspective Commentary

    Directory of Open Access Journals (Sweden)

    Courtney Premer

    2013-01-01

    Full Text Available Angiotensin II increases blood pressure and stimulates thirst and sodium appetite in the brain. It also stimulates secretion of aldosterone from the adrenal zona glomerulosa and epinephrine from the adrenal medulla. The rat has 3 subtypes of angiotensin II receptors: AT1a, AT1b, and AT2. mRNAs for all three subtypes occur in the adrenal and brain. To immunohistochemically differentiate these receptor subtypes, rabbits were immunized with C-terminal fragments of these subtypes to generate receptor subtype-specific antibodies. Immunofluorescence revealed AT1a and AT2 receptors in adrenal zona glomerulosa and medulla. AT1b immunofluorescence was present in the zona glomerulosa, but not the medulla. Ultrastructural immunogold labeling for the AT1a receptor in glomerulosa and medullary cells localized it to plasma membrane, endocytic vesicles, multivesicular bodies, and the nucleus. AT1b and AT2, but not AT1a, immunofluorescence was observed in the anterior pituitary. Stellate cells were AT1b positive while ovoid cells were AT2 positive. In the brain, neurons were AT1a, AT1b, and AT2 positive, but glia was only AT1b positive. Highest levels of AT1a, AT1b, and AT2 receptor immunofluorescence were in the subfornical organ, median eminence, area postrema, paraventricular nucleus, and solitary tract nucleus. These studies complement those employing different techniques to characterize Ang II receptors.

  10. The physiological role of AT1 receptors in the ventrolateral medulla

    Directory of Open Access Journals (Sweden)

    T. Tagawa

    2000-06-01

    Full Text Available Neurons in the rostral and caudal parts of the ventrolateral medulla (VLM play a pivotal role in the regulation of sympathetic vasomotor activity and blood pressure. Studies in several species, including humans, have shown that these regions contain a high density of AT1 receptors specifically associated with neurons that regulate the sympathetic vasomotor outflow, or the secretion of vasopressin from the hypothalamus. It is well established that specific activation of AT1 receptors by application of exogenous angiotensin II in the rostral and caudal VLM excites sympathoexcitatory and sympathoinhibitory neurons, respectively, but the physiological role of these receptors in the normal synaptic regulation of VLM neurons is not known. In this paper we review studies which have defined the effects of specific activation or blockade of these receptors on cardiovascular function, and discuss what these findings tell us with regard to the physiological role of AT1 receptors in the VLM in the tonic and phasic regulation of sympathetic vasomotor activity and blood pressure.

  11. Angiotensin II AT(1) receptor blockers as treatments for inflammatory brain disorders.

    Science.gov (United States)

    Saavedra, Juan M

    2012-11-01

    The effects of brain AngII (angiotensin II) depend on AT(1) receptor (AngII type 1 receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT(1) receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood-brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurodegerative, mood and traumatic brain disorders, and cognitive decline. In rodents, ARBs (AT(1) receptor blockers) ameliorate stress-induced disorders, anxiety and depression, protect cerebral blood flow during stroke, decrease brain inflammation and amyloid-β neurotoxicity and reduce traumatic brain injury. Direct anti-inflammatory protective effects, demonstrated in cultured microglia, cerebrovascular endothelial cells, neurons and human circulating monocytes, may result not only in AT(1) receptor blockade, but also from PPARγ (peroxisome-proliferator-activated receptor γ) stimulation. Controlled clinical studies indicate that ARBs protect cognition after stroke and during aging, and cohort analyses reveal that these compounds significantly reduce the incidence and progression of Alzheimer's disease. ARBs are commonly used for the therapy of hypertension, diabetes and stroke, but have not been studied in the context of neurodegenerative, mood or traumatic brain disorders, conditions lacking effective therapy. These compounds are well-tolerated pleiotropic neuroprotective agents with additional beneficial cardiovascular and metabolic profiles, and their use in central nervous system disorders offers a novel therapeutic approach of immediate translational value. ARBs should be tested for the prevention and therapy of neurodegenerative disorders, in particular Alzheimer's disease, affective disorders, such as co-morbid cardiovascular disease and depression, and traumatic

  12. The angiotensin II-AT1 receptor stimulates reactive oxygen species within the cell nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Pendergrass, Karl D.; Gwathmey, TanYa M. [The Hypertension and Vascular Research Center, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States); Michalek, Ryan D.; Grayson, Jason M. [Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157 (United States); Chappell, Mark C., E-mail: mchappel@wfubmc.edu [The Hypertension and Vascular Research Center, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States)

    2009-06-26

    We and others have reported significant expression of the Ang II Type 1 receptor (AT1R) on renal nuclei; thus, the present study assessed the functional pathways and distribution of the intracellular AT1R on isolated nuclei. Ang II (1 nM) stimulated DCF fluorescence, an intranuclear indicator of reactive oxygen species (ROS), while the AT1R antagonist losartan or the NADPH oxidase (NOX) inhibitor DPI abolished the increase in ROS. Dual labeling of nuclei with antibodies against nucleoporin 62 (Nup62) and AT1R or the NADPH oxidase isoform NOX4 revealed complete overlap of the Nup62 and AT1R (99%) by flow cytometry, while NOX4 was present on 65% of nuclei. Treatment of nuclei with a PKC agonist increased ROS while the PKC inhibitor GF109203X or PI3 kinase inhibitor LY294002 abolished Ang II stimulation of ROS. We conclude that the Ang II-AT1R-PKC axis may directly influence nuclear function within the kidney through a redox sensitive pathway.

  13. Expression of a naturally occurring angiotensin AT1 receptor cleavage fragment elicits caspase-activation and apoptosis

    OpenAIRE

    Cook, Julia L.; Singh, Akannsha; DeHaro, Dawn; Alam, Jawed; Re, Richard N.

    2011-01-01

    Several transmembrane receptors are documented to accumulate in nuclei, some as holoreceptors and others as cleaved receptor products. Our prior studies indicate that a population of the 7-transmembrane angiotensin type-1 receptor (AT1R) is cleaved in a ligand-augmented manner after which the cytoplasmic, carboxy-terminal cleavage fragment (CF) traffics to the nucleus. In the present report, we determine the precise cleavage site within the AT1R by mass spectrometry and Edman sequencing. Clea...

  14. Enhanced water and salt intake in transgenic mice with brain-restricted overexpression of angiotensin (AT1) receptors

    OpenAIRE

    Lazartigues, Eric; Sinnayah, Puspha; Augoyard, Ginette; Gharib, Claude; Johnson, Alan Kim; Davisson, Robin L.

    2008-01-01

    To address the relative contribution of central and peripheral angiotensin II (ANG II) type 1A receptors (AT1A) to blood pressure and volume homeostasis, we generated a transgenic mouse model [neuron-specific enolase (NSE)-AT1A] with brain-restricted overexpression of AT1A receptors. These mice are normotensive at baseline but have dramatically enhanced pressor and bradycardic responses to intracerebroventricular ANG II or activation of endogenous ANG II production. Here our goal was to exami...

  15. The potential role of AT(1)-receptor blockade in the prevention and reversal of atherosclerosis.

    Science.gov (United States)

    Papademetriou, V

    2002-08-01

    The renin-angiotensin system may contribute to the development and progression of atherosclerosis both by increasing blood pressure and by direct effects on all phases of the atherogenic process. Genetic determinants of renin-angiotensin system activation, notably the DD genotype of angiotensin converting enzyme (ACE), are associated with an increased risk of cardiovascular events, as is increased plasma renin activity. In addition, angiotensin II has been shown to increase the uptake and oxidation of low density lipoprotein (LDL) by macrophages and endothelial cells. Angiotensin II also stimulates the production of interleukin 6 and activates the pro-inflammatory factor nuclear factor kappa(B), leading to expression of adhesion molecules and recruitment of monocytes and macrophages, and increases the production of pro-coagulatory factors. In animal experiments, treatment with ACE inhibitors or angiotensin AT(1)-receptor blockers has been shown to have anti-atherogenic effects. Studies with candesartan have shown that this agent produces a dose-dependent reduction in uptake of oxidised LDL by mouse macrophages in vitro, and reduces cholesterol accumulation and atherosclerosis development in the aorta of Watanabe rabbits. These effects were independent of changes in blood pressure. Such findings suggest that AT(1)-receptor blockers may be beneficial in reducing mortality and morbidity resulting from atherosclerotic disease, and are consistent with the findings from large outcome trials with ACE inhibitors in patients at risk of cardiovascular events. PMID:12140726

  16. Angiotensin AT1-receptor blockers and cerebrovascular protection: do they actually have a cutting edge over angiotensin-converting enzyme inhibitors?

    DEFF Research Database (Denmark)

    Oprisiu-Fournier, Roxana; Faure, Sébastien; Mazouz, Hakim;

    2009-01-01

    is presented to support the hypothesis that antihypertensive drugs that increase angiotensin II formation, such as diuretics, AT1-receptor blockers and dihydropyridines, may have greater brain anti-ischemic effects than antihypertensive drugs that decrease angiotensin II formation, such as beta-blockers...

  17. Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications.

    Science.gov (United States)

    Saavedra, Juan M; Sánchez-Lemus, Enrique; Benicky, Julius

    2011-01-01

    Poor adaptation to stress, alterations in cerebrovascular function and excessive brain inflammation play critical roles in the pathophysiology of many psychiatric and neurological disorders such as major depression, schizophrenia, post traumatic stress disorder, Parkinson's and Alzheimer's diseases and traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of major importance. Recently, attention has been focused on the role of a brain regulatory peptide, Angiotensin II, and in the translational value of the blockade of its physiological AT(1) receptors. In addition to its well-known cardiovascular effects, Angiotensin II, through AT(1) receptor stimulation, is a pleiotropic brain modulatory factor involved in the control of the reaction to stress, in the regulation of cerebrovascular flow and the response to inflammation. Excessive brain AT(1) receptor activity is associated with exaggerated sympathetic and hormonal response to stress, vulnerability to cerebrovascular ischemia and brain inflammation, processes leading to neuronal injury. In animal models, inhibition of brain AT(1) receptor activity with systemically administered Angiotensin II receptor blockers is neuroprotective; it reduces exaggerated stress responses and anxiety, prevents stress-induced gastric ulcerations, decreases vulnerability to ischemia and stroke, reverses chronic cerebrovascular inflammation, and reduces acute inflammatory responses produced by bacterial endotoxin. These effects protect neurons from injury and contribute to increase the lifespan. Angiotensin II receptor blockers are compounds with a good margin of safety widely used in the treatment of hypertension and their anti-inflammatory and vascular protective effects contribute to reduce renal and cardiovascular failure. Inhibition of brain AT(1) receptors in humans is also neuroprotective

  18. Angiotensin II (AT1) Receptor Blockade Reduces Vascular Tissue Factor in Angiotensin II-Induced Cardiac Vasculopathy

    OpenAIRE

    Dominik N Müller; Mervaala, Eero M A; Dechend, Ralf; Fiebeler, Anette; Park, Joon-Keun; Schmidt, Folke; Theuer, Jürgen; Breu, Volker; Mackman, Nigel; Luther, Thomas; Schneider, Wolfgang; Gulba, Dietrich; Ganten, Detlev; Haller, Hermann; Luft, Friedrich C.

    2000-01-01

    Tissue factor (TF), a main initiator of clotting, is up-regulated in vasculopathy. We tested the hypothesis that chronic in vivo angiotensin (ANG) II receptor AT1 receptor blockade inhibits TF expression in a model of ANG II-induced cardiac vasculopathy. Furthermore, we explored the mechanisms by examining transcription factor activation and analyzing the TF promoter. Untreated transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR) feature hypertension and severe left...

  19. The effects of repeated delivery of angiotensin II AT1 receptor antisense on distinct vasoactive systems in Ren-2 transgenic rats: young vs. adult animals

    Czech Academy of Sciences Publication Activity Database

    Vaněčková, Ivana; Dobešová, Zdenka; Kuneš, Jaroslav; Zicha, Josef

    2012-01-01

    Roč. 35, č. 7 (2012), s. 761-768. ISSN 0916-9636 R&D Projects: GA AV ČR(CZ) IAA500110902; GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : AT(1) receptor * BP regulation * gene therapy * oligodeoxynucleotides * vasodilator and vasoconstrictor systems Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.791, year: 2012

  20. Estimation of the number of angiotensin II AT1 receptors in rat kidney afferent and efferent arterioles

    DEFF Research Database (Denmark)

    Razga, Zsolt; Nyengaard, Jens Randel

    2007-01-01

    OBJECTIVE: To examine the effects of the renin-angiotensin system (RAS) on renal arterioles to determine the association between the distribution of angiotensin II AT1 receptors and the morphologic and physiologic heterogeneity of renal arterioles. STUDY DESIGN: To estimate the number of angioten...

  1. Curcumin Exerts its Anti-hypertensive Effect by Down-regulating the AT1 Receptor in Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Yao, Yonggang; Wang, Wei; Li, Meixiang; Ren, Hongmei; Chen, Caiyu; Wang, Jialiang; Wang, Wei Eric; Yang, Jian; Zeng, Chunyu

    2016-01-01

    Curcumin exerts beneficial effects on cardiovascular diseases, including hypertension. However, its mechanisms are unknown. We propose that curcumin prevents the development of hypertension by regulating AT1 receptor (AT1R) expression in arteries. The present study examined how curcumin regulates AT1R expression in vascular smooth muscle cells and investigated the physiological significance of this regulation in angiotensin (Ang) II-induced hypertension. The results showed that curcumin decreased AT1R expression in a concentration- and time-dependent manner in vascular smooth muscle cells. Using luciferase reporters with an entire AT1 or a mutant AT1R in A10 cells, the AT1R promoter activity was inhibited by 10(-6 )M curcumin, and the proximal element (from -61 to +25 bp) of the AT1R promoter was crucial for curcumin-induced AT1R down-regulation. An electrophoretic mobility shift assay showed that curcumin decreased specificity protein 1 (SP1) binding with the AT1R promoter in A10 cells. Curcumin treatment reduced Ang II-induced hypertension in C57Bl/6J mice, which was accompanied by lower AT1R expression in the arteries and decreased Ang II-mediated vasoconstriction in the mesenteric artery. These findings indicate that curcumin down-regulates AT1R expression in A10 cells by affecting SP1/AT1R DNA binding, thus reducing AT1R-mediated vasoconstriction and subsequently prevents the development of hypertension in an Ang II-induced hypertensive model. PMID:27146402

  2. Curcumin Exerts its Anti-hypertensive Effect by Down-regulating the AT1 Receptor in Vascular Smooth Muscle Cells

    Science.gov (United States)

    Yao, Yonggang; Wang, Wei; Li, Meixiang; Ren, Hongmei; Chen, Caiyu; Wang, Jialiang; Wang, Wei Eric; Yang, Jian; Zeng, Chunyu

    2016-01-01

    Curcumin exerts beneficial effects on cardiovascular diseases, including hypertension. However, its mechanisms are unknown. We propose that curcumin prevents the development of hypertension by regulating AT1 receptor (AT1R) expression in arteries. The present study examined how curcumin regulates AT1R expression in vascular smooth muscle cells and investigated the physiological significance of this regulation in angiotensin (Ang) II-induced hypertension. The results showed that curcumin decreased AT1R expression in a concentration- and time-dependent manner in vascular smooth muscle cells. Using luciferase reporters with an entire AT1 or a mutant AT1R in A10 cells, the AT1R promoter activity was inhibited by 10−6 M curcumin, and the proximal element (from −61 to +25 bp) of the AT1R promoter was crucial for curcumin-induced AT1R down-regulation. An electrophoretic mobility shift assay showed that curcumin decreased specificity protein 1 (SP1) binding with the AT1R promoter in A10 cells. Curcumin treatment reduced Ang II-induced hypertension in C57Bl/6J mice, which was accompanied by lower AT1R expression in the arteries and decreased Ang II-mediated vasoconstriction in the mesenteric artery. These findings indicate that curcumin down-regulates AT1R expression in A10 cells by affecting SP1/AT1R DNA binding, thus reducing AT1R-mediated vasoconstriction and subsequently prevents the development of hypertension in an Ang II-induced hypertensive model. PMID:27146402

  3. ANG Ⅱ-AT1 Receptor Pathway Is Involved in the Anti-fibrotic Effect of β-elemene

    Institute of Scientific and Technical Information of China (English)

    Rui ZHU; Ling YANG; Lin SHEN; Jin YE; Jianguo LIU; Shenjun HU

    2009-01-01

    To investigate the effects of β-elemene on the ANG β -AT1 receptor pathway in rats with liver fibrosis,a model of hepatic fibrosis was induced by hypodermical injection of carbon tetrachloride (CCl4) into Wistar male rats.β-elemene was intraperitonealy administered into the rats for 8 weeks (0.1 mL/100 g body weight per day).Masson staining was used to observe the liver fibrosis of rats and liver functions were measured by enzymatic kinetic analysis.The content of hydroxyproline in liver tissues was detected by specimen alkaline hydrolysis.The level of plasma ANG Ⅱ in bloodplasma was detected by radioimmunoassay.The expression of AT1R in rat liver were measured using reverse transcriptional-polymerase chain reaction and immunohistochemistry respectively.The results showed that β-elemene could reduce the collagen disposition in liver and inhibit the progression of liver fibrosis.In addition,the levels of plasma ANG Ⅱ and the expression of hepatic AT1R in rats with liver fibrosis were also suppressed by β-elemene.It is concluded that the ANG Ⅱ -AT1 receptor pathway plays an important role in the development of hepatic fibrosis and β-elemene could down-regulate the levels of plasma ANG Ⅱ and the expression of hepatic AT1R in rats with liver fibrosis.

  4. A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor

    International Nuclear Information System (INIS)

    Highlights: → A new FRET-based method detects AT1/B2 receptor heterodimerization. → First time application of AT1-Cerulean as a FRET donor. → Method relies on signal peptide-enhanced cell surface delivery of AT1-Cerulean. → A high FRET efficiency revealed efficient heterodimerization of AT1/B2R proteins. → AT1/B2R heterodimers were functionally coupled to desensitization mechanisms. -- Abstract: Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R heterodimerization, confocal FRET imaging of

  5. A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Quitterer, Ursula, E-mail: ursula.quitterer@pharma.ethz.ch [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland); Pohl, Armin; Langer, Andreas; Koller, Samuel; AbdAlla, Said [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland)

    2011-06-10

    Highlights: {yields} A new FRET-based method detects AT1/B2 receptor heterodimerization. {yields} First time application of AT1-Cerulean as a FRET donor. {yields} Method relies on signal peptide-enhanced cell surface delivery of AT1-Cerulean. {yields} A high FRET efficiency revealed efficient heterodimerization of AT1/B2R proteins. {yields} AT1/B2R heterodimers were functionally coupled to desensitization mechanisms. -- Abstract: Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R

  6. Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency

    Directory of Open Access Journals (Sweden)

    Xuejun Yang

    2014-01-01

    Full Text Available Objective: To observe the efficacy of Shenxinning Decoction (SXND in ventricular remodeling in AT1 receptor-knockout (AT1-KO mice with chronic renal insufficiency (CRI. Materials and Methods: AT1-KO mice modeled with subtotal (5/6 nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN, serum creatinine (SCr, brain natriuretic peptide (BNP, echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF, collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1 of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. Results: AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice′s BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. Conclusion: SXND may antagonize the renin-angiotensin system (RAS and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1.

  7. AT1 receptor induced alterations in histone H2A reveal novel insights into GPCR control of chromatin remodeling.

    Directory of Open Access Journals (Sweden)

    Rajaganapathi Jagannathan

    Full Text Available Chronic activation of angiotensin II (AngII type 1 receptor (AT(1R, a prototypical G protein-coupled receptor (GPCR induces gene regulatory stress which is responsible for phenotypic modulation of target cells. The AT(1R-selective drugs reverse the gene regulatory stress in various cardiovascular diseases. However, the molecular mechanisms are not clear. We speculate that activation states of AT(1R modify the composition of histone isoforms and post-translational modifications (PTM, thereby alter the structure-function dynamics of chromatin. We combined total histone isolation, FPLC separation, and mass spectrometry techniques to analyze histone H2A in HEK293 cells with and without AT(1R activation. We have identified eight isoforms: H2AA, H2AG, H2AM, H2AO, H2AQ, Q96QV6, H2AC and H2AL. The isoforms, H2AA, H2AC and H2AQ were methylated and H2AC was phosphorylated. The relative abundance of specific H2A isoforms and PTMs were further analyzed in relationship to the activation states of AT(1R by immunochemical studies. Within 2 hr, the isoforms, H2AA/O exchanged with H2AM. The monomethylated H2AC increased rapidly and the phosphorylated H2AC decreased, thus suggesting that enhanced H2AC methylation is coupled to Ser1p dephosphorylation. We show that H2A125Kme1 promotes interaction with the heterochromatin associated protein, HP1α. These specific changes in H2A are reversed by treatment with the AT(1R specific inhibitor losartan. Our analysis provides a first step towards an awareness of histone code regulation by GPCRs.

  8. Modelling of absorption, distribution and physicochemical properties of AT1 receptor antagonists / Modelovanie absorpcie, distribúcie a fyzikálnochemických vlastnosti antagonistov AT1 receptorov

    Directory of Open Access Journals (Sweden)

    Ježko Pavol

    2015-12-01

    Full Text Available The theoretical chemistry methods were used to elucidate absorption, distribution and physicochemical properties of AT1 receptor antagonists and dual angiotensin II and endothelin A receptor antagonist (PS-433540. Computed partition coefficients (ALOGPS method studied for drugs varied between 2.98 and 6.66. Neutral compounds are described as lipophilic drugs. Telmisartan is a drug with the highest lipophilicity. The neutral forms of the studied AT1 receptor antagonists are practically insoluble in water, and their computed solubilities is in interval between 2.04 and 22.65 mg/l (ALOGpS method. The calculated pKa values for tetrazolyle moiety are in the range 3.92-5.00 and for carboxylic moiety 3.12-5.50. Telmisartan (polar surface area = 72.95 A and irbesartan (polar surface area = 87.14 A belong to the AT1 receptor antagonists with increased absorption.

  9. AT(1) receptor Gαq protein-independent signalling transcriptionally activates only a few genes directly, but robustly potentiates gene regulation from the β2-adrenergic receptor

    DEFF Research Database (Denmark)

    Christensen, Gitte Lund; Knudsen, Steen; Schneider, Mikael; Aplin, Mark; Gammeltoft, Steen; Sheikh, Søren P; Hansen, Jakob L

    2011-01-01

    potentiated β2-adrenergic receptor-stimulated gene expression. These novel findings indicate that the Gαq protein-independent signalling mainly modifies the transcriptional response governed by other signalling pathways, while direct induction of gene expression by the AT(1)R is dependent on classical Gαq......-independent signalling from the AT(1)R interact with transcriptional regulators and promote phosphorylation of nuclear proteins. However, the relative contribution of Gαq protein-independent signalling in AT(1)R mediated transcriptional regulation remains elusive. We here present a comprehensive comparative analysis of...... Gαq protein-dependent and -independent regulation of AT(1)R mediated gene expression. We found angiotensin II to regulate 212 genes, whereas Gαq-independent signalling obtained with the biased agonist, SII angiotensin II only regulated few genes. Interestingly, SII angiotensin II, like Ang II vastly...

  10. AT1a Receptor Has Interacted with Angiotensin-converting Enzymes 2 mRNA Expression in Mouse Brainstem

    Institute of Scientific and Technical Information of China (English)

    Zhanyi Lin; Shuguang Lin

    2008-01-01

    Objectives To examine in vivo interactions between angiotensin Ⅱ(Ang Ⅱ) AT1a receptor (AT1aR),angiotensin-converting enzymes (ACE) and ACE2 using small hairpin RNA (shRNA) gene-silencing methods in mice brainstem nucleus ttactus solitarius (NTS).Methods C57BL mice (n=8) were used as animal model.Method of microinjection in the nucleus of NTS was adopted.After ten days,mice were killed and their brain tissue were fixed and sectioned.The expression levels of AT1 aR,ACE and ACE2 mRNA at both sides of NTS were examined by in situ hybridization.Based on compared t-test,the changing for mRNA expression was examined.Results After the expression of AT1aR mRNA was significantly inhibited (61.6%±6.8% ) by AT1aR-shRNA,it was associated with decreases in ACE2 mRNA expression from (1.05±0.12) μCi/mg to (0.74±0.09) μCi/mg (29.0%±14.5%,P<0.01) on the same side of the brainstem.ACE mRNA expression was consistent at both sides (0.50 μCi/mg±0.09 μCi/mg and 0.53 μCi/mg±0.08 μCi/mg),with insignificant difference (P>0.05).Condusions The gene silencing result showed that there were interactions between brainstem AT1aR and ACE2.ACE mRNA expression was not altered by RNA interference treatment at AT1aR.

  11. Interaction of signal transduction between angiotensin AT1 and AT2 receptor subtypes in rat senescent heart

    Institute of Scientific and Technical Information of China (English)

    SHI Shu-tian; LI Yan-fang

    2007-01-01

    Background Angiotensin Ⅱ (Ang Ⅱ) acting at angiotensin AT1 receptor (AT1R) has well documented effects on cardiovascular structure such as the promotion of cardiovascular hypertrophy and fibrosis, which are believed to be opposed by angiotensin AT2 receptor (AT2R) stimulation. The expressions of AT1R and AT2R are up-regulated in senescent hearts. The purpose of this study was to investigate the interaction of signal transduction between AT1R and AT2R, and to detect whether there is any difference in the interaction in rat hearts of different age.Methods In 3.5-, 12-, 18- and 24-month-old rats, the heart cell membrane activities of protein kinase C (PKC) andtyrosine kinase were measured when AT1R and AT2R were both activated by Ang Ⅱ or just the AT1R was activated by Ang Ⅱ and PD123319. The activities of cytosolic phospholipase A2 (cPLA2) and the levels of cGMP were investigated when AT1R and AT2R were both activated by Ang Ⅱ or just the AT2R was activated by Ang Ⅱ and Iosartan.Results When AT1R and AT2R were both activated compared to when the AT1R was activated, the activities of PKC were not different in hearts from 3.5- and 12-month-old rats, but decreased significantly in 18- and 24-month-old rats; the activities of tyrosine kinase were not different in 3.5-month-old rats but decreased significantly in 12-, 18- and 24-month-old rats. The activities of cPLA2 were all decreased significantly in rats of different age when AT1R and AT2R were both activated compared to when the AT2R was activated. Treatment with Ang Ⅱ alone compared to Ang Ⅱ and losartan decreased the levels of cGMP (fmol/mg) in rats of different age (102.7±12.7 versus 86.0±8.0 in 3.5-month-old rats, P<0.05; 81.0±9.4 versus 70.0±6.3 in 12-month-old rats, P<0.05; 69.8±5.6 versus 54.2±5.3 in 18-month-old rats,P<0.01; 57.7±8.0 versus 39.0±3.0 in 24-month-old rats, P<0.01).Conclusions The activation of AT1R inhibited the signal transduction of AT2R during the aging

  12. AT1-IR-beta Association: A New Mechanism for the Inhibition of Insulin Receptor Function in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Lakshmi Pulakat

    2008-01-01

    Full Text Available Epidemiological evidence show that increased mortality in breast cancer is linked to hypertension and insulin resistance. Because Angiotensin II (Ang II, a hormone implicated in hypertension and insulin resistance, is a normal mitogen for breast tissue and elevated expression of the Ang II receptor AT1 is seen in breast cancer, we analyzed the effects of Ang II exposure on the functions of IR in human breast cancer cell line MCF-7. Exposure of MCF-7 to Ang II for 2 hours a significantly reduced 125I-insulin binding to IR, and b induced co-immuno-precipitation of the AT1 with IR-beta subunit. These Ang II-mediated effects on IR were inhibited by the AT1 antagonist losartan, and were not observed when exposure time was below 1-hour. These observations suggest extended exposure to Ang II have detrimental effects on insulin binding to IR that were not discovered in the previous studies where Ang II-exposure of insulin responsive cells was performed for periods less than one hour. In addition, they suggest a novel mechanism that involves AT1-IR-beta association for the inhibition of insulin binding to IR in response to extended exposure (2-hours of breast cancer cells to elevated levels of Ang II (as seen in hypertensive patients, and provides a molecular link for the inhibition of normal IR signaling by Ang II in breast cancer.

  13. Expression of a naturally occurring angiotensin AT(1) receptor cleavage fragment elicits caspase-activation and apoptosis.

    Science.gov (United States)

    Cook, Julia L; Singh, Akannsha; DeHaro, Dawn; Alam, Jawed; Re, Richard N

    2011-11-01

    Several transmembrane receptors are documented to accumulate in nuclei, some as holoreceptors and others as cleaved receptor products. Our prior studies indicate that a population of the 7-transmembrane angiotensin type-1 receptor (AT(1)R) is cleaved in a ligand-augmented manner after which the cytoplasmic, carboxy-terminal cleavage fragment (CF) traffics to the nucleus. In the present report, we determine the precise cleavage site within the AT(1)R by mass spectrometry and Edman sequencing. Cleavage occurs between Leu(305) and Gly(306) at the junction of the seventh transmembrane domain and the intracellular cytoplasmic carboxy-terminal domain. To evaluate the function of the CF distinct from the holoreceptor, we generated a construct encoding the CF as an in-frame yellow fluorescent protein fusion. The CF accumulates in nuclei and induces apoptosis in CHO-K1 cells, rat aortic smooth muscle cells (RASMCs), MCF-7 human breast adenocarcinoma cells, and H9c2 rat cardiomyoblasts. All cell types show nuclear fragmentation and disintegration, as well as evidence for phosphotidylserine displacement in the plasma membrane and activated caspases. RASMCs specifically showed a 5.2-fold increase (P < 0.001) in CF-induced active caspases compared with control and a 7.2-fold increase (P < 0.001) in cleaved caspase-3 (Asp174). Poly(ADP-ribose)polymerase was upregulated 4.8-fold (P < 0.001) in CF expressing cardiomyoblasts and colocalized with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). CF expression also induces DNA laddering, the gold-standard for apoptosis in all cell types studied. CF-induced apoptosis, therefore, appears to be a general phenomenon as it is observed in multiple cell types including smooth muscle cells and cardiomyoblasts. PMID:21813711

  14. Functional enhancement of AT1R potency in the presence of the TPαR is revealed by a comprehensive 7TM receptor co-expression screen.

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    Jonas Tind Hansen

    Full Text Available BACKGROUND: Functional cross-talk between seven transmembrane (7TM receptors can dramatically alter their pharmacological properties, both in vitro and in vivo. This represents an opportunity for the development of novel therapeutics that potentially target more specific biological effects while causing fewer adverse events. Although several studies convincingly have established the existence of 7TM receptor cross-talk, little is known about the frequencey and biological significance of this phenomenon. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the extent of synergism in 7TM receptor signaling, we took a comprehensive approach and co-expressed 123 different 7TM receptors together with the angiotensin II type 1 receptor (AT1R and analyzed how each receptor affected the angiotensin II (AngII response. To monitor the effect we used integrative receptor activation/signaling assay called Receptor Selection and Amplification Technology (R-SAT. In this screen the thromboxane A2α receptor (TPαR was the only receptor which significantly enhanced the AngII-mediated response. The TPαR-mediated enhancement of AngII signaling was significantly reduced when a signaling deficient receptor mutant (TPαR R130V was co-expressed instead of the wild-type TPαR, and was completely blocked both by TPαR antagonists and COX inhibitors inhibiting formation of thromboxane A2 (TXA2. CONCLUSIONS/SIGNIFICANCE: We found a functional enhancement of AT1R only when co-expressed with TPαR, but not with 122 other 7TM receptors. In addition, the TPαR must be functionally active, indicating the AT1R enhancement is mediated by a paracrine mechanism. Since we only found one receptor enhancing AT1R potency, our results suggest that functional augmentation through 7TM receptor cross-talk is a rare event that may require specific conditions to occur.

  15. Long-term Angiotensin II AT1 receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPARγ.

    OpenAIRE

    Zorad, Stefan; Jing-tao DOU; Benicky, Julius; Hutanu, Daniel; Tybitanclova, Katarina; Zhou, Jin; Saavedra, Juan M

    2006-01-01

    To clarify the mechanism of the effects of angiotensin II AT1 receptor antagonists on adipose tissue, we treated 8 week-old male Wistar Kyoto rats with the angiotensin II AT1 receptor antagonist Candesartan cilexetil (10 mg/kg/day) for 18 weeks. Candesartan cilexetil reduced body weight gain, decreased fat tissue mass due to hypotrophy of epididymal and retroperitoneal adipose tissue and decreased adipocyte size without changing the number of adipocytes. Candesartan cilexetil decreased serum ...

  16. Cooperative effect of angiotensin AT(1) and endothelin ET(A) receptor antagonism limits the brain damage after ischemic stroke in rat

    DEFF Research Database (Denmark)

    Stenman, Emelie; Jamali, Roya; Henriksson, Marie;

    2007-01-01

    Cerebral ischemia results in enhanced expression of smooth muscle cell endothelin and angiotensin receptors in cerebral arteries. We hypothesise that this phenomenon may be detrimental and that acute treatment with a combined non-hypotensive dose of the angiotensin AT(1) receptor inhibitor candes...

  17. Lasting Effects of a 2-Year Diabetes Self-Management Support Intervention: Outcomes at 1-Year Follow-Up

    OpenAIRE

    Tang, Tricia S.; Funnell, Martha M.; Oh, Mary

    2012-01-01

    Introduction Diabetes-related health improvements achieved from self-management education interventions are not sustained long-term. We examined the health effects at 1 year follow-up of a 2-year, empowerment-based, diabetes self-management support intervention designed for African Americans. Methods We collected data from 52 African American adults with type 2 diabetes who completed the 3-year study. The intervention consisted of weekly groups led by 2 health care professionals and emphasize...

  18. Increased perfusion pressure enhances the expression of endothelin (ETB) and angiotensin II (AT1, AT2) receptors in rat mesenteric artery smooth muscle cells

    DEFF Research Database (Denmark)

    Lindstedt, Isak; Xu, Cang-Bao; Zhang, Yaping;

    2009-01-01

    In the present study, we hypothesized that changes in perfusion pressure result in altered expression of mRNA and protein encoding for the ETA-, ETB-, AT1- and AT2-receptors in rat mesenteric vessels. Segments of the rat mesenteric artery were cannulated with glass micropipettes, pressurized and...

  19. The role of AT1 and AT2 angiotensin receptors in the mechanism of apoptosis in renal tubular cells after physical exercise.

    Science.gov (United States)

    Podhorska-Okołów, M; Dziegiel, P; Gomułkiewicz, A; Dolińska-Krajewska, B; Murawska-Ciałowicz, E; Jethon, Z; Zabel, M

    2004-01-01

    Intensive physical exercise disturbs the entire homeostasis in the body and leads to changes in haemodynamic and metabolic alterations not only in skeletal muscles but also in many distant organs. In response to acute physical exercise, a decrease of the glomerular filtration may occur, followed by stimulation of the renin-angiotensin system (RAS). Recent studies have shown that both AT1 and AT2 angiotensin receptors may play a role in mediating the apoptotic process in the kidney. Our previous studies have demonstrated an occurrence of apoptosis in rat renal tubular cells after an excessive exercise. The aim of the present study was to determine the possible mechanism of exercise-induced apoptosis in rat kidney. The analysis was performed on kidneys of rats, subjected to treadmill running until exhaustion. Apoptosis was detected in paraffin sections by the TUNEL technique. The expression of AT1 and AT2 receptors in renal tubular cells was examined by immunohistochemistry and Western blot. Our results confirmed that apoptosis after physical exercise is present in renal distal tubular cells. Moreover, there was an increased expression of AT1 and AT2 receptors in distal tubular cells. These studies suggest that physical exercise may induce apoptosis by a mechanism, involving the activation of angiotensin AT1 and AT2 receptors. PMID:15638358

  20. Long-term angiotensin II AT1 receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPARgamma.

    Science.gov (United States)

    Zorad, Stefan; Dou, Jing-tao; Benicky, Julius; Hutanu, Daniel; Tybitanclova, Katarina; Zhou, Jin; Saavedra, Juan M

    2006-12-15

    To clarify the mechanism of the effects of angiotensin II AT(1) receptor antagonists on adipose tissue, we treated 8 week-old male Wistar Kyoto rats with the angiotensin II AT(1) receptor antagonist Candesartan cilexetil (10 mg/kg/day) for 18 weeks. Candesartan cilexetil reduced body weight gain, decreased fat tissue mass due to hypotrophy of epididymal and retroperitoneal adipose tissue and decreased adipocyte size without changing the number of adipocytes. Candesartan cilexetil decreased serum leptin levels and epididymal leptin mRNA, increased serum adiponectin levels and epididymal adiponectin mRNA, decreased epididymal tumor necrosis factor alpha (TNFalpha) mRNA, and increased fatty acid synthase mRNA. Considered free of peroxisome proliferator-activated receptor gamma (PPARgamma) agonist activity, Candesartan cilexetil increased epididymal expression of PPARgamma mRNA. The effects of Candesartan cilexetil on adipokine production and release may be attributable to PPARgamma activation and/or decrease in adipocyte cell size. In addition, Candesartan cilexetil treatment increased the expression of epididymal angiotensin II AT(2) receptor mRNA and protein and decreased the expression of renin receptor mRNA. These results suggest that Candesartan cilexetil influences lipid metabolism in adipose tissue by promoting adipose tissue rearrangement and modulating adipokine expression and release. These effects are probably consequences of local angiotensin II AT(1) receptor inhibition, angiotensin II AT(2) receptor stimulation, and perhaps additional angiotensin II-independent mechanisms. Our results indicate that the activity of local renin-angiotensin system plays an important role in adipose tissue metabolism. The decrease in the pro-inflammatory cytokine TNFalpha and the increase in the anti-inflammatory adipokine adiponectin indicate that Candesartan cilexetil may exert significant anti-inflammatory properties. PMID:17064684

  1. Antibodies against AT1 receptors are associated with vascular endothelial and smooth muscle function impairment: protective effects of hydroxysafflor yellow A.

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    Zhu Jin

    Full Text Available Ample evidence has shown that autoantibodies against AT1 receptors (AT1-AA are closely associated with human cardiovascular disease. The aim of this study was to investigate mechanisms underlying AT1-AA-induced vascular structural and functional impairments in the formation of hypertension, and explore ways for preventive treatment. We used synthetic peptide corresponding to the sequence of the second extracellular loop of the AT1 receptor (165-191 to immunize rats and establish an active immunization model. Part of the model received preventive therapy by losartan (20 mg/kg/day and hyroxysafflor yellow A (HSYA (10 mg/kg/day. The result show that systolic blood pressure (SBP and heart rate (HR of immunized rats was significantly higher, and closely correlated with the plasma AT1-Ab titer. The systolic response of thoracic aortic was increased, but diastolic effects were attenuated markedly. Histological observation showed that the thoracic aortic endothelium of the immunized rats became thinner or ruptured, inflammatory cell infiltration, medial smooth muscle cell proliferation and migration, the vascular wall became thicker. There was no significant difference in serum antibody titer between losartan and HSYA groups and the immunized group. The vascular structure and function were reversed, and plasma biochemical parameters were also improved significantly in the two treatment groups. These results suggest that AT1-Ab could induce injury to vascular endothelial cells, and proliferation of smooth muscle cells. These changes were involved in the formation of hypertension. Treatment with AT1 receptor antagonists and anti oxidative therapy could block the pathogenic effect of AT1-Ab on vascular endothelial and smooth muscle cells.

  2. In vitro inhibition of [3H]-angiotensin II binding on the human AT1 receptor by proanthocyanidins from Guazuma ulmifolia bark.

    Science.gov (United States)

    Caballero-George, Catherina; Vanderheyden, Patrick M L; De Bruyne, Tess; Shahat, Abdel-Atty; Van den Heuvel, Hilde; Solis, Pablo N; Gupta, Mahabir P; Claeys, Magda; Pieters, Luc; Vauquelin, Georges; Vlietinck, Arnold J

    2002-12-01

    A bioassay-guided fractionation of the 70% acetone extract of the bark of Guazuma ulmifolia Lam. on the inhibition of angiotensin II binding to the AT 1 receptor led to the isolation and identification of bioactive oligomeric and polymeric proanthocyanidins consisting mainly of (-)-epicatechin units. The displacement of [3H]-angiotensin II binding was dose-dependent and correlated with the degree of polymerization of the different fractions containing proanthocyanidins. A strong displacement was seen for the residual fraction suggesting that the most active substances corresponding to the highly polymerized proanthocyanidins. Angiotensin II AT 1 receptor binding might be considered as a potentially interesting biological activity of proanthocyanidins contributing to the very broad spectrum of biological activities of the condensed tannins. PMID:12494331

  3. Elevated AT1 receptor protein but lower angiotensin II-binding in adipose tissue of rats with monosodium glutamate-induced obesity

    Czech Academy of Sciences Publication Activity Database

    Pinterová, L.; Železná, Blanka; Ficková, M.; Macho, L.; Križanová, O.; Ježová, D.; Zórad, Š.

    2001-01-01

    Roč. 33, č. 12 (2001), s. 708-12. ISSN 0018-5043 R&D Projects: GA ČR GA204/99/1453 Grant ostatní: VEGA(SK) VEGA 2/7213; VEGA(SK) VEGA 2/6084; VEGA(SK) VEGA 2/7158 Keywords : AT1 receptor * fat tissue * MSG rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.910, year: 2001

  4. Endothelin-1 induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel, Ca2+-induced Ca2+ release and a pathway involving ETA receptors, PKC, PKA and AT1 receptors in cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    ZENG QingHua; LI XingTing; ZHONG GuoGan; ZHANG WenJie; SUN ChengWen

    2009-01-01

    Using fura-2-acetoxymethyl eater (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]1) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats.The effect of ET-1 on [Ca2+]1 elevation was abolished in the presence of the ETA receptor blocker BQ123,but was not affected by the ETa receptor blocker BQ788. ET-1-induced an increase in [Ca2+]1, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibltors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an Increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETa receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.

  5. Endothelin-1 induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel, Ca2+-induced Ca2+ release and a pathway involving ETA receptors, PKC, PKA and AT1 receptors in cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats. The effect of ET-1 on [Ca2+]i elevation was abolished in the presence of the ETA receptor blocker BQ123, but was not affected by the ETB receptor blocker BQ788. ET-1-induced an increase in [Ca2+]i, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibitors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETA receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.

  6. AT1 receptor blockade attenuates insulin resistance and myocardial remodeling in rats with diet-induced obesity.

    Directory of Open Access Journals (Sweden)

    Silvio A Oliveira-Junior

    Full Text Available BACKGROUND: Although obesity has been associated with metabolic and cardiac disturbances, the carrier mechanisms for these responses are poorly understood. This study analyzed whether angiotensin II blockade attenuates metabolic and cardiovascular disorders in rats with diet-induced obesity. MATERIAL AND METHODS: Wistar-Kyoto (n = 40 rats were subjected to control (C; 3.2 kcal/g and hypercaloric diets (OB; 4.6 kcal/g for 30 weeks. Subsequently, rats were distributed to four groups: C, CL, OB, and OBL. L groups received Losartan (30 mg/kg/day for five weeks. After this period we performed in vivo glucose tolerance and insulin tolerance tests, and measured triacylglycerol, insulin, angiotensin-converting enzyme activity (ACE, and leptin levels. Cardiovascular analyzes included systolic blood pressure (SBP, echocardiography, myocardial morphometric study, myosin heavy chain composition, and measurements of myocardial protein levels of angiotensin, extracellular signal-regulated (ERK1/2, c-Jun amino-terminal kinases (JNK, insulin receptor subunit β (βIR, and phosphatidylinositol 3-kinase (PI3K by Western Blot. RESULTS: Glucose metabolism, insulin, lipid, and ACE activity disorders observed with obesity were minimized by Losartan. Moreover, obesity was associated with increased SBP, myocardial hypertrophy, interstitial fibrosis and improved systolic performance; these effects were also minimized with Losartan. On a molecular level, OB exhibited higher ERK, Tyr-phosphorylated βIR, and PI3K expression, and reduced myocardial angiotensin and JNK expression. ERK and JNK expression were regulated in the presence of Losartan, while angiotensin, Tyr-βRI, total and Tyr-phosphorylated PI3K expression were elevated in the OBL group. CONCLUSION: Angiotensin II blockade with Losartan attenuates obesity-induced metabolic and cardiovascular changes.

  7. Increased perfusion pressure enhances the expression of endothelin (ETB) and angiotensin II (AT1, AT2) receptors in rat mesenteric artery smooth muscle cells

    DEFF Research Database (Denmark)

    Lindstedt, Isak; Xu, Cang-Bao; Zhang, Yaping;

    2009-01-01

    In the present study, we hypothesized that changes in perfusion pressure result in altered expression of mRNA and protein encoding for the ETA-, ETB-, AT1- and AT2-receptors in rat mesenteric vessels. Segments of the rat mesenteric artery were cannulated with glass micropipettes, pressurized and...... luminally perfused in a perfusion chamber. After either exposure to no ("organ culture" (0 mmHg)), normal (85/75 mmHg) or high pressure (160/150 mmHg) at constant flow for 1-17 h, the vessel segments were snap frozen and real-time polymerase chain reaction was performed to quantify the ET- and AT-receptor m......RNA content, or immersed in a fixative solution, dehydrated, frozen, cut in a cryostat and immunohistology stained for ET- and AT-receptor protein. The mRNA expressions of ETB and of AT2 were significantly enhanced in vessels exposed to high perfusion pressure, compared with normal and no perfusion pressure...

  8. Angiotensin II induces the production of MMP-3 and MMP-13 through the MAPK signaling pathways via the AT(1) receptor in osteoblasts.

    Science.gov (United States)

    Nakai, Kumiko; Kawato, Takayuki; Morita, Toyoko; Iinuma, Toshimitsu; Kamio, Noriaki; Zhao, Ning; Maeno, Masao

    2013-04-01

    Angiotensin II (Ang II) plays an important role in the maintenance of bone mass and integrity by activation of the mitogen-activated protein kinases (MAPKs) and by modulation of balance between resorption by osteoclasts and formation by osteoblasts. However, the role of Ang II in the turnover of extracellular matrix (ECM) in osteoid by osteoblasts remains unclear. Therefore, we examined the effect of Ang II on the expression of matrix metalloproteinases (MMPs), plasminogen activators (PAs), and their inhibitors [i.e., tissue inhibitors of metalloproteinases (TIMPs) and PA inhibitor-1 (PAI-1)] using osteoblastic ROS17/2.8 cells. Treatment with Ang II strikingly increased the expressions of MMP-3 and -13 and promoted cell proliferation associated with reduced alkaline phosphatase activity as well as enhanced phosphorylated expression of extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and stress-activated protein kinases/c-jun N-terminal kinases (SAPK/JNK) in ROS17/2.8 cells. However, Ang II had no effect on the expression of MMP-2, -9, -14, urokinase-type PA, tissue-type PA, TIMP-1, -2, -3, and PAI-1 in cells. Losartan (AT1 receptor blocker) blocked Ang II-induced expression of MMP-3 and -13, whereas PD123319 (AT2 receptor blocker) did not completely block these responses. Losartan also blocked the Ang II-induced phosphorylation of ERK1/2, p38 MAPK, and SAPK/JNK. MAPK kinase 1/2 inhibitor PD98059 and JNK inhibitor SP600125 suppressed Ang II-induced expression of MMP-3 and -13. These results suggested that Ang II stimulated the degradation process that occurs during ECM turnover in osteoid by increasing the production of MMP-3 and -13 through MAPK signaling pathways via the AT1 receptor in osteoblasts. Furthermore, our findings suggest that Ang II does not influence the plasminogen/plasmin pathway in osteoblasts. PMID:23277113

  9. Angiotensin II reduces cardiac AdipoR1 expression through AT1 receptor/ROS/ERK1/2/c-Myc pathway.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2 mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1 receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII.

  10. Insight into the structural requirement of substituted quinazolinone biphenyl acylsulfonamides derivatives as Angiotensin II AT1 receptor antagonist: 2D and 3D QSAR approach

    Directory of Open Access Journals (Sweden)

    Mukesh C. Sharma

    2014-01-01

    Full Text Available A series of 19 molecules substituted quinazolinone biphenyl acylsulfonamides derivatives displaying variable inhibition of Angiotensin II receptor AT1 activity were selected to develop models for establishing 2D and 3D QSAR. The compounds in the selected series were characterized by spatial, molecular and electro topological descriptors using QSAR module of Molecular Design Suite (VLife MDS™ 3.5. The best 2D QSAR model was selected, having correlation coefficient r2 (0.8056 and cross validated squared correlation coefficient q2 (0.6742 with external predictive ability of pred_r2 0.7583 coefficient of correlation of predicted data set (pred_r2se 0.2165. The results obtained from QSAR studies could be used in designing better Ang II activity among the congeners in future. The optimum QSAR model showed that the parameters SsssCHE index, SddCE-index, T_2_Cl_4, and SssNHE-index contributed in the model. 3D QSAR analysis by kNN-molecular field analysis approach developed based on principles of the k-nearest neighbor method combined with Genetic algorithms, stepwise forward variable selection approach; a leave-one-out cross-validated correlation coefficient (q2 of 0.6516 and a non-cross-validated correlation coefficient (r2 of 0.8316 and pred_r2 0.6954 were obtained. Contour maps using this approach showed that steric, electrostatic, and hydrophobic field effects dominantly determine binding affinities. The information rendered by 3D QSAR models may lead to a better understanding of structural requirements of Angiotensin II receptor and can help in the design of novel potent antihypertensive molecules.

  11. Angiotensin II AT1 receptor blockade decreases vasopressin-induced water reabsorption and AQP2 levels in NaCl-restricted rats

    DEFF Research Database (Denmark)

    Kwon, Tae-Hwan; Nielsen, Jakob; Knepper, M.A.;

    2005-01-01

    Vasopressin and ANG II, which are known to play a major role in renal water and sodium reabsorption, are mainly coupled to the cAMP/PKA and phosphoinositide pathways, respectively. There is evidence for cross talk between these intracellular signaling pathways. We therefore hypothesized that...... vasopressin-induced water reabsorption could be attenuated by ANG II AT1 receptor blockade in rats. To address this, three protocols were used: 1) DDAVP treatment (20 ng/h sc for 7 days, n = 8); 2) DDAVP (20 ng/h sc for 7 days) and candesartan (1 mg·kg−1·day−1 sc for 7 days) cotreatment (n = 8); and 3......) vehicle infusion as the control (n = 8). All rats were maintained on a NaCl-deficient diet (0.1 meq Na+·200 g body wt−1·day−1) during the experiment. DDAVP treatment alone resulted in a significant decrease in urine output (3.1 ± 0.2 ml/day) compared with controls (11.5 ± 2.2 ml/day, P < 0.05), whereas...

  12. Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor.

    Science.gov (United States)

    Yamada, Akihiro; Maeda, Kazuya; Kamiyama, Emi; Sugiyama, Daisuke; Kondo, Tsunenori; Shiroyanagi, Yoshiyuki; Nakazawa, Hayakazu; Okano, Teruo; Adachi, Masashi; Schuetz, John D; Adachi, Yasuhisa; Hu, Zhuohan; Kusuhara, Hiroyuki; Sugiyama, Yuichi

    2007-12-01

    Olmesartan, a novel angiotensin II AT1-receptor antagonist, is excreted into both bile and urine, with minimal metabolism. Because olmesartan is a hydrophilic anionic compound, some transporters could be involved in its hepatic and renal clearance. In this study, we characterized the role of human drug transporters in the pharmacokinetics of olmesartan and determined the contribution of each transporter to the overall clearance of olmesartan. Olmesartan was significantly taken up into human embryonic kidney 293 cells expressing organic anion-transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, and OAT3. We also observed its saturable uptake into human hepatocytes and kidney slices. Estimated from the relative activity factor method and application of specific inhibitors, the relative contributions of OATP1B1 and OATP1B3 to the uptake of olmesartan in human hepatocytes were almost the same, whereas OAT3 was predominantly involved in its uptake in kidney slices. The vectorial transport of olmesartan was observed in OATP1B1/multidrug resistance-associated protein (MRP) 2 double transfectants, but not in OATP1B1/multidrug resistance (MDR) 1 and OATP1B1/breast cancer resistance protein (BCRP) transfectants. ATP-dependent transport into membrane vesicles expressing human MRP2 and MRP4 was clearly observed, with K(m) values of 14.9 and 26.2 microM, respectively, whereas the urinary excretion of olmesartan in Mrp4-knockout mice was not different from that of control mice. We also investigated the transcellular transport of olmesartan medoxomil, a prodrug of olmesartan. Vectorial basal-to-apical transport was observed in OATP1B1/MRP2, OATP1B1/MDR1 double, and OATP1B1/BCRP double transfectants, suggesting the possible involvement of MRP2, MDR1, and BCRP in the limit of intestinal absorption of olmesartan medoxomil. From these results, we suggest that multiple transporters make a significant contribution to the pharmacokinetics of olmesartan and

  13. Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ETB, 5-HT1B and AT1 Receptor-Mediated Contractility Downstream of Occlusion

    DEFF Research Database (Denmark)

    Rasmussen, Marianne N P; Hornbak, Malene; Larsen, Stine S; Sheykhzade, Majid; Edvinsson, Lars

    2013-01-01

    . This functional increase did not seem to relate to ischemic tissue damage, inflammatory cell infiltration or the element of reperfusion. Interestingly, immunohistochemistry did not show any difference in the level of immunoreactivity towards endothelin B (ETB) receptors between groups. Conclusion...

  14. Cardiac hypertrophy induced by exercise training:the function of AT1 receptor, autophagy and miRNAs%运动性心脏肥大:AT1受体、细胞自噬和 miRNAs 的调节

    Institute of Scientific and Technical Information of China (English)

    钱帅伟; 张瑞萍; 张安民

    2014-01-01

    As a mechanical and exogenous stimulus , exercise training induces cardiac physiological hypertro-phy, and the cardiac structure is changed slowly , steadily and coordinately.Simultaneously, energy metabolism and func-tion of the cardiac muscle are also improved .These are positive adaptations in the heart when experiencing endurance exer -cise training.Recently, angiotensinⅡtype 1 (AT1) receptor, autophagy and miRNAs are all considered as important reg-ulators to cardiac hypertrophy induced by exercise training at different molecular levels .Fully understanding the relations and the important role of AT1 receptor, autophagy and miRNAs in cardiac physiological hypertrophy will further enrich the signaling pathway of cardiac hypertrophy induced by exercise training .

  15. Angiotensin II Type 1 receptor (AT1) signaling in astrocytes regulates synaptic degeneration-induced leukocyte entry to the central nervous system

    DEFF Research Database (Denmark)

    Füchtbauer, L; Groth-Rasmussen, Maria; Holm, Thomas Hellesøe; Løbner, M; Toft-Hansen, Henrik; Khorooshi, Reza M. H.; Owens, T

    2011-01-01

    the dentate gyrus following axonal transection was totally abrogated in GFAP-IκBα-dn mice. Whereas angiotensin II was upregulated in microglia and astrocytes in the dentate gyrus post-lesion, AT1 was exclusively expressed on astrocytes. Blocking AT1 with Candesartan led to significant increase in...

  16. Suppression of WIF-1 through promoter hypermethylation causes accelerated proliferation of the aryl hydrocarbon receptor (AHR) overexpressing MCF10AT1 breast cancer cells

    International Nuclear Information System (INIS)

    Highlights: → 5-Aza-2'-deoxycytidine (AZ) causes proliferation suppression and ERα recovery. → AZ down-regulates Wnt/β-catenin pathway mainly by increasing WIF-1 expression. → Both ERα and AhR have some effects on DNA methylation in breast cancer cells. → Artificial overexpression of ERα in ER negative cells increases WIF-1 expression. → WIF-1 promoter hypermethylation is one of the major causes for accelerated proliferation. -- Abstract: The cause for increased cell proliferation in AHR overexpressing breast cancer cells still remains unknown. Here we studied the molecular basis of aggressive cell proliferation of an AHR overexpressing and ERα functionally down-regulated MCF10AT1 cell line, designated as P20E, in comparison to a matched sub-line, P20C with normal AHR expression and ERα function. We found that a 4-day treatment of P20E cells with 5-aza-2'-deoxycytidine (AZ) caused a significant suppression of cell proliferation. Such an effect of AZ was accompanied with the significant recovery of ERα function. Among diagnostic markers of AZ-induced cellular changes we found conspicuous up-regulation of mRNA expression of Wnt inhibitory factor-1 (WIF-1), particularly in P20E. The possibility of AZ-induced demethylation on the promoter of WIF-1 gene was confirmed through methylation specific PCR assay. Such AZ-induced changes in P20E cells were also accompanied with the decrease in the binding of nuclear proteins to the 32P labeled TRE (TCF response element) and the reduced accumulation of β-catenin protein in the cell nucleus, indicating the importance of Wnt/β-catenin pathway in maintaining the increased cell proliferation in P20E line over P20C line. The importance of WIF-1 in this regard has been validated by transfecting cells with siRNA against WIF-1, which caused an increase in cell proliferation. Moreover, artificial overexpression of ERα in both P20E as well as MDA-MB-231 cells increased the mRNA expression of WIF-1. Together these

  17. Expression and transport of Angiotensin II AT1 receptors in spinal cord, dorsal root ganglia and sciatic nerve of the rat

    OpenAIRE

    Pavel, Jaroslav; Tang, Hui; Brimijoin, Stephen; Moughamian, Armen; Nishioku, Tsuyoshi; Benicky, Julius; Saavedra, Juan M.

    2008-01-01

    To clarify the role of Angiotensin II in the regulation of peripheral sensory and motor systems, we initiated a study of the expression, localization and transport of Angiotensin II receptor types in the rat sciatic nerve pathway, including L4–L5 spinal cord segments, the corresponding dorsal root ganglia (DRGs) and the sciatic nerve.

  18. Functional enhancement of AT1R potency in the presence of the TPαR is revealed by a comprehensive 7TM receptor co-expression screen

    DEFF Research Database (Denmark)

    Hansen, Jonas Tind; Lyngsø, Christina; Speerschneider, Tobias;

    2013-01-01

    Functional cross-talk between seven transmembrane (7TM) receptors can dramatically alter their pharmacological properties, both in vitro and in vivo. This represents an opportunity for the development of novel therapeutics that potentially target more specific biological effects while causing few...

  19. Culture, distress, and oxytocin receptor polymorphism (OXTR) interact to influence emotional support seeking

    OpenAIRE

    Kim, Heejung S.; Sherman, David K.; Sasaki, Joni Y.; Xu, Jun; Chu, Thai Q.; Ryu, Chorong; Suh, Eunkook M.; Graham, Kelsey; Taylor, Shelley E.

    2010-01-01

    Research has demonstrated that certain genotypes are expressed in different forms, depending on input from the social environment. To examine sensitivity to cultural norms regarding emotional support seeking as a type of social environment, we explored the behavioral expression of oxytocin receptor polymorphism (OXTR) rs53576, a gene previously related to socio-emotional sensitivity. Seeking emotional support in times of distress is normative in American culture but not in Korean culture. Con...

  20. Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans

    OpenAIRE

    Chen, Frances S.; Kumsta, Robert; von Dawans, Bernadette; Monakhov, Mikhail; Ebstein, Richard P.; Heinrichs, Markus

    2011-01-01

    The neuropeptide oxytocin has played an essential role in the regulation of social behavior and attachment throughout mammalian evolution. Because recent studies in humans have shown that oxytocin administration reduces stress responses and increases prosocial behavior, we investigated whether a common single nucleotide polymorphism (rs53576) in the oxytocin receptor gene (OXTR) might interact with stress-protective effects of social support. Salivary cortisol samples and subjective stress ra...

  1. New zircon data supporting models of short-lived igneous activity at 1.89 Ga in the western Skellefte District, central Fennoscandian Shield

    OpenAIRE

    P. Skyttä; Hermansson, T.; Andersson, J.; M. Whitehouse; P. Weihed

    2011-01-01

    New U-Th-Pb zircon data (SIMS) from three intrusive phases of the Palaeoproterozoic Viterliden intrusion in the western Skellefte District, central Fennoscandian Shield, dates igneous emplacement in a narrow time interval at about 1.89 Ga. A locally occurring quartz-plagioclase porphyritic tonalite, here dated at 1889 ± 3 Ma, is considered the youngest of the intrusive units, based on the new age data and field evidence. This supports an existing interpretation of its fault-controlled emplace...

  2. New zircon data supporting models of short-lived igneous activity at 1.89 Ga in the western Skellefte District, central Fennoscandian Shield

    Directory of Open Access Journals (Sweden)

    P. Skyttä

    2011-10-01

    Full Text Available New U-Th-Pb zircon data (SIMS from three intrusive phases of the Palaeoproterozoic Viterliden intrusion in the western Skellefte District, central Fennoscandian Shield, dates igneous emplacement in a narrow time interval at about 1.89 Ga. A locally occurring quartz-plagioclase porphyritic tonalite, here dated at 1889 ± 3 Ma, is considered the youngest of the intrusive units, based on the new age data and field evidence. This supports an existing interpretation of its fault-controlled emplacement after intrusion of the dominating hornblende-tonalite units, in this study dated at 1892 ± 3 Ma. The Viterliden magmatism was synchronous with the oldest units of the Jörn type early-orogenic intrusions in the eastern part of the district (1.89–1.88 Ga; cf. Gonzàles Roldán, 2010. A U-Pb zircon age for a felsic metavolcanic rock from the hanging-wall to the Kristineberg VMS deposit, immediately south of the Viterliden intrusion, is constrained at 1883 ± 6 Ma in this study. It provides a minimum age for the Kristineberg ore deposit and suggests contemporaneous igneous/volcanic activity throughout the Skellefte District. Furthermore, it supports the view that the Skellefte Group defines a laterally continuous belt throughout this "ore district". Tentative correlation of the 1889 ± 3 Ma quartz-plagioclase porphyritic tonalite with the Kristineberg "mine porphyry" suggests that these units are coeval at about 1.89 Ga. Based on the new age determinations, the Viterliden intrusion may equally well have intruded into or locally acted as a basement for the ore-hosting Skellefte Group volcanic rocks.

  3. New zircon data supporting models of short-lived igneous activity at 1.89 Ga in the western Skellefte District, central Fennoscandian Shield

    Directory of Open Access Journals (Sweden)

    P. Skyttä

    2011-04-01

    Full Text Available New U-Th-Pb zircon data (SIMS from three intrusive phases of the Palaeoproterozoic Viterliden intrusion in the western Skellefte District, central Fennoscandian Shield, dates igneous emplacement in a narrow time interval at about 1.89 Ga. A locally occurring quartz-plagioclase porphyritic tonalite, here dated at 1889 ± 3 Ma, is, based on the new age data and field evidence, considered the youngest of the intrusive units. This supports an existing interpretation of its fault-controlled emplacement after intrusion of the dominating hornblende-tonalite units, in this study dated at 1892 ± 3 Ma. The Viterliden magmatism was synchronous with the oldest units of the Jörn type early-orogenic intrusions in the eastern part of the district (1.89–1.88 Ga; cf. Gonzàles Roldán, 2010. A U-Pb zircon age for a felsic metavolcanic rock from the hanging-wall to the Kristineberg VMS deposit, immediately south of the Viterliden intrusion, is in this study constrained in the 1.89–1.88 Ga time interval. It provides a minimum age for the Kristineberg ore deposit and suggests contemporaneous igneous/volcanic activity throughout the Skellefte District. Furthermore, it supports the view that the Skellefte Group defines a laterally continuous belt throughout this "ore district". Tentative correlation of the 1889 ± 3 Ma quartz-plagioclase porphyritic tonalite with the Kristineberg "mine porphyry", which cuts the altered ore-hosting metavolcanic rocks, further constrain the minimum age for ore deposition at 1889 ± 3 Ma. Based on the new age determinations, the Viterliden intrusion may equally well have intruded into, or locally acted as a basement for the ore-hosting Skellefte Group volcanic rocks.

  4. How validated receptor occupancy flow cytometry assays can impact decisions and support drug development.

    Science.gov (United States)

    Moulard, Maxime; Ozoux, Marie-Laure

    2016-03-01

    Because of the pressure of significant attrition in drug development, demonstration of target engagement after drug administration enables dose and regimen optimization, patient selection, and stratification from the earliest stages of drug development. The determination of receptor occupancy (RO) can support these efforts. Flow cytometry is one of the preferred technologies to be used based on the important advances in the technology over the last years enabling the simultaneous determination on target cells, of multi intra or surface cell parameters with adequate precision in a regulated environment. Nevertheless, compared to other platforms using the same antigen-antibody binding concept, the flow cytometry approach has faced several challenges, not only due to the technology per se and the diversity of receptor occupancy approaches, but also related to the nature of the matrix where the determination is performed. To illustrate these points, three case studies (antibody-drug conjugate and naked antibody) are provided here to highlight the importance of the choice of the right antibody pair to measure both receptor density (RD) and occupancy by the drug on cancer cells in blood and in bone marrow and the possibility to circumvent the lack of a critical reagent with an innovative approach. In addition, the use of RO data to determine the minimum anticipated biological effect level (MABEL) with translational data from preclinical to human studies, selection of starting dose for the first in man study will be discussed. © 2015 International Clinical Cytometry Society. PMID:26332593

  5. Influence of Angiotensin II Subtype 2 Receptor (AT2R Antagonist, PD123319, on Cardiovascular Remodelling of Aged Spontaneously Hypertensive Rats during Chronic Angiotensin II Subtype 1 Receptor (AT1R Blockade

    Directory of Open Access Journals (Sweden)

    Emma S. Jones

    2012-01-01

    Adult (20 weeks and senescent (20 months spontaneously hypertensive rats (SHRs were treated with either the AT1R antagonist, candesartan cilexetil (2 mg/kg/day, the AT2R antagonist, PD123319 (10 mg/kg/day, or a combination of the 2 compounds. Mean arterial pressure (MAP and left ventricular volume were markedly decreased by candesartan cilexetil, however, simultaneous treatment with PD123319 had no additional effect on either parameter. Perivascular fibrosis was significantly reduced by candesartan cilexetil in aged animals only, and this effect was reversed by concomitant PD123319 administration. Vascular hypertrophy was reduced by candesartan cilexetil, and these effects were reversed by simultaneous PD123319. These results suggest that AT2R stimulation does not significantly influence the antihypertensive effect of chronic AT1R blockade, but plays a role in the regulation of vascular structure. The severe degree of cardiac perivascular fibrosis in senescent animals was regressed by AT1R blockade and this effect was reversed by simultaneous AT2R inhibition, demonstrating an antifibrotic role of AT2R stimulation in the aging hypertensive heart.

  6. Oxytocin receptor gene polymorphism, perceived social support, and psychological symptoms in maltreated adolescents.

    Science.gov (United States)

    Hostinar, Camelia E; Cicchetti, Dante; Rogosch, Fred A

    2014-05-01

    Despite the detrimental consequences of child maltreatment on developmental processes, some individuals show remarkable resilience, with few signs of psychopathology, while others succumb to dysfunction. Given that oxytocin has been shown to be involved in social affiliation, attachment, social support, trust, empathy, and other social or reproductive behaviors, we chose to examine the possible moderation of maltreatment effects on perceived social support and on psychological symptoms by a common single nucleotide polymorphism (rs53576) in the oxytocin receptor gene. We studied adolescents (N = 425) aged approximately 13-15, including participants with objectively documented maltreatment histories (N = 263) and a nonmaltreated comparison group from a comparable low socioeconomic status background (N = 162). There was a significant genotype by maltreatment interaction, such that maltreated adolescents with the G/G genotype perceived significantly lower social support compared to maltreated A-carriers, with no effect of genotype in the comparison group. Maltreated G/Gs also reported higher levels of internalizing symptoms than did A-carriers, even though they did not differ from them on objective measures of maltreatment (type, duration, or severity). G/G homozygotes may be more attuned to negative social experiences, such as family maltreatment, while maltreated A-carriers were indistinguishable from nonmaltreated adolescents in levels of mental health symptoms. PMID:24621832

  7. Wozu AT1-Rezeptorantagonisten?

    Directory of Open Access Journals (Sweden)

    Berent R

    2000-01-01

    Full Text Available ACE-Hemmer sind nun seit fast 20 Jahren im klinischen Einsatz. Ihre Effektivität in der Behandlung der arteriellen Hypertonie, der Herzinsuffizienz und bei nephrologischen Erkrankungen wurde durch eine große Zahl an randomisierten, prospektiven Studien belegt. Zusätzlich ist das Nebenwirkungsprofil (inklusive seltener Nebenwirkungen dieser Substanzklasse durch die langjährige Anwendung gut dokumentiert. Unter einer AT1-Rezeptorantagonistentherapie konnte bislang eindeutig gezeigt werden, daß das Auftreten von Nebenwirkungen, im speziellen des Reizhustens, deutlich seltener ist und im Placebobereich liegt, was die Compliance der Patienten sicherlich erhöht. Klinisch finden sich allerdings kaum Unterschiede in der Hämodynamik bei der Einnahme von ACE-Hemmern oder AT1-Rezeptorantagonisten. AT1-Rezeptorantagonisten blockieren sicherlich effektiver die AT1-rezeptorvermittelte Vasokonstriktion, währenddessen sich die ACE-Hemmerwirkung aus einer partiellen Abnahme der Angiotensin-II-Bildung und der Akkumulation von Bradykinin zusammensetzt. Aufgrund der derzeitigen Datenlage kann der AT1-Rezeptorantagonist nicht als Alternative zum ACE-Hemmer empfohlen werden, außer ein Absetzen des ACE-Hemmers ist wegen Nebenwirkungen notwendig. Auch die Kombinationstherapie, AT1-Rezeptorantagonist plus ACE-Hemmer, stellt zum jetzigen Zeitpunkt noch keine etablierte Therapie dar.

  8. The Dopamine D2 Receptor Gene, Perceived Parental Support, and Adolescent Loneliness: Longitudinal Evidence for Gene-Environment Interactions

    Science.gov (United States)

    van Roekel, Eeske; Goossens, Luc; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Verhagen, Maaike

    2011-01-01

    Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental support,…

  9. Efficient Prediction of Progesterone Receptor Interactome Using a Support Vector Machine Model

    Directory of Open Access Journals (Sweden)

    Ji-Long Liu

    2015-03-01

    Full Text Available Protein-protein interaction (PPI is essential for almost all cellular processes and identification of PPI is a crucial task for biomedical researchers. So far, most computational studies of PPI are intended for pair-wise prediction. Theoretically, predicting protein partners for a single protein is likely a simpler problem. Given enough data for a particular protein, the results can be more accurate than general PPI predictors. In the present study, we assessed the potential of using the support vector machine (SVM model with selected features centered on a particular protein for PPI prediction. As a proof-of-concept study, we applied this method to identify the interactome of progesterone receptor (PR, a protein which is essential for coordinating female reproduction in mammals by mediating the actions of ovarian progesterone. We achieved an accuracy of 91.9%, sensitivity of 92.8% and specificity of 91.2%. Our method is generally applicable to any other proteins and therefore may be of help in guiding biomedical experiments.

  10. Functional nicotinic acetylcholine receptor reconstitution in Au(111)-supported thiolipid monolayers

    Science.gov (United States)

    Pissinis, Diego E.; Diaz, Carolina; Maza, Eliana; Bonini, Ida C.; Barrantes, Francisco J.; Salvarezza, Roberto C.; Schilardi, Patricia L.

    2015-09-01

    The insertion and function of the muscle-type nicotinic acetylcholine receptor (nAChR) in Au(111)-supported thiolipid self-assembled monolayers have been studied by atomic force microscopy (AFM), surface plasmon resonance (SPR), and electrochemical techniques. It was possible for the first time to resolve the supramolecular arrangement of the protein spontaneously inserted in a thiolipid monolayer in an aqueous solution. Geometric supramolecular arrays of nAChRs were observed, most commonly in a triangular form compatible with three nAChR dimers of ~20 nm each. Addition of the full agonist carbamoylcholine activated and opened the nAChR ion channel, as revealed by the increase in capacitance relative to that of the nAChR-thiolipid system under basal conditions. Thus, the self-assembled system appears to be a viable biomimetic model to measure ionic conductance mediated by ion-gated ion channels under different experimental conditions, with potential applications in biotechnology and pharmacology.

  11. Successful virtual screening for a submicromolar antagonist of the neurokinin-1 receptor based on a ligand-supported homology model.

    Science.gov (United States)

    Evers, Andreas; Klebe, Gerhard

    2004-10-21

    The neurokinin-1 (NK1) receptor belongs to the family of G-protein-coupled receptors (GPCRs), which represents one of the most relevant target families in small-molecule drug design. In this paper, we describe a homology modeling of the NK1 receptor based on the high-resolution X-ray structure of rhodopsin and the successful virtual screening based on this protein model. The NK1 receptor model has been generated using our new MOBILE (modeling binding sites including ligand information explicitly) approach. Starting with preliminary homology models, it generates improved models of the protein binding pocket together with bound ligands. Ligand information is used as an integral part in the homology modeling process. For the construction of the NK1 receptor, antagonist CP-96345 was used to restrain the modeling. The quality of the obtained model was validated by probing its ability to accommodate additional known NK1 antagonists from structurally diverse classes. On the basis of the generated model and on the analysis of known NK1 antagonists, a pharmacophore model was deduced, which subsequently guided the 2D and 3D database search with UNITY. As a following step, the remaining hits were docked into the modeled binding pocket of the NK1 receptor. Finally, seven compounds were selected for biochemical testing, from which one showed affinity in the submicromolar range. Our results suggest that ligand-supported homology models of GPCRs may be used as effective platforms for structure-based drug design. PMID:15481976

  12. In vitro evidence in rainbow trout supporting glucosensing mediated by sweet taste receptor, LXR, and mitochondrial activity in Brockmann bodies, and sweet taste receptor in liver.

    Science.gov (United States)

    Otero-Rodiño, Cristina; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2016-10-01

    We previously obtained evidence in rainbow trout peripheral tissues such as liver and Brockmann bodies (BB) for the presence and response to changes in circulating levels of glucose (induced by intraperitoneal hypoglycaemic and hyperglycaemic treatments) of glucosensing mechanisms others than that mediated by glucokinase (GK). There were based on mitochondrial production of reactive oxygen species (ROS) leading to increased expression of uncoupling protein 2 (UCP2), and sweet taste receptor in liver and BB, and on liver X receptor (LXR) and sodium/glucose co-transporter 1 (SGLT-1) in BB. We aimed in the present study to obtain further in vitro evidence for the presence and functioning of these systems. In a first experiment, pools of sliced liver and BB were incubated for 6h at 15°C in modified Hanks' medium containing 2, 4, or 8mM d-glucose, and we assessed the response of parameters related to these glucosensing mechanisms. In a second experiment, pools of sliced liver and BB were incubated for 6h at 15°C in modified Hanks' medium with 8mM d-glucose alone (control) or containing 1mM phloridzin (SGLT-1 antagonist), 20μM genipin (UCP2 inhibitor), 1μM trolox (ROS scavenger), 100μM bezafibrate (T1R3 inhibitor), and 50μM geranyl-geranyl pyrophosphate (LXR inhibitor). The results obtained in both experiments support the presence and functioning of glucosensor mechanisms in liver based on sweet taste receptor whereas in BB the evidence support those based on LXR, mitochondrial activity and sweet taste receptor. PMID:27139261

  13. Design and Synthesis of 11C-Labelled Compound Libraries for the Molecular Imaging of EGFr, VEGFr-2, AT1 and AT2 Receptors: Transition-Metal Mediated Carbonylations Using [11C]Carbon Monoxide

    International Nuclear Information System (INIS)

    This work deals with radiochemistry and new approaches to develop novel PET tracers labelled with the radionuclide 11C. Two methods for the synthesis of 11C-labelled acrylamides have been explored. First, [1-11C]-acrylic acid was obtained from a palladium(0)-mediated 11C-carboxylation of acetylene with [11C]carbon monoxide; this could be converted to the corresponding acyl chloride and then combined with benzylamine to form N-benzyl[carbonyl-11C]acrylamide. In the second method, the palladium(0)-mediated carbonylation of vinyl halides with [11C]carbon monoxide was explored. This latter method, yielded labelled acrylamides in a single step with retention of configuration at the C=C double bond, and required less amine compared to the acetylene method. The vinyl halide method was used to synthesize a library of 11C-labelled EGFr-inhibitors in 7-61% decay corrected radiochemical yield via a combinatorial approach. The compounds were designed to target either the active or the inactive form of EGFr, following computational docking studies. The rhodium(I)-mediated carbonylative cross-coupling of an azide and an amine was shown to be a very general reaction and was used to synthesize a library of dual VEGFr-2/PDGFrβ inhibitors that were 11C-labelled at the urea position in 38-78% dc rcy. The angiotensin II AT1 receptor antagonist eprosartan was 11C-labelled at one of the carboxyl groups in one step using a palladium(0)-mediated carboxylation. Autoradiography shows specific binding in rat kidney, lung and adrenal cortex, and organ distribution shows a high accumulation in the intestines, kidneys and liver. Specific binding in frozen sections of human adrenal incidentalomas warrants further investigations of this tracer. Three angiotensin II AT2 ligands were 11C-labelled at the amide group in a palladium(0)-mediated aminocarbonylation in 16-36% dc rcy. One of the compounds was evaluated using in vitro using autoradiography, and in vivo using organ distribution and animal

  14. The P2X7 Receptor Supports Both Life and Death in Fibrogenic Pancreatic Stellate Cells

    DEFF Research Database (Denmark)

    Haanes, Kristian; Schwab, Albrecht; Novak, Ivana

    2012-01-01

    The pancreatic stellate cells (PSCs) have complex roles in pancreas, including tissue repair and fibrosis. PSCs surround ATP releasing exocrine cells, but little is known about purinergic receptors and their function in PSCs. Our aim was to resolve whether PSCs express the multifunctional P2X7...... fibrosis and cancer....

  15. Predicting the Coupling Specificity of G-protein Coupled Receptors to G-proteins by Support Vector Machines

    Institute of Scientific and Technical Information of China (English)

    Cui-Ping Guan; Zhen-Ran Jiang; Yan-Hong Zhou

    2005-01-01

    G-protein coupled receptors (GPCRs) represent one of the most important classes of drug targets for pharmaceutical industry and play important roles in cellular signal transduction. Predicting the coupling specificity of GPCRs to G-proteins is vital for further understanding the mechanism of signal transduction and the function of the receptors within a cell, which can provide new clues for pharmaceutical research and development. In this study, the features of amino acid compositions and physiochemical properties of the full-length GPCR sequences have been analyzed and extracted. Based on these features, classifiers have been developed to predict the coupling specificity of GPCRs to G-proteins using support vector machines. The testing results show that this method could obtain better prediction accuracy.

  16. Angiotensin type 2 receptors

    DEFF Research Database (Denmark)

    Sumners, Colin; de Kloet, Annette D; Krause, Eric G;

    2015-01-01

    In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral....... However, stimulation of AT2R locally within the brain or the kidney apparently elicits a systemic blood pressure lowering effect. A systemic effect of AT2R stimulation on blood pressure can also be achieved, when the prevailing effect of continuous background AT1R-stimulation is attenuated by low-dose AT1......R blockade. Despite a lack of effect on blood pressure, AT2R stimulation still protects from hypertensive end-organ damage. Current data and evidence therefore suggest that AT2R agonists will not be suitable as future anti-hypertensive drugs, but that they may well be useful for end-organ protection...

  17. The discovery of new potent non-peptide Angiotensin II AT1 receptor blockers: A concise synthesis, molecular docking studies and biological evaluation of N-substituted 5-butylimidazole derivatives

    Czech Academy of Sciences Publication Activity Database

    Agelis, G.; Resvani, A.; Durdagi, S.; Spyridaki, K.; Tůmová, Tereza; Slaninová, Jiřina; Giannopoulos, P.; Vlahakos, D.; Liapakis, G.; Mavromoustakos, T.; Matsoukas, J.

    2012-01-01

    Roč. 55, Sep (2012), s. 358-374. ISSN 0223-5234 Institutional research plan: CEZ:AV0Z40550506 Keywords : synthesis * angiotensin II receptor blockers * N-substituted 5-butylimidazole derivatives * antihypertensive activity * molecular docking Subject RIV: CC - Organic Chemistry Impact factor: 3.499, year: 2012

  18. Tempol improves AT1 receptor expression in kidney of obese-related hypertensive rats by reducing oxidative stress%Tempol通过降低氧化应激下调肥胖相关性高血压大鼠肾脏AT1受体表达

    Institute of Scientific and Technical Information of China (English)

    罗浩; 王新全; 王甲良; 陈彩宇; 周发英; 曾敬; 张骏; 曾春雨

    2014-01-01

    目的 探讨Tempol通过降低氧化应激,下调肥胖Zucker大鼠肾脏AT1受体的表达及功能.方法 选用12周龄的雄性瘦型(体质量260 ~280 g)及肥胖型(体质量400 ~ 420 g)Zucker大鼠各10只,实验分为瘦型对照组、肥胖对照组、瘦型处理组及肥胖处理组.对照组给予正常饮水,处理组给予Tempol(1.0 mmol/L)处理,4周后通过血糖仪测定血糖,ELISA法测定血清胰岛素,血浆生化仪测定甘油三酯及总胆固醇,无创鼠尾侧压仪测定血压,比较4组Zucker大鼠一般生理参数.ELISA法测定4组大鼠血清氧化应激(MDA、SOD)水平变化.通过肾上腺动脉灌注AT1受体阻断剂(坎地沙坦)测定4组大鼠尿钠排泄,在体观察肾脏AT1受体功能.qRT-PCR检测大鼠肾脏AT1的mRNA表达,Western blot法测定大鼠肾脏AT1受体的蛋白表达.结果 肥胖Zucker大鼠体质量、肾脏大小、甘油三酯、胆固醇、空腹血糖、胰岛素及血压较瘦型Zucker大鼠均显著升高(P<0.05).肾上腺动脉灌注坎地沙坦后,肥胖Zucker大鼠的排钠利尿反应性明显强于瘦型大鼠[尿流速:(4.90±0.40)vs(13.30±0.78) μL/min,P<0.05;尿钠排泄率:(0.44±0.07)vs(1.63 ±0.18)μmol/min,P<0.05],同时AT1受体的mRNA及蛋白表达在肥胖Zucker大鼠肾脏也显著高于瘦型大鼠[mRNA:(0.38±0.11) vs(0.88±0.21),P<0.05;蛋白:(0.85 ±0.03) vs (1.26 ±0.05),P<0.05].通过Tempol处理4周后,可明显改善肥胖Zucker大鼠上述变化,而Tempol对瘦型Zucker大鼠无相应作用.结论 Tempol通过降低氧化应激下调肥胖相关性高血压Zucker大鼠肾脏AT1受体的表达及功能.

  19. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  20. NMDA receptors on non-dopaminergic neurons in the VTA support cocaine sensitization.

    Directory of Open Access Journals (Sweden)

    Yu Luo

    Full Text Available BACKGROUND: The initiation of behavioral sensitization to cocaine and other psychomotor stimulants is thought to reflect N-methyl-D-aspartate receptor (NMDAR-mediated synaptic plasticity in the mesolimbic dopamine (DA circuitry. The importance of drug induced NMDAR mediated adaptations in ventral tegmental area (VTA DA neurons, and its association with drug seeking behaviors, has recently been evaluated in Cre-loxp mice lacking functional NMDARs in DA neurons expressing Cre recombinase under the control of the endogenous dopamine transporter gene (NR1(DATCre mice. METHODOLOGY AND PRINCIPAL FINDINGS: Using an additional NR1(DATCre mouse transgenic model, we demonstrate that while the selective inactivation of NMDARs in DA neurons eliminates the induction of molecular changes leading to synaptic strengthening, behavioral measures such as cocaine induced locomotor sensitization and conditioned place preference remain intact in NR1(DATCre mice. Since VTA DA neurons projecting to the prefrontal cortex and amygdala express little or no detectable levels of the dopamine transporter, it has been speculated that NMDA receptors in DA neurons projecting to these brain areas may have been spared in NR1(DATCre mice. Here we demonstrate that the NMDA receptor gene is ablated in the majority of VTA DA neurons, including those exhibiting undetectable DAT expression levels in our NR1(DATCre transgenic model, and that application of an NMDAR antagonist within the VTA of NR1(DATCre animals still blocks sensitization to cocaine. CONCLUSIONS/SIGNIFICANCE: These results eliminate the possibility of NMDAR mediated neuroplasticity in the different DA neuronal subpopulations in our NR1(DATCre mouse model and therefore suggest that NMDARs on non-DA neurons within the VTA must play a major role in cocaine-related addictive behavior.

  1. The impact of luteal phase support on endometrial estrogen and progesterone receptor expression: a randomized control trial

    Directory of Open Access Journals (Sweden)

    Brezina Paul R

    2012-02-01

    Full Text Available Abstract Background To assess the impact of luteal phase support on the expression of estrogen receptor (ER alpha and progesterone receptors B (PR-B on the endometrium of oocyte donors undergoing controlled ovarian hyperstimulation (COH. Methods A prospective, randomized study was conducted in women undergoing controlled ovarian hyperstimulation for oocyte donation. Participants were randomized to receive no luteal support, vaginal progesterone alone, or vaginal progesterone plus orally administered 17 Beta estradiol. Endometrial biopsies were obtained at 4 time points in the luteal phase and evaluated by tissue microarray for expression of ER alpha and PR-B. Results One-hundred and eight endometrial tissue samples were obtained from 12 patients. No differences were found in expression of ER alpha and PR-B among all the specimens with the exception of one sample value. Conclusions The administration of progesterone during the luteal phase of COH for oocyte donor cycles, either with or without estrogen, does not significantly affect the endometrial expression of ER alpha and PR.

  2. Oxytocin Receptor Gene (OXTR) Polymorphism, Perceived Social Support, and Psychological Symptoms in Maltreated Adolescents

    OpenAIRE

    Hostinar, Camelia E.; Cicchetti, Dante; Rogosch, Fred A.

    2014-01-01

    Despite the detrimental consequences of child maltreatment on developmental processes, some individuals show remarkable resilience, with few signs of psychopathology, while others succumb to dysfunction. Given that oxytocin has been shown to be involved in social affiliation, attachment, social support, trust, empathy, and other social or reproductive behaviors, we chose to examine the possible moderation of maltreatment effects on perceived social support and on psychological symptoms by a c...

  3. Identification of G protein-coupled receptors for Drosophila PRXamide peptides, CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution

    OpenAIRE

    Park, Yoonseong; KIM, YOUNG-JOON; Adams, Michael E.

    2002-01-01

    G-protein coupled receptors (GPCRs) are ancient, ubiquitous sensors vital to environmental and physiological signaling throughout organismal life. With the publication of the Drosophila genome, numerous “orphan” GPCRs have become available for functional analysis. Here we characterize two groups of GPCRs predicted as receptors for peptides with a C-terminal amino acid sequence motif consisting of −PRXamide (PRXa). Assuming ligand-receptor coevolution, two alternative hypotheses were construct...

  4. Differential extracellular signal-regulated kinases 1 and 2 activation by the angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael;

    2007-01-01

    The angiotensin II (AngII) type 1 receptor (AT(1)R) is a seven-transmembrane receptor well established to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) by discrete G protein-dependent and beta-arrestin2-dependent pathways. The biological importance of this, however, remains obs...... obscure. Application of the modified analogue [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) allowed us to dissect the two pathways of ERK1/2 activation in native cardiac myocytes. Although cytosol-retained, the beta-arrestin2-bound pool of ERK1/2 represents an active signalling component...

  5. Altered efficacy of AT1R-targeted treatment after spontaneous cancer cell-AT1R upregulation

    International Nuclear Information System (INIS)

    Targeting of the renin angiotensin system (RAS) reduces tumour growth in experimental models of cancer. We aimed to establish if combined targeting of the 'classical' and 'alternative' arms of the RAS could result in synergistic inhibition of colorectal cancer (CRC) liver metastases. Immediately following induction of CRC liver metastases through intrasplenic injection of murine CRC cells, treatment with irbesartan (AT1R blocker; 50 mg/kg/day s.c.), captopril (ACE inhibitor; 750 mg/kg/day i.p.), CGP42112A (AT2R agonist; 0.6 μg/kg/hr i.p.), and/or ANG-(1-7) (24 μg/kg/hr i.p.) began and continued for 21 days. Liver to body weight ratio and/or stereology were used as a measure of tumour burden. Immunohistochemistry was used to determine AT1R and VEGF expression as well as proliferation (Ki67), apoptosis (active caspase 3) and angiogenesis (CD34). Combined RAS therapies failed to improve upon single arm therapies. However, while irbesartan previously inhibited tumour growth in this model, in the current experiments irbesartan failed to affect tumour burden. Subsequent analysis showed a cancer-cell specific upregulation of the angiotensin II type I receptor (AT1R) in irbesartan-insensitive compared to irbesartan-sensitive tumours. The upregulation of AT1R was associated with an increase in proliferation and VEGF expression by cancer cells. While animals bearing irbesartan-sensitive tumours showed a marked decrease in the number of proliferating cells in the liver and VEGF-expressing infiltrating cells in the tumour following AT1R treatment, these were unchanged by treatment in animals bearing irbesartan-insensitive (high AT1R expressing) tumours. Although the results do not support increased efficacy of combined treatment, they provide intriguing evidence of the importance of RAS expression in determining patient response and tumour growth potential and suggest that components of the RAS could be used as biomarkers to aid in patient selection

  6. A novel fractal approach for predicting G-protein-coupled receptors and their subfamilies with support vector machines.

    Science.gov (United States)

    Nie, Guoping; Li, Yong; Wang, Feichi; Wang, Siwen; Hu, Xuehai

    2015-01-01

    G-protein-coupled receptors (GPCRs) are seven membrane-spanning proteins and regulate many important physiological processes, such as vision, neurotransmission, immune response and so on. GPCRs-related pathways are the targets of a large number of marketed drugs. Therefore, the design of a reliable computational model for predicting GPCRs from amino acid sequence has long been a significant biomedical problem. Chaos game representation (CGR) reveals the fractal patterns hidden in protein sequences, and then fractal dimension (FD) is an important feature of these highly irregular geometries with concise mathematical expression. Here, in order to extract important features from GPCR protein sequences, CGR algorithm, fractal dimension and amino acid composition (AAC) are employed to formulate the numerical features of protein samples. Four groups of features are considered, and each group is evaluated by support vector machine (SVM) and 10-fold cross-validation test. To test the performance of the present method, a new non-redundant dataset was built based on latest GPCRDB database. Comparing the results of numerical experiments, the group of combined features with AAC and FD gets the best result, the accuracy is 99.22% and Matthew's correlation coefficient (MCC) is 0.9845 for identifying GPCRs from non-GPCRs. Moreover, if it is classified as a GPCR, it will be further put into the second level, which will classify a GPCR into one of the five main subfamilies. At this level, the group of combined features with AAC and FD also gets best accuracy 85.73%. Finally, the proposed predictor is also compared with existing methods and shows better performances. PMID:26405954

  7. Extended and Structurally Supported Insights into Extracellular Hormone Binding, Signal Transduction and Organization of the Thyrotropin Receptor

    OpenAIRE

    Krause, Gerd; Kreuchwig, Annika; Kleinau, Gunnar

    2012-01-01

    The hormone thyrotropin (TSH) and its receptor (TSHR) are crucial for the growth and function of the thyroid gland. The TSHR is evolutionary linked with the receptors of follitropin (FSHR) and lutropin/choriogonadotropin (LHR) and their sequences and structures are similar. The extracellular region of TSHR contains more than 350 amino acids and binds hormone and antibodies. Several important questions related to functions and mechanisms of TSHR are still not comprehensively understood. One ma...

  8. [AT1-blockers in the treatment of hypertension: summary].

    Science.gov (United States)

    Jr, Jiří Widimský

    2016-02-01

    Angiotensin receptor antagonists (AT(1)-blockers) are considered as one of the major classes of antihypertensive drugs suitable for monotherapy as well as for combination treatment. AT(1)-blockers have comparable antihypertensive efficacy with other major classes of antihypertensive drugs. AT(1)-blockers are considered by current guidelines of Czech society of hypertension altogether with ACE-inhibitors and calcium channel blockers as universal antihypertensive drug class. AT(1)-blockers has the lowest profile of side-effects among all antihypertensive drug classes and thus very high persistence to therapy. Mechanisms of antihypertensive effects of AT(1)-blockers are discussed altogether with the results of large clinical trials and indications in the treatment of hypertension. PMID:27172437

  9. Effects of multivalent histamine supported on gold nanoparticles: activation of histamine receptors by derivatized histamine at subnanomolar concentrations.

    Science.gov (United States)

    Gasiorek, Friederike; Pouokam, Ervice; Diener, Martin; Schlecht, Sabine; Wickleder, Mathias S

    2015-10-21

    Colloidal gold nanoparticles with a functionalized ligand shell were synthesized and used as new histamine receptor agonists. Mercaptoundecanoic acid moieties were attached to the surface of the nanoparticles and derivatized with native histamine. The multivalent presentation of the immobilized ligands carried by the gold nanoparticles resulted in extremely low activation concentrations for histamine receptors on rat colonic epithelium. As a functional read-out system, chloride secretion resulting from stimulation of neuronal and epithelial histamine H1 and H2 receptors was measured in Ussing chamber experiments. These responses were strictly attributed to the histamine entities as histamine-free particles Au-MUDOLS or the monovalent ligand AcS-MUDA-HA proved to be ineffective. The vitality of the tissues used was not impaired by the nanoparticles. PMID:26289108

  10. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease.

    Science.gov (United States)

    Barnich, Nicolas; Carvalho, Frédéric A; Glasser, Anne-Lise; Darcha, Claude; Jantscheff, Peter; Allez, Matthieu; Peeters, Harald; Bommelaer, Gilles; Desreumaux, Pierre; Colombel, Jean-Frédéric; Darfeuille-Michaud, Arlette

    2007-06-01

    The ileal mucosa of Crohn disease (CD) patients is abnormally colonized by adherent-invasive E. coli (AIEC) that are able to adhere to and invade intestinal epithelial cells. Here, we show that CD-associated AIEC strains adhere to the brush border of primary ileal enterocytes isolated from CD patients but not controls without inflammatory bowel disease. AIEC adhesion is dependent on type 1 pili expression on the bacterial surface and on carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression on the apical surface of ileal epithelial cells. We report also that CEACAM6 acts as a receptor for AIEC adhesion and is abnormally expressed by ileal epithelial cells in CD patients. In addition, our in vitro studies show that there is increased CEACAM6 expression in cultured intestinal epithelial cells after IFN-gamma or TNF-alpha stimulation and after infection with AIEC bacteria, indicating that AIEC can promote its own colonization in CD patients. PMID:17525800

  11. Histamine-1 receptor blockade does not prevent nitroglycerin induced migraine. Support for the NO-hypothesis of migraine

    DEFF Research Database (Denmark)

    Lassen, L H; Thomsen, L L; Kruuse, C; Iversen, Helle Klingenberg; Olesen, J

    1996-01-01

    evaluate whether GTN causes headache via liberation of histamine, we studied the effect of GTN 0.5 micrograms.kg-1.min-1 for 20 min in seven migraine sufferers, once after pretreatment with the histamine-1 (H1)-receptor blocker mepyramine (0.5 mg.kg-1) and once without pretreatment. This mepyramine dose is......It has previously been shown that in migraine sufferers infusion of glyceryl trinitrate (GTN) and histamine causes an immediate headache during the infusion and a genuine migraine attack one to several hours after the infusion. This identical time profile indicates a common mechanism of action. To...... known to completely abolish histamine-induced headache. After pretreatment with mepyramine five patients experienced migraine, and without pretreatment six patients did so. The median peak headache score was 7 on a 0-10 scale with and without mepyramine pretreatment. The arterial responses, evaluated...

  12. Hydrogen adsorption on palladium and palladium hydride at 1 bar

    DEFF Research Database (Denmark)

    Johansson, Martin; Skulason, Egill; Nielsen, Gunver;

    2010-01-01

    The dissociative sticking probability for H-2 on Pd films supported on sputtered Highly Ordered Pyrolytic Graphite (HOPG) has been derived from measurements of the rate of the H-D exchange reaction at 1 bar. The sticking probability for H-2, S. is higher on Pd hydride than on Pd (a factor of 1.4 ...

  13. DNA Methylation at the Neonatal State and at the Time of Diagnosis: Preliminary Support for an Association with the Estrogen Receptor 1, Gamma-Aminobutyric Acid B Receptor 1, and Myelin Oligodendrocyte Glycoprotein in Female Adolescent Patients with OCD

    Science.gov (United States)

    Nissen, Judith Becker; Hansen, Christine Søholm; Starnawska, Anna; Mattheisen, Manuel; Børglum, Anders Dupont; Buttenschøn, Henriette Nørmølle; Hollegaard, Mads

    2016-01-01

    Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder. Non-genetic factors and their interaction with genes have attracted increasing attention. Epigenetics is regarded an important interface between environmental signals and activation/repression of genomic responses. Epigenetic mechanisms have not previously been examined in OCD in children and adolescents. The aim of the present study was to examine the DNA methylation profile of selected genes in blood spots from neonates later diagnosed with OCD and in the same children/adolescents at the time of diagnosis compared with age- and sex-matched controls. Furthermore, we wanted to characterize the association of the differential methylation profiles with the severity of OCD and treatment outcome. Dried and new blood spot samples were obtained from 21 female children/adolescents with verified OCD and 12 female controls. The differential methylation was analyzed using a linear model and the correlation with the severity of OCD and treatment outcome was analyzed using the Pearson correlation. We evaluated selected Illumina Infinium HumanMethylation450 BeadChip probes within and up to 100,000 bp up- and downstream of 14 genes previously associated with OCD (SLC1A1, SLC25A12, GABBR1, GAD1, DLGAP1, MOG, BDNF, OLIG2, NTRK2 and 3, ESR1, SL6A4, TPH2, and COMT). The study found no significantly differential methylation. However, preliminary support for a difference was found for the gamma-aminobutyric acid (GABA) B receptor 1 (cg10234998, cg17099072) in blood samples at birth and for the estrogen receptor 1 (ESR1) (cg10939667), the myelin oligodendrocyte glycoprotein (MOG) (cg16650906), and the brain-derived neurotrophic factor (BDNF) (cg14080521) in blood samples at the time of diagnosis. Preliminary support for an association was observed between the methylation profiles of GABBR1 and MOG and baseline severity, treatment effect, and responder status; and between the methylation profile of ESR1 and baseline

  14. Toll-like receptors 2 and 4 mediate the capacity of mesenchymal stromal cells to support the proliferation and differentiation of CD34{sup +} cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xingbing, E-mail: wangxingbing91@hotmail.com [Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui (China); Cheng, Qiansong; Li, Lailing; Wang, Jian; Xia, Liang [Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui (China); Xu, Xiucai [The Center Laboratory of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui (China); Sun, Zimin [Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui (China)

    2012-02-01

    Bone marrow derived-mesenchymal stromal cells (BM-MSCs) are multipotent, nonhematopoietic progenitors in a hematopoietic microenvironment and indispensable for regulating hematopoiesis. Several studies have reported that toll-like receptors (TLRs) are expressed in mesenchymal stromal cells (MSCs) to modulate their biological functions. In this study, we investigated the possible role(s) of TLRs in mediating the hematopoiesis-supporting role of human BM-MSCs. Human BM-MSCs were analyzed for mRNA expression of TLR1-10 by reverse transcription-polymerase chain reaction. TLR1-6, but not TLR7-10 were expressed by BM-MSCs. The protein expression of TLR2 and TLR4 was also confirmed by flow cytometry. We further explored the role of TLR2 and TLR4 in mediating the capacity of BM-MSCs to support the proliferation and differentiation of CD34{sup +} hematopoietic stem/progenitor cells obtained from cord blood. BM-MSCs increased proliferation of CD34{sup +} cells and promoted the differentiation towards the myeloid lineage 7 or 14 days after co-culture, as well as colony formation by those cells and the production of interleukin 1 (IL-1), IL-8, IL-11, stem cell factor (SCF), granulocyte colony-stimulating factor (CSF), macrophage CSF and granulocyte-macrophage CSF, if MSCs had been stimulated with TLR2 agonist (PAM{sub 3}CSK{sub 4}) or TLR4 agonist (LPS). Interestingly, although these effects were elevated in a different degree, a synergistic effect was not observed in BM-MSCs co-stimulated with PAM{sub 3}CSK{sub 4} and LPS. Together, our findings suggest that TLR2 and TLR4 signaling may indirectly regulate hematopoiesis by modulating BM-MSCs' functions. The increased hematopoietic proliferation and differentiation could be mediated, at least in part, by augmented hematopoiesis-related cytokine production of BM-MSCs.

  15. An evolutionary conserved region (ECR in the human dopamine receptor D4 gene supports reporter gene expression in primary cultures derived from the rat cortex

    Directory of Open Access Journals (Sweden)

    Haddley Kate

    2011-05-01

    Full Text Available Abstract Background Detecting functional variants contributing to diversity of behaviour is crucial for dissecting genetics of complex behaviours. At a molecular level, characterisation of variation in exons has been studied as they are easily identified in the current genome annotation although the functional consequences are less well understood; however, it has been difficult to prioritise regions of non-coding DNA in which genetic variation could also have significant functional consequences. Comparison of multiple vertebrate genomes has allowed the identification of non-coding evolutionary conserved regions (ECRs, in which the degree of conservation can be comparable with exonic regions suggesting functional significance. Results We identified ECRs at the dopamine receptor D4 gene locus, an important gene for human behaviours. The most conserved non-coding ECR (D4ECR1 supported high reporter gene expression in primary cultures derived from neonate rat frontal cortex. Computer aided analysis of the sequence of the D4ECR1 indicated the potential transcription factors that could modulate its function. D4ECR1 contained multiple consensus sequences for binding the transcription factor Sp1, a factor previously implicated in DRD4 expression. Co-transfection experiments demonstrated that overexpression of Sp1 significantly decreased the activity of the D4ECR1 in vitro. Conclusion Bioinformatic analysis complemented by functional analysis of the DRD4 gene locus has identified a a strong enhancer that functions in neurons and b a transcription factor that may modulate the function of that enhancer.

  16. Parcels and Land Ownership, Contains parcels, subdivisions, CSMs, Condominiums, Rights of Way and supporting annotation. Data within the City of West Bend are maintained by the City. Some areas are mapped at 1:1200, Published in 2013, 1:2400 (1in=200ft) scale, Washington County Planning and Parks Department.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Parcels and Land Ownership dataset, published at 1:2400 (1in=200ft) scale, was produced all or in part from Published Reports/Deeds information as of 2013. It...

  17. Beta-adrenergic receptors support attention to extinction learning that occurs in the absence, but not the presence, of a context change

    Directory of Open Access Journals (Sweden)

    Marion Emma André

    2015-05-01

    Full Text Available The noradrenergic (NA-system is an important regulator of cognitive function. It contributes to extinction learning(EL, and in disorders where EL is impaired NA-dysfunction has been postulated. We explored whether NA acting on beta-adrenergic-receptors (β-AR, regulates EL that depends on context, but is not fear-associated. We assessed behaviour in an ‘AAA’ or ‘ABA’ paradigm: rats were trained for 3 days in a T-maze(context-A to learn that a reward is consistently found in the goal arm, despite low reward probability. This was followed on day 4 by EL(unrewarded, whereby in the ABA-paradigm, EL was reinforced by a context change (B, and in the AAA-paradigm, no context change occurred. On day 5, re-exposure to the A-context (unrewarded occurred. Typically, in control ‘AAA’ animals EL occurred on day 4 that progressed further on day 5. In control ‘ABA’ animals, EL also occurred on day 4, followed by renewal of the previously learned (A behavior on day 5, that was followed (in day 5 by extinction of this behavior, as the animals realised that no food reward would be given.Treatment with the β-AR-antagonist, propranolol, prior to EL on day 4, impaired EL in the AAA-paradigm. In the ‘ABA’ paradigm, antagonist treatment on day 4, had no effect on extinction that was reinforced by a context change (B. Furthermore, β-AR-antagonism prior to renewal testing (on day 5 in the ABA-paradigm, resulted in normal renewal behavior, although subsequent extinction of responses during day 5 was prevented by the antagonist. Thus, under both treatment conditions, β-AR-antagonism prevented extinction of the behavior learned in the ‘A’ context.β-AR-blockade during an overt context change did not prevent EL, whereas β-AR were required for EL in an unchanging context. These data suggest that β-AR may support EL by reinforcing attention towards relevant changes in the previously learned experience, and that this process supports extinction

  18. Functional interaction between angiotensin II receptor type 1 and chemokine (C-C motif receptor 2 with implications for chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Mohammed Akli Ayoub

    Full Text Available Understanding functional interactions between G protein-coupled receptors is of great physiological and pathophysiological importance. Heteromerization provides one important potential mechanism for such interaction between different signalling pathways via macromolecular complex formation. Previous studies suggested a functional interplay between angiotensin II receptor type 1 (AT1 and Chemokine (C-C motif Receptor 2 (CCR2. However the molecular mechanisms are not understood. We investigated AT1-CCR2 functional interaction in vitro using bioluminescence resonance energy transfer in HEK293 cells and in vivo using subtotal-nephrectomized rats as a well-established model for chronic kidney disease. Our data revealed functional heteromers of these receptors resulting in CCR2-Gαi1 coupling being sensitive to AT1 activation, as well as apparent enhanced β-arrestin2 recruitment with agonist co-stimulation that is synergistically reversed by combined antagonist treatment. Moreover, we present in vivo findings where combined treatment with AT1- and CCR2-selective inhibitors was synergistically beneficial in terms of decreasing proteinuria, reducing podocyte loss and preventing renal injury independent of blood pressure in the subtotal-nephrectomized rat model. Our findings further support a role for G protein-coupled receptor functional heteromerization in pathophysiology and provide insights into previous observations indicating the importance of AT1-CCR2 functional interaction in inflammation, renal and hypertensive disorders.

  19. AT1R blockade in adverse milieus: role of SMRT and corepressor complexes.

    Science.gov (United States)

    Singh, Tejinder; Ayasolla, Kamesh; Rai, Partab; Chandel, Nirupama; Haque, Shabirul; Lederman, Rivka; Husain, Mohammad; Vethantham, Vasupradha; Chawla, Amrita; Vashistha, Himanshu; Saleem, Moin A; Ding, Guohua; Chander, Praveen N; Malhotra, Ashwani; Meggs, Leonard G; Singhal, Pravin C

    2015-08-01

    ANG II type 1 receptor blockade (AT1R-BLK) is used extensively to slow down the progression of proteinuric kidney diseases. We hypothesized that AT1R-BLK provides podocyte protection through regulation of silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and vitamin D receptor (VDR) expression under adverse milieus such as high glucose and human immunodeficiency virus infection. Both AT1R-BLK and VDR agonists (VDAs) stimulated VDR complex formation that differed not only in their composition but also in their functionality. AT1R-BLK-induced VDR complexes contained predominantly unliganded VDR, SMRT, and phosphorylated histone deacetylase 3, whereas VDA-VDR complexes were constituted by liganded VDR and CREB-binding protein/p300. AT1R-BLK-induced complexes attenuated podocyte acetyl-histone 3 levels as well as cytochrome P-450 family 24A1 expression, thus indicating their deacetylating and repressive properties. On the other hand, VDA-VDR complexes not only increased podocyte acetyl-histone 3 levels but also enhanced cytochrome P-450 family 24A1 expression, thus suggesting their acetylating and gene activation properties. AT1R-BLK- induced podocyte SMRT inhibited expression of the proapoptotic gene BAX through downregulation of Wip1 and phosphorylation of checkpoint kinase 2 in high-glucose milieu. Since SMRT-depleted podocytes lacked AT1R-BLK-mediated protection against DNA damage, it appears that SMRT is necessary for DNA repairs during AT1R-BLK. We conclude that AT1R-BLK provides podocyte protection in adverse milieus predominantly through SMRT expression and partly through unliganded VDR expression in 1,25(OH)2D-deficient states; on the other hand, AT1R-BLK contributes to liganded VDR expression in 1,25(OH)2D-sufficient states. PMID:26084932

  20. Monellin (MNEI) at 1.15 Å resolution

    International Nuclear Information System (INIS)

    The crystal structure of the sweet protein MNEI at 1.15 Å resolution reveals networks of alternate conformations and stably bound negative ions. The X-ray crystal structure of a single-chain monellin protein (MNEI) has been determined at 1.15 Å resolution. The model was refined to convergence employing anisotropic displacement parameters and riding H atoms to produce a final model with Rwork and Rfree values of 0.132 and 0.162, respectively. The crystal contains a single MNEI protein in the asymmetric unit and unusually lacks the dimer interface observed in all previous crystal structures of monellin and its single-chain derivatives. The high resolution allowed a more detailed view of MNEI than previously possible, with 38 of the 96 residues modelled with alternative side-chain conformations, including four core residues Thr12, Cys41, Leu62 and Ile75. Four stably bound negative ions were also located, providing new insight into potential electrostatic interactions of MNEI with the largely negatively charged surface of the sweet taste receptor T1R2–T1R3

  1. Enhanced central serotonin release from slices of rat hypothalamus following repeated nialamide administration: evidence supporting the overactive serotonin receptor theory of depression

    International Nuclear Information System (INIS)

    Researchers are suggesting unipolar affective disorders may be related to an abnormality in biogenic amine receptor-sensitivity. This abnormality may be a result of a dysfunction in central serotonin (5-HT) release mechanisms. 5-HT neurotransmission is modulated by presynaptic autoreceptors, which are members of the 5-HT1 receptor subtype. The autoreceptor is thought to play an important role in the homeostasis of the central 5-HT synapse and could be a site at which some antidepressants mediate their therapeutic effect. The number of 5-HT1 type receptor binding sites are reduced and behavior mediated by this receptor is abolished following repeated injections of monoamine oxidase inhibitor type antidepressants. These changes did not occur following a single injection. It was hypothesized that repeated treatment with a monoamine oxidase inhibitor would reduce the sensitivity of 5-HT autoreceptors and enhance 5-HT release. Rats were pretreated with single or repeated (twice daily for 7 days) intraperitoneal injections of nialamide (40 mg/kg) or chlorimipramine (10 mg/kg) and the ability of the autoreceptor agonist to inhibit potassium-induced 3H-5-HT release was evaluated using an in vitro superfusion system. These changes in 5-HT autoreceptor activity are consistent with other reports evaluating monoamine oxidase inhibitors on 5-HT1 type receptors. It is hypothesized that the changes in 5-HT neurotransmission are related to the antidepressant mechanism of monoamine oxidase inhibitors

  2. Tsh receptor

    OpenAIRE

    Frauman, Albert

    2013-01-01

    The TSH receptor is a member of the G protein-coupled receptor(GPCR)family. It is one of the glycoprotein hormone receptors, which also includes the FSH and LH/CG receptors. The TSH receptor mediates the action of the pituitary-derived glycoprotein, TSH (thyroid stimulating hormone, thyrotropin or thyrotrophin). TSH binds to the TSH receptor which is located on thyroid follicular cells (but is also expressed in extrathyroidal sites). Glycosylation of the TSH receptor occurs, as does cleavage ...

  3. Mitochondrial calcium uniporter MCU supports cytoplasmic Ca2+ oscillations, store-operated Ca2+ entry and Ca2+-dependent gene expression in response to receptor stimulation.

    Directory of Open Access Journals (Sweden)

    Krishna Samanta

    Full Text Available Ca2+ flux into mitochondria is an important regulator of cytoplasmic Ca2+ signals, energy production and cell death pathways. Ca2+ uptake can occur through the recently discovered mitochondrial uniporter channel (MCU but whether the MCU is involved in shaping Ca2+ signals and downstream responses to physiological levels of receptor stimulation is unknown. Here, we show that modest stimulation of leukotriene receptors with the pro-inflammatory signal LTC4 evokes a series of cytoplasmic Ca2+ oscillations that are rapidly and faithfully propagated into mitochondrial matrix. Knockdown of MCU or mitochondrial depolarisation, to reduce the driving force for Ca2+ entry into the matrix, prevents the mitochondrial Ca2+ rise and accelerates run down of the oscillations. The loss of cytoplasmic Ca2+ oscillations appeared to be a consequence of enhanced Ca2+-dependent inactivation of InsP3 receptors, which arose from the loss of mitochondrial Ca2+ buffering. Ca2+ dependent gene expression in response to leukotriene receptor activation was suppressed following knockdown of the MCU. In addition to buffering Ca2+ release, mitochondria also sequestrated Ca2+ entry through store-operated Ca2+ channels and this too was prevented following loss of MCU. MCU is therefore an important regulator of physiological pulses of cytoplasmic Ca2+.

  4. Activation of adenosine A3 receptors supports hematopoiesis-stimulating effects of granulocyte colony-stimulating factor in sublethally irradiated mice

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Pospíšil, Milan; Šefc, L.; Dušek, L.; Vacek, Antonín; Holá, Jiřina; Hoferová, Zuzana; Štreitová, Denisa

    2010-01-01

    Roč. 86, č. 8 (2010), s. 649-656. ISSN 0955-3002 R&D Projects: GA ČR(CZ) GA305/08/0158 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : ionising radiation * hematopoiesis * adenosine A3 receptors Subject RIV: BO - Biophysics Impact factor: 1.861, year: 2010

  5. Expression of G protein-coupled receptor 19 in human lung cancer cells is triggered by entry into S phase and supports G2/M cell cycle progression

    International Nuclear Information System (INIS)

    G protein-coupled receptors (GPCRs) represent the largest family of cell surface receptors. However, only a fraction of the more than 800 receptors have been characterized to an extent that their physiological role is reasonably well understood. In fact, current pharmacotherapy only addresses some 60 receptors with a large collection of compounds that represent about 30% of the available drugs. It has long been known that GPCRs are subject to illegitimate expression in cancer cells. Presumably, hijacking the normal physiological functions of GPCRs contributes to all biological capabilities acquired during the multistep development of human cancers. With the goal of linking G protein-coupled receptors to malignant diseases, GPCRs were searched for that revealed high expression levels in small cell lung cancer (SCLC): The mRNA encoding orphan G protein-coupled receptor 19 (GPR19) was found to be frequently overexpressed in tissue samples obtained from patients with SCLC in contrast to samples derived from non-SCLC or normal lung. Several observations indicate that overexpression of Gpr19 confers a specific advantage to human lung cancer-derived cells regarding the transition through the cell cycle. Knockdown of Gpr19 mRNA by RNA interference reduced cell growth of human lung cancer cell lines and led to cell death. Cell cycle progression through G2/M phase was impaired and this was associated with increased protein levels of cyclin B1 and phosphorylated histone H3. Gpr19 exhibited a cell cycle-dependent expression pattern in lung cancer cell lines. When cell cycle distribution profiles of cells released from cell cycle arrest were related to Gpr19 mRNA levels, a peak Gpr19 expression was detected during S phase. The control of Gpr19 expression by E2F transcription factors, which drive gene expression of many genes important for cell cycle progression, was verified by chromatin immunoprecipitation: Antibodies directed against E2F-1 to E2F-4 allowed for the recovery of

  6. G Protein-coupled receptors

    OpenAIRE

    Ross, Elliott M.

    2014-01-01

    G protein-coupled receptors and heterotrimeric G proteins can diffuse laterally in the plasma membrane such that one receptor can catalyze the activation (GDP/GTP exchange) of multiple G proteins. In some cases, these processes are fast enough to support molecular signal amplification, where a single receptor maintains the activation of multiple G proteins at steady-state. Amplification in cells is probably highly regulated. It depends upon the identities of the G receptor and G protein - som...

  7. Characterization of 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine at androgen receptor: mechanistic support for its role in prostate cancer.

    Science.gov (United States)

    Glass-Holmes, Mashunté; Aguilar, Byron J; Gragg, Richard D; Darling-Reed, Selina; Goodman, Carl B

    2015-01-01

    2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) is a dietary mutagenic carcinogen that has been shown not only to induce the formation of DNA adducts, but is capable of inducing tumors in the colon, mammary, and prostate glands. The normal development and maturation of the prostate gland, as well as early progression of prostate cancer, is dependent on androgens acting on the androgen receptor (AR). The actual mechanism by which PhIP interacts with our biological system and its potential interaction at the AR has yet to be fully defined. Here, we describe our work in evaluating the molecular events associated with PhIP-mediated disruption of AR function in LNCaP human prostate cancer cells. We demonstrate, by molecular docking simulation, that PhIP and its metabolite can bind to the ligand-binding domain (LBD). The binding competes with dihydrotestosterone (DHT) in the native AR binding cavity of the receptor. In vitro assays show that PhIP increase AR protein expression in LNCaP cells and alters its responsiveness through PSA protein and mRNA expression. We propose that the mechanism for the tissue-specific carcinogenicity seen in the rat prostate tumors and the presumptive human prostate cancer associated with the consumption of well-done meat may be mediated by this receptor activation. Our results indicate that PhIP may play an important role in modifications of AR function. PMID:25628930

  8. Characterization of 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine at androgen receptor: mechanistic support for its role in prostate cancer

    OpenAIRE

    Glass-Holmes, Mashunté; Aguilar, Byron J.; Richard D. Gragg; DARLING-REED, SELINA; GOODMAN, CARL B.

    2014-01-01

    2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) is a dietary mutagenic carcinogen that has been shown not only to induce the formation of DNA adducts, but is capable of inducing tumors in the colon, mammary, and prostate glands. The normal development and maturation of the prostate gland, as well as early progression of prostate cancer, is dependent on androgens acting on the androgen receptor (AR). The actual mechanism by which PhIP interacts with our biological system and its potentia...

  9. Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs.

    Directory of Open Access Journals (Sweden)

    Jason T Kaelber

    Full Text Available Parvoviruses exploit transferrin receptor type-1 (TfR for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species modified the interactions with parvovirus capsids by reducing the level of binding. These data, along with signatures of positive selection in the TFRC gene, are consistent with an evolutionary arms race between the TfR of the Caniform clade and parvoviruses. As well as the modifications of amino acid sequence which modify binding, we found that a glycosylation site mutation in the TfR of dogs which provided resistance to the carnivore parvoviruses which were in circulation prior to about 1975 predates the speciation of coyotes and dogs. Because the closely-related black-backed jackal has a TfR similar to their common ancestor and lacks the glycosylation site, reconstructing this mutation into the jackal TfR shows the potency of that site in blocking binding and infection and explains the resistance of dogs until recent times. This alters our understanding of this well-known example of viral emergence by indicating that canine parvovirus emergence likely resulted from the re-adaptation of a parvovirus to the resistant receptor of a former host.

  10. Rational design, efficient syntheses and biological evaluation of N,N '-symmetrically bis-substituted butylimidazole analogs as a new class of potent Angiotensin II receptor blockers

    Czech Academy of Sciences Publication Activity Database

    Agelis, G.; Resvani, A.; Koukoulitsa, C.; Tůmová, Tereza; Slaninová, Jiřina; Kalavrizioti, D.; Spyridaki, K.; Afantitis, A.; Melagraki, G.; Siafaka, A.; Gkini, E.; Megariotis, G.; Grdadolnik, S. G.; Papadopoulos, M. G.; Vlahakos, D.; Maragoudakis, M.; Liapakis, G.; Mavromoustakos, T.; Matsoukas, J.

    2013-01-01

    Roč. 62, Apr (2013), s. 352-370. ISSN 0223-5234 Institutional support: RVO:61388963 Keywords : AT1 receptor blockers * N,N '-Bis-alkylated butylimidazole analogs * synthesis * Wittig reaction * hydroxymethylation * structure elucidation Subject RIV: CC - Organic Chemistry Impact factor: 3.432, year: 2013

  11. A novel radioligand for imaging the AT1 angiotensin receptor with PET

    International Nuclear Information System (INIS)

    2-Butyl-5-methoxymethyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine (KR31173) was radiolabeled by coupling a tetrazole-protected hydroxy precursor with [11C] methyl iodide and removing the protecting group by acid hydrolysis. In mice, the highest uptake of [11C] KR31173 was in the adrenal glands, kidneys, and liver. Tissue to blood ratios were generally greater than 10:1. Uptake of the tracer in the adrenal glands, kidneys, lungs, and heart was blocked with a 1 mg/kg dose of KR31173 or MK-996

  12. Lack of evidence for AT1R/B2R heterodimerization in COS-7, HEK293, and NIH3T3 cells: how common is the AT1R/B2R heterodimer?

    DEFF Research Database (Denmark)

    Hansen, Jakob L; Hansen, Jonas T; Speerschneider, Tobias;

    2008-01-01

    dimerization using bioluminescence resonance energy transfer and regulated secretion/aggregation technology. However, although both the AT1Rs and B2Rs were functional in our systems and the systems were fine tuned to detect small changes in receptor function, we failed to detect any functional modulation...

  13. Self-Organizing Map (SOM) and Support Vector Machine (SVM) Models for the Prediction of Human Epidermal Growth Factor Receptor (EGFR/ ErbB-1) Inhibitors.

    Science.gov (United States)

    Kong, Yue; Qu, Dan; Chen, Xiaoyan; Gong, Ya-Nan; Yan, Aixia

    2016-01-01

    EGFR (ErbB-1/HER1) kinase plays an important role in cancer therapy. Two classification models were established to predict whether a compound is an inhibitor or a decoy of human EGFR (ErbR-1) by using Kohonen's self-organizing map (SOM) and support vector machine (SVM). A dataset containing 1248 ATP binding site inhibitors and 3090 decoys was collected and randomly divided into a training set (831 inhibitors and 2064 decoys) and a test set (417 inhibitors and 1029 decoys). The descriptors that represent molecular structures were calculated by software ADRIANA.Code. Thirteen significant descriptors including five global descriptors and eight 2D property autocorrelation descriptors were selected by Pearson correlation analysis and stepwise analysis. The prediction accuracies on training set and test set are 98.5% and 96.3% for SOM model, 99.0% and 97.0% for SVM model, respectively. Both of these two classification models have good performance on distinguishing EGFR inhibitors from decoys. PMID:27074760

  14. Protein-Protein Interactions at the Adrenergic Receptors

    OpenAIRE

    Cotecchia, Susanna; Stanasila, Laura; Diviani, Dario

    2012-01-01

    The adrenergic receptors are among the best characterized G protein-coupled receptors (GPCRs) and knowledge on this receptor family has provided several important paradigms about GPCR function and regulation. One of the most recent paradigms initially supported by studies on adrenergic receptors is that both βarrestins and G protein-coupled receptors themselves can act as scaffolds binding a variety of proteins and this can result in growing complexity of the receptor-mediated cellular effect...

  15. Molecular determinants of angiotensin II type 1 receptor functional selectivity

    DEFF Research Database (Denmark)

    Aplin, Mark; Bonde, Marie Mi; Hansen, Jakob Lerche

    2008-01-01

    The angiotensin AT(1) receptor is an important pharmacological target in the treatment of cardiovascular disorders, such as hypertension, diabetic nephropathy, cardiac hypertrophy, arrhythmia and failure. Simultaneously, the AT(1) receptor has emerged to be a prominent model for the emerging...... concept that receptors may attain multiple active states with differentiated functional outcomes. Two major signalling pathways are employed by the AT(1) receptor, namely 1) the canonical G(q) protein-dependent activation of inositol phosphate turnover and intracellular calcium release, and 2) G protein......-independent recruitment of beta-arrestin-scaffolded signalling complexes that activate protein kinase pathways. Different states of receptor activation with preference for individual downstream pathways (functional selectivity) have been demonstrated in mutational studies of the AT(1) receptor and by pharmacological...

  16. AT2R autoantibodies block angiotensin II and AT1R autoantibody-induced vasoconstriction.

    Science.gov (United States)

    Liles, Campbell; Li, Hongliang; Veitla, Vineet; Liles, Jonathan T; Murphy, Taylor A; Cunningham, Madeleine W; Yu, Xichun; Kem, David C

    2015-10-01

    Activating autoantibodies to the angiotensin type 1 receptor (AT1R) are associated with hypertensive disorders. The angiotensin type 2 receptor (AT2R) is known to counter-regulate the actions of AT1R. We investigated whether AT2R autoantibodies produced in immunized rabbits will activate AT2R and suppress the vasopressor responses to angiotensin II and AT1R-activating autoantibodies. Five rabbits immunized with a peptide corresponding to the second extracellular loop of AT2R developed high AT2R antibody titers. Rabbit anti-AT2R sera failed to directly dilate isolated rat cremaster arterioles; however, when co-perfused with angiotensin II or AT1R-activating autoantibodies, the anti-AT2R sera significantly inhibited their contractile effects. Rabbit anti-AT2R sera recognized a predominant sequence near the N-terminus of the AT2R second extracellular loop. A decoy peptide based on this sequence effectively reversed the opposing effect of the anti-AT2R sera on angiotensin II-induced contraction of rat cremaster arterioles. A similar blockade of the anti-AT2R sera effect was observed with the AT2R antagonist PD 123319 and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Rabbit anti-AT2R sera reacted specifically with AT2R. No cross-reactivity with AT1R was observed. Blood pressure did not change in immunized animals. However, the pressor responses to incremental angiotensin II infusions were blunted in immunized animals. Thirteen subjects with primary aldosteronism demonstrated increased AT2R autoantibody levels compared with normal controls. In conclusion, AT2R autoantibodies produced in immunized rabbits have the ability to activate AT2R and counteract the AT1R-mediated vasoconstriction. These autoantibodies provide useful and selective tools for the study of their roles in blood pressure regulation and possible therapeutic intervention. PMID:26259590

  17. Variability of Sagittarius A* - Flares at 1 Millimeter

    CERN Document Server

    Zhao, J H; Herrnstein, R M G; Ho, P T P; Tsutsumi, T; Lo, K Y; Goss, W M; Bower, G C; Zhao, Jun-Hui

    2003-01-01

    We report the results from recent observations of Sgr A* at short-/sub-millimeter wavelengths made with the partially finished Sub-Millimeter Array (SMA) on Mauna Kea. A total of 25 epochs of observations were carried out over the past 15 months in 2001 March to 2002 May. Noticeable variations in flux density at 1.3 mm were observed showing three ``flares''. The SMA observations suggest that Sgr~A* highly increases towards submillimeter wavelengths during a flare suggesting the presence of a break wavelength in spectral index around 3 mm. A cross-correlation of the SMA data at 1 mm with the VLA data at 1 cm show a global delay of $t_{delay} > 3d$, suggesting that sub-millimeter wavelengths tend to peak first. Only marginal day-to-day variations in flux density (2-3 $\\sigma$) have been detected at 1.3 mm. No significant flares on a short time scale ($\\sim1$ hr) have been observed at 1.3 mm. We also failed to detect significant periodic signals at a level of 5% (3$\\sigma$) from Sgr A* in a periodic searching wi...

  18. Lipoxin Receptors

    Directory of Open Access Journals (Sweden)

    Mario Romano

    2007-01-01

    Full Text Available Lipoxins (LXs represent a class of arachidonic acid (AA metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4 and LXB4 being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2 in cooperation with 5-LO. 15-epi-LXA4 is also termed aspirin-triggered LX (ATL. In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4 receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1. This receptor binds with high affinity and stereoselectivity LXA4 and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.

  19. AT2 Receptors Targeting Cardiac Protection Post-Myocardial Infarction

    DEFF Research Database (Denmark)

    Kaschina, Elena; Lauer, Dilyara; Schmerler, Patrick; Unger, Thomas; Steckelings, Ulrike Muscha

    2014-01-01

    The angiotensin AT2-receptor mediates tissue protective actions. Its regenerative potential has been tested in multiple disease models including models of myocardial infarction. These studies used different experimental approaches in order to detect AT2-receptor-related effects such as AT2-receptor...... deficiency or overexpression, treatment with an AT1-receptor blocker leading to indirect stimulation of the unopposed AT2-receptor, or studies using AT2-receptor agonists. It is a common finding in these studies that the AT2-receptor improves cardiac function in the early phase post-MI, and that this effect...... is preserved over periods of up to four months. Depending on the experimental protocol, the AT2R also attenuates post-MI left ventricular remodeling or protects the heart from early left ventricular thinning and rupture. In combination with AT1-receptor blockade or deficiency, post-MI cardiac...

  20. AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease

    OpenAIRE

    LIU, TIAN-JING; SHI, YONG-YAN; WANG, EN-BO; Zhu, Tong; Zhao, Qun

    2015-01-01

    Angiotensin II, which is the main effector of the renin-angiotensin system, has an important role in intestinal inflammation via the angiotensin II type 1 receptor (AT1R). The present study aimed to investigate the protective effects of the AT1R blocker losartan on 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis. Losartan was administered to male adult C57BL/6 J mice 2 weeks prior to the induction of colitis, and images of the whole colon were captured to record changes, scored acc...

  1. Integrin αvβ3 and CD44 pathways in metastatic prostate cancer cells support osteoclastogenesis via a Runx2/Smad 5/receptor activator of NF-κB ligand signaling axis

    Directory of Open Access Journals (Sweden)

    Gupta Aditi

    2012-09-01

    Full Text Available Abstract Background Bone loss and pathological fractures are common skeletal complications associated with androgen deprivation therapy and bone metastases in prostate cancer patients. We have previously demonstrated that prostate cancer cells secrete receptor activator of NF-kB ligand (RANKL, a protein essential for osteoclast differentiation and activation. However, the mechanism(s by which RANKL is produced remains to be determined. The objective of this study is to gain insight into the molecular mechanisms controlling RANKL expression in metastatic prostate cancer cells. Results We show here that phosphorylation of Smad 5 by integrin αvβ3 and RUNX2 by CD44 signaling, respectively, regulates RANKL expression in human-derived PC3 prostate cancer cells isolated from bone metastasis. We found that RUNX2 intranuclear targeting is mediated by phosphorylation of Smad 5. Indeed, Smad5 knock-down via RNA interference and inhibition of Smad 5 phosphorylation by an αv inhibitor reduced RUNX2 nuclear localization and RANKL expression. Similarly, knockdown of CD44 or RUNX2 attenuated the expression of RANKL. As a result, conditioned media from these cells failed to support osteoclast differentiation in vitro. Immunohistochemistry analysis of tissue microarray sections containing primary prostatic tumor (grade2-4 detected predominant localization of RUNX2 and phosphorylated Smad 5 in the nuclei. Immunoblotting analyses of nuclear lysates from prostate tumor tissue corroborate these observations. Conclusions Collectively, we show that CD44 signaling regulates phosphorylation of RUNX2. Localization of RUNX2 in the nucleus requires phosphorylation of Smad-5 by integrin αvβ3 signaling. Our results suggest possible integration of two different pathways in the expression of RANKL. These observations imply a novel mechanistic insight into the role of these proteins in bone loss associated with bone metastases in patients with prostate cancer.

  2. Purification of Intact Plant Protoplasts by Flotation at 1g

    OpenAIRE

    John Graham

    2002-01-01

    From a standard plant tissue digest adjusted to a density of 1.07 g/ml, protoplasts can be harvested by flotation through a low density barrier (1.03 g/ml). The delicate nature of these bodies is suited to this flotation strategy which can be carried out at 1g.

  3. Quantitative receptor radioautography in the study of receptor-receptor interactions in the nucleus tractus solitarii

    Directory of Open Access Journals (Sweden)

    Fior-Chadi D.R.

    1998-01-01

    Full Text Available The nucleus tractus solitarii (NTS in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanisms of central blood pressure control. Angiotensin II (Ang II, neuropeptide Y (NPY and noradrenaline (NA are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on a2-adrenoceptors in the NTS. Using quantitative receptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of a2-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II or of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the a2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II at1 receptors and NPY receptor subtypes with the a2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the a2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension

  4. Extracellular Neurotransmitter Receptor Clustering: Think Outside the Box

    Institute of Scientific and Technical Information of China (English)

    Matthias Kneussel

    2010-01-01

    @@ Postsynaptic submembrane scaffolds cluster neurotransmitter receptors through intracellular protein-protein interactions. Growing evidence supports the view that extracellular factors can be almost as important to trigger synaptic receptor aggregation.

  5. Multiple adrenal masses: MRI tissue differentiation of pheochromocytoma and adenoma at 1.5 T

    International Nuclear Information System (INIS)

    We present the case of 38-year-old hypertensive patient with bilateral adrenal masses and with clinical and biochemical suspicion of pheochromocytoma. Magnetic resonance imaging at 1.5 T established correct diagnosis of coexisting adrenal pheochromocytoma and adenoma (nonhyperfunctioning). The case supports the usefulness of MRI for definitive evaluation of bilateral adrenal masses in patients with suspicion of pheochromocytoma. (orig.). With 2 figs

  6. Nuclear receptors and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Cave, Matthew C; Clair, Heather B; Hardesty, Josiah E; Falkner, K Cameron; Feng, Wenke; Clark, Barbara J; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A; McClain, Craig J; Prough, Russell A

    2016-09-01

    Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

  7. Adrenal mass evaluation at 1.5 T

    International Nuclear Information System (INIS)

    At 1.5 T (Signa, General Electric), 30 adrenal masses were evaluated with spin-echo imaging in an effort to differentiate adenomas from nonadenomas. There were eight nonhyperfunctioning adenomas, four hyperfunctioning adenomas, eight metastases, three primary adenocarcinomas, four pheochromocytomas, two infectious masses, and one cystic ganglioneuroma. T1-weighted (repetition time [TR]/echo time [TE] = 500/20,25 msec) and T2-weighted (TR/TE = 2,000, 2,500/80) pulse sequences were used. T2 relaxation time and adrenal mass signal intensity were measured and compared with those of liver, fat, and muscle. Adenomas could not be distinguished from nonadenomas at any signal intensity ratios. With T2 relaxation times and a cutoff of 60 msec, adenomas could be distinguished from nonadenomas with a 92% specificity and a 94% sensitivity. At 1.5 T, the adrenal mass T2 relaxation time should be used in differentiating adenomas from nonadenomas

  8. Glutamate receptors

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Geballe, Matthew T; Snyder, James P;

    2006-01-01

    Fast excitatory synaptic transmission in the CNS relies almost entirely on the neurotransmitter glutamate and its family of ion channel receptors. An appreciation of the coupling between agonist binding and channel opening has advanced rapidly during the past five years, largely as a result of ne...

  9. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette;

    2003-01-01

    In 1972, Brazeau et al. isolated somatostatin (somatotropin release-inhibiting factor, SRIF), a cyclic polypeptide with two biologically active isoforms (SRIF-14 and SRIF-28). This event prompted the successful quest for SRIF receptors. Then, nearly a quarter of a century later, it was announced...

  10. Formation of muonic hydrogen at 1/4 torr

    International Nuclear Information System (INIS)

    Muonic hydrogen has been produced at 1, 1/2 and 1/4 Torr H2 pressure using the magnetic bottle technique. At these very low pressures the slowing down time T of negative muons from kinetic energies around 2000 eV until atomic capture could be measured. The time structure of the light produced during the slowing down of the muon in the stop chamber follows the dE/dt function. The time of the sharp decrease in the dE/dt curve (corresponding to kinetic energies around 2000 eV) is determined for each event by fitting the stored light distribution. (Auth.)

  11. Simulation of the Polarized Sky at 1.4 GHz

    CERN Document Server

    O'Sullivan, S P; Taylor, A R; Ricci, R; Grant, J K; Shorten, K

    2009-01-01

    We present results from simulations of the extragalactic polarized sky at 1.4 GHz. As the basis for our polarization models, we use a semi-empirical simulation of the extragalactic total intensity (Stokes I) continuum sky developed at the University of Oxford (http://scubed.physics.ox.ac.uk) under the European SKA Design Study (SKADS) initiative, and polarization distributions derived from analysis of polarization observations. By considering a luminosity dependence for the polarization of AGN, we are able to fit the 1.4 GHz polarized source counts derived from the NVSS and the DRAO ELAIS N1 deep field survey down to approximately 1 mJy. This trend is confirmed by analysis of the polarization of a complete sample of bright AGN. We are unable to fit the additional flattening of the polarized source counts from the deepest observations of the ELAIS N1 survey, which go down to ~0.5 mJy. Below 1 mJy in Stokes I at 1.4 GHz, starforming galaxies become an increasingly important fraction of all radio sources. We use...

  12. Counting NMDA Receptors at the Cell Surface

    Czech Academy of Sciences Publication Activity Database

    Horák, Martin; Suh, Y. H.

    Totowa: Humana Press Inc., 2016, s. 31-44. (Neuromethods. 106). ISBN 978-1-4939-2811-8 R&D Projects: GA ČR(CZ) GA14-02219S Institutional support: RVO:67985823 Keywords : NMDA receptor * ionotropic glutamate receptor * mammalian cell lines * intracellular trafficking * quantitative assay * biotinylation assay * biochemistry Subject RIV: FH - Neurology

  13. AT2 Receptor and Tissue Injury

    DEFF Research Database (Denmark)

    Namsolleck, Pawel; Recarti, Chiara; Foulquier, Sébastien;

    2014-01-01

    The renin-angiotensin system (RAS) plays an important role in the initiation and progression of tissue injuries in the cardiovascular and nervous systems. The detrimental actions of the AT1 receptor (AT1R) in hypertension and vascular injury, myocardial infarction and brain ischemia are well...... established. In the past twenty years, protective actions of the RAS, not only in the cardiovascular, but also in the nervous system, have been demonstrated. The so-called protective arm of the RAS includes AT2-receptors and Mas receptors (AT2R and MasR) and is characterized by effects different from and...... often opposing those of the AT1R. These include anti-inflammation, anti-fibrosis, anti-apoptosis and neuroregeneration that can counterbalance pathological processes and enable recovery from disease. The recent development of novel, small-molecule AT2R agonists offers a therapeutic potential in humans...

  14. Magnetic shape memory effect at 1.7 K

    Czech Academy of Sciences Publication Activity Database

    Heczko, Oleg; Kopecký, Vít; Sozinov, A.; Straka, L.

    2013-01-01

    Roč. 103, č. 7 (2013), "072405-1"-"072405-4". ISSN 0003-6951 R&D Projects: GA ČR(CZ) GAP107/11/0391 Institutional support: RVO:68378271 Keywords : shape memory alloy s Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.515, year: 2013 http://dx.doi.org/10.1063/1.4817941

  15. Magnetically induced reorientation (MIR) at 1.7 K

    Czech Academy of Sciences Publication Activity Database

    Heczko, Oleg; Kopecký, Vít; Sozinov, A.; Straka, L.

    Boise, Idaho : Boise, 2013, s. 104-105. [International Conference on Ferromagnetic Shape Memory Alloy s /4./ - ICFSMA 2013. Boise, Idaho (US), 03.06.2013-07.06.2013] R&D Projects: GA ČR(CZ) GAP107/11/0391 Institutional support: RVO:68378271 Keywords : martensite * MIR Subject RIV: BM - Solid Matter Physics ; Magnetism

  16. Angiotensin Receptors, Autoimmunity, and Preeclampsia1

    OpenAIRE

    Xia, Yang; Zhou, Cissy Chenyi; RAMIN, Susan M.; Kellems, Rodney E.

    2007-01-01

    Preeclampsia is a pregnancy-induced hypertensive disorder that causes substantial maternal and fetal morbidity and mortality. Despite being a leading cause of maternal death and a major contributor to maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia are poorly understood. Recent studies indicate that women with preeclampsia have autoantibodies that activate the angiotensin receptor, AT1, and that autoantibody-mediated receptor activation contri...

  17. Hormone activation of baculovirus expressed progesterone receptors.

    Science.gov (United States)

    Elliston, J F; Beekman, J M; Tsai, S Y; O'Malley, B W; Tsai, M J

    1992-03-15

    Human and chicken progesterone receptors (A form) were overproduced in a baculovirus expression system. These recombinant progesterone receptors were full-length bound progesterone specifically and were recognized by monoclonal antibodies, AB52 and PR22, specific for human and chicken progesterone receptor, respectively. In gel retardation studies, binding of recombinant human and chicken progesterone receptors to their progesterone response element (PRE) was specific and was enhanced in the presence of progesterone. Binding of human progesterone receptor to the PRE was also enhanced in the presence of the antiprogestin, RU486, but very little effect was observed in the presence of estradiol, dexamethasone, testosterone, and vitamin D. In our cell-free transcription system, human progesterone receptor induced transcription in a receptor-dependent and hormone-activable manner. Receptor-stimulated transcription required the presence of the PRE in the test template and could be specifically inhibited by excess PRE oligonucleotides. Furthermore, chicken progesterone receptor also induced in vitro transcription in a hormone-activable manner. These results demonstrate that steroid receptors overexpressed in a baculovirus expression system are functional and exhibit steroid-responsive binding and transcription. These observations support our present understanding of the mechanism of steroid receptor-regulated gene expression and provide a technological format for studies of the role of hormone and antihormone in altering gene expression. PMID:1544902

  18. AT2 receptor: Its role in obesity associated hypertension

    Science.gov (United States)

    Ali, Quaisar; Hussain, Tahir

    2016-01-01

    The renin-angiotensin system (RAS) is a hormonal cascade that acts together to regulate blood pressure. Angiotensin II (Ang II) is the major octapeptide of RAS and mediates its cellular and physiological actions by acting on AT1 and AT2 receptor. Most of the cellular and physiological actions of Ang II such as cellular growth and proliferation, vasoconstriction, antinatriuresis and increase in blood pressure are mediated via AT1 receptor. The functions associated with the AT2 receptors are less studied, in part, due to its lower expression in adult tissues. However, AT2 receptor has been suggested as functional antagonist of AT1 receptors and thereby opposes the actions of Ang II mediated via AT1 receptor. Thus, the activation of AT2 receptors has been shown to cause vasodilatation, natriuresis and decrease in blood pressure. After the discovery of the AT2 receptor in various parts of the kidney, including in proximal tubules, there has been an interest in establishing a link between the renal AT2 receptor, renal Na-excretion and blood pressure regulation. Earlier, we have reported that activation of renal AT2 receptors increases urinary Na excretion in obese Zucker rats, in part via inhibiting Na+/K+- ATPase (NKA) activity and stimulating nitric oxide/cGMP pathway in the proximal tubules. An impaired pressure natriuresis and increased AT1 receptor function is believed to be the cause of hypertension in obese Zucker rats and other animal models of obesity. In this review, we are focussing on the role of renin angiotensin system especially AT2 receptors in obesity associated hypertension.

  19. The clinical outcome of scaphoid fracture malunion at 1 year.

    Science.gov (United States)

    Forward, D P; Singh, H P; Dawson, S; Davis, T R C

    2009-02-01

    The aim of this study was to assess the effect of malunion of scaphoid fractures on the clinical outcome at 1 year. Forty-two consecutive patients with united scaphoid waist fractures which had been treated non-operatively underwent longitudinal CT scans to confirm union and assess malunion at 12 to 18 weeks after injury. A blind clinical assessment was made and the Patient Evaluation Measure (PEM) and DASH questionnaires were completed by all the patients 1 year after injury. The group consisted of 38 men and four women with a mean age of 31 years at the time of injury. Correlation analysis revealed no significant relationships between any of the outcome measures (range of motion, grip strength and PEM and DASH scores) and any of the three measures of malunion (height-to-length ratio, the dorsal cortical angle and the lateral intra-scaphoid angle). PMID:19129358

  20. Large Cryogenics Systems at 1.8 K

    CERN Document Server

    Tavian, L

    2000-01-01

    Cryogenics is now widely present in large accelerator projects using applied superconductivity. Economical considerations permanently require an increase of the performance of superconducting devices. One way to do this consists to lower their operating temperature and to cool them with superfluid helium. For this purpose, large cryogenic systems at 1.8 K producing refrigeration capacity in the kW range have to be developed and implemented. These cryogenic systems require large pumping capacity at very low pressure based on integral cold compression or mixed cold-warm compression. This paper describes and compares the different cooling methods with saturated or pressurised superfluid helium, gives the present status of the available process machinery with their practical performance, and reviews the different thermodynamical cycles for producing refrigeration below 2 K, with emphasis on their operational compliance.

  1. Null polarimetry near shot noise limit at 1 Hz

    Science.gov (United States)

    He, Dechao; Xie, Boya; Feng, Sheng

    2016-04-01

    We describe the principle and report on the realization of a null polarimeter with two demonstrated features: (1) the sensitivity of the system is near shot noise limit and (2) quasi-stationary signals at 1 Hz can be measured without signal modulation. The achieved single-pass sensitivity is 7 × 10-9 rad/ √{ Hz } with a pair of Glan-Taylor polarizers, which should be of great interest for experiments such as observation of vacuum magnetic birefringence and search for new particles. The system is brought near its shot noise limit by appropriate polarization control and coherent heterodyne detection of light, resulting in a sensitivity improvement by two orders of magnitude in comparison with the case of no control on light polarization.

  2. Radioligand Binding at Muscarinic Receptors

    Czech Academy of Sciences Publication Activity Database

    El-Fakahany, E. E.; Jakubík, Jan

    New York: Springer, 2016 - (Mysliveček, J.; Jakubík, J.), s. 37-68. (Neuromethods. 107). ISBN 978-1-4939-2857-6 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : muscarinic acetylcholine receptors * radioligand binding Subject RIV: ED - Physiology

  3. Allosteric Modulation of Muscarinic Receptors

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; El-Fakahany, E. E.

    New York: Springer, 2016 - (Mysliveček, J.; Jakubík, J.), s. 95-130. (Neuromethods. 107). ISBN 978-1-4939-2857-6 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : muscarinic receptors * allosteric modulation * radioligand binding functional response Subject RIV: ED - Physiology

  4. Forecasting coronal mass ejections at 1 AU using Heliospheric Imagers

    Science.gov (United States)

    Moestl, C.; Amla, K.; Temmer, M.; Hall, J. R.; Liewer, P. C.; De Jong, E. M.; Davies, J.; Lugaz, N.; Rollett, T.; Veronig, A.; Liu, Y.; Farrugia, C. J.; Luhmann, J. G.; Galvin, A. B.; Zhang, T.

    2012-12-01

    We study the feasibility of using a Heliospheric Imager (HI) instrument, such as STEREO/HI, for space weather forecasting of interplanetary coronal mass ejections (ICMEs) at 1 AU. We compare the predictions for speed and arrival time for ~15 ICME events, each observed remotely by one STEREO spacecraft, to the speed and arrival time observed at in situ observatories. We use three different models with varying ICME geometry, from point-like (Fixed-Phi) to a circle with a given width (Self-Similar-Expansion) to a very wide circle (Harmonic Mean). The models are fitted to density tracks on HI Jmaps with the SolarSoft SATPLOT tool. All these techniques assume constant ICME speed and direction. Partly, the configuration mimics the situation of a single HI observatory parked at the L4 or L5 point in the Sun-Earth system. We discuss problems associated with this study, such as CME-CME interactions leading to complicated Jmaps. For assessing the accuracy of these predictions we look at in situ data by Wind/ACE, STEREO-A/B, and Venus Express and MESSENGER. We also look at the ratio of prediction lead time to its accuracy, and see if there is a preferred value for the ICME width.

  5. Kinins and peptide receptors.

    Science.gov (United States)

    Regoli, Domenico; Gobeil, Fernand

    2016-04-01

    This paper is divided into two sections: the first contains the essential elements of the opening lecture presented by Pr. Regoli to the 2015 International Kinin Symposium in S. Paulo, Brazil on June 28th and the second is the celebration of Dr. Regoli's 60 years of research on vasoactive peptides. The cardiovascular homeostasis derives from a balance of two systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS). The biologically active effector entity of RAS is angiotensin receptor-1 (AT-1R), and that of KKS is bradykinin B2 receptor (B2R). The first mediates vasoconstriction, the second is the most potent and efficient vasodilator. Thanks to its complex and multi-functional mechanism of action, involving nitric oxide (NO), prostacyclin and endothelial hyperpolarizing factor (EDHF). B2R is instrumental for the supply of blood, oxygen and nutrition to tissues. KKS is present on the vascular endothelium and functions as an autacoid playing major roles in cardiovascular diseases (CVDs) and diabetes. KKS exerts a paramount role in the prevention of thrombosis and atherosclerosis. Such knowledge emphasizes the already prominent value of the ACE-inhibitors (ACEIs) for the treatment of CVDs and diabetes. Indeed, the ACEIs, thanks to their double action (block of the RAS and potentiation of the KKS) are the ideal agents for a rational treatment of these diseases. PMID:26408609

  6. Localization of mineralocorticoid receptors at mammalian synapses.

    Directory of Open Access Journals (Sweden)

    Eric M Prager

    Full Text Available In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.

  7. Structure of archaerhodopsin-2 at 1.8 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Kouyama, Tsutomu, E-mail: kouyama@bio.phys.nagoya-u.ac.jp [Nagoya University, Nagoya (Japan); RIKEN Harima Institute/SPring-8, 1-1-1 Kouto, Mikazuki, Sayo, Hyogo (Japan); Fujii, Ryudo; Kanada, Soun; Nakanishi, Taichi; Chan, Siu Kit; Murakami, Midori [Nagoya University, Nagoya (Japan)

    2014-10-01

    The same hexagonal array of archaerhodpsin-2 trimers as observed in the native membrane is reconstituted in a three-dimensional crystal prepared by the membrane fusion method. In this crystal, a pair of conserved glutamate residues in the proton-release pathway is maintained by a low-barrier hydrogen bond. Archaerhodopsin-2 (aR2), the sole protein found in the claret membrane of Halorubrum sp. Aus-2, functions as a light-driven proton pump. In this study, structural analysis of aR2 was performed using a novel three-dimensional crystal prepared by the successive fusion of claret membranes. The crystal is made up of stacked membranes, in each of which aR2 trimers are arranged on a hexagonal lattice. This lattice structure resembles that found in the purple membrane of H. salinarum, except that lipid molecules trapped within the trimeric structure are not distributed with perfect threefold symmetry. Nonetheless, diffraction data at 1.8 Å resolution provide accurate structural information about functionally important residues. It is shown that two glutamates in the proton-release channel form a paired structure that is maintained by a low-barrier hydrogen bond. Although the structure of the proton-release pathway is highly conserved among proton-pumping archaeal rhodopsins, aR2 possesses the following peculiar structural features: (i) the motional freedom of the tryptophan residue that makes contact with the C13 methyl group of retinal is restricted, affecting the formation/decay kinetics of the L state, and (ii) the N-terminal polypeptide folds into an Ω-loop, which may play a role in organizing the higher-order structure.

  8. Luminal leptin inhibits L-glutamine transport in rat small intestine: involvement of ASCT2 and B0AT1

    OpenAIRE

    Ducroc, R. (Robert); Sakar, Y. (Yassine); Fanjul, C. (Carmen); Barber, A. (Ana); Bado, A.; Lostao, M.P. (María Pilar)

    2010-01-01

    International audience l-glutamine is the primary metabolic fuel for enterocytes. Glutamine from the diet is transported into the absorptive cells by two sodium-dependent neutral amino acid transporters present at the apical membrane: ASCT2/SLC1A5 and B(0)AT1/SLC6A19. We have demonstrated that leptin is secreted into the stomach lumen after a meal and modulates the transport of sugars after binding to its receptors located at the brush border of the enterocytes. The present study was desig...

  9. BLOCKADE OF BRAIN ANGIOTENSIN II AT1 RECEPTORS AMELIORATES STRESS, ANXIETY, BRAIN INFLAMMATION AND ISCHEMIA: THERAPEUTIC IMPLICATIONS

    OpenAIRE

    Saavedra, Juan M.; Sánchez-Lemus, Enrique; BENICKY, Julius

    2010-01-01

    Poor adaptation to stress, alterations in cerebrovascular function and excessive brain inflammation play critical roles in the pathophysiology of many psychiatric and neurological disorders such as major depression, schizophrenia, post traumatic stress disorder, Parkinson's and Alzheimer's diseases and traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of...

  10. Cerebrovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Ansar, Saema; Vikman, Petter; Nielsen, Marianne; Edvinsson, Lars

    2007-01-01

    with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 microl blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular...

  11. Efficient Synthesis and Biological Evaluation of Imidazole AT1 Ang II Receptor Antagonists Based on 4(5)-Butylimidazole

    Czech Academy of Sciences Publication Activity Database

    Agelis, G.; Resvani, A.; Tůmová, T.; Slaninová, Jiřina; Matsoukas, J.

    Copenhagen : European Peptide Society, 2010, s. 246-247 ISBN 0-9715560-5-9. [Peptides 2010: Tales of Peptides. Proceedings of the European Peptide Symposium /31./. Copenhagen (DK), 05.09.2010-09.09.2010] Institutional research plan: CEZ:AV0Z40550506 Keywords : angiotensin II * analogues * antagonism * rat uterus assay Subject RIV: CC - Organic Chemistry

  12. The linear electric motor: Instability at 1,000 g's

    International Nuclear Information System (INIS)

    When fluid of high density is supported against gravity by a less dense liquid, the system is unstable, and microscopic perturbations grow at the interface between the fluids. This phenomenon, called the Rayleigh-Taylor instability, also occurs when a bottle of oil-and-vinegar salad dressing is turned upside down. The instability causes spikes of the dense fluid to penetrate the light fluid, while bubbles of the lighter fluid rise into the dense fluid. The same phenomenon occurs when a light fluid is used to accelerate a dense fluid, causing the two fluids to mix at a very high rate. For example, during the implosion of an ICF capsule, this instability can cause enough mixing to contaminate, cool, and degrade the yield of the thermonuclear fuel. The LEM is an excellent tool for studying this instability, but what is it? Think of a miniature high-speed electric train (the container) hurtling down a track (the electrodes) while diagnostic equipment (optical and laser) photographs it. The LEM, consists of four linear electrodes, or rails, that carry an electrical current to a pair of sliding armatures on the container. A magnetic field is produced that works in concert with the rail-armature current to accelerate the container--just as in an electric motor, but in a linear fashion rather than in rotation. The magnetic field is augmented with elongated coils just as in a conventional electric motor. This configuration also helps hold the armatures against the electrodes to prevent arcing. The electrical energy (0.6 megajoules) is provided by 16 capacitor banks that can be triggered independently to produce different acceleration profiles (i.e., how the acceleration varies with time)

  13. Nutritional Support

    Science.gov (United States)

    Nutritional support is therapy for people who cannot get enough nourishment by eating or drinking. You may need ... absorb nutrients through your digestive system You receive nutritional support through a needle or catheter placed in your ...

  14. Impact of receptor clustering on ligand binding

    Directory of Open Access Journals (Sweden)

    Caré Bertrand R

    2011-03-01

    Full Text Available Abstract Background Cellular response to changes in the concentration of different chemical species in the extracellular medium is induced by ligand binding to dedicated transmembrane receptors. Receptor density, distribution, and clustering may be key spatial features that influence effective and proper physical and biochemical cellular responses to many regulatory signals. Classical equations describing this kind of binding kinetics assume the distributions of interacting species to be homogeneous, neglecting by doing so the impact of clustering. As there is experimental evidence that receptors tend to group in clusters inside membrane domains, we investigated the effects of receptor clustering on cellular receptor ligand binding. Results We implemented a model of receptor binding using a Monte-Carlo algorithm to simulate ligand diffusion and binding. In some simple cases, analytic solutions for binding equilibrium of ligand on clusters of receptors are provided, and supported by simulation results. Our simulations show that the so-called "apparent" affinity of the ligand for the receptor decreases with clustering although the microscopic affinity remains constant. Conclusions Changing membrane receptors clustering could be a simple mechanism that allows cells to change and adapt its affinity/sensitivity toward a given stimulus.

  15. Crystal Structure of Botulinum Neurotoxin Type a in Complex With the Cell Surface Co-Receptor GT1b-Insight Into the Toxin-Neuron Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, P.; Dupuy, J.; Inamura, A.; Kiso, M.; Stevens, R.C.

    2009-05-26

    Botulinum neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in the toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.

  16. Child Support

    OpenAIRE

    Bradshaw, J. (Jonathan)

    2006-01-01

    Child support is a private transfer, which for many people is mediated by the government, and which mainly benefits lone parents. Children in lone parent families represented 42 per cent of all poor children in 2003/4. Therefore child support might play an important part in reducing child poverty. Although this was not an aspiration of the 1991 Child Support Act it was certainly the main aspiration of the Child Support, Pensions and Social Security Act 2000. This paper is a review of the pote...

  17. Peer Support.

    Science.gov (United States)

    Forchuk, Cheryl; Solomon, Michelle; Viran, Tazim

    2016-01-01

    The Mental Health Commission of Canada defines peer support as "a supportive relationship between people who have a lived experience in common … in relation to a mental health challenge or illness … related to their own mental health or that of a loved one" (Sunderland et al. 2013: 11). In Ontario, a key resource for peer support is the Ontario Peer Development Initiative (OPDI), which is an umbrella organization of mental health Consumer/Survivor Initiatives (CSIs) and peer support organizations across the province of Ontario. Member organizations are run by and for people with lived experience of a mental health or addiction issue and provide a wide range of services and activities within their communities. The central tenet of member organizations is the common understanding that people can and do recover with the proper supports in place and that peer support is integral to successful recovery. Nationally, Peer Support Accreditation and Certification Canada has recently been established. The relatively new national organization focuses on training and accrediting peer support workers. This paper focuses on a range of diverse peer support groups and CSIs that operate in London and surrounding areas. PMID:26854546

  18. Estrogen receptor β in male mice

    Czech Academy of Sciences Publication Activity Database

    Dostálová, Pavla; Děd, Lukáš; Dorosh, Andriy; Elzeinová, Fatima; Pěknicová, Jana

    Elsinore: International Society of Andrology, 2014. s. 48-48. [18th European Testis Workshop. 13.05.2014-17.05.2014, Elsinore] R&D Projects: GA MŠk(CZ) CZ1.05/1.1.00/02.0109; GA ČR GA14-05547S Institutional support: RVO:86652036 Keywords : estrogen receptor alpha * estrogen receptor beta * spermatozoa Subject RIV: EB - Genetics ; Molecular Biology

  19. C-type lectin receptors and RIG-I-like receptors: new points on the oncogenomics map

    International Nuclear Information System (INIS)

    The group of pattern recognition receptors includes families of Toll-like receptors, NOD-like receptors, C-type lectin receptors, and RIG-I-like receptors. They are key sensors for a number of infectious agents, some of which are oncogenic, and they launch an immune response against them, normally promoting their eradication. Inherited variations in genes encoding these receptors and proteins and their signaling pathways may affect their function, possibly modulating cancer risk and features of cancer progression. There are numerous studies investigating the association of single nucleotide polymorphisms within or near genes encoding Toll-like receptors and NOD-like receptors, cancer risk, and features of cancer progression. However, there is an almost total absence of articles analyzing the correlation between polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors and cancer risk or progression. Nevertheless, there is some evidence supporting the hypothesis that inherited C-type lectin receptor and RIG-I-like receptor variants can be associated with increased cancer risk. Certain C-type lectin receptors and RIG-I-like receptors recognize pathogen-associated molecular patterns of potentially oncogenic infectious agents, and certain polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors may have functional consequences at the molecular level that can lead to association of such single nucleotide polymorphisms with risk or progression of some diseases that may modulate cancer risk, so these gene polymorphisms may affect cancer risk indirectly. Polymorphisms of genes encoding C-type lectin receptors and RIG-I-like receptors thereby may be correlated with a risk of lung, oral, esophageal, gastric, colorectal, and liver cancer, as well as nasopharyngeal carcinoma, glioblastoma, multiple myeloma, and lymphoma. The list of the most promising polymorphisms for oncogenomic investigations may include rs1926736, rs2478577

  20. Positioning support

    International Nuclear Information System (INIS)

    A positioning support for infants during X-ray examinations is described. The support which can be placed on the X-ray examination table has a simple structure and can easily be handled. It guarantees a stable positioning of the patient at a short object-film distance

  1. The androgen receptor and estrogen receptor

    OpenAIRE

    Oosterkamp, H.M.; Bernards, R.A.

    2002-01-01

    The androgen receptor (AR) and the estrogen receptors (ER) are members of the nuclear receptor (NR) family. These NRs are distinguished from the other transcription factors by their ability to control gene expression upon ligand binding (steroids, retinoids, thyroid hormone, vitamin D, fatty acids, and other small hydrophobic molecules). Their combined effects are vast, influencing virtually every fundamental biological process, from development and homeostasis, to proliferation and different...

  2. Breast cancer surface receptors predict risk for developing brain metastasis and subsequent prognosis

    OpenAIRE

    Grewal, Jai; Kesari, Santosh

    2008-01-01

    Determining the status of breast cancer surface receptors (estrogen receptor, progesterone receptor, HER2/neu) has become routine in the care of patients with this disease and has proven to be helpful in guiding treatment. For this reason, breast cancer has become a model for molecularly guided therapy in solid tumors. Emerging data support that these receptors are associated with risk for developing brain metastases. Additionally, once brain metastases have occurred these receptors may also ...

  3. Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

    International Nuclear Information System (INIS)

    Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy

  4. Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pires, L.A. [Laboratório de Metabolismo de Lípides, Instituto do Coração, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Departamento de Ginecologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Hegg, R. [Departamento de Ginecologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Freitas, F.R.; Tavares, E.R.; Almeida, C.P. [Laboratório de Metabolismo de Lípides, Instituto do Coração, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Baracat, E.C. [Departamento de Ginecologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Maranhão, R.C. [Laboratório de Metabolismo de Lípides, Instituto do Coração, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-05-04

    Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

  5. Identification of the salmon somatolactin receptor, a new member of the cytokine receptor family.

    Science.gov (United States)

    Fukada, Haruhisa; Ozaki, Yuichi; Pierce, Andrew L; Adachi, Shinji; Yamauchi, Kohei; Hara, Akihiko; Swanson, Penny; Dickhoff, Walton W

    2005-05-01

    Somatolactin (SL) is a pituitary hormone of the GH/prolactin (PRL) family that so far has been found only in fish. Compared with GH and PRL, the primary structure of SL is highly conserved among divergent fish species, suggesting it has an important function and a discriminating receptor that constrains structural change. However, SL functions are poorly understood, and receptors for SL have not yet been identified. During cloning of GH receptor cDNA from salmon, we found a variant with relatively high (38-58%) sequence identity to vertebrate GH receptors and low (28-33%) identity to PRL receptors; however, the recombinant protein encoding the extracellular domain showed only weak binding of GH. Ligand binding of the recombinant extracellular domain for this receptor confirmed that the cDNA encoded a specific receptor for SL. The SL receptor (SLR) has common features of a GH receptor including FGEFS motif, six cysteine residues in the extracellular domain, a single transmembrane region, and Box 1 and 2 regions in the intracellular domain. These structural characteristics place the SLR in the cytokine receptor type I homodimeric group, which includes receptors for GH, PRL, erythropoietin, thrombopoietin, granulocyte-colony stimulating factor, and leptin. Transcripts for SLR were found in 11 tissues with highest levels in liver and fat, supporting the notion that a major function of SL is regulation of lipid metabolism. Cloning SLR cDNA opens the way for discovery of new SL functions and target tissues in fish, and perhaps novel members of this receptor family in other vertebrates. PMID:15718271

  6. Supportive Care.

    Science.gov (United States)

    Olsen, Pia Riis; Lorenzo, Rosalía

    2016-01-01

    This chapter takes its point of departure in psychosocial aspects of supportive care in adolescent and young adult cancer care. The purpose is to describe some of the challenges that these young people face following a cancer diagnosis and guide healthcare professionals in how to provide care that improves the quality of life. In most hospitals and healthcare systems, adolescents and young adults are cared for and treated in settings for children or adults. Accordingly, healthcare professionals may lack attention to and knowledge about what characterize young peoples' life situation, their special needs and how to meet them. The topics we include in the chapter are the following: the youth friendly environment, social support and social network, parents, information during a psychosocial crisis event, the use of HEADSS, peer support, fertility, body image and self-esteem, after treatment and future challenges and palliative and end of life care. PMID:27595353

  7. Rat liver insulin receptor

    International Nuclear Information System (INIS)

    Using insulin affinity chromatography, the authors have isolated highly purified insulin receptor from rat liver. When evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the rat liver receptor contained the M/sub r/ 125,000 α-subunit, the M/sub r/ 90,000 β-subunit, and varying proportions of the M/sub r/ 45,000 β'-subunit. The specific insulin binding of the purified receptor was 25-30 μg of 125I-insulin/mg of protein, and the receptor underwent insulin-dependent autophosphorylation. Rat liver and human placental receptors differ from each other in several functional aspects: (1) the adsorption-desorption behavior from four insulin affinity columns indicated that the rat liver receptor binds less firmly to immobilized ligands; (2) the 125I-insulin binding affinity of the rat liver receptor is lower than that of the placental receptor; (3) partial reduction of the rat liver receptor with dithiothreitol increases its insulin binding affinity whereas the binding affinity of the placental receptor is unchanged; (4) at optimal insulin concentration, rat liver receptor autophosphorylation is stimulated 25-50-fold whereas the placental receptor is stimulated only 4-6-fold. Conversion of the β-subunit to β' by proteolysis is a major problem that occurs during exposure of the receptor to the pH 5.0 buffer used to elute the insulin affinity column. Proteolytic destruction and the accompanying loss of insulin-dependent autophosphorylation can be substantially reduced by proteolysis inhibitors. In summary, rat liver and human placental receptors differ functionally in both α- and β-subunits. Insulin binding to the α-subunit of the purified rat liver receptor communicates a signal that activates the β-subunit; however, major proteolytic destruction of the β-subunit does not affect insulin binding to the α-subunit

  8. Crystal structure of human interferon-γ receptor 2 reveals the structural basis for receptor specificity.

    Science.gov (United States)

    Mikulecký, Pavel; Zahradník, Jirí; Kolenko, Petr; Černý, Jiří; Charnavets, Tatsiana; Kolářová, Lucie; Nečasová, Iva; Pham, Phuong Ngoc; Schneider, Bohdan

    2016-09-01

    Interferon-γ receptor 2 is a cell-surface receptor that is required for interferon-γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. A crystal structure of the extracellular part of human interferon-γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. Similar to other class 2 receptors, IFNγR2 has two fibronectin type III domains. The characteristic structural features of IFNγR2 are concentrated in its N-terminal domain: an extensive π-cation motif of stacked residues KWRWRH, a NAG-W-NAG sandwich (where NAG stands for N-acetyl-D-glucosamine) and finally a helix formed by residues 78-85, which is unique among class 2 receptors. Mass spectrometry and mutational analyses showed the importance of N-linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. Structure-based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon-γ and receptor 1, the ligands of IFNγR2. PMID:27599734

  9. Muscarinic Receptor Signaling in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Raufman

    2011-03-01

    Full Text Available According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  10. Muscarinic Receptor Signaling in Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rosenvinge, Erik C. von, E-mail: evonrose@medicine.umaryland.edu; Raufman, Jean-Pierre [University of Maryland School of Medicine, Division of Gastroenterology & Hepatology, 22 S. Greene Street, N3W62, Baltimore, MD 21201 (United States); Department of Veterans Affairs, VA Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201 (United States)

    2011-03-02

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  11. Muscarinic Receptor Signaling in Colon Cancer

    International Nuclear Information System (INIS)

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer

  12. Interaction of the C-terminal acidic domain of the insulin receptor with histone modulates the receptor kinase activity.

    Science.gov (United States)

    Baron, V; Kaliman, P; Alengrin, F; Van Obberghen, E

    1995-04-01

    In this study, we investigated the role of the insulin receptor domain 1270-1280, an acid-rich sequence located in the receptor C-terminus. Antipeptide IgG raised against this sequence were obtained and used to analyze their effect on receptor function. Antipeptide IgG inhibited receptor autophosphorylation at Tyr1146, Tyr1150 and Tyr1151. These sites are known to be key modulators of the receptor activity. Autophosphorylation at other sites may also have been inhibited. The antipeptide antibody decreased the receptor kinase activity measured with poly(Glu80Tyr20) and a synthetic peptide corresponding to the proreceptor sequence 1142-1158. We provide evidence that the effect of the antibody on substrate phosphorylation may result from the control of the phosphorylation level of the receptor. Concerning the action of the antipeptide IgG on the receptor kinase activity, histone did not behave similarly to poly(Glu80Tyr20). The antibody recognizing sequence 1270-1280 competed with histone for an overlapping binding site. Histone also modulated insulin receptor autophosphorylation, supporting the idea that interference with domain 1270-1280 alters the receptor kinase. Our data suggest that the acidic region including residues 1270-1280 of the insulin receptor C-terminus is involved in the following events: (a) receptor binding with histone, an exogenous substrate of the receptor kinase, and (b) the regulation of receptor autophosphorylation and kinase activity. Based on these observations, we would like to propose that this insulin receptor domain could interact with cellular proteins modulating the receptor kinase. PMID:7744039

  13. Supporting ATLAS

    CERN Multimedia

    maximilien brice

    2003-01-01

    Eighteen feet made of stainless steel will support the barrel ATLAS detector in the cavern at Point 1. In total, the ATLAS feet system will carry approximately 6000 tons, and will give the same inclination to the detector as the LHC accelerator.

  14. The meth brain: methamphetamines alter brain functions via NMDA receptors

    Czech Academy of Sciences Publication Activity Database

    Proft, Juliane; Weiss, Norbert

    2015-01-01

    Roč. 34, č. 1 (2015), s. 1-3. ISSN 0231-5882 R&D Projects: GA ČR GA15-13556S Institutional support: RVO:61388963 Keywords : ion channel * methamphetamine * piriform cortex * NMDA receptor * AMPA receptor Subject RIV: CE - Biochemistry Impact factor: 1.173, year: 2014

  15. Transcriptional up-regulation in expression of 5-hydroxytryptamine2A and transcriptional down-regulation of angiotensin II type 1 receptors during organ culture of rat mesenteric artery

    DEFF Research Database (Denmark)

    Luo, Guogang; Xu, Cang-Bao; Cao, Yong-Xiao;

    2004-01-01

    receptors (5-HT(2A)) and angiotensin II type 1 receptors (AT(1)) demonstrated that the contractions occurred via 5-HT(2A) and AT(1) receptors, respectively. Real-time PCR revealed that the 5-HT(2A) receptor mRNA was up-regulated in parallel with the contractile response while there was a down-regulation of...... AT(1) receptor mRNA. Transcriptional inhibitor actinomycin D and specific protein kinase C inhibitor Ro31-8220 demonstrated that it was a transcriptional mechanism with involvement of protein kinase C that regulated the enhanced expression of 5-HT(2A) receptors in the mesenteric artery....

  16. The rest-frame optical morphology of starburst galaxies at 1 < z < 3.5

    Science.gov (United States)

    Lee, Bomee; Giavalisco, Mauro; Candels, Goods-Hershcel

    2015-01-01

    Using CANDELS combined with GOODS-Herschel in the GOODS-North and South field, we investigate the rest-frame optical morphologies of starburst galaxies at 1 We compare morphologies of MS and SB galaxies using non-parametric (Sersic Index) and parametric measures as well as the visual identification. FIR luminous starburst galaxies are usually interpreted as major wet mergers. We find that the average morphologies of SB galaxies are disky and generally have much more diffuse optical light profile than massive compact early-type galaxies (ETGs), challenging gas-rich merging as the primary dissipative mechanism to assemble very compact, massive galaxies. We find that the sizes of the SB galaxies are clearly larger than those of the MS galaxies on average. NIR to MIR colors of starburst galaxies show no evidence of highly dust-obscured compact component, which could eventually emerge as the massive compact core. Very compact SB galaxies are rather rare, and hence even from a statistical standpoint, our morphological analysis of starburst galaxies does not support the popular mechanism that powerful starburst in a highly dissipative wet merger of gas-rich disks, and subsequent quenching, is the key driver behind the formation of the massive, compact early-type galaxies observed at z~2. The light distribution of the bulk of stars in starburst galaxies is simply not compact enough to eventually evolve into the massive ultra compact ETGs at high redshift universe.

  17. Functional interaction between angiotensin II receptor type 1 and chemokine (C-C Motif) receptor 2 with implications for chronic kidney disease

    OpenAIRE

    Mohammed Akli Ayoub; Yuan Zhang; Kelly, Robyn S.; Heng B See; Johnstone, Elizabeth K.M.; McCall, Elizabeth A.; Williams, James H; Kelly, Darren J.; Pfleger, Kevin D.G.

    2015-01-01

    Understanding functional interactions between G protein-coupled receptors is of great physiological and pathophysiological importance. Heteromerization provides one important potential mechanism for such interaction between different signalling pathways via macromolecular complex formation. Previous studies suggested a functional interplay between angiotensin II receptor type 1 (AT1) and Chemokine (C-C motif) Receptor 2 (CCR2). However the molecular mechanisms are not understood. We investiga...

  18. Supporting members

    Science.gov (United States)

    Life Supporting Members L. Thomas Aldrich Thomas D. Barrow Hugh J . A. Chivers Allan V. Cox Samuel S. Goldich Pembroke J. Hart A. Ivan Johnson Helmut E. Landsberg Paolo Lanzano Murli H. Manghnani L. L. Nettleton Charles B. Officer Hyman Orlin Ned A. Ostenso Erick O. Schonstedt Waldo E. Smith Athelstan Spilhaus A. F. Spilhaus, Jr. John W. Townsend, Jr. James A. Van Allen Leonard W. Weis Charles A. Whitten J. Tuzo Wilson

  19. Optical coherence transfer over 50-km spooled fiber with frequency instability of 2×10-17 at 1 s

    Science.gov (United States)

    Ma, Chao-Qun; Li-Fei, Wu; Jiang, Yan-Yi; Yu, Hong-Fu; Bi, Zhi-Yi; Ma, Long-Sheng

    2015-08-01

    We demonstrate coherent transfer of an ultra-stable optical frequency at 192.8 THz over 50-km spooled fiber. Random phase noise induced by environmental disturbance through fiber is detected and suppressed by feeding a correctional signal into an acousto-optic modulator. After being compensated, the fiber-induced frequency instability is 2×10-17 at 1-s averaging time and reaches 8×10-20 after 16 h. The noise floor of the compensation system could be as low as 2×10-18 at 1-s averaging time. Project supported by the National Natural Science Foundation of China (Grant Nos. 11127405, 11334002, and 11374102) and the National Basic Research Program of China (Grant No. 2012CB821302).

  20. P2X receptors.

    Science.gov (United States)

    North, R Alan

    2016-08-01

    Extracellular adenosine 5'-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2X receptors have a widespread tissue distribution. On some smooth muscle cells, P2X receptors mediate the fast excitatory junction potential that leads to depolarization and contraction. In the central nervous system, activation of P2X receptors allows calcium to enter neurons and this can evoke slower neuromodulatory responses such as the trafficking of receptors for the neurotransmitter glutamate. In primary afferent nerves, P2X receptors are critical for the initiation of action potentials when they respond to ATP released from sensory cells such as taste buds, chemoreceptors or urothelium. In immune cells, activation of P2X receptors triggers the release of pro-inflammatory cytokines such as interleukin 1β. The development of selective blockers of different P2X receptors has led to clinical trials of their effectiveness in the management of cough, pain, inflammation and certain neurodegenerative diseases.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377721

  1. Klotho inhibits angiotensin II-induced cardiomyocyte hypertrophy through suppression of the AT1R/beta catenin pathway.

    Science.gov (United States)

    Yu, Liangzhu; Meng, Wei; Ding, Jieqiong; Cheng, Menglin

    2016-04-29

    Myocardial hypertrophy is an independent risk factor for cardiac morbidity and mortality. The antiaging protein klotho reportedly possesses a protective role in cardiac diseases. However, the precise mechanisms underlying the cardioprotective effects of klotho remain unknown. This study was aimed to determine the effects of klotho on angiotensin II (Ang II)-induced hypertrophy in neonatal rat cardiomyocytes and the possible mechanism of actions. We found that klotho significantly inhibited Ang II-induced hypertrophic growth of neonatal cardiomyocytes, as evidenced by decreased [(3)H]-Leucine incorporation, cardiomyocyte surface area and β-myosin heavy chain (β-MHC) mRNA expression. Meanwhile, klotho inhibited Ang II-stimulated activation of the Wnt/β-catenin pathway in cardiomyocytes, as evidenced by decreased protein expression of active β-catenin, downregulated protein and mRNA expression of the β-catenin target genes c-myc and cyclin D1, and increased β-catenin phosphorylation. Inhibition of the Wnt/β-catenin pathway by the specific inhibitor XAV939 markedly attenuated Ang II-induced cardiomyocyte hypertrophy. The further study revealed that klotho treatment significantly downregulated protein expression of Ang II receptor type I (AT1R) but not type II (AT2R). The AT1R antagonist losartan inhibited Ang II-stimulated activation of the Wnt/β-catenin pathway and cardiomyocyte hypertrophy. Our findings suggest that klotho inhibits Ang II-induced cardiomyocyte hypertrophy through suppression of the AT1R/β-catenin signaling pathway, which may provide new insights into the mechanism underlying the protective effects of klotho in heart diseases, and raise the possibility that klotho may act as an endogenous antihypertrophic factor by inhibiting the Ang II signaling pathway. PMID:26970306

  2. AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease.

    Science.gov (United States)

    Liu, Tian-Jing; Shi, Yong-Yan; Wang, En-Bo; Zhu, Tong; Zhao, Qun

    2016-02-01

    Angiotensin II, which is the main effector of the renin‑angiotensin system, has an important role in intestinal inflammation via the angiotensin II type 1 receptor (AT1R). The present study aimed to investigate the protective effects of the AT1R blocker losartan on 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis. Losartan was administered to male adult C57BL/6 J mice 2 weeks prior to the induction of colitis, and images of the whole colon were captured to record changes, scored according to a microscopic scoring system, and reverse transcription-quantitative polymerase chain reaction were performed in order to investigate colonic inflammation. In addition, intestinal epithelial barrier permeability was evaluated, and intestinal epithelial cell (IEC) apoptosis was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and apoptosis-related protein expression levels were detected by western blotting. Losartan was able to attenuate TNBS-induced body weight loss and colonic damage. Furthermore, T helper 1-mediated proinflammatory cytokines were suppressed by losartan, and gut permeability was largely preserved. TUNEL staining revealed reduced IEC apoptosis in the losartan-treated mice. Losartan also increased the B-cell lymphoma 2 (Bcl2)/Bcl-2-associated X protein (Bax) ratio and suppressed caspase-3 induction. These results suggested that the AT1R blocker losartan may attenuate TNBS-induced colitis by inhibiting the apoptosis of IECs. The effects of losartan were partially mediated through increasing the Bcl-2/Bax ratio and subsequently suppressing the induction of the proapoptotic mediator caspase-3. PMID:26676112

  3. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  4. GABA receptor imaging

    International Nuclear Information System (INIS)

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABAA-receptor that allows chloride to pass through a ligand gated ion channel and GABAB-receptor that uses G-proteins for signaling. The GABAA-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABAA-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18F-fluoroflumazenil (FFMZ) has been developed to overcome 11C's short half-life. 18F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '11C-FMZ PET instead of 18F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABAA receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  5. α5GABAA receptor deficiency causes autism-like behaviors.

    Science.gov (United States)

    Zurek, Agnieszka A; Kemp, Stephen W P; Aga, Zeenia; Walker, Susan; Milenkovic, Marija; Ramsey, Amy J; Sibille, Etienne; Scherer, Stephen W; Orser, Beverley A

    2016-05-01

    The prevalence of autism spectrum disorders (ASDs), which affect over 1% of the population, has increased twofold in recent years. Reduced expression of GABAA receptors has been observed in postmortem brain tissue and neuroimaging of individuals with ASDs. We found that deletion of the gene for the α5 subunit of the GABAA receptor caused robust autism-like behaviors in mice, including reduced social contacts and vocalizations. Screening of human exome sequencing data from 396 ASD subjects revealed potential missense mutations in GABRA5 and in RDX, the gene for the α5GABAA receptor-anchoring protein radixin, further supporting a α5GABAA receptor deficiency in ASDs. PMID:27231709

  6. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Mohammad eKhanfar

    2016-05-01

    Full Text Available With the very recent market approval of pitolisant (Wakix®, the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  7. Histamine H2 receptor - Involvement in gastric ulceration

    Science.gov (United States)

    Brown, P. A.; Vernikos-Danellis, J.; Brown, T. H.

    1976-01-01

    The involvement of the H1 and H2 receptors for histamine in the pathogenesis of gastric ulcers was investigated in rats. Metiamide, an H2 receptor antagonist, reliably reduced ulceration produced by stress alone or by a combination of stress and aspirin. In contrast, pyrilamine, which blocks only the H1 receptor, was without effect under these same conditions. The results support the hypothesis that histamine mediates both stress and stress plus aspirin induced ulceration by a mechanism involving the H2 receptor.

  8. Development of polyclonal antibodies against angiotensin type 2 receptors

    OpenAIRE

    1994-01-01

    Murine neuroblastoma N1E-115 cells are a useful system in which to study neuronal angiotensin II (AngII) receptors. N1E-115 cells possess both type 1 (AT1) and type 2 (AT2) AngII receptor subtypes, as does mammalian brain. AT2 receptors in brain or N1E-115 cells can be solubilized in 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. In the present study, heparin-Sepharose chromatography was used to partially purify solubilized N1E-115 membranes to produce an enriched population of AT...

  9. The landslide susceptibility map of Italy at 1:1 Million scale

    Science.gov (United States)

    Trigila, A.; Catani, F.; Casagli, N.; Crosta, G.; Esposito, C.; Frattini, P.; Iadanza, C.; Lagomarsino, D.; Lari, S.; Scarascia Mugnozza, G.; Segoni, S.; Spizzichino, D.; Tofani, V.

    2012-04-01

    a significant number of statistical units. These tests also demonstrated that large grid-cells (100x100 m, 500x500 m) are suitable terrain units for the scale of the analysis. Considering the results of the tests, the Bayesian Tree Random Forest model was selected to produce the 1:1,000,000 susceptibility map of Italy. Landslide susceptibility map of Italy at 1:1,000,000 scale can be an important support for the implementation of pan-European landslide susceptibility map and a useful tools for the EU policies and measures finalized to the landslide risk reduction and mitigation.

  10. Gq-coupled receptors as mechanosensors mediating myogenic vasoconstriction

    Science.gov (United States)

    y Schnitzler, Michael Mederos; Storch, Ursula; Meibers, Simone; Nurwakagari, Pascal; Breit, Andreas; Essin, Kirill; Gollasch, Maik; Gudermann, Thomas

    2008-01-01

    Despite the central physiological function of the myogenic response, the underlying signalling pathways and the identity of mechanosensors in vascular smooth muscle (VSM) are still elusive. In contrast to present thinking, we show that membrane stretch does not primarily gate mechanosensitive transient receptor potential (TRP) ion channels, but leads to agonist-independent activation of Gq/11-coupled receptors, which subsequently signal to TRPC channels in a G protein- and phospholipase C-dependent manner. Mechanically activated receptors adopt an active conformation, allowing for productive G protein coupling and recruitment of β-arrestin. Agonist-independent receptor activation by mechanical stimuli is blocked by specific antagonists and inverse agonists. Increasing the AT1 angiotensin II receptor density in mechanically unresponsive rat aortic A7r5 cells resulted in mechanosensitivity. Myogenic tone of cerebral and renal arteries is profoundly diminished by the inverse angiotensin II AT1 receptor agonist losartan independently of angiotensin II (AII) secretion. This inhibitory effect is enhanced in blood vessels of mice deficient in the regulator of G-protein signalling-2. These findings suggest that Gq/11-coupled receptors function as sensors of membrane stretch in VSM cells. PMID:18987636

  11. Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype

    DEFF Research Database (Denmark)

    Figueroa, Jonine D; Garcia-Closas, Montserrat; Humphreys, Manjeet;

    2011-01-01

    A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer As...

  12. [Nuclear receptors PPARalpha].

    Science.gov (United States)

    Soska, V

    2006-06-01

    Mechanism of the fibrates action is mediated by nuclear PPARalpha receptors (Peroxisome Proliferator-Activated Receptor). These receptors regulate a number of genes that are involved both in lipids and lipoproteins metabolism and other mediators (e.g. inflammatory mediatores). Due to PPARalpha activation by fibrates, triglycerides and small dense LDL concentration is decreased, HDL cholesterol is increased and both inflammation and prothrombotic status are reduced. These effects are very important in patients with metabolic syndrom. PMID:16871768

  13. Novel cannabinoid receptors

    OpenAIRE

    Brown, A J

    2007-01-01

    Cannabinoids have numerous physiological effects. In the years since the molecular identification of the G protein-coupled receptors CB1 and CB2, the ion channel TRPV1, and their corresponding endogenous ligand systems, many cannabinoid-evoked actions have been shown conclusively to be mediated by one of these specific receptor targets. However, there remain several examples where these classical cannabinoid receptors do not explain observed pharmacology. Studies using mice genetically delete...

  14. Insights into the molecular basis of action of the AT1 antagonist losartan using a combined NMR spectroscopy and computational approach.

    Science.gov (United States)

    Zervou, Maria; Cournia, Zoe; Potamitis, Constantinos; Patargias, George; Durdagi, Serdar; Grdadolnik, Simona Golic; Mavromoustakos, Thomas

    2014-03-01

    The drug:membrane interactions for the antihypertensive AT1 antagonist losartan, the prototype of the sartans class, are studied herein using an integrated approach. The pharmacophore arrangement of the drug was revealed by rotating frame nuclear Overhauser effect spectroscopy (2D ROESY) NMR spectroscopy in three different environments, namely water, dimethyl sulfoxide (DMSO), and sodium dodecyl sulfate (SDS) micellar solutions mimicking conditions of biological transport fluids and membrane lipid bilayers. Drug association with micelles was monitored by diffusion ordered spectroscopy (2D DOSY) and drug:micelle intermolecular interactions were characterized by ROESY spectroscopy. The localisation of the drug in the micellar environment was investigated by introducing 5-doxyl and 16-doxyl stearic acids. The use of spin labels confirmed that losartan resides close to the micelle:water interface with the hydroxymethyl group and the tetrazole heterocyclic aromatic ring facing the polar surface with the potential to interact with SDS charged polar head groups in order to increase amphiphilic interactions. The spontaneous insertion, the diffusion pathway and the conformational features of losartan were monitored by Molecular Dynamics (MD) simulations in a modeled SDS micellar aggregate environment and a long exploratory MD run (580ns) in a phospholipid dipalmitoylphosphatidylcholine (DPPC) bilayer with the AT1 receptor embedded. MD simulations were in excellent agreement with experimental results and further revealed the molecular basis of losartan:membrane interactions in atomic-level detail. This applied integrated approach aims to explore the role of membranes in losartan's pathway towards the AT1 receptor. PMID:24374319

  15. Pharmacologic perspectives of functional selectivity by the angiotensin II type 1 receptor

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Hansen, Jakob Lerche

    2008-01-01

    The angiotensin II type 1 (AT(1)) receptor plays a key role in cardiovascular pathophysiology, and it is a major pharmacologic target in the treatment of many cardiovascular disorders. However, AT(1) receptor activation is also involved in adaptive responses to altered hemodynamic demands and to...... sudden injury occurring in the circulatory system. Hence, current drugs that block all AT(1) receptor actions most likely leave room for improvement. Recent developments show that two major signaling pathways used by the AT(1) receptor may be dissected by pharmacologic means. Key pathologic responses...... blockade of G protein actions and simultaneous activation of G protein-dependent or -independent signaling could therefore be desirable in certain situations. The previously unappreciated concept of "functional selectivity" makes this exact strategy feasible and may yield improved drugs for cardiovascular...

  16. Profiling epidermal growth factor receptor and heregulin receptor 3 heteromerization using receptor tyrosine kinase heteromer investigation technology.

    Directory of Open Access Journals (Sweden)

    Mohammed Akli Ayoub

    Full Text Available Heteromerization can play an important role in regulating the activation and/or signal transduction of most forms of receptors, including receptor tyrosine kinases (RTKs. The study of receptor heteromerization has evolved extensively with the emergence of resonance energy transfer based approaches such as bioluminescence resonance energy transfer (BRET. Here, we report an adaptation of our Receptor-Heteromer Investigation Technology (Receptor-HIT that has recently been published as the G protein-coupled receptor (GPCR Heteromer Identification Technology (GPCR-HIT. We now demonstrate the utility of this approach for investigating RTK heteromerization by examining the functional interaction between the epidermal growth factor (EGF receptor (EGFR; also known as erbB1/HER1 and heregulin (HRG receptor 3 (HER3; also known as erbB3 in live HEK293FT cells using recruitment of growth factor receptor-bound protein 2 (Grb2 to the activated receptors. We found that EGFR and HER3 heteromerize specifically as demonstrated by HRG inducing a BRET signal between EGFR/Rluc8 and Grb2/Venus only when HER3 was co-expressed. Similarly, EGF stimulation promoted a specific BRET signal between HER3/Rluc8 and Grb2/Venus only when EGFR was co-expressed. Both EGF and HRG effects on Grb2 interaction are dose-dependent, and specifically blocked by EGFR inhibitor AG-1478. Furthermore, truncation of HER3 to remove the putative Grb2 binding sites appears to abolish EGF-induced Grb2 recruitment to the EGFR-HER3 heteromer. Our results support the concept that EGFR interacts with Grb2 in both constitutive and EGF-dependent manners and this interaction is independent of HER3 co-expression. In contrast, HER3-Grb2 interaction requires the heteromerization between EGFR and HER3. These findings clearly indicate the importance of EGFR-HER3 heteromerization in HER3-mediated Grb2-dependent signaling pathways and supports the central role of HER3 in the diversity and regulation of HER

  17. Serial femtosecond crystallography datasets from G protein-coupled receptors.

    Science.gov (United States)

    White, Thomas A; Barty, Anton; Liu, Wei; Ishchenko, Andrii; Zhang, Haitao; Gati, Cornelius; Zatsepin, Nadia A; Basu, Shibom; Oberthür, Dominik; Metz, Markus; Beyerlein, Kenneth R; Yoon, Chun Hong; Yefanov, Oleksandr M; James, Daniel; Wang, Dingjie; Messerschmidt, Marc; Koglin, Jason E; Boutet, Sébastien; Weierstall, Uwe; Cherezov, Vadim

    2016-01-01

    We describe the deposition of four datasets consisting of X-ray diffraction images acquired using serial femtosecond crystallography experiments on microcrystals of human G protein-coupled receptors, grown and delivered in lipidic cubic phase, at the Linac Coherent Light Source. The receptors are: the human serotonin receptor 2B in complex with an agonist ergotamine, the human δ-opioid receptor in complex with a bi-functional peptide ligand DIPP-NH2, the human smoothened receptor in complex with an antagonist cyclopamine, and finally the human angiotensin II type 1 receptor in complex with the selective antagonist ZD7155. All four datasets have been deposited, with minimal processing, in an HDF5-based file format, which can be used directly for crystallographic processing with CrystFEL or other software. We have provided processing scripts and supporting files for recent versions of CrystFEL, which can be used to validate the data. PMID:27479354

  18. "Assessment of human AT1 Binding Affinity of Some Novel 2-alkylthio-1-[4-(N-α-ethoxycarbonyl-nzylaminobenzyl-5-hydroxymethylimidazoles "

    Directory of Open Access Journals (Sweden)

    Setareh Badakhshannoory

    2004-06-01

    Full Text Available Antagonists of various components of the renin-angiotensin system have been the subject of many studies for the control of blood pressure. Compounds with a phenoxyphenylacetic acid moiety that mimic the structure of losartan which is a powerful competitive antagonist of angiotensin receptor, have shown to be effective. In this study, the affinity of some 2-alkylthio-1-[4-(N-α-ethoxycarbonylbenzylaminobenzyl]-5-hydroxymethyl imidazoles for the human AT1 receptor was assessed in a radioligand binding assay. It was found that an alkyl chain of appropriate length would be most suitable if situated on the imidazole ring. Furthermore, variations of the lower phenyl rings demonstrated that introduction of a methyl group in this position will account for the most desired effect.

  19. Documentation of angiotensin II receptors in glomerular epithelial cells

    Science.gov (United States)

    Sharma, M.; Sharma, R.; Greene, A. S.; McCarthy, E. T.; Savin, V. J.; Cowley, A. W. (Principal Investigator)

    1998-01-01

    Angiotensin II decreases glomerular filtration rate, renal plasma flow, and glomerular capillary hydraulic conductivity. Although angiotensin II receptors have been demonstrated in mesangial cells and proximal tubule cells, the presence of angiotensin II receptors in glomerular epithelial cells has not previously been shown. Previously, we have reported that angiotensin II caused an accumulation of cAMP and a reorganization of the actin cytoskeleton in cultured glomerular epithelial cells. Current studies were conducted to verify the presence of angiotensin II receptors by immunological and non-peptide receptor ligand binding techniques and to ascertain the activation of intracellular signal transduction in glomerular epithelial cells in response to angiotensin II. Confluent monolayer cultures of glomerular epithelial cells were incubated with angiotensin II, with or without losartan and/or PD-123,319 in the medium. Membrane vesicle preparations were obtained by homogenization of washed cells followed by centrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins followed by multiscreen immunoblotting was used to determine the presence of angiotensin II receptor type 1 (AT1) or type 2 (AT2). Angiotensin II-mediated signal transduction in glomerular epithelial cells was studied by measuring the levels of cAMP, using radioimmunoassay. Results obtained in these experiments showed the presence of both AT1 and AT2 receptor types in glomerular epithelial cells. Angiotensin II was found to cause an accumulation of cAMP in glomerular epithelial cells, which could be prevented only by simultaneous use of losartan and PD-123,319, antagonists for AT1 and AT2, respectively. The presence of both AT1 and AT2 receptors and an increase in cAMP indicate that glomerular epithelial cells respond to angiotensin II in a manner distinct from that of mesangial cells or proximal tubular epithelial cells. Our results suggest that glomerular epithelial

  20. Angiotensin II Receptors Modulate Muscle Microvascular and Metabolic Responses to Insulin In Vivo

    OpenAIRE

    Chai, Weidong; Wang, WenHui; Dong, Zhenhua; Cao, Wenhong; Liu, Zhenqi

    2011-01-01

    OBJECTIVE Angiotensin (ANG) II interacts with insulin-signaling pathways to regulate insulin sensitivity. The type 1 (AT1R) and type 2 (AT2R) receptors reciprocally regulate basal perfusion of muscle microvasculature. Unopposed AT2R activity increases muscle microvascular blood volume (MBV) and glucose extraction, whereas unopposed AT1R activity decreases both. The current study examined whether ANG II receptors modulate muscle insulin delivery and sensitivity. RESEARCH DESIGN AND METHODS Ove...

  1. Supporting ATLAS

    CERN Multimedia

    2003-01-01

    Eighteen feet made of stainless steel will support the barrel ATLAS detector in the cavern at Point 1. In total, the ATLAS feet system will carry approximately 6000 tons, and will give the same inclination to the detector as the LHC accelerator. The installation of the feet is scheduled to finish during January 2004 with an installation precision at the 1 mm level despite their height of 5.3 metres. The manufacture was carried out in Russia (Company Izhorskiye Zavody in St. Petersburg), as part of a Russian and JINR Dubna in-kind contribution to ATLAS. Involved in the installation is a team from IHEP-Protvino (Russia), the ATLAS technical co-ordination team at CERN, and the CERN survey team. In all, about 15 people are involved. After the feet are in place, the barrel toroid magnet and the barrel calorimeters will be installed. This will keep the ATLAS team busy for the entire year 2004.

  2. Biased Signaling of the Angiotensin II Type 1 Receptor Can Be Mediated through Distinct Mechanisms

    OpenAIRE

    Bonde, Marie Mi; Hansen, Jonas Tind; Sanni, Samra Joke; Haunsø, Stig; Gammeltoft, Steen; Lyngsø, Christina; Hansen, Jakob Lerche

    2010-01-01

    Background Seven transmembrane receptors (7TMRs) can adopt different active conformations facilitating a selective activation of either G protein or β-arrestin-dependent signaling pathways. This represents an opportunity for development of novel therapeutics targeting selective biological effects of a given receptor. Several studies on pathway separation have been performed, many of these on the Angiotensin II type 1 receptor (AT1R). It has been shown that certain ligands or mutations facilit...

  3. Muscarinic receptor signaling and colon cancer progression

    Institute of Scientific and Technical Information of China (English)

    Guofeng Xie; Jean-Pierre Raufman

    2016-01-01

    Due to the lack of effective treatments, advanced colorectal cancer (CRC) remains a leading cause of cancer death in the United States. Emerging evidence supports the observation that muscarinic receptor (MR) signaling plays a critical role in growth and progression of CRC. MR activation by acetylcholine and bile acids results in transactivation of epidermal growth factor receptors (EGFR) and post-EGFR signal transduction that enhances cell proliferation, migration, and invasion. Here, the authors review recent progress in understanding the molecular mechanisms underlying MR-mediated CRC progression and its therapeutic implications.

  4. POLLUTANT PARTICLES PRODUCE VASOCONSTRICTION AND ENHANCE MAPK SIGNALING VIA ANGIOTENSIN TYPE 1 RECEPTOR

    Science.gov (United States)

    Exposure to particulate matter (PM) is associated with acute cardiovascular mortality and morbidity, but the mechanisms are not entirely clear. In this study, we hypothesized that PM may activate the angiotensin type 1 receptor (AT1R), a G protein-coupled receptor that regulates ...

  5. No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation

    DEFF Research Database (Denmark)

    Estrup, T M; Paulson, O B; Strandgaard, S

    2001-01-01

    Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT1-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT2-receptors in the regulation of the cerebral cir...

  6. Increased angiotensin II type 1 receptor expression in temporal arteries from patients with giant cell arteritis

    DEFF Research Database (Denmark)

    Dimitrijevic, Ivan; Malmsjö, Malin; Andersson, Christina; Rissler, Pehr; Edvinsson, Lars

    2009-01-01

    peptide involved in vessel inflammation during atherosclerosis, and angiotensin II receptor inhibitors are effective in preventing atherosclerosis. The present study was performed to elucidate the role of angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors in GCA. DESIGN: Experimental retrospective...

  7. Determination of the exact molecular requirements for type 1 angiotensin receptor epidermal growth factor receptor transactivation and cardiomyocyte hypertrophy.

    Science.gov (United States)

    Smith, Nicola J; Chan, Hsiu-Wen; Qian, Hongwei; Bourne, Allison M; Hannan, Katherine M; Warner, Fiona J; Ritchie, Rebecca H; Pearson, Richard B; Hannan, Ross D; Thomas, Walter G

    2011-05-01

    Major interest surrounds how angiotensin II triggers cardiac hypertrophy via epidermal growth factor receptor transactivation. G protein-mediated transduction, angiotensin type 1 receptor phosphorylation at tyrosine 319, and β-arrestin-dependent scaffolding have been suggested, yet the mechanism remains controversial. We examined these pathways in the most reductionist model of cardiomyocyte growth, neonatal ventricular cardiomyocytes. Analysis with [(32)P]-labeled cardiomyocytes, wild-type and [Y319A] angiotensin type 1 receptor immunoprecipitation and phosphorimaging, phosphopeptide analysis, and antiphosphotyrosine blotting provided no evidence for tyrosine phosphorylation at Y319 or indeed of the receptor, and mutation of Y319 (to A/F) did not prevent either epidermal growth factor receptor transactivation in COS-7 cells or cardiomyocyte hypertrophy. Instead, we demonstrate that transactivation and cardiomyocyte hypertrophy are completely abrogated by loss of G-protein coupling, whereas a constitutively active angiotensin type 1 receptor mutant was sufficient to trigger transactivation and growth in the absence of ligand. These results were supported by the failure of the β-arrestin-biased ligand SII angiotensin II to transactivate epidermal growth factor receptor or promote hypertrophy, whereas a β-arrestin-uncoupled receptor retained these properties. We also found angiotensin II-mediated cardiomyocyte hypertrophy to be attenuated by a disintegrin and metalloprotease inhibition. Thus, G-protein coupling, and not Y319 phosphorylation or β-arrestin scaffolding, is required for epidermal growth factor receptor transactivation and cardiomyocyte hypertrophy via the angiotensin type 1 receptor. PMID:21383310

  8. GABAA receptors, but not dopamine, serotonin or NMDA receptors, are increased in the frontal cortex from schizophrenic subjects

    International Nuclear Information System (INIS)

    Full text: Having shown changed 5HT2A receptor density in the frontal cortex (FC) from schizophrenic subjects (1) we now report on further studies of the molecular neuroanatomy of the FC in schizophrenia. We used in situ radioligand binding and autoradiography to measure the density of [3H]8OH-DPAT (1 nM) binding (5HT1A receptors) and [3H]GR113808 (2.4nM) binding (5HT4 receptors) in Brodmann's areas (BA) 8, 9 and 10 from 10 schizophrenic and 10 controls subjects. In addition, [3H]muscimol (100 nM) binding (GABAA receptors), [3H]TCP (20nM) binding (NMDA receptors), [3H]SCH 23390 (3nM) binding (DA D1like receptors) and [3H]YM-09151-2 (4nM) binding (DA D2-like receptors) was measured in BA 9 from 17 schizophrenic and 17 control subjects. Subjects were matched for age and sex and the post-mortem interval for tissue collection did not differ. There was a significant increase (18%) in the density of GABAA receptors in BA 9 from subjects with schizophrenia (p<0.05) with no change in NMDA, dopamine or serotonin receptors. These data support the hypothesis that there are selective changes in neurotransmitter receptors in the FC of subjects with schizophrenia. It is not yet clear if such changes contribute to the pathology of the illness. Copyright (1998) Australian Neuroscience Society

  9. 30 CFR 57.22236 - Actions at 1.0 percent methane (VI mines).

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 1.0 percent methane (VI mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22236 Actions at 1.0 percent methane (VI mines). If methane reaches 1.0 percent in the mine atmosphere, all persons other...

  10. Role of angiotensin II and vasopressin receptors within the supraoptic nucleus in water and sodium intake induced by the injection of angiotensin II into the medial septal area

    Directory of Open Access Journals (Sweden)

    Antunes V.R.

    1998-01-01

    Full Text Available In this study we investigated the effects of the injection into the supraoptic nucleus (SON of non-peptide AT1- and AT2-angiotensin II (ANG II receptor antagonists, DuP753 and PD123319, as well as of the arginine-vasopressin (AVP receptor antagonist d(CH25-Tyr(Me-AVP, on water and 3% NaCl intake induced by the injection of ANG II into the medial septal area (MSA. The effects on water or 3% NaCl intake were assessed in 30-h water-deprived or in 20-h water-deprived furosemide-treated adult male rats, respectively. The drugs were injected in 0.5 ml over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. Antagonists were injected at doses of 20, 80 and 180 nmol. Water and sodium intake was measured over a 2-h period. Previous administration of the AT1 receptor antagonist DuP753 into the SON decreased water (65%, N = 10, P<0.01 and sodium intake (81%, N = 8, P<0.01 induced by the injection of ANG II (10 nmol into the MSA. Neither of these responses was significantly changed by injection of the AT2-receptor antagonist PD123319 into the SON. On the other hand, while there was a decrease in water intake (45%, N = 9, P<0.01, ANG II-induced sodium intake was significantly increased (70%, N = 8, P<0.01 following injection of the V1-type vasopressin antagonist d(CH25-Tyr(Me-AVP into the SON. These results suggest that both AT1 and V1 receptors within the SON may be involved in water and sodium intake induced by the activation of ANG II receptors within the MSA. Furthermore, they do not support the involvement of MSA AT2 receptors in the mediation of these responses.

  11. EXPERIMENT STUDIES OF ANTITUMOR PROLIFERATION AND METASTASIS OF A NEW CHINESE HERB AT-1

    Institute of Scientific and Technical Information of China (English)

    曲迅; 郑广娟; 杨美香; 周文; 赵丽霞

    2003-01-01

    Objective: To study the effects of a new Chinese herb AT-1 on the tumor cell proliferation and metastasis in vitro. Methods: Tumor cell proliferation activity was tested by MTT. The ability of tumor cell invasion and migration was assayed by counting the number of tumor cells going throw matrigel. The expression changes of CD44 genes in PG cells treated with AT-1 were tested by FACS. Results: Compared with the control, the proliferation activity of the cells treated with the At-1 was restrained. The invasion and migration ability of PG cells and the expression of the cell adherence related gene CD44 was decreased treatment with AT-1. Conclusion: AT-1 is a new antitumor proliferation and metastasis agent. Its antitumor metastasis effect might be achieved by decreasing the expression of the cell adherence-associate gene CD44.

  12. Support facilities

    International Nuclear Information System (INIS)

    Computer support is centered on the Remote Access Data Station (RADS), which is equipped with a 1000 lpm printer, 1000 cpm reader, and a 300 cps paper tape reader with 500-foot spools. The RADS is located in a data preparation room with four 029 key punches (two of which interpret), a storage vault for archival magnetic tapes, card files, and a 30 cps interactive terminal principally used for job inquiry and routing. An adjacent room provides work space for users, with a documentation library and a consultant's office, plus file storage for programs and their documentations. The facility has approximately 2,600 square feet of working laboratory space, and includes two fully equipped photographic darkrooms, sectioning and autoradiographic facilities, six microscope cubicles, and five transmission electron microscopes and one Cambridge scanning electron microscope equipped with an x-ray energy dispersive analytical system. Ancillary specimen preparative equipment includes vacuum evaporators, freeze-drying and freeze-etching equipment, ultramicrotomes, and assorted photographic and light microscopic equipment. The extensive physical plant of the animal facilities includes provisions for holding all species of laboratory animals under controlled conditions of temperature, humidity, and lighting. More than forty rooms are available for studies of the smaller species. These have a potential capacity of more than 75,000 mice, or smaller numbers of larger species and those requiring special housing arrangements. There are also six dog kennels to accommodate approximately 750 dogs housed in runs that consist of heated indoor compartments and outdoor exercise areas

  13. Photoaffinity ligand for dopamine D2 receptors: azidoclebopride

    Energy Technology Data Exchange (ETDEWEB)

    Niznik, H.B.; Guan, J.H.; Neumeyer, J.L.; Seeman, P.

    1985-02-01

    In order to label D2 dopamine receptors selectively and covalently by means of a photosensitive compound, azidoclebopride was synthesized directly from clebopride. The dissociation constant (KD) of clebopride for the D2 dopamine receptor (canine brain striatum) was 1.5 nM, while that for azidoclebopride was 21 nM. The affinities of both clebopride and azidoclebopride were markedly reduced in the absence of sodium chloride. In the presence of ultraviolet light, azidoclebopride inactivated D2 dopamine receptors irreversibly, as indicated by the inability of the receptors to bind (/sup 3/H)spiperone. Maximal photoinactivation of about 60% of the D2 dopamine receptors occurred at 1 microM azidoclebopride; 30% of the receptors were inactivated at 80 nM azidoclebopride (pseudo-IC50). Dopamine agonists selectively protected the D2 receptors from being inactivated by azidoclebopride, the order of potency being (-)-N-n-propylnorapomorphine greater than apomorphine greater than (+/-)-6,7-dihydroxy-2-aminotetralin greater than (+)-N-n-propylnorapomorphine greater than dopamine greater than noradrenaline greater than serotonin. Similarly, dopaminergic antagonists prevented the photoinactivation of D2 receptors by azidoclebopride with the following order of potency: spiperone greater than (+)-butaclamol greater than haloperidol greater than clebopride greater than (-)-sulpiride greater than (-)-butaclamol.

  14. Mechanism of FGF receptor dimerization and activation

    Science.gov (United States)

    Sarabipour, Sarvenaz; Hristova, Kalina

    2016-01-01

    Fibroblast growth factors (fgfs) are widely believed to activate their receptors by mediating receptor dimerization. Here we show, however, that the FGF receptors form dimers in the absence of ligand, and that these unliganded dimers are phosphorylated. We further show that ligand binding triggers structural changes in the FGFR dimers, which increase FGFR phosphorylation. The observed effects due to the ligands fgf1 and fgf2 are very different. The fgf2-bound dimer structure ensures the smallest separation between the transmembrane (TM) domains and the highest possible phosphorylation, a conclusion that is supported by a strong correlation between TM helix separation in the dimer and kinase phosphorylation. The pathogenic A391E mutation in FGFR3 TM domain emulates the action of fgf2, trapping the FGFR3 dimer in its most active state. This study establishes the existence of multiple active ligand-bound states, and uncovers a novel molecular mechanism through which FGFR-linked pathologies can arise.

  15. Involvement of Ca2+-activated K+ Channels in Receptor-Regulated Sperm Motility in Rats

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Previous voltage-clamp studies have demonstrated the modulation of sperm Ca2+-activated K+ (KCa) channels expressed in Xenopus oocytes by angiotensin Ⅱ (Ang Ⅱ)and extracellular ATP via AT1 receptor and P2U receptor, respectively. In the presentstudy, we investigated the involvement of KCa channels in receptor-regulated spermmotility of the rat using a computer-aided sperm analysis system, HTM-IVOS, in con-junction with Ca2+-mobilizing agents, receptor agonists/antagonists and KCa channelsblockers.The percentage of motile sperm was increased by ionomycin (0. 5 μmol/L), whichcould be inhibited by K+ channel blockers, tetraethylammonium (TEA 1 μmol/L ) orcharybdotoxin (ChTX, 300 nmol/L) indicating the presence of KCa channels. AngⅡ, at low concentration, 10 nmol/L, was found to increase motility, however, athigher concentration, 1 μmol/L, percentage of motility was found to be suppressed.Both stimulatory and inhibitory effects of Ang Ⅱ could be reversed by losartan, aspecific antagonist of AT 1 receptors, but not AT 2 antagonist PD123177, indicating theinvolvement of AT1 but not AT2 receptor in mediating both effects. ChTX also abol-ished both stimulatory and inhibitory effects of Ang H, suggesting the involvement ofKCa channels. The percentage of motility was also enhanced by extracellular ATP, afactor known to be involved in sperm activation. The ATP-enhanced sperm motilitywas mimicked by UTP , and inhibited by ChTX and reactive blue, an antagonist of P2receptor, indicating the involvement of both P2U and KCa channels. RT-PCR studywas also conducted to confirm the expression of KCa channels, AT1 receptors and P2Ureceptor, but not AT2 receptor, in rat caudal epididymal sperm. The present findingssuggest an important role of KCa channels in the regulation of sperm motility by AT1and P 2U receptors.

  16. Not only dopamine D2 receptors involved in Peony-Glycyrrhiza Decoction, an herbal preparation against antipsychotic-associated hyperprolactinemia.

    Science.gov (United States)

    Wang, Di; Wong, Hei Kiu; Zhang, Li; McAlonan, Grainne M; Wang, Xiao-Min; Sze, Stephen Cho Wing; Feng, Yi-Bin; Zhang, Zhang-Jin

    2012-12-01

    Clinical studies have demonstrated the effectiveness of an herbal preparation called Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL). In the present study, we further examined the pharmacological action of PGD on prolactin (PRL) secretion using in vitro and in vivo models, with specific attention to the role of dopaminergic mediators and other sex hormones. Treatment with PGD at 1-5mg/ml significantly suppressed PRL secretion and synthesis in MMQ cells, a model of hyperPRL derived from pituitary adenoma cells. The suppressive effects were completely abolished by pretreatment with 10μM haloperidol, a dopamine D(2) receptor antagonist. Consistent with a D(2)-action, PGD did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D(2) receptor expression but significantly increased the expression of D(2) receptors and dopamine transporters (DAT) in PC12 cells. In a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide (MCP), chronic PGD (2.5-10g/kg daily) significantly reduced elevated serum PRL. The reduction in magnitude was similar to that elicited by bromocriptine (BMT), a dopamine D(2) receptor agonist currently used for treatment of hyperPRL. Neither PGD nor BMT altered serum estradiol, but PGD reversed decreased serum progesterone to control level, whereas BMT did not. These results indicate that the anti-hyperPRL effects of PGD are associated not only with D(2) receptor and DAT modulation, but also with a normalization of other sex hormone dysfunction. This experimental evidence supports clinical use of PGD as an effective treatment of antipsychotic-induced hyperPRL. PMID:22796279

  17. Comparison of the antagonistic effects of different angiotensin II receptor blockers in human coronary arteries

    DEFF Research Database (Denmark)

    Pantev, Emil; Stenman, Emelie; Wackenfors, Angelica;

    2002-01-01

    undertaken to evaluate the inhibitory effects of ARBs on vasoconstriction in humans. METHODS: Vasomotor tone was analyzed in endothelium denuded, human coronary artery (HCA) segments. Ang II type 1 (AT(1)) and type 2 (AT(2)) receptor mRNA expression was examined by reverse transcriptase-polymerase chain...... presence of 100 nM losartan elicited a depression of the Ang II response to 32%. Its active metabolite, EXP 3174 (1 nM),abolished the Ang II contraction. The AT(1) receptor antagonists had the following order of blocking effect; EXP 3174 > candesartan = valsartan > losartan. The AT(2) receptor antagonist...

  18. Promotion of breast cancer by β-Hexachlorocyclohexane in MCF10AT1 cells and MMTV-neu mice

    International Nuclear Information System (INIS)

    Exposure to β-Hexachlorocyclohexane (β-HCH), a contaminant of the hexachlorohexane pesticide lindane, has been implicated as a risk factor in the development of breast cancers in epidemiological studies. Previous studies in our laboratory have demonstrated the ability of β-HCH to elicit its actions via a ligand-independent activation of the estrogen receptor through increased c-Neu (= erbB2 or HER-2) expression and kinase activation in both the BG-1 and MCF-7 cell lines. In addition, long term exposure (33 passages) to β-HCH was shown to promote the selection of MCF-7 cells which exhibit a more metastatic phenotype. In this current study, we decided to investigate the long-term effects of β-HCH in both the MCF10AT1 cell line which was derived from a normal epithelial cell line by stably transfecting a mutated c-Ha-ras and a MMTV-Neu mouse model for mammary cancer in vivo. MCF10AT1 cells were exposed for 20 passages with β-HCH, 4-OH-Tamoxifen (Tam), or 17-β-estradiol (E2) after which cells were analyzed for proliferation rates and mRNA expression by RT-PCR. In our in vivo studies, MMTV-Neu mice were injected with β-HCH and observed for tumor formation over a 70 week period. β-HCH and Tam selected MCF10AT1 cells demonstrated increased mRNA expression of MMP-13 (collagenase-3) a marker of increased invasiveness. β-HCH treatment was also seen to increase the expression in a number of proto-oncogenes (c-Neu, Cyclin D1, p27), cell status markers (Met-1, CK19), and the inflammatory marker NFκB. Previous studies, have demonstrated the role of these markers as evidence of malignant transformations, and further illustrate the ability of β-HCH to be carcinogenic. To demonstrate β-HCH's tumorigenic properties in an in vivo system, we used an MMTV-Neu mouse model. MMTV-Neu is a c-Neu overexpressing strain which has been shown to spontaneously develop mammary tumors at later stages of aging. In this experiment, β-HCH exposure was shown to both accelerate the

  19. Single-Frequency Semiconductor Lasers Operating at 1.5 and 2.0 microns Project

    Data.gov (United States)

    National Aeronautics and Space Administration — While conventional injection seeding sources (such as DFB diode lasers and rare-earth doped solid-state microchip lasers) are available at 1.5 microns, these...

  20. U.S. Autism Rate Unchanged at 1 in 68 Kids: CDC

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_158064.html U.S. Autism Rate Unchanged at 1 in 68 Kids: CDC ... 2016 THURSDAY, March 31, 2016 (HealthDay News) -- The autism rate among school-aged children in the United ...

  1. Narrow Wavelength, Frequency Modulated Source at 1.5 Wavelength Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Ultrastable, narrow linewidth, tunable, high reliability sources at 1.5 or 2mm are needed for high performance LIDARs for several NASA applications, including wind...

  2. Molecular evolution of the neuropeptide S receptor.

    Directory of Open Access Journals (Sweden)

    Thejkiran Pitti

    Full Text Available The neuropeptide S receptor (NPSR is a recently deorphanized member of the G protein-coupled receptor (GPCR superfamily and is activated by the neuropeptide S (NPS. NPSR and NPS are widely expressed in central nervous system and are known to have crucial roles in asthma pathogenesis, locomotor activity, wakefulness, anxiety and food intake. The NPS-NPSR system was previously thought to have first evolved in the tetrapods. Here we examine the origin and the molecular evolution of the NPSR using in-silico comparative analyses and document the molecular basis of divergence of the NPSR from its closest vertebrate paralogs. In this study, NPSR-like sequences have been identified in a hemichordate and a cephalochordate, suggesting an earlier emergence of a NPSR-like sequence in the metazoan lineage. Phylogenetic analyses revealed that the NPSR is most closely related to the invertebrate cardioacceleratory peptide receptor (CCAPR and the group of vasopressin-like receptors. Gene structure features were congruent with the phylogenetic clustering and supported the orthology of NPSR to the invertebrate NPSR-like and CCAPR. A site-specific analysis between the vertebrate NPSR and the well studied paralogous vasopressin-like receptor subtypes revealed several putative amino acid sites that may account for the observed functional divergence between them. The data can facilitate experimental studies aiming at deciphering the common features as well as those related to ligand binding and signal transduction processes specific to the NPSR.

  3. Corazonin receptor signaling in ecdysis initiation.

    Science.gov (United States)

    Kim, Young-Joon; Spalovská-Valachová, Ivana; Cho, Kook-Ho; Zitnanova, Inka; Park, Yoonseong; Adams, Michael E; Zitnan, Dusan

    2004-04-27

    Corazonin is a highly conserved neuropeptide hormone of wide-spread occurrence in insects yet is associated with no universally recognized function. After discovery of the corazonin receptor in Drosophila, we identified its ortholog in the moth, Manduca sexta, as a prelude to physiological studies. The corazonin receptor cDNA in M. sexta encodes a protein of 436 amino acids with seven putative transmembrane domains and shares common ancestry with its Drosophila counterpart. The receptor exhibits high sensitivity and selectivity for corazonin when expressed in Xenopus oocytes (EC(50) approximately 200 pM) or Chinese hamster ovary cells (EC(50) approximately 75 pM). Northern blot analysis locates the receptor in peripheral endocrine Inka cells, the source of preecdysis- and ecdysis-triggering hormones. Injection of corazonin into pharate larvae elicits release of these peptides from Inka cells, which induce precocious preecdysis and ecdysis behaviors. In vitro exposure of isolated Inka cells to corazonin (25-100 pM) induces preecdysis- and ecdysis-triggering hormone secretion. Using corazonin receptor as a biosensor, we show that corazonin concentrations in the hemolymph 20 min before natural preecdysis onset range from 20 to 80 pM and then decline over the next 30-40 min. These findings support the role of corazonin signaling in initiation of the ecdysis behavioral sequence. We propose a model for peptide-mediated interactions between Inka cells and the CNS underlying this process in insect development. PMID:15096620

  4. Angiotensin II receptors and peritoneal dialysis-induced peritoneal fibrosis.

    Science.gov (United States)

    Morinelli, Thomas A; Luttrell, Louis M; Strungs, Erik G; Ullian, Michael E

    2016-08-01

    The vasoactive hormone angiotensin II initiates its major hemodynamic effects through interaction with AT1 receptors, a member of the class of G protein-coupled receptors. Acting through its AT1R, angiotensin II regulates blood pressure and renal salt and water balance. Recent evidence points to additional pathological influences of activation of AT1R, in particular inflammation, fibrosis and atherosclerosis. The transcription factor nuclear factor κB, a key mediator in inflammation and atherosclerosis, can be activated by angiotensin II through a mechanism that may involve arrestin-dependent AT1 receptor internalization. Peritoneal dialysis is a therapeutic modality for treating patients with end-stage kidney disease. The effectiveness of peritoneal dialysis at removing waste from the circulation is compromised over time as a consequence of peritoneal dialysis-induced peritoneal fibrosis. The non-physiological dialysis solution used in peritoneal dialysis, i.e. highly concentrated, hyperosmotic glucose, acidic pH as well as large volumes infused into the peritoneal cavity, contributes to the development of fibrosis. Numerous trials have been conducted altering certain components of the peritoneal dialysis fluid in hopes of preventing or delaying the fibrotic response with limited success. We hypothesize that structural activation of AT1R by hyperosmotic peritoneal dialysis fluid activates the internalization process and subsequent signaling through the transcription factor nuclear factor κB, resulting in the generation of pro-fibrotic/pro-inflammatory mediators producing peritoneal fibrosis. PMID:27167177

  5. Androgen receptor mutations

    OpenAIRE

    Brinkmann, Albert; Jenster, Guido; Ris-Stalpers, Carolyn; Korput, J. A G M; Brüggenwirth, Hennie; Boehmer, A.L.; Trapman, Jan

    1995-01-01

    textabstractMale sexual differentiation and development proceed under direct control of androgens. Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. At least three pathological situations are associated with abnormal androgen receptor structure and function: androgen insensitivity syndrome (AIS), spinal and bulbar muscular atrophy (SBMA) and prostate cancer. In the X-linked androgen insensitivity syn...

  6. Serotonin Receptors in Hippocampus

    OpenAIRE

    Laura Cristina Berumen; Angelina Rodríguez; Ricardo Miledi; Guadalupe García-Alcocer

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a fu...

  7. Imidazoline receptors ligands

    Directory of Open Access Journals (Sweden)

    Agbaba Danica

    2012-01-01

    Full Text Available Extensive biochemical and pharmacological studies have determined three different subtypes of imidazoline receptors: I1-imidazoline receptors (I1-IR involved in central inhibition of sympathicus that produce hypotensive effect; I2-imidazoline receptors (I2-IR modulate monoamine oxidase B activity (MAO-B; I3-imidazoline receptors (I3-IR regulate insulin secretion from pancreatic β-cells. Therefore, the I1/I2/I3 imidazoline receptors are selected as new, interesting targets for drug design and discovery. Novel selective I1/I2/I3 agonists and antagonists have been recently developed. In the present review, we provide a brief update to the field of imidazoline research, highlighting some of the chemical diversity and progress made in the 2D-QSAR, 3D-QSAR and quantitative pharmacophore development studies of I1-IR and I2-IR imidazoline receptor ligands. Theoretical studies of I3-IR ligands are not yet performed because of insufficient number of synthesized I3-IR ligands.

  8. Behavioral effects of D3 receptor inhibition and 5-HT4 receptor activation on animals undergoing chronic cannabinoid exposure during adolescence.

    Science.gov (United States)

    Abboussi, Oualid; Said, Nadia; Fifel, Karim; Lakehayli, Sara; Tazi, Abdelouahhab; El Ganouni, Soumaya

    2016-04-01

    Chronic exposure to cannabinoids during adolescence results in long-lasting behavioral deficits that match some symptomatologic aspects of schizophrenia. The aim of this study was to investigate the reversibility of the emotional and the cognitive effects of chronic exposure to cannabinoids during adolescence, via subsequent modulation of the serotoninergic 5-HT4 and dopaminergic D3 receptors. RS67333 as a 5-HT4 agonist and U-99194A as a D3 antagonist were administered separately at 1 mg/kg and 20 mg/kg, and in combination at 0.5 mg/kg and 10 mg/kg to adult animals undergoing chronic treatment with the synthetic cannabinoid receptor agonist WIN55,212-2 (1 mg/kg) during adolescence. Animals were tested for anxiety-like behavior and episodic-like memory in the open field and novel object recognition tests respectively 30 minutes after the last drug administration. Chronic WIN55,212-2 treated animals exhibited a lasting disruption of episodic memory and increased anxiety levels. The effect on episodic-like memory were partially restored by acute administration of RS67333 and U-99194A and completely by administration of both drugs in combination at lower doses. However, only RS67333 (20 mg/kg) improved the anxiogenic-like effect of WIN55,212-2. These findings give further support that chronic exposure to cannabinoids during adolescence may be used as an animal model for schizophrenia, and highlight D3 and 5-HT4 receptors as potential targets for an enhanced treatment of the cognitive aspect of this disease. PMID:26497809

  9. Poststroke depression and risk of recurrent stroke at 1 year in a Chinese cohort study.

    Directory of Open Access Journals (Sweden)

    Huai Wu Yuan

    Full Text Available BACKGROUND: Studies show that poststroke depression (PSD increases mortality risk at 1 year. However, whether PSD increases the risk of recurrent stroke at 1 year remains unclear. This study was to investigate whether PSD at 2 weeks following a stroke could increase risk of recurrent stroke at 1 year. METHODS AND RESULTS: This was a multi-centered prospective cohort study. A total of 2306 patients with acute stroke were enrolled in our study. PSD was diagnosed according to the criteria set by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV. The outcomes of recurrent stroke were followed up via face-to-face or phone interview. A total of 1713 patients had complete follow-up data, with 481 (28.1% cases of PSD and 158 (9.2% cases of cumulative recurrent stroke at 1 year. Multivariate logistic regression analysis showed a 49% increase of OR of recurrent stroke at 1 year in patients with PSD, compared to patients without PSD following a stroke (OR=1.49, 95%CI: 1.03-2.15. There was no significant correlation between anti-depressant drugs and the risk of recurrent stroke at 1 year following a stroke (OR=1.96, 95%: CI 0.95-4.04. CONCLUSIONS: Based on the DSM-IV diagnostic criteria, nearly 3 out of 10 hospitalized stroke patients in China were diagnosed with PSD at 2 weeks following a stroke. PSD is associated with a higher risk of recurrent stroke at 1 year. Our study did not find benefit of anti-depressant drugs in reducing such risk.

  10. NMDA Receptors in Glial Cells: Pending Questions

    Czech Academy of Sciences Publication Activity Database

    Džamba, Dávid; Honsa, Pavel; Anděrová, Miroslava

    2013-01-01

    Roč. 11, č. 3 (2013), s. 250-262. ISSN 1570-159X R&D Projects: GA ČR GA309/08/1381; GA ČR(CZ) GBP304/12/G069 Grant ostatní: GA UK(CZ) 604212 Institutional support: RVO:68378041 Keywords : astrocytes * ischemia * NMDA receptors Subject RIV: FH - Neurology Impact factor: 2.347, year: 2013

  11. The Quantum Nature of Drug-Receptor Interactions: Deuteration Changes Binding Affinities for Histamine Receptor Ligands

    Science.gov (United States)

    Repič, Matej; Zakšek, Maja; Kotnik, Kristina; Fijan, Estera; Mavri, Janez

    2016-01-01

    In this article we report a combined experimental and computational study concerning the effects of deuteration on the binding of histamine and two other histaminergic agonists to 3H-tiotidine-labeled histamine H2 receptor in neonatal rat astrocytes. Binding affinities were measured by displacing radiolabeled tiotidine from H2 receptor binding sites present on cultured neonatal rat astrocytes. Quantum-chemical calculations were performed by employing the empirical quantization of nuclear motion within a cluster model of the receptor binding site extracted from the homology model of the entire H2 receptor. Structure of H2 receptor built by homology modelling is attached in the supporting information (S1 Table) Experiments clearly demonstrate that deuteration affects the binding by increasing the affinity for histamine and reducing it for 2-methylhistamine, while basically leaving it unchanged for 4-methylhistamine. Ab initio quantum-chemical calculations on the cluster system extracted from the homology H2 model along with the implicit quantization of the acidic N–H and O–H bonds demonstrate that these changes in the binding can be rationalized by the altered strength of the hydrogen bonding upon deuteration known as the Ubbelohde effect. Our computational analysis also reveals a new mechanism of histamine binding, which underlines an important role of Tyr250 residue. The present work is, to our best knowledge, the first study of nuclear quantum effects on ligand receptor binding. The ligand H/D substitution is relevant for therapy in the context of perdeuterated and thus more stable drugs that are expected to enter therapeutic practice in the near future. Moreover, presented approach may contribute towards understanding receptor activation, while a distant goal remains in silico discrimination between agonists and antagonists based on the receptor structure. PMID:27159606

  12. Expression and clinical significance of angiotensin II type 1 receptor in human hepatocellular carcinoma

    OpenAIRE

    Duan, Yun-fei; Li, Xiao-dong; Zhu, Feng; Zhang, Feng

    2013-01-01

    This study aimed to investigate the expression of angiotensin II type 1 receptor (AT-1R) mRNA and the AT-1R protein in human primary hepatocellular carcinoma (PHC), and to attempt to elucidate their association with pathological and clinical characteristics. Fresh tumor and normal liver tissues were obtained from 44 patients with PHC following hepatectomies. AT-1R mRNA levels were quantitatively analyzed by quantitative polymerase chain reaction (qPCR) while the protein levels were assessed b...

  13. Oligomeric forms of G protein-coupled receptors (GPCRs)

    OpenAIRE

    Palczewski, Krzysztof

    2010-01-01

    Oligomerization is a general characteristic of cell membrane receptors that is shared by G protein-coupled receptors (GPCRs) together with their G protein partners. Recent studies of these complexes, both in vivo and in purified reconstituted forms, unequivocally support this contention for GPCRs, perhaps with only rare exceptions. As evidence has evolved from experimental cell lines to more relevant in vivo studies and from indirect biophysical approaches to well defined isolated complexes o...

  14. Calculations show substantial serial engagement of T cell receptors.

    OpenAIRE

    Wofsy, C; Coombs, D; Goldstein, B

    2001-01-01

    The serial engagement model provides an attractive and plausible explanation for how a typical antigen presenting cell, exhibiting a low density of peptides recognized by a T cell, can initiate T cell responses. If a single peptide displayed by a major histocompatibility complex (MHC) can bind, sequentially, to different T cell receptors (TCR), then a few peptides can activate many receptors. To date, arguments supporting and questioning the prevalence of serial engagement have centered on th...

  15. Different effects of lobeline on neuronal and muscle nicotinic receptors

    Czech Academy of Sciences Publication Activity Database

    Kaniaková, Martina; Skřenková, Kristýna; Adámek, S.; Vyskočil, František; Krůšek, Jan

    2014-01-01

    Roč. 738, Sep 5 (2014), s. 352-359. ISSN 0014-2999 R&D Projects: GA ČR(CZ) GA202/09/0806; GA AV ČR(CZ) IAA500110905; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : neuronal nicotinic receptor alpha3beta4 * lobeline * embryonic muscle nicotinic receptor Subject RIV: ED - Physiology Impact factor: 2.532, year: 2014

  16. Brain penetration of telmisartan, a unique centrally acting angiotensin II type 1 receptor blocker, studied by PET in conscious rhesus macaques

    International Nuclear Information System (INIS)

    Introduction: Telmisartan is a widely used, long-acting antihypertensive agent. Known to be a selective angiotensin II type 1 (AT1) receptor (AT1R) blocker (ARB), telmisartan acts as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and inhibits centrally mediated effects of angiotensin II in rats following peripheral administration, although the brain penetration of telmisartan remains unclear. We investigated the brain concentration and localization of telmisartan using 11 C-labeled telmisartan and positron emission tomography (PET) in conscious rhesus macaques. Methods: Three male rhesus macaques were bolus intravenously administered [11 C]telmisartan either alone or as a mixture with unlabeled telmisartan (1 mg/kg). Dynamic PET images were acquired for 95 min following administration. Blood samples were collected for the analysis of plasma concentration and metabolites, and brain and plasma concentrations were calculated from detected radioactivity using the specific activity of the administered drug preparation, in which whole blood radioactivity was used for the correction of intravascular blood radioactivity in brain. Results: Telmisartan penetrated into the brain little but enough to block AT1R and showed a consistently increasing brain/plasma ratio within the PET scanning period, suggesting slow clearance of the compound from the brain compared to the plasma clearance. Brain/plasma ratios at 30, 60, and 90 min were 0.06, 0.13, and 0.18, respectively. No marked localization according to the AT1R distribution was noted over the entire brain, even on tracer alone dosing. Conclusions: Telmisartan penetrated into the brain enough to block AT1R and showed a slow clearance from the brain in conscious rhesus macaques, supporting the long-acting and central responses of telmisartan as a unique property among ARBs.

  17. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  18. Convulsant bicuculline modifies CNS muscarinic receptor affinity

    Directory of Open Access Journals (Sweden)

    Rodríguez de Lores Arnaiz Georgina

    2006-04-01

    itself. Findings support the notion that the muscarinic receptors play a major role in experimental epilepsy and provide a new example of differential neuronal plasticity.

  19. Olfactory receptor signaling.

    Science.gov (United States)

    Antunes, Gabriela; Simoes de Souza, Fabio Marques

    2016-01-01

    The guanine nucleotide protein (G protein)-coupled receptors (GPCRs) superfamily represents the largest class of membrane protein in the human genome. More than a half of all GPCRs are dedicated to interact with odorants and are termed odorant-receptors (ORs). Linda Buck and Richard Axel, the Nobel Prize laureates in physiology or medicine in 2004, first cloned and characterized the gene family that encode ORs, establishing the foundations to the understanding of the molecular basis for odor recognition. In the last decades, a lot of progress has been done to unravel the functioning of the sense of smell. This chapter gives a general overview of the topic of olfactory receptor signaling and reviews recent advances in this field. PMID:26928542

  20. Selective orexin receptor antagonists.

    Science.gov (United States)

    Lebold, Terry P; Bonaventure, Pascal; Shireman, Brock T

    2013-09-01

    The orexin, or hypocretin, neuropeptides (orexin-A and orexin-B) are produced on neurons in the hypothalamus which project to key areas of the brain that control sleep-wake states, modulation of food intake, panic, anxiety, emotion, reward and addictive behaviors. These neuropeptides exert their effects on a pair of G-protein coupled receptors termed the orexin-1 (OX1) and orexin-2 (OX2) receptors. Emerging biology suggests the involvement of these receptors in psychiatric disorders as they are thought to play a key role in the regulation of multiple systems. This review is intended to highlight key selective OX1 or OX2 small-molecule antagonists. PMID:23891187

  1. Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction.

    Science.gov (United States)

    Zeng, Jianwen; Ekman, Mari; Jiang, Chonghe; Uvelius, Bengt; Swärd, Karl

    2015-09-01

    The aim of the present study was to investigate the expression and distribution of membrane receptors after bladder outlet obstruction (BOO). Partial bladder outlet obstruction (BOO) was induced in female rats and bladders were harvested after either 10 days or 6 weeks of BOO. The expression of different receptors was surveyed by microarrays and corroborated by immunohistochemistry and western blotting. A microarray experiment identified 10 membrane receptors that were differentially expressed compared to sham-operated rats including both upregulated and downregulated receptors. Four of these were selected for functional experiments on the basis of magnitude of change and relevance to bladder physiology. At 6 weeks of BOO, maximal contraction was reduced for neuromedin B and vasopressin (AVP), consistent with reductions of receptor mRNA levels. Glycine receptor-induced contraction on the other hand was increased and receptor mRNA expression was accordingly upregulated. Maximal relaxation by the β3-adrenergic receptor agonist CL316243 was reduced as was the receptor mRNA level. Immunohistochemistry supported reduced expression of neuromedin B receptors, V1a receptors and β3-adrenergic receptors, but glycine receptor expression appeared unchanged. Western blotting confirmed repression of V1a receptors and induction of glycine receptors in BOO. mRNA for vasopressin was detectable in the bladder, suggesting local AVP production. We conclude that changes in receptor expression following bladder outlet obstruction are non-uniform. Some receptors are upregulated, conferring increased responsiveness to agonist, whereas others are downregulated, leading to decreased agonist-induced responses. This study might help to select pharmacological agents that are effective in modulating lower urinary tract symptoms in BOO. PMID:26004535

  2. Status Report on UH/ALOHA Participation in the ATS-1 Computer Communications Experiment.

    Science.gov (United States)

    Wax, David W.

    Current developments in an experiment on Computer Communications via the ATS-1 geosynchronous satellite are described. Initiated by the Spacecraft Data Systems Branch of the Ames Research Center, NASA, this experiment is designed to demonstrate the feasibility of utilizing satellite communication links to provide computer-computer and…

  3. Was leisten ACE-Hemmer und AT1-Antagonisten jenseits der Blutdrucksenkung?

    Directory of Open Access Journals (Sweden)

    Goebel M

    2004-01-01

    Full Text Available ACE-Hemmer und AT1-Rezeptorantagonisten spielen eine wichtige Rolle in der Behandlung kardiovaskulärer und renaler Erkrankungen. Nach den Kriterien der evidenzbasierten Medizin gelten die ACE-Hemmer (in entsprechender Kombination mit anderen kardiovaskulären Therapeutika weiterhin als Mittel der ersten Wahl für die Indikationen chronische Herzinsuffizienz, Postmyokardinfarkt mit eingeschränkter Ventrikelfunktion, kardiovaskuläres Hochrisiko und diabetische (Typ 1 Nephropathie. Hier sollten AT1-Rezeptorantagonisten v. a. bei Unverträglichkeiten gegenüber ACE-Hemmern eingesetzt werden. Die AT1-Rezeptorantagonisten haben durch viele Studien ihre Wirksamkeit und gute Verträglichkeit bewiesen und ziehen in vielen Indikationen mit den ACE-Hemmern gleich. Für die Indikation „Diabetische Nephropathie“ hypertoner Typ 2-Diabetiker werden bevorzugt Irbesartan und Losartan in entsprechend hoher Dosierung verwendet. Für den Wert einer Kombinationstherapie gibt es mit vorläufiger Ausnahme der chronischen Herzinsuffizienz (s. CHARM-Studie keinen gesicherten Hinweis auf Vorteile. Die LIFE-Studie zeigt erstmalig die Überlegenheit eines AT1-Rezeptorantagonisten gegenüber einem etablierten Betarezeptorenblocker bei Hypertonikern mit gesteigertem Risiko (linksventrikuläre Hypertrophie, insbesondere wenn bei diesen Patienten zusätzlich Diabetes mellitus droht oder vorliegt.

  4. Ultrasound backscatter from free-swimming fish at 1 MHz for fish identification

    DEFF Research Database (Denmark)

    Pham, An Hoai; Lundgren, Bo; Stage, Bjarne;

    2012-01-01

    In the frequency range well below 1 MHz, the swimbladder is often considered the most important part for acoustic fish detection. In this work a portable system was developed to not only detect but also try to identify free-swimming fish. It has been used to measure the ultrasound backscatter at 1...

  5. Estrogen receptor scintigraphy.

    Science.gov (United States)

    Scheidhauer, K; Scharl, A; Schicha, H

    1998-03-01

    Radio-labeled estrogen receptor ligands are tracers that can be used for functional receptor diagnosis. Their specificity towards receptors, together with the fact that only 50-70% of mammary carcinomas are receptor positive, renders them unsuitable for detection of primary tumors or metastases, and this means that estrogen receptor scintigraphy can be used neither for tumor screening nor for staging. However, both 18F-labeled and 123I-labeled estradiol derivatives are suitable for in vivo imaging of estrogen receptors. Their high specificity, established in animal experiments and in vitro studies has been reproduced in in vivo applications in humans. Tracers with positron radiation emitters are, however, hardly suitable for broad application owing to the short half-life of 18F, which would mean that users would need to be situated close to a cyclotron and a correspondingly equipped radiochemical laboratory. The number of available PET scanners, on the other hand, has increased over the last few years, especially in Germany, so that this, at least, does not present a limiting factor. All the same, 123I-labeled estradiol derivatives will find more widespread application, since the number of gamma-cameras incorporating modern multi-head systems is several times greater. The results of studies with 123I-E2-scintigraphy published to date are very promising, even given the initial technical problems mentioned above. As a method of examination, it could be optimised by using improved tracers with a higher tumor contrast and less disturbance from overlapping in diagnostically relevant locations, for instance, by selecting tracers with higher activities whose excretion is more renal than hepatobiliary. The use of modern multi-head camera systems can also be expected to improve the photon yield. PMID:9646642

  6. Biomimetic Receptors and Sensors

    Directory of Open Access Journals (Sweden)

    Franz L. Dickert

    2014-11-01

    Full Text Available In biomimetics, living systems are imitated to develop receptors for ions, molecules and bioparticles. The most pertinent idea is self-organization in analogy to evolution in nature, which created the key-lock principle. Today, modern science has been developing host-guest chemistry, a strategy of supramolecular chemistry for designing interactions of analytes with synthetic receptors. This can be realized, e.g., by self-assembled monolayers (SAMs or molecular imprinting. The strategies are used for solid phase extraction (SPE, but preferably in developing recognition layers of chemical sensors.

  7. Chemokine Receptors and Transplantation

    Institute of Scientific and Technical Information of China (English)

    Jinquan Tan; Gang Zhou

    2005-01-01

    A complex process including both the innate and acquired immune responses results in allograft rejection. Some chemokine receptors and their ligands play essential roles not only for leukocyte migration into the graft but also in facilitating dendritic and T cell trafficking between lymph nodes and the transplant in the early and late stage of the allogeneic response. This review focuses on the impact of these chemoattractant proteins on transplant outcome and novel diagnostic and therapeutic approaches for antirejection therapy based on targeting of chemokine receptors and/or their ligands. Cellular & Molecular Immunology.

  8. Beyond the Receptor

    Institute of Scientific and Technical Information of China (English)

    Russell Jones

    2008-01-01

    @@ Had this Special Issue on plant hormones been published 5 years ago,it is likely that details about biosynthetic pathways would have taken center stage.As articles in this issue show,however,the field of plant hormone research has progressed rapidly and is now moving beyond the search for receptors.Progress in research on the mechanism of action of plant hormones has been rapid;receptors for the main classes of hormones have been identified;and the search is on for players downstream in signal-transduction chains.

  9. Somatostatin receptor imaging

    International Nuclear Information System (INIS)

    The intention of the meeting was to present: 1.Results from large-scale diagnositc imaging studies, carried out in various somatostatin receptorpositive tumors by Germany nuclear medicine specialists; 2. Potential clinical indications for somatostatin receptor scintigraphy in gastroenterology, endocrinology, and other clinical disciplines. These presentations were balanced by the reports of distinguished clinicians on their experience with somatostatin analogs in therapeutic settings and by the comments of a number of investigators on the basic mechanisms of somatostatin-receptor/ligand-system(s) and on peptide radiopharmacology. Separate entries are proposed for 8 of the 11 individual papers presented at the conference. (orig./MG). 48 figs., 22 tabs

  10. Taste receptors for umami: the case for multiple receptors1234

    OpenAIRE

    Chaudhari, Nirupa; Pereira, Elizabeth; Roper, Stephen D.

    2009-01-01

    Umami taste is elicited by many small molecules, including amino acids (glutamate and aspartate) and nucleotides (monophosphates of inosinate or guanylate, inosine 5′-monophosphate and guanosine-5′-monophosphate). Mammalian taste buds respond to these diverse compounds via membrane receptors that bind the umami tastants. Over the past 15 y, several receptors have been proposed to underlie umami detection in taste buds. These receptors include 2 glutamate-selective G protein–coupled receptors,...

  11. Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer

    International Nuclear Information System (INIS)

    Both the non-receptor tyrosine kinase, c-Src, and members of the epidermal growth factor (EGF) receptor family are overexpressed in high percentages of human breast cancers. Because these molecules are plasma membrane-associated and involved in mitogenesis, it has been speculated that they function in concert with one another to promote breast cancer development and progression. Evidence to date supports a model wherein c-Src potentiates the survival, proliferation and tumorigenesis of EGF receptor family members, in part by associating with them. Phosphorylation of the EGF receptor by c-SRC is also critical for mitogenic signaling initiated by the EGF receptor itself, as well as by several G-protein coupled receptors (GPCRs), a cytokine receptor, and the estrogen receptor. Thus, c-Src appears to have pleiotropic effects on cancer cells by modulating the action of multiple growth-promoting receptors

  12. Group Decision Process Support

    DEFF Research Database (Denmark)

    Gøtze, John; Hijikata, Masao

    1997-01-01

    Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists.......Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists....

  13. Structure-Function Basis of Attenuated Inverse Agonism of Angiotensin II Type 1 Receptor Blockers for Active-State Angiotensin II Type 1 Receptor.

    Science.gov (United States)

    Takezako, Takanobu; Unal, Hamiyet; Karnik, Sadashiva S; Node, Koichi

    2015-09-01

    Ligand-independent signaling by the angiotensin II type 1 receptor (AT1R) can be activated in clinical settings by mechanical stretch and autoantibodies as well as receptor mutations. Transition of the AT1R to the activated state is known to lower inverse agonistic efficacy of clinically used AT1R blockers (ARBs). The structure-function basis for reduced efficacy of inverse agonists is a fundamental aspect that has been understudied not only in relation to the AT1R but also regarding other homologous receptors. Here, we demonstrate that the active-state transition in the AT1R indeed attenuates an inverse agonistic effect of four biphenyl-tetrazole ARBs through changes in specific ligand-receptor interactions. In the ground state, tight interactions of four ARBs with a set of residues (Ser109(TM3), Phe182(ECL2), Gln257(TM6), Tyr292(TM7), and Asn295(TM7)) results in potent inverse agonism. In the activated state, the ARB-AT1R interactions shift to a different set of residues (Val108(TM3), Ser109(TM3), Ala163(TM4), Phe182(ECL2), Lys199(TM5), Tyr292(TM7), and Asn295(TM7)), resulting in attenuated inverse agonism. Interestingly, V108I, A163T, N295A, and F182A mutations in the activated state of the AT1R shift the functional response to the ARB binding toward agonism, but in the ground state the same mutations cause inverse agonism. Our data show that the second extracellular loop is an important regulator of the functional states of the AT1R. Our findings suggest that the quest for discovering novel ARBs, and improving current ARBs, fundamentally depends on the knowledge of the unique sets of residues that mediate inverse agonistic potency in the two states of the AT1R. PMID:26121982

  14. The angiotensin II type 1 receptor antagonist Losartan binds and activates bradykinin B2 receptor signaling

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Olsen, Kristine Boisen; Erikstrup, Niels;

    2011-01-01

    The angiotensin II type 1 receptor (AT1R) blocker (ARB) Losartan has cardioprotective effects during ischemia-reperfusion injury and inhibits reperfusion arrhythmias -effects that go beyond the benefits of lowering blood pressure. The renin-angiotensin and kallikrein-kinin systems are intricately...... connected and some of the cardioprotective effects of Losartan are abolished by blocking the bradykinin B2 receptor (B2R) signaling. In this study, we investigated the ability of six clinically available ARBs to specifically bind and activate the B2R. First, we investigated their ability to activate...... phosphoinositide (PI) hydrolysis in COS-7 cells transiently expressing the B2R. We found that only Losartan activated the B2R, working as a partial agonist compared to the endogenous ligand bradykinin. This effect was blocked by the B2R antagonist HOE 140. A competitive binding analysis revealed that Losartan does...

  15. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  16. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea; Bräuner-Osborne, Hans; Stensbøl, Tine B; Nielsen, Birgitte; Karla, Rolf; Santi, Flavio; Krogsgaard-Larsen, Povl; Madsen, Ulf

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  17. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    polyamines are known to modulate the function of these receptors in vivo. In this study, recent developments in the medicinal chemistry of polyamine-based ligands are given, particularly focusing on the use of solid-phase synthesis (SPS) as a tool for the facile generation of libraries of polyamine toxin...

  18. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.;

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown...

  19. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over th...

  20. Vasopressin and Vasopressin Receptor Antagonists

    OpenAIRE

    Oh, Yun Kyu

    2008-01-01

    Vasopressin, a neurohypophyseal peptide hormone, is the endogenous agonist at V1a, V1b, and V2 receptors. The most important physiological function of vasopressin is the maintenance of water homeostasis through interaction with V2 receptors in the kidney. Vasopressin binds to V2 receptor and increases the number of aquaporin-2 at the apical plasma membrane of collecting duct principal cells. That induces high water permeability across the membrane. Several non-peptide vasopressin receptor ant...

  1. Nuclear Receptors and Inflammatory Diseases

    OpenAIRE

    Wang, Kun; Wan, Yu-Jui Yvonne

    2008-01-01

    It is well known that the steroid hormone glucocorticoid and its nuclear receptor regulate the inflammatory process, a crucial component in the pathophysiological process related to human diseases that include atherosclerosis, obesity and type II diabetes, inflammatory bowel disease, Alzheimer’s disease, multiple sclerosis, and liver tumors. Growing evidence demonstrates that orphan and adopted orphan nuclear receptors, such as peroxisome proliferator-activated receptors, liver × receptors, t...

  2. Characteristics of the solar wind at 1 a.u. in relation to Hale sector boundaries

    International Nuclear Information System (INIS)

    A study is made of the solar wind characteristics at 1 a.u. in the vicinity of Hale and anti-Hale sector boundaries (SBs), after isolating the SBs with solar activity related temporal flows and/or transient interplanetary structures (magnetic clouds) around them. It is found that, on average, the profile of the solar wind flow speed prior to SB passage and the minimum in flow speed at the SB do not differ for the two types of SBs. The flow speed 1-2 days after the passage of anti-Hale SB is found, however, to be significantly higher compared to Hale SB. The results indicate that the polarity configurations of the solar sectorial magnetic field structures with reference to the zonal (activity) structures influence the characteristics of coronal sources of high-speed streams, that accompany SB crossings at 1 a.u. (author)

  3. Promotion of breast cancer by β-Hexachlorocyclohexane in MCF10AT1 cells and MMTV-neu mice

    Directory of Open Access Journals (Sweden)

    Matsumura Fumio

    2007-07-01

    Full Text Available Abstract Background Exposure to β-Hexachlorocyclohexane (β-HCH, a contaminant of the hexachlorohexane pesticide lindane, has been implicated as a risk factor in the development of breast cancers in epidemiological studies. Previous studies in our laboratory have demonstrated the ability of β-HCH to elicit its actions via a ligand-independent activation of the estrogen receptor through increased c-Neu (= erbB2 or HER-2 expression and kinase activation in both the BG-1 and MCF-7 cell lines. In addition, long term exposure (33 passages to β-HCH was shown to promote the selection of MCF-7 cells which exhibit a more metastatic phenotype. Methods In this current study, we decided to investigate the long-term effects of β-HCH in both the MCF10AT1 cell line which was derived from a normal epithelial cell line by stably transfecting a mutated c-Ha-ras and a MMTV-Neu mouse model for mammary cancer in vivo. MCF10AT1 cells were exposed for 20 passages with β-HCH, 4-OH-Tamoxifen (Tam, or 17-β-estradiol (E2 after which cells were analyzed for proliferation rates and mRNA expression by RT-PCR. In our in vivo studies, MMTV-Neu mice were injected with β-HCH and observed for tumor formation over a 70 week period. Results β-HCH and Tam selected MCF10AT1 cells demonstrated increased mRNA expression of MMP-13 (collagenase-3 a marker of increased invasiveness. β-HCH treatment was also seen to increase the expression in a number of proto-oncogenes (c-Neu, Cyclin D1, p27, cell status markers (Met-1, CK19, and the inflammatory marker NFκB. Previous studies, have demonstrated the role of these markers as evidence of malignant transformations, and further illustrate the ability of β-HCH to be carcinogenic. To demonstrate β-HCH's tumorigenic properties in an in vivo system, we used an MMTV-Neu mouse model. MMTV-Neu is a c-Neu overexpressing strain which has been shown to spontaneously develop mammary tumors at later stages of aging. In this experiment,

  4. Immunohistochemical study of androgen, estrogen and progesterone receptors in salivary gland tumors

    Directory of Open Access Journals (Sweden)

    Fabio Augusto Ito

    2009-12-01

    Full Text Available The aim of this work was to study the immunohistochemical expression of androgen receptor, estrogen receptor and progesterone receptor in pleomorphic adenomas, Warthin's tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas of salivary glands. A total of 41 pleomorphic adenomas, 30 Warthin's tumors, 30 mucoepidermoid carcinomas and 30 adenoid cystic carcinomas were analyzed, and the immunohistochemical expression of these hormone receptors were assessed. It was observed that all cases were negative for estrogen and progesterone receptors. Androgen receptor was positive in 2 cases each of pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma. In conclusion, the results do not support a role of estrogen and progesterone in the tumorigenesis of pleomorphic adenomas, Warthin's tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas. However, androgen receptors can play a role in a small set of salivary gland tumors, and this would deserve further studies.

  5. 28 MHz swept source at 1.0 μm for ultrafast quantitative phase imaging

    OpenAIRE

    Wei, Xiaoming; Lau, Andy K. S.; Xu, Yiqing; Tsia, Kevin K.; Wong, Kenneth K. Y.

    2015-01-01

    Emerging high-throughput optical imaging modalities, in particular those providing phase information, necessitate a demanding speed regime (e.g. megahertz sweep rate) for those conventional swept sources; while an effective solution is yet to be demonstrated. We demonstrate a stable breathing laser as inertia-free swept source (BLISS) operating at a wavelength sweep rate of 28 MHz, particularly for the ultrafast interferometric imaging modality at 1.0 μm. Leveraging a tunable dispersion compe...

  6. The Sunyaev-Zeldovich effect at 1.15 mm wavelength

    International Nuclear Information System (INIS)

    The Sunyaev-Zeldovich (S-Z) effect is a spectral distortion of the Cosmic Background Radiation, induced by inverse Compton scattering of the microwave photons by energetic electrons in hot astrophysical plasmas. The paper reports the first ever attempt to detect the S-Z effect at 1.15 mm wavelength, using bolometric detection techniques. A marginal detection of the effect in the distant cluster 0016+16 was found, but not in the cluster A478. (U.K.)

  7. Femtosecond micromachining of symmetric waveguides at 1.5 microm by astigmatic beam focusing.

    Science.gov (United States)

    Cerullo, G; Osellame, R; Taccheo, S; Marangoni, M; Polli, D; Ramponi, R; Laporta, P; De Silvestri, S

    2002-11-01

    We report on a new spatial beam-shaping approach for fabrication of waveguides with a circular transverse profile by femtosecond laser pulses, using an astigmatic beam and controlling both beam waist and focal position in the tangential and sagittal planes. We apply this technique to write single-mode active waveguides at 1.5microm in Er:Yb-doped glass substrates. The experimental results are well described by a simple nonlinear absorption model. PMID:18033408

  8. The 400W at 1.8K Test Facility at CEA-Grenoble

    Science.gov (United States)

    Roussel, P.; Girard, A.; Jager, B.; Rousset, B.; Bonnay, P.; Millet, F.; Gully, P.

    2006-04-01

    A new test facility with a cooling capacity respectively of 400W at 1.8K or 800W at 4.5K, is now under nominal operation in SBT (Low Temperature Department) at CEA Grenoble. It has been recently used for thermohydraulic studies of two phase superfluid helium in autumn 2004. In the near future, this test bench will allow: - to test industrial components at 1.8K (magnets, cavities of accelerators) - to continue the present studies on thermohydraulics of two phase superfluid helium - to develop and simulate new cooling loops for ITER Cryogenics, and other applications such as high Reynolds number flows This new facility consists of a cold box connected to a warm compressor station (one subatmospheric oil ring pump in series with two screw compressors). The cold box, designed by AIR LIQUIDE, comprises two centrifugal cold compressors, a cold turbine, a wet piston expander, counter flow heat exchangers and two phase separators at 4.5K and 1.8K. The new facility uses a Programmable Logic Controller (PLC) connected to a bus for the measurements. The design is modular and will allow the use of saturated fluid flow (two phase flow at 1.8K or 4.5K) or single phase fluid forced flow. Experimental results and cooling capacity in different operation modes are detailed.

  9. NFAD Arrays for Single Photon Optical Communications at 1.5 um Project

    Data.gov (United States)

    National Aeronautics and Space Administration — For this program, we propose to develop large pixel-count single photon counting detector arrays suitable for deployment in spacecraft terminal receivers supporting...

  10. Vasopressin receptor antagonists: Characteristics and clinical role.

    Science.gov (United States)

    Rondon-Berrios, Helbert; Berl, Tomas

    2016-03-01

    Hyponatremia, the most common electrolyte disorder in hospitalized patients is associated with increased risk of mortality even when mild and apparently asymptomatic. Likewise morbidity manifested as attention deficits, gait disturbances, falls, fractures, and osteoporosis is more prevalent in hyponatremic subjects. Hyponatremia also generates a significant financial burden. Therefore, it is important to explore approaches that effectively and safely treat hyponatremia. Currently available strategies are physiologically sound and affordable but lack evidence from clinical trials and are limited by variable efficacy, slow response, and/or poor compliance. The recent emergence of vasopressin receptor antagonists provides a class of drugs that target the primary pathophysiological mechanism, namely vasopressin mediated impairment of free water excretion. This review summarizes the historical development, pharmacology, clinical trials supporting efficacy and safety, shortcomings, as well as practical suggestions for the use of vasopressin receptor antagonists. PMID:27156765

  11. Retinoic Acid-mediated Nuclear Receptor Activation and Hepatocyte Proliferation

    Science.gov (United States)

    Bushue, Nathan; Wan, Yu-Jui Yvonne

    2016-01-01

    Due to their well-known differentiation and apoptosis-inducing abilities, retinoic acid (RA) and its analogs have strong anti-cancer efficacy in human cancers. However, in vivo RA is a liver mitogen. While speculation has persisted that RA-mediated signaling is likely involved in hepatocyte proliferation during liver regeneration, direct evidence is still required. Findings in support of this proposition include observations that a release of retinyl palmitate (the precursor of RA) occurs in liver stellate cells following liver injury. Nevertheless, the biological action of this released vitamin A is virtually unknown. More likely is that the released vitamin A is converted to RA, the biological form, and then bound to a specific receptor (retinoid x receptor; RXRα), which is most abundantly expressed in the liver. Considering the mitogenic effects of RA, the RA-activated RXRα would likely then influence hepatocyte proliferation and liver tissue repair. At present, the mechanism by which RA stimulates hepatocyte proliferation is largely unknown. This review summarizes the activation of nuclear receptors (peroxisome proliferator activated receptor-α, pregnane x receptor, constitutive androstane receptor, and farnesoid x receptor) in an RXRα dependent manner to induce hepatocyte proliferation, providing a link between RA and its proliferative role.

  12. Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Malmsjö Malin

    2009-08-01

    Full Text Available Abstract Background Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. Methods Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG surgery because of ischemic heart disease (n = 15, patients with angina pectoris without established myocardial infarction (n = 15 and matched cardiovascular healthy controls (n = 15. Endothelin type A (ETA and type B (ETB, and angiotensin type 1 (AT1 and type 2 (AT2 receptors expression and function were examined using immunohistochemistry, Western blot and in vitro pharmacology. Results ETA and, to a lesser extent, ETB receptor staining was observed in the healthy vascular smooth muscle cells. The level of ETB receptor expression was higher in patients undergoing CABG surgery (250% ± 23%; P B receptor agonist sarafotoxin S6c, compared to healthy controls (P A receptors. AT1 and, to a lesser extent, AT2 receptor immunostaining was seen in the vascular smooth muscle cells. The level of AT1 receptor expression was higher in both the angina pectoris (128% ± 25%; P 1 receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s. Conclusion The results demonstrate, for the first time, upregulation of ETB and AT1 receptors in vascular smooth muscle cells in ischemic heart disease. These receptors may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions.

  13. Administration of an anti-interleukin 2 receptor monoclonal antibody prolongs cardiac allograft survival in mice

    OpenAIRE

    1985-01-01

    Administration of the monoclonal antibody M7/20, which binds to the murine interleukin-2 (IL) receptor, significantly prolongs cardiac allograft survival in two H-2-incompatible strain combinations of inbred mice. The results support the important role of the IL-2 receptor in the mechanism of graft rejection, and suggest its suitability as a target for immunosuppressive therapy.

  14. Lack of adenosine A(3) receptors causes defects in mouse peripheral blood parameters

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Komůrková, Denisa

    2014-01-01

    Roč. 10, č. 3 (2014), s. 509-514. ISSN 1573-9538 R&D Projects: GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : Adenosine A(3) receptor * Adenosine A(3) receptor knockout mice * Hematopoiesis Subject RIV: BO - Biophysics Impact factor: 3.886, year: 2014

  15. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  16. Review: Novel roles of nuclear angiotensin receptors and signaling mechanisms

    OpenAIRE

    Gwathmey, TanYa M.; Alzayadneh, Ebaa M.; Karl D. Pendergrass; Chappell, Mark C.

    2011-01-01

    The renin-angiotensin system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. The dysregulation of the RAS is considered a major influence in the development and progression of cardiovascular disease and other pathologies. Indeed, experimental and clinical evidence indicates that blockade of this system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 1 receptor (AT1R) antagonists is an effective therapy to attenuate hype...

  17. A different role of angiotensin II type 1a receptor in the development and hypertrophy of plantaris muscle in mice.

    Science.gov (United States)

    Zempo, Hirofumi; Suzuki, Jun-Ichi; Ogawa, Masahito; Watanabe, Ryo; Isobe, Mitsuaki

    2016-02-01

    The role of angiotensin II type 1 (AT1) receptors in muscle development and hypertrophy remains unclear. This study was designed to reveal the effects that a loss of AT1 receptors has on skeletal muscle development and hypertrophy in mice. Eight-week-old male AT1a receptor knockout (AT1a(-/-)) mice were used for this experiment. The plantaris muscle to body weight ratio, muscle fiber cross-sectional area, and number of muscle fibers of AT1a(-/-) mice was significantly greater than wild type (WT) mice in the non-intervention condition. Next, the functional overload (OL) model was used to induce plantaris muscle hypertrophy by surgically removing the two triceps muscles consisting of the calf, soleus, and gastrocnemius muscles in mice. After 14 days of OL intervention, the plantaris muscle weight, the amount of fiber, and the fiber area increased. However, the magnitude of the increment of plantaris weight was not different between the two strains. Agtr1a mRNA expression did not change after OL in WT muscle. Actually, the Agt mRNA expression level of WT-OL was lower than WT-Control (C) muscle. An atrophy-related gene, atrogin-1 mRNA expression levels of AT1a(-/-)-C, WT-OL, and AT1a(-/-)-OL muscle were lower than that of WT-C muscle. Our findings suggest that AT1 receptor contributes to plantaris muscle development via atrogin-1 in mice. PMID:26025227

  18. Ligand-Receptor Interactions

    CERN Document Server

    Bongrand, Pierre

    2008-01-01

    The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the ...

  19. Radio-loud CMEs from the Disk Center Lacking Shocks at 1 AU

    Science.gov (United States)

    Gopalswamy, N; Makela, P.; Akiyama, S.; Yashiro, S.; Xie, H.; MacDowall, R. J.; Kaiser, M. L.

    2013-01-01

    A coronal mass ejection (CME) associated with a type II burst and originating close to the center of the solar disk typically results in a shock at Earth in 2-3 days and hence can be used to predict shock arrival at Earth. However, a significant fraction (about 28%) of such CMEs producing type II bursts were not associated with shocks at Earth. We examined a set of 21 type II bursts observed by the Wind/WAVES experiment at decameter-hectometric (DH) wavelengths that had CME sources very close to the disk center (within a central meridian distance of 30 degrees), but did not have a shock at Earth. We find that the near-Sun speeds of these CMEs average to 644 km/s, only slightly higher than the average speed of CMEs associated with radio-quiet shocks. However, the fraction of halo CMEs is only 30%, compared to 54% for the radio-quiet shocks and 91% for all radio-loud shocks. We conclude that the disk-center radio-loud CMEs with no shocks at 1 AU are generally of lower energy and they drive shocks only close to the Sun and dissipate before arriving at Earth. There is also evidence for other possible processes that lead to the lack of shock at 1 AU: (i) overtaking CME shocks merge and one observes a single shock at Earth, and (ii) deflection by nearby coronal holes can push the shocks away from the Sun-Earth line, such that Earth misses these shocks. The probability of observing a shock at 1 AU increases rapidly above 60% when the CME speed exceeds 1000 km/s and when the type II bursts propagate to frequencies below 1 MHz.

  20. Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts.

    Science.gov (United States)

    Loupy, Alexandre; Vernerey, Dewi; Tinel, Claire; Aubert, Olivier; Duong van Huyen, Jean-Paul; Rabant, Marion; Verine, Jérôme; Nochy, Dominique; Empana, Jean-Philippe; Martinez, Frank; Glotz, Denis; Jouven, Xavier; Legendre, Christophe; Lefaucheur, Carmen

    2015-07-01

    Kidney allograft rejection can occur in clinically stable patients, but long-term significance is unknown. We determined whether early recognition of subclinical rejection has long-term consequences for kidney allograft survival in an observational prospective cohort study of 1307 consecutive nonselected patients who underwent ABO-compatible, complement-dependent cytotoxicity-negative crossmatch kidney transplantation in Paris (2000-2010). Participants underwent prospective screening biopsies at 1 year post-transplant, with concurrent evaluations of graft complement deposition and circulating anti-HLA antibodies. The main analysis included 1001 patients. Three distinct groups of patients were identified at the 1-year screening: 727 (73%) patients without rejection, 132 (13%) patients with subclinical T cell-mediated rejection (TCMR), and 142 (14%) patients with subclinical antibody-mediated rejection (ABMR). Patients with subclinical ABMR had the poorest graft survival at 8 years post-transplant (56%) compared with subclinical TCMR (88%) and nonrejection (90%) groups (P<0.001). In a multivariate Cox model, subclinical ABMR at 1 year was independently associated with a 3.5-fold increase in graft loss (95% confidence interval, 2.1 to 5.7) along with eGFR and proteinuria (P<0.001). Subclinical ABMR was associated with more rapid progression to transplant glomerulopathy. Of patients with subclinical TCMR at 1 year, only those who further developed de novo donor-specific antibodies and transplant glomerulopathy showed higher risk of graft loss compared with patients without rejection. Our findings suggest that subclinical TCMR and subclinical ABMR have distinct effects on long-term graft loss. Subclinical ABMR detected at the 1-year screening biopsy carries a prognostic value independent of initial donor-specific antibody status, previous immunologic events, current eGFR, and proteinuria. PMID:25556173

  1. Central 56-Fe-nucleus reactions at 1.7 GeV/nucleon

    International Nuclear Information System (INIS)

    Preliminary results on multiplicity and angular distributions in 56Fe-nucleus reactions at 1.7 GeV/nucleon are given. In particular we study central collisions in C, N and O. These reactions show a very characteristic behaviour with all charged particles in the forward hemisphere in the lab system, but with very few particles within the expected projectile fragmentation cone. Furthermore in these reactions a large number of fast protons (p > 1 GeV/c) originate from the target nucleus

  2. High Resolution and High Sensitivity Measurement of Methane at 1.51 μm

    Institute of Scientific and Technical Information of China (English)

    DENG Lun-Hua; GAO Xiao-Ming; CAO Zhen-Song; ZHAO Wei-Xiong; ZHANG Wei-Jun

    2006-01-01

    @@ The high-resolution absorption spectrum of CH4 at 1.51 μm is observed by direct absorption spectroscopy technique with a White absorption cell. Multi-peak fitting technique is adopted to reveal line positions and line intensities of CH4 from 6608 cm-1 to 6625 cm-1. Special attention is paid on the determination of the line positions, and the accuracy is better than ±0.002 cm-1. A minimum measurable absorption of 2.1 × 10-s (3σr) has been achieved based on the measured direct absorption spectroscopy.

  3. Helium 2 S-3-2(1)S metrology at 1.557 mu m

    OpenAIRE

    van, Leeuwen, M.; Vassen, W.

    2006-01-01

    An experiment is proposed to excite the "forbidden" 1s2s(3) S-1 - 1s2s(1) S-0 magnetic dipole (M1) transition at 1.557 mu m in a collimated and slow atomic beam of metastable helium atoms. It is demonstrated that an excitation rate of 5000 s(-1) can be realised with the beam of a 2W narrow-band telecom fiber laser intersecting the atomic beam perpendicularly. A Doppler-limited sub-MHz spectroscopic linewidth is anticipated. Doppler-free excitation of 2% of trapped and cooled atoms may be real...

  4. Is there Δ-matter at 1 GeV/nucleon?

    International Nuclear Information System (INIS)

    We investigate the possibility of creating a new form of highly excited nuclear matter, Δ-matter, in heavy ion collisions at 1 GeV/nucleon. At this incident energy, which is accessible through the SIS accelerator facility, enough Δ-resonances are produced to show collective effects. Maximum densities for the resonances around 50% ground state density of nuclear matter are reached. However, the multiplicity of Δ-resonances reaches only 20% of the baryon multiplicity and therefore is not high enough to justify the term Δ-matter. (orig.)

  5. The Deep Diffuse Extragalactic Radio Sky at 1.75 GHz

    OpenAIRE

    Vernstrom, T.; Norris, Ray P.; Scott, Douglas; Wall, J. V.

    2014-01-01

    We present a study of diffuse extragalactic radio emission at $1.75\\,$GHz from part of the ELAIS-S1 field using the Australia Telescope Compact Array. The resulting mosaic is $2.46\\,$deg$^2$, with a roughly constant noise region of $0.61\\,$deg$^2$ used for analysis. The image has a beam size of $150 \\times60\\,$arcsec and instrumental $\\langle\\sigma_{\\rm n}\\rangle= (52\\pm5)\\, \\mu$Jy beam$^{-1}$. Using point-source models from the ATLAS survey, we subtract the discrete emission in this field fo...

  6. Ultrasonic-assisted friction stir welding on V95AT1 (7075) aluminum alloy

    Science.gov (United States)

    Tarasov, S. Yu.; Rubtsov, V. Ye.; Kolubaev, E. A.; Ivanov, A. N.; Fortuna, S. V.; Eliseev, A. A.

    2015-10-01

    Ultrasonic-assisted friction stir butt welding on aluminum alloy V95AT1 (7075) has been carried out. Samples have been characterized using metallography, microhardness and XRD. As shown, ultrasonic treatment during welding provides extra plasticizing of metal and better stirring efficiency. The latter serves for elimination of defects, such as root flaw and grain refining in the stir zone. The stress state in the welded joint is characterized by tensile stress in the direction of the weld seam centerline and compression in the transversal direction. The ultrasonic treatment was shown to increase the compression stress and relieve the tensile one.

  7. Accuracy of measurement of thickness of a 6061 aluminum sample at 1-mm lift off

    International Nuclear Information System (INIS)

    The accuracy of measurement of a 0.51-mm thick, 6061 aluminum sample under lift-off variations of 0.25 mm at 1.08 is shown to be 5 percent by means of a complex-reluctance plane analysis. The analysis is shown to depend critically on the statistical accuracy of such measurements. Large lift-off measurements of aluminum thickness with large lift-off variations can be important for measurement of samples with radii of curvature such as aluminum cans, for measurements of sheets in rolling mills, and for reducing measurement problems in automatic scanning of aircraft skins where corrosion or spalling may have occurred

  8. Azimuthal correlations of pions in relativistic heavy ion collisions at 1 GeV/nucl

    International Nuclear Information System (INIS)

    Triple differential cross sections of pions in heavy ion collisions at 1 GeV/nucl. are studied with the IQMD model. After discussing general properties of Δ resonance and pion production we focus an azimuthal correlations: At projectile- and target-rapidities we observe an anticorrelation in the in-plane transverse momentum between pions and protons. At c.m.-rapidity, however, we find that high pt pions are being preferentially emitted perpendicular to the event-plane. We investigate the causes of those correlations and their sensitivity on the density and momentum dependence of the real and imaginary part of the nucleon and pion optical potential. (orig.)

  9. On the collective mode spectrum for composite fermions at 1/3 filling factor

    International Nuclear Information System (INIS)

    The collective mode spectrum of the composite fermion state at 1/3 filling factor is evaluated. At zero momentum, the result coincides with the cyclotron energy at the external magnetic field value, and not at the effective field, in spite of the fact that only the former enter in the equations, thus, the Kohn theorem is satisfied. Unexpectedly, in place of the magneto-roton minimum, the collective mode gets a threshold indicating the instability of the mean field composite fermion state under the formation of crystalline structures. However, the question about if this outcome only appears within the mean field approximation should be further considered. (author). 9 refs, 1 fig

  10. Glutamate Receptors in Plants

    OpenAIRE

    Davenport, Romola

    2002-01-01

    Ionotropic glutamate receptors function in animals as glutamate‐gated non‐selective cation channels. Numerous glutamate receptor‐like (GLR) genes have been identified in plant genomes, and plant GLRs are predicted, on the basis of sequence homology, to retain ligand‐binding and ion channel activity. Non‐selective cation channels are ubiquitous in plant membranes and may function in nutrient uptake, signalling and intra‐plant transport. However, there is little evidence for amino acid gating o...

  11. Sensory receptors in monotremes.

    OpenAIRE

    Proske, U; Gregory, J E; Iggo, A.

    1998-01-01

    This is a summary of the current knowledge of sensory receptors in skin of the bill of the platypus, Ornithorhynchus anatinus, and the snout of the echidna, Tachyglossus aculeatus. Brief mention is also made of the third living member of the monotremes, the long-nosed echidna, Zaglossus bruijnii. The monotremes are the only group of mammals known to have evolved electroreception. The structures in the skin responsible for the electric sense have been identified as sensory mucous glands with a...

  12. Somatostatin receptor skintigrafi

    DEFF Research Database (Denmark)

    Rasmussen, Karin; Nielsen, Jørn Theil; Rehling, Michael

    2005-01-01

    Somatostatin receptor scintigraphy (SRS) is a very valuable imaging technique for visualisation of a diversity of neuroendocrine tumours. The sensitivity for localisation of carcinoid tumours is high, but somewhat lower for other neuroendocrine tumours. The methodology, multiple clinical aspects...... and limitations of the examination are described. The value of the method in patients with non-neuroendocrine tumours has yet to be established. The development of new radio-labelled somatostatin analogues for diagnosis and treatment is briefly discussed....

  13. Functional Analyses of Bitter Taste Receptors in Domestic Cats (Felis catus).

    Science.gov (United States)

    Lei, Weiwei; Ravoninjohary, Aurore; Li, Xia; Margolskee, Robert F; Reed, Danielle R; Beauchamp, Gary K; Jiang, Peihua

    2015-01-01

    Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor) genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus) should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in understanding the forces

  14. Functional Analyses of Bitter Taste Receptors in Domestic Cats (Felis catus.

    Directory of Open Access Journals (Sweden)

    Weiwei Lei

    Full Text Available Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in

  15. [Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?].

    Science.gov (United States)

    Fournier, A; Ghitu, A; Darabont, R; Mazouz, H; Makdassi, R; Canaple, S; Rosa, A; Fernandez, L A

    Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities. PMID:10360191

  16. GABA(B) receptor phosphorylation regulates KCTD12-induced K+ current desensitization

    Czech Academy of Sciences Publication Activity Database

    Adelfinger, L.; Tureček, Rostislav; Ivankova, K.; Jensen, A. A.; Moss, S. J.; Gassmann, M.; Bettler, B.

    2014-01-01

    Roč. 91, č. 3 (2014), s. 369-379. ISSN 0006-2952 Institutional support: RVO:68378041 Keywords : GABA -B * G-protein coupled receptor * GPCR Subject RIV: FH - Neurology Impact factor: 5.009, year: 2014

  17. Evidence for Alpha Receptors in the Human Ureter

    Science.gov (United States)

    Madeb, Ralph; Knopf, Joy; Golijanin, Dragan; Bourne, Patricia; Erturk, Erdal

    2007-04-01

    immunohistochemistry and molecular techniques. These findings may lend support to the preliminary studies of the effectiveness of alpha-receptor blockade on ureteral colic and stone passage.

  18. Radio variability in the Phoenix Deep Survey at 1.4GHz

    CERN Document Server

    Hancock, Paul; Bell, Martin; Murphy, Tara; Gaensler, Bryan

    2016-01-01

    We use archival data from the Phoenix Deep Survey to investigate the variable radio source population above 1mJy/beam at 1.4GHz. Given the similarity of this survey to other such surveys we take the opportunity to investigate the conflicting results which have appeared in the literature. Two previous surveys for variability conducted with the Very Large Array (VLA) achieved a sensitivity of 1mJy/beam. However, one survey found an areal density of radio variables on timescales of decades that is a factor of ~4 times greater than a second survey which was conducted on timescales of less than a few years. In the Phoenix deep field we measure the density of variable radio sources to be $\\rho =0.98\\mathrm{deg}^{-2}$ on timescales of 6 months to 8 years. We make use of WISE infrared cross-ids, and identify all variable sources as an AGN of some description. We suggest that the discrepancy between previous VLA results is due to the different time scales probed by each of the surveys, and that radio variability at 1....

  19. Mr angiography of peripheral arteries using an automatic tracking technique at 1.0 Tesla

    International Nuclear Information System (INIS)

    Purpose: Assessment of the value of contrast-enhanced MR angiography (ceMRA) using an automatic tracking technique at 1.0 Tesla in comparison with digital subtraction angiography (DSA) of the pelvic and lower limb arteries. Materials and Methods: In 15 patients with peripheral arterial occlusive disease a ceMRA (3D FLASH, TR/TE = 6.2/2.3 ms, Flip angle α = 30 , Matrix 170 x 256) using a new automatic cracking technique was accomplished. The reference method was DSA. Twenty-one vessel segments of each patient were graded as normal, stenosed (> 50%) or occluded. Image material was evaluated independently by two radiologists. Results: In comparison, the interobserver agreement showed a good (Cohen's kappa > 71%) concordance for 38% of the 21 vessel segments, a moderate (Cohen's kappa between 31%-70%) for 21% and a poor (Cohen's kappa < 30%) concordance for 38% of the 21 vessel segments. Regarding the MRA and DSA results, a good concordance was achieved for 62% of the 21 vessel segments, 14% showed a moderate concordance and 24% only a poor concordance. Conclusion: In patients with peripheral arterial occlusive disease ceMRA using an automatic tracking technique enables a reliable evaluation of pelvis and upper limb arteries at 1.0 Tesla. However, a reliable evaluation of lower limb arteries is not yet possible. (orig.)

  20. Local Interstellar Hydrogen's Disappearance at 1 Au: Four Years of IBEX in the Rising Solar Cycle

    CERN Document Server

    Saul, Lukas; Fuselier, Stephen; Kubiak, Marzena; McComas, Dave; Möbius, Eberhard; Sokół, Justina; Rodríguez, Diego; Scheer, Juergen; Wurz, Peter

    2013-01-01

    NASA's Interstellar Boundary Explorer (IBEX) mission has recently opened a new window on the interstellar medium (ISM) by imaging neutral atoms. One "bright" feature in the sky is the interstellar wind flowing into the solar system. Composed of remnants of stellar explosions as well as primordial gas and plasma, the ISM is by no means uniform. The interaction of the local ISM with the solar wind shapes our heliospheric environment with hydrogen being the dominant component of the very local ISM. In this paper, we report on direct sampling of the neutral hydrogen of the local ISM over four years of IBEX observations. The hydrogen wind observed at 1 AU has decreased and nearly disappeared as the solar activity has increased over the last four years; the signal at 1 AU has dropped off in 2012 by a factor of ~8 to near background levels. The longitudinal offset has also increased with time presumably due to greater radiation pressure deflecting the interstellar wind. We present longitudinal and latitudinal arriva...

  1. Test Results of the LARP HQ02b Magnet at 1.9 K

    CERN Document Server

    Bajas, H; Bottura, L; Chiuchiolo, A; Dunkel, O; Ferracin, P; Feuvrier, J; Giloux, Chr; Todesco, E; Ravaioli, E; Caspi, S; Dietderich, D; Felice, H; Hafalia, A R; Marchevsky, M; Sabbi, G L; Wang, X; Salmi, T; Ghosh, A; Schmalzle, J; Wanderer, P; Anerella, M; Ambrosio, G; Bossert, R; Chlachidze, G; Yu, M

    2015-01-01

    The HQ magnet is a 120 mm aperture, 1-meter-long Nb3Sn quadrupole developed by the LARP collaboration in the framework of the High-Luminosity LHC project. A first series of coils was assembled and tested in 5 assemblies of the HQ01 series. The HQ01e model achieved a maximum gradient of 170 T/m at 4.5 K at LBNL in 2010-2011 and reached 184 T/m at 1.9 K at CERN in 2012. A new series of coils incorporating major design changes was fabricated for the HQ02 series. The first model, HQ02a, was tested at Fermilab where it reached 98% of the short sample limit at 4.5 K with a gradient of 182 T/m in 2013. However, the full training of the coils at 1.9 K could not be performed due to a current limit of 15 kA. Following this test, the azimuthal coil pre-load was increased by about 30 MPa and an additional current lead was installed at the electrical center of the magnet for quench protection studies. The test name of this magnet changed to HQ02b. In 2014, HQ02b was then shipped to CERN as the first opportunity for full t...

  2. Galaxy Clusters around radio-loud AGN at 1.3 < z < 3.2 as seen by Spitzer

    CERN Document Server

    Wylezalek, D; Stern, D; Vernet, J; De Breuck, C; Seymour, N; Brodwin, M; Eisenhardt, P M; Gonzalez, A H; Hatch, N; Jarvis, M; Rettura, A; Stanford, S A; Stevens, J A

    2013-01-01

    We report the first results from the Clusters Around Radio-Loud AGN (CARLA) program, a Cycle 7 and 8 Spitzer Space Telescope snapshot program to investigate the environments of a large sample of obscured and unobscured luminous radio-loud AGN at 1.2 -0.1 (AB), which efficiently selects high-redshift (z > 1.3) galaxies of all types, we identify galaxy cluster member candidates in the fields of the radio-loud AGN. The local density of these IRAC-selected sources is compared to the density of similarly selected sources in blank fields. We find that 92% of the radio-loud AGN reside in environments richer than average. The majority (55%) of the radio-loud AGN fields are found to be overdense at a > 2 {\\sigma} level; 10% are overdense at a > 5 {\\sigma} level. A clear rise in surface density of IRAC-selected sources towards the position of the radio-loud AGN strongly supports an association of the majority of the IRAC-selected sources with the radio-loud AGN. Our results provide solid statistical evidence that radi...

  3. P2X receptor channels in endocrine glands

    Czech Academy of Sciences Publication Activity Database

    Stojilkovic, S. S.; Zemková, Hana

    2013-01-01

    Roč. 2, č. 4 (2013), s. 173-180. ISSN 2190-460X R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : ATP * purinergic P2X receptor channels * pituitary * endocrine glands Subject RIV: ED - Physiology

  4. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  5. Teaching old receptors new tricks: biasing seven-transmembrane receptors

    OpenAIRE

    Rajagopal, Sudarshan; Rajagopal, Keshava; Lefkowitz, Robert J.

    2010-01-01

    Seven-transmembrane receptors (7TMRs; also known as G protein-coupled receptors) are the largest class of receptors in the human genome and are common targets for therapeutics. Originally identified as mediators of 7TMR desensitization, β-arrestins (arrestin 2 and arrestin 3) are now recognized as true adaptor proteins that transduce signals to multiple effector pathways. Signalling that is mediated by β-arrestins has distinct biochemical and functional consequences from those mediated by G p...

  6. Dilepton spectroscopy at intermediate energies; the carbon - carbon reaction at 1 GeV/A

    International Nuclear Information System (INIS)

    The Physics context of this work is heavy ion collisions at relativistic energies where di-electron provide informations on the produced hot and dense nuclear matter. The experiment is performed by the DiLepton Spectrometer (DLS) Collaboration at the Lawrence Berkeley's Bevalac. After a description of the apparatus, we review the whole program and the main results so far obtained: first evidence of a significant di-electron signal at energies above 1 GeV/A; improvement of the understanding of di-electron production (electromagnetic decays of hadrons, π+π- annihilation and hadronic Bremsstrahlung). The results of p-p, p-d reactions from 1 to 4.9 GeV/A show that hadronic Bremsstrahlung (pp, pn) should be reformulated. Our analysis, optimized on the reaction Carbon-Carbon at 1 GeV/A, has been applied to α-Ca and d-Ca. We have developed two main aspects: improvement of the time resolution (500 ps) in order to eliminate all of the protons. Improvement of the space resolution (300 μ) for better mass resolution, in particular in the ρ region. We obtain the cross section of di-electron production as a function of mass, transverse momentum and rapidity from the C-C, α-Ca and d-Ca reactions at 1 GeV/A. We also compare the cross section for all of the measured systems at 1 GeV/A, including Ca-Ca, and we show a (ApAt)α dependence with α ≅ 1.1. A study of the associated multiplicity has also been performed. Nevertheless, the limited acceptance of the DLS and its poor mass resolution to identify the ρ, ω vector mesons, do not allow to conclude on hadron behaviour in nuclear matter. This point is one of the main goal of the HADES project at GSI (Darmstadt), which we give a brief description of the main features. (authors). 60 refs

  7. Platelet alpha 2-adrenergic receptors in major depressive disorder. Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment

    International Nuclear Information System (INIS)

    The specific binding of tritiated (3H)-clonidine, an alpha 2-adrenergic receptor agonist, to platelet membranes was measured in normal subjects and in patients with major depressive disorder. The number of platelet alpha 2-adrenergic receptors from the depressed group was significantly higher than that found in platelets obtained from the control population. Treatment with tricyclic antidepressant drugs led to significant decreases in the number of platelet alpha 2-adrenergic receptors. These results support the hypothesis that the depressive syndrome is related to an alpha 2-adrenergic receptor supersensitivity and that the clinical effectiveness of tricyclic antidepressant drugs is associated with a decrease in the number of these receptors

  8. Endothelin receptor-mediated vasodilatation

    DEFF Research Database (Denmark)

    Nilsson, David; Wackenfors, Angelica; Gustafsson, Lotta;

    2008-01-01

    Culture of intact arteries is a frequently employed experimental model for investigating the mechanisms governing the regulation of vascular endothelin receptors. Endothelin type A (ET(A)) and type B (ET(B)) receptors on vascular smooth muscle cells are up-regulated in organ culture and the...... enhanced vasoconstriction mimics the changes that occur in cardiovascular disease. The effect of organ culture on endothelial dilatory endothelin ET(B) receptors is not known. We hypothesize that organ culture decreases the endothelin receptor-mediated dilatation and that this is one possible mechanism by...... denudation. The increase in sarafotoxin 6c contraction after removal of the endothelium was more pronounced before than after organ culture, suggesting down-regulated endothelial endothelin ET(B) receptors. Also, the immunofluorescence staining intensities for endothelial endothelin ET(B) receptors were...

  9. Calixarene-supported clusters

    DEFF Research Database (Denmark)

    Taylor, Stephanie M.; McIntosh, Ruaraidh D.; Piligkos, Stergios; Dalgarno, Scott J.; Brechin, Euan K.

    2012-01-01

    A combination of complementary cluster ligands results in the formation of a new calixarene-supported ferromagnetic [Mn(5)] cage that displays the characteristic bonding modes of each support.......A combination of complementary cluster ligands results in the formation of a new calixarene-supported ferromagnetic [Mn(5)] cage that displays the characteristic bonding modes of each support....

  10. Surface coil magnetic resonance imaging of the orbit at 1.5 T

    International Nuclear Information System (INIS)

    MRI of the orbit at 1.5-Tesla was performed in 5 healthy volunteers and 30 patients with a variety of pathological intraocular or intraconal conditions. Major advantages of MRI over CT include higher spatial resolution, higher tissue contrast, possibility of direct multiplanar imaging, absence of bony and dental artifacts, and of ionising radiation. Specific indications of MRI in orbital pathology concern differentiation of uveal melanoma from subretinal haemorrhage, identification of lesions of the orbital apex, the orbital fissure or the optic canal, differentiation if inflammatory pseudotumour from malignant lesions, determination of the posterior extension of lesions of the optic nerve, and detection of abnormal flow in normal or hypertrophic intraorbital vessels. Limitations are due to motion artifacts on T2 weighted sequences, less accurate visualisation of calcification, poor specificity of some findings, and absence of signal from cortical bone. (orig.)

  11. A multi-milliJoule femtosecond Raman laser emitting at 1.28 um

    CERN Document Server

    Vicario, Carlo; Konyashchenko, Aleksandr; Losev, Leonid; Hauri, Christoph P

    2016-01-01

    We report on the generation of broadband, high-energy femtosecond pulses centered at 1.28 um by stimulated Raman scattering in pressurized hydrogen cell. Stimulated Raman scattering is performed by two chirped and delayed pulses originating from a multi-mJ Ti:Sapphire amplifier. The Stokes pulse carries energy of 4.4 mJ and is recompressed down to 66 fs by reflective grating pair. We characterized the short-wavelength mid-infrared source in view of energy stability, beam profile and conversion efficiency at a repetition rate of 100 Hz and 10 Hz. The demonstrated laser will benefit intense THz generation applications from highly nonlinear organic crystals.

  12. Polarimetry at 1.3 mm using MILLIPOL - methods and preliminary results for Orion

    International Nuclear Information System (INIS)

    This paper describes a polarimeter for use at wavelengths near 1 mm, designed to be self-contained and portable. Only minor modifications should be required to adapt this instrument for use on any of several millimeter and submillimeter telescopes. The polarimeter system and data-taking techniques are described, and a preliminary measurement is reported of the polarized dust emission from the Orion KL region at 1.3 mm using the NRAO 12 m telescope. The results are similar to previous polarization measurements of Orion at far-infrared and submillimeter wavelengths. The magnetic field direction implied by the polarization position angle is parallel to that found in the surrounding Orion region using optical and near- to midinfrared polarimetric techniques. 17 references

  13. Gold nanorod saturable absorber for passive mode-locking at 1 μm wavelength

    International Nuclear Information System (INIS)

    Gold nanorods (GNRs) were used as a saturable absorber (SA) for passive mode-locking at 1 μm wavelength. The GNR-SA film was fabricated by mixing GNRs with sodium carboxymethylcellulose. The longitudinal surface plasmon resonance absorption of GNRs was used to induce mode-locking. By using the GNR-SA film, stable passive mode-locking at 1039 nm was experimentally demonstrated in an ytterbium-doped fiber laser cavity pumped by a 980 nm laser diode. The laser produced ∼440 ps pulses with a repetition rate of 36.6 MHz and an average output power of ∼1.25 mW for a pump power of ∼82 mW. (letter)

  14. Gold nanorod saturable absorber for passive mode-locking at 1 μm wavelength

    Science.gov (United States)

    Kang, Z.; Li, Q.; Gao, X. J.; Zhang, L.; Jia, Z. X.; Feng, Y.; Qin, G. S.; Qin, W. P.

    2014-03-01

    Gold nanorods (GNRs) were used as a saturable absorber (SA) for passive mode-locking at 1 μm wavelength. The GNR-SA film was fabricated by mixing GNRs with sodium carboxymethylcellulose. The longitudinal surface plasmon resonance absorption of GNRs was used to induce mode-locking. By using the GNR-SA film, stable passive mode-locking at 1039 nm was experimentally demonstrated in an ytterbium-doped fiber laser cavity pumped by a 980 nm laser diode. The laser produced ˜440 ps pulses with a repetition rate of 36.6 MHz and an average output power of ˜1.25 mW for a pump power of ˜82 mW.

  15. MR imaging (at 1.5 T) of the brachial plexus

    International Nuclear Information System (INIS)

    Brachial plexus pathology can at times be difficult to visualize on CT, relative to normal structures, even with the aid of intravenous contrast. MR images of this area routinely give excellent anatomic delineation, due to the marked contrast in signal between fat in the axillary fossa, muscle, and pathology. The authors studied 15 patients at 1.5 T, eight normal and seven abnormal, with visualization of the trunks and cords. Some of the positive cases included metastatic deposits, cervical rib, severe vascular ectasia, a postangiography hematoma, etc. The distinct signal of pathologic tissue compared with the distinct signals of normal structures and the ability to evaluate vascular patency make MR imaging ideally suited in the evaluation of this region without the need of intravenous contrast

  16. Ion collisional transport coefficients in the solar wind at 1 AU

    CERN Document Server

    Hellinger, Petr

    2016-01-01

    Proton and alpha particle collisional transport coefficients (isotropization, relative deceleration frequencies and heating rates) at 1 AU are quantified using the WIND/SWE data. In agreement with previous studies the ion-ion Coulomb collisions are generally important for slow solar wind streams and tend to reduce the temperature anisotropies, the differential streaming and the differences between proton and alpha particle temperatures. In slow solar wind streams the Coulomb collisions between protons and alpha particles are important for the overall proton energetics as well as for the relative deceleration between the two species. It is also shown that ion temperature anisotropies and differential streaming need to be generally taken into account for evaluation of the collisional transport coefficients.

  17. Remote sensing of soil moisture content over bare field at 1.4 GHz frequency

    Science.gov (United States)

    Wang, J. R.; Choudhury, B. J.

    1981-01-01

    An algorithm for estimating moisture content of a bare soil from the observed brightness temperature at 1.4 GHz is discussed and applied to a limited data base. The method is based on a radiative transfer model calculation, which has been successfully used in the past to account for many observational results, with some modifications to take into account the effect of surface roughness. Besides the measured brightness temperatures, the three additional inputs required by the method are the effective soil thermodynamic temperature, the precise relation between moisture content and the smooth field brightness temperatures and a pair of parameters related to surface roughness. The procedures of estimating surface roughness parameters and of obtaining moisture content from observed brightness temperature are discussed. The algorithm is applied to observations from truck mounted and airborne radiometers. The estimated moisture contents compare favorably with the observations in the top 2 cm layer.

  18. Crystal structure of a yeast aquaporin at 1.15 angstrom reveals a novel gating mechanism.

    Directory of Open Access Journals (Sweden)

    Gerhard Fischer

    2009-06-01

    Full Text Available Aquaporins are transmembrane proteins that facilitate the flow of water through cellular membranes. An unusual characteristic of yeast aquaporins is that they frequently contain an extended N terminus of unknown function. Here we present the X-ray structure of the yeast aquaporin Aqy1 from Pichia pastoris at 1.15 A resolution. Our crystal structure reveals that the water channel is closed by the N terminus, which arranges as a tightly wound helical bundle, with Tyr31 forming H-bond interactions to a water molecule within the pore and thereby occluding the channel entrance. Nevertheless, functional assays show that Aqy1 has appreciable water transport activity that aids survival during rapid freezing of P. pastoris. These findings establish that Aqy1 is a gated water channel. Mutational studies in combination with molecular dynamics simulations imply that gating may be regulated by a combination of phosphorylation and mechanosensitivity.

  19. Dissociated incretin response to oral glucose at 1 year after restrictive vs. malabsorptive bariatric surgery

    DEFF Research Database (Denmark)

    Guldstrand, M; Ahrén, B; Näslund, E;

    2009-01-01

    AIM: Compare the response to oral glucose of the two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) at 1 year after restrictive vs. malabsorptive bariatric surgery. METHODS: Vertical banded gastroplasty (VBG, n = 7) or jejunoileal bypass...... operation, reduction in body weight, actual body weight, fasting glucose or insulin, or the glucose and insulin responses to oral glucose did not differ significantly between the groups. Similarly, fasting GIP and GLP-1 levels did not differ significantly between the groups. In contrast, the GIP and GLP-1...... responses to oral glucose were different between the groups in a dissociated pattern. Thus, AUC(GIP) was significantly higher after VBG than after JIB (53 +/- 8 vs. 26 +/- 6 pmol/l/min, p = 0.003). In contrast, AUC(GLP-1) was significantly higher after JIB than after VBG (49 +/- 5 vs. 20 +/- 3 pmol/l/min, p...

  20. Dual-laser absorption spectroscopy of C2H2 at 1.4 μ m

    Science.gov (United States)

    Fasci, E.; Odintsova, T. A.; Castrillo, A.; De Vizia, M. D.; Merlone, A.; Bertiglia, F.; Moretti, L.; Gianfrani, L.

    2016-04-01

    Spectroscopic parameters (line intensity factor, pressure self-broadening, and shifting coefficients) of C2H2 at 1.4 μ m were accurately measured using a dual-laser approach, based upon the technique of optical phase locking. This generated an absolute frequency scale underneath the absorption spectra. A pair of extended-cavity diode lasers was used. One of them, the probe laser, is forced to maintain a precise frequency offset from a reference laser, which is an optical frequency standard based on noise-immune cavity-enhanced optical heterodyne molecular spectroscopy. Laser-gas interaction takes place inside an isothermal multipass cell that is stabilized at the temperature of the triple point of water. The fidelity in the observation of the shape associated to the Pe(14) line of the 2 ν3+ν5 band allowed us to measure the spectroscopic parameters, with a global uncertainty for the line strength of 0.22%.

  1. Relationship Between Alfvenic Fluctuations and Heavy Ion Heating in the Cusp at 1 Re

    Science.gov (United States)

    Coffey, Victoria; Chandler, Michael; Singh, Nagendra

    2008-01-01

    We look at the effect of heavy ion heating from their coupling with observed broadband (BB-ELF) emissions. These wave fluctuations are common to many regions of the ionosphere and magnetosphere and have been described as spatial turbulence of dispersive Alfven waves (DAW) with short perpendicular wavelengths. With Polar passing through the cusp at 1 Re in the Spring of 1996, we show the correlation of their wave power with mass-resolved O+ derived heating rates. This relationship lead to the study of the coupling of the thermal O+ ions and these bursty electric fields. We demonstrate the role of these measurements in the suggestion of DAW and stochastic ion heating and the observed density cavity characteristics.

  2. The absolute vertical muonic intensity on sea level at 1 GeV/c

    International Nuclear Information System (INIS)

    The absolute differential and integral muonic intensity at 1 GeV/c was measured vertically at sea level with the aid of a range spectrometer. The spectrometer has a product of solid angle and area of 1.13 cm2sr and consists of two lead absorbers of a thickness of 60 cm and 15 cm (anticoincidence method) and 5 scintillation counters. The measured rates were corrected with regard to inefficiency of the apparatus, cosmic-ray showers, multiple scattering, muon straggling and variations of intensity (caused by atmospheric effects and solar influences). The findings of this paper as well as recent measurements of other authors show that the value of 1 GeV/c (ROSSI point) which has up to now been used as normalization point for muon spectres should be raised by 25%. (orig./AK)

  3. Crystal structure of a thiolase from Escherichia coli at 1.8 Å resolution.

    Science.gov (United States)

    Ithayaraja, M; Janardan, N; Wierenga, Rik K; Savithri, H S; Murthy, M R N

    2016-07-01

    Thiolases catalyze the Claisen condensation of two acetyl-CoA molecules to give acetoacetyl-CoA, as well as the reverse degradative reaction. Four genes coding for thiolases or thiolase-like proteins are found in the Escherichia coli genome. In this communication, the successful cloning, purification, crystallization and structure determination at 1.8 Å resolution of a homotetrameric E. coli thiolase are reported. The structure of E. coli thiolase co-crystallized with acetyl-CoA at 1.9 Å resolution is also reported. As observed in other tetrameric thiolases, the present E. coli thiolase is a dimer of two tight dimers and probably functions as a biodegradative enzyme. Comparison of the structure and biochemical properties of the E. coli enzyme with those of other well studied thiolases reveals certain novel features of this enzyme, such as the modification of a lysine in the dimeric interface, the possible oxidation of the catalytic Cys88 in the structure of the enzyme obtained in the presence of CoA and active-site hydration. The tetrameric enzyme also displays an interesting departure from exact 222 symmetry, which is probably related to the deformation of the tetramerization domain that stabilizes the oligomeric structure of the protein. The current study allows the identification of substrate-binding amino-acid residues and water networks at the active site and provides the structural framework required for understanding the biochemical properties as well as the physiological function of this E. coli thiolase. PMID:27380370

  4. Performance Evaluation of a Loeb-Eiber Mass Filter at 1 Torr

    Science.gov (United States)

    Hoffmann, William D.; Jin, Feng; Pedder, Randall E.; Taormina, Christopher; Jackson, Glen P.

    2015-02-01

    The Loeb-Eiber mass filter is best operated at relatively high pressures—such as 1 Torr—where collisional dampening of ions up to the mass filter thermalizes the ions' kinetic energy, which is a requirement for effective filtering. The inter-electrode gaps of ~8 μm require rf amplitudes on the order of 0-5 V p-p at approximately 50 MHz to achieve mass filtering up to m/z 40. Mass filtering between the 25-μm diameter wires, therefore, takes place on time frames less than the collision frequency at ~1 Torr. The low power and high pressure capabilities of the Loeb-Eiber mass filter make it ideally suited for miniaturization, where power and space are a premium. In the present work, a Loeb-Eiber mass filter was constructed using commercial silicon-on-insulator (SOI) microfabrication techniques. Ions transmitting through the chip-based Loeb-Eiber mass filter were characterized in real time using a traditional linear quadrupole mass analyzer in series with the Loeb-Eiber mass filter. The new hybrid instrument has enabled us to verify several important claims regarding the operation of the Loeb-Eiber mass filter: (1) that ions can be effectively filtered at ~1 Torr, (2) that for ions of a fixed mass-to-charge ratio, the ion transmission current decreases linearly with increasing rf amplitude on the Loeb-Eiber mass filter, (3) that the cutoff voltage at which all ions of a particular m/z value are effectively blocked is linearly related to mass-to-charge, and (4) that square waveforms can filter ions more effectively than sinusoidal waveforms for a given peak-to-peak rf amplitude.

  5. Quantification of dextrose in model solution by 1H MR spectroscopy at 1.5T

    International Nuclear Information System (INIS)

    To evaluate the feasibility of proton magnetic resonance spectroscopy (1H-MRS) using a 1.5T magnetic resonance (MR) imager for quantification of the contents of model solutions. We prepared model solutions of dextrose +water and dextrose +water + ethanol at dextrose concentrations of 0.01% to 50% and 0.01% to 20%, respectively. Using these solutions and a 1.5T MR imager together with a high-resolution nuclear magnetic resonance (NMR) spectroscope, we calculated the ratios of dextrose to water peak, (dextrose +ethanol) to water peak, and (dextrose + ethanol) to ethanol peak, as seen on MR and NMR spectra, analysing the relationships between dextrose concentration and the ratios of peaks, and between the ratios of the peaks seen on MR spectra and those seen on NMR spectra. Changes in the ratios between dextrose concentration and dextrose to water peak, (dextrose + ethanol) to water peak and (dextrose + ethanol) to ethanol peak, as seen on MR spectra, were statistically significant, and there was good linear regression. There was also close correlation between the ratios of the observed on MR and NMR spectra. The results depict the quantification of dextrose concentration according to the ratios of spectral peaks obtained by proton MRS at 1.5T. Using proton MRS at 1.5T, and on the basis of the ratios of spectcal peaks, it was possible to quantify the concentration of dextrose in model solutions of dextrose + water and dextrose + water+ ethanol. The results of this study suggest that for quantifying the contents of biofluids, the use of low-tesla 1H-MRS is feasible

  6. Tubular crystals of acetylcholine receptor

    OpenAIRE

    1984-01-01

    Well-ordered tubular crystals of acetylcholine receptor were obtained from suspensions of Torpedo marmorata receptor-rich vesicles. They are composed of pairs of oppositely oriented molecules arranged on the surface lattice with the symmetry of the plane group p2 (average unit cell dimensions: a = 90 A, b = 162 A, gamma = 117 degrees). The receptor in this lattice has an asymmetric distribution of mass around its perimeter, yet a regular pentagonal shape; thus its five transmembrane subunits ...

  7. Receptors of mammalian trace amines

    OpenAIRE

    Lewin, Anita H.

    2006-01-01

    The discovery of a family of G-protein coupled receptors, some of which bind and are activated by biogenic trace amines, has prompted speculation as to the physiological role of these receptors. Observations associated with the distribution of these trace amine associated receptors (TAARs) suggest that they may be involved in depression, attention-deficit hyperactivity disorder, eating disorders, migraine headaches, and Parkinson's disease. Preliminary in vitro data, obtained using cloned rec...

  8. Immunobiology of the TAM receptors

    OpenAIRE

    Lemke, Greg; Rothlin, Carla V.

    2008-01-01

    Recent studies have revealed that the TAM receptor protein tyrosine kinases — TYRO3, AXL and MER — have pivotal roles in innate immunity. They inhibit inflammation in dendritic cells and macrophages, promote the phagocytosis of apoptotic cells and membranous organelles, and stimulate the maturation of natural killer cells. Each of these phenomena may depend on a cooperative interaction between TAM receptor and cytokine receptor signalling systems. Although its importance was previously unreco...

  9. Serotonin receptors as cardiovascular targets

    OpenAIRE

    Villalón, Carlos; De Vries, Peter; Saxena, Pramod Ranjan

    1997-01-01

    textabstractSerotonin exerts complex effects in the cardiovascular system, including hypotension or hypertension, vasodilatation or vasoconstriction, and/or bradycardia or tachycardia; the eventual response depends primarily on the nature of the 5-HT receptors involved. In the light of current 5-HT receptor classification, the authors reanalyse the cardiovascular responses mediated by 5-HT receptors and discuss the established and potential therapeutic applications of 5-HT ligands in the trea...

  10. Flavonoid modulation of GABAA receptors

    OpenAIRE

    Jane R. Hanrahan; Chebib, Mary; Johnston, Graham A. R.

    2011-01-01

    There has been a resurgence of interest in synthetic and plant-derived flavonoids as modulators of γ-amino butyric acid-A (GABAA) receptor function influencing inhibition mediated by the major inhibitory neurotransmitter GABA in the brain. Areas of interest include (i) flavonoids that show subtype selectivity in recombinant receptor studies in vitro consistent with their behavioural effects in vivo, (ii) flumazenil-insensitive modulation of GABAA receptor function by flavonoids, (iii) the abi...

  11. Silver-Coated Teflon Tubes for Waveguiding at 1-2 THz

    Science.gov (United States)

    Navarro-Cía, Miguel; Melzer, Jeffrey E.; Harrington, James A.; Mitrofanov, Oleg

    2015-06-01

    Realization of single-mode low-loss waveguides for 1.0-2.0 THz remains a challenging problem due to large absorption in most dielectrics and ohmic losses in metals. To address this problem, we investigate dielectric-lined hollow metallic waveguides fabricated by coating 1-mm diameter 38-μm-thick polytetrafluoroethylene tubes with silver. These waveguides support a hybrid HE11 mode, which exhibits low attenuation and low dispersion. Quasi-single-mode propagation is achieved in the band of 1.0-1.6 THz, in which the hybrid HE11 mode is supported by the waveguide. In this band, the experimentally measured loss is ~20 dB/m (~0.046 cm-1), whereas the numerically computed loss is ~7 dB/m (~0.016 cm-1). The difference is attributed to additional losses in the dielectric layer, which can be reduced by using alternative polymers.

  12. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R; Schwartz, T W

    2001-01-01

    A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...... expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets....

  13. Solar Wind Protons at 1 AU: Trends and Bounds, Constraints and Correlations

    Czech Academy of Sciences Publication Activity Database

    Hellinger, Petr; Trávníček, Pavel M.

    2014-01-01

    Roč. 784, č. 1 (2014), L15/1-L15/5. ISSN 2041-8205 R&D Projects: GA ČR GAP209/12/2023 Grant ostatní: EU(XE) SHOCK Project No. 284515 Institutional support: RVO:67985815 Keywords : instabilities * plasmas * solar wind Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 5.339, year: 2014

  14. Angiotensin II type 1 receptors and systemic hemodynamic and renal responses to stress and altered blood volume in conscious rabbits

    Directory of Open Access Journals (Sweden)

    RogerGeorgeEvans

    2011-07-01

    Full Text Available We examined how systemic blockade of type 1 angiotensin (AT1- receptors affects reflex control of the circulation and the kidney. In conscious rabbits, the effects of candesartan on responses of systemic and renal hemodynamics and renal excretory function to acute hypoxia, mild hemorrhage and plasma volume expansion were tested. Candesartan reduced resting mean arterial pressure (MAP, -8 ± 2% without significantly altering cardiac output (CO, increased renal blood flow (RBF, +38 ± 9% and reduced renal vascular resistance (RVR, -32 ± 6%. Glomerular filtration rate (GFR was not significantly altered but sodium excretion (UNa+V increased four-fold. After vehicle treatment, hypoxia (10% inspired O2 for 30 min did not significantly alter MAP or CO, but reduced HR (-17 ± 6%, increased RVR (+33 ± 16% and reduced GFR (-46 ± 16% and UNa+V (-41 ± 17%. Candesartan did not significantly alter these responses. After vehicle treatment, plasma volume expansion increased CO (+35 ± 7%, reduced total peripheral resistance (TPR, -26 ± 5%, increased RBF (+62 ± 23% and reduced RVR (-32 ± 9%, but did not significantly alter MAP or HR. It also increased UNa+V (803 ± 184% yet reduced GFR (-47 ± 9%. Candesartan did not significantly alter these responses. After vehicle treatment, mild hemorrhage did not significantly alter MAP but increased HR (+16 ± 3%, reduced CO (-16 ± 4% and RBF (-18 ± 6%, increased TPR (+18 ± 4% and tended to increase RVR (+18 ± 9%, P = 0.1, but had little effect on GFR or UNa+V. But after candesartan treatment MAP fell during hemorrhage (-19 ± 1%, while neither TPR nor RVR increased, and GFR (-64 ± 18% and UNa+V (-83 ± 10% fell. AT1-receptor activation supports MAP and GFR during hypovolemia. But AT1-receptors appear to play little role in the renal vasoconstriction, hypofiltration and antinatriuresis accompanying hypoxia, or the systemic and renal vasodilatation and natriuresis accompanying plasma volume expansion.

  15. Biochemical and biological properties of the nerve growth factor receptor

    International Nuclear Information System (INIS)

    We have utilized a monoclonal antibody (192-IgG) to study the rat nerve growth factor receptor. After intraocular injection, 125I-192-IgG was retrogradely transported in sympathetic neuronal axons to the superior cervical ganglion. When the sciatic nerve was ligated to induce the accumulation of axonally transported materials, 192-IgG immunostaining was observed on both sides of the ligature, indicating that NGF receptors are transported in both orthograde and retrograde directions. By using 125I-NGF crosslinking and 192-IgG immunoprecipitation, we detected receptor molecules throughout the rat brain, thereby supporting the hypothesis that NGF is active in the central nervous system. We also discovered that sciatic nerve transection leads to a dramatic increase in the amount of NGF receptor found in the distal portion of the nerve. Immunostaining revealed that all Schwann cells in the distal axotomized nerve were expressing NGF receptors. We examined phosphorylation of NGF receptor in cultured sympathetic neurons and PC12 cells. We also examined pharmacological effects of 192-IgG. Systemic injection of 192-IgG into neonatal rats caused a permanent partial sympathectomy in a dose-dependent manner; a maximum of 50% of the cells were killed

  16. Antipsychotic efficacy: relationship to optimal D2-receptor occupancy.

    Science.gov (United States)

    Pani, Luca; Pira, Luigi; Marchese, Giorgio

    2007-07-01

    Clinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords 'antipsychotic or neuroleptic', 'receptor' and 'occupancy' and 'dopamine' and 'D2' supplemented by the authors' knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a 'therapeutic window' between approximately 65 and approximately 80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia. PMID:17419008

  17. Angiotensin-2-mediated Ca2+ signaling in the retinal pigment epithelium: role of angiotensin-receptor-associated-protein and TRPV2 channel.

    Directory of Open Access Journals (Sweden)

    Rene Barro-Soria

    Full Text Available Angiotensin II (AngII receptor (ATR is involved in pathologic local events such as neovascularisation and inflammation including in the brain and retina. The retinal pigment epithelium (RPE expresses ATR in its AT1R form, angiotensin-receptor-associated protein (Atrap, and transient-receptor-potential channel-V2 (TRPV2. AT1R and Atrap co-localize to the basolateral membrane of the RPE, as shown by immunostaining. Stimulation of porcine RPE (pRPE cells by AngII results in biphasic increases in intracellular free Ca(2+inhibited by losartan. Xestospongin C (xest C and U-73122, blockers of IP3R and PLC respectively, reduced AngII-evoked Ca(2+response. RPE cells from Atrap(-/- mice showed smaller AngII-evoked Ca(2+peak (by 22% and loss of sustained Ca(2+elevation compared to wild-type. The TRPV channel activator cannabidiol (CBD at 15 µM stimulates intracellular Ca(2+-rise suggesting that porcine RPE cells express TRPV2 channels. Further evidence supporting the functional expression of TRPV2 channels comes from experiments in which 100 µM SKF96365 (a TRPV channel inhibitor reduced the cannabidiol-induced Ca(2+-rise. Application of SKF96365 or reduction of TRPV2 expression by siRNA reduced the sustained phase of AngII-mediated Ca(2+transients by 53%. Thus systemic AngII, an effector of the local renin-angiotensin system stimulates biphasic Ca(2+transients in the RPE by releasing Ca(2+from cytosolic IP3-dependent stores and activating ATR/Atrap and TRPV2 channels to generate a sustained Ca(2+elevation.

  18. Differential effects of chronic hyperammonemia on modulation of the glutamate-nitric oxide-cGMP pathway by metabotropic glutamate receptor 5 and low and high affinity AMPA receptors in cerebellum in vivo.

    Science.gov (United States)

    Cabrera-Pastor, Andrea; Llansola, Marta; Reznikov, Vitaliy; Boix, Jordi; Felipo, Vicente

    2012-07-01

    Previous studies show that chronic hyperammonemia impairs learning ability of rats by impairing the glutamate-nitric oxide (NO)-cyclic guanosine mono-phosphate (cGMP) pathway in cerebellum. Three types of glutamate receptors cooperate in modulating the NO-cGMP pathway: metabotropic glutamate receptor 5 (mGluR5), (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartic acid (NMDA) receptors. The aim of this work was to assess whether hyperammonemia alters the modulation of this pathway by mGluR5 and AMPA receptors in cerebellum in vivo. The results support that in control rats: (1) low AMPA concentrations (0.1mM) activate nearly completely Ca(2+)-permeable (glutamate receptor subunit 2 (GluR2)-lacking) AMPA receptors and the NO-cGMP pathway; (2) higher AMPA concentrations (0.3 mM) also activate Ca(2+)-impermeable (GluR2-containing) AMPA receptors, leading to activation of NMDA receptors and of NO-cGMP pathway. Moreover, the data support that chronic hyperammonemia: (1) reduces glutamate release and activation of the glutamate-NO-cGMP pathway by activation of mGluR5; (2) strongly reduces the direct activation by AMPA receptors of the NO-cGMP pathway, likely due to reduced entry of Ca(2+) through GluR2-lacking, high affinity AMPA receptors; (3) strongly increases the indirect activation of the NO-cGMP pathway by high affinity AMPA receptors, likely due to increased entry of Na(+) through GluR2-lacking AMPA receptors and NMDA receptors activation; (4) reduces the indirect activation of the NO-cGMP pathway by low affinity AMPA receptors, likely due to reduced activation of NMDA receptors. PMID:22521775

  19. Compressional and Shear Wave Velocities of an Antigorite Rock at 1 GPa up to 550C

    Science.gov (United States)

    Yano, H.; Watanabe, T.; Yoneda, A.

    2008-12-01

    Serpentines play key roles in the water transportation in a subduction zone, the slab-mantle coupling and the generation of slab earthquakes. Geophysical mapping of serpentinized regions is important for understanding of subduction zone processes. There are three major forms of serpentine: antigorite, lizardite and chrysotile. Antigorite is stable up to 600°C at 1 GPa, while lizardite and chrysotile are stable below 300°C. Watanabe et al. (2007) showed that High-T type (containing antigorite) serpentinized peridotites have distinctive higher velocity and lower Poisson's ratio than Low-T type (containing lizardite and/or chrysotile) with the same density. Seismological observations on warm subduction zones like Costa Rica should be interpreted on the basis of antigorite properties. However, our knowledge on elastic properties of antigorite is still lacking. We have measured compressional and shear wave velocities on an antigorite rock at 1 GPa up to 550°C. The rock sample is mostly composed of antigorite (>95 vol.%) and grains are well aligned. The lineation is interpreted to be parallel to crystallographic b-axis, and cleavages normal to c-axis. Measuremens were made with various directions of propagation and oscillation. Reflecting the crystallographic structure, the sample shows strong anisotropy of velocity. The fastest direction of compressional wave is the b-axis direction (8.39±0.04 km/s at 550°C), and the slowest the c-axis direction (5.78±0.06 km/s at 550°C). No significant temperature dependence of Vp is observed in the b-axis direction, while Vp decreases by 3.3% from room temperature to 550°C in the c-axis direction. Shear wave velocity propagating in the c-axis direction at 550°C is 3.15±0.05 km/s and 3.44±0.03 km/s for oscillating parallel to the a- and b-axes, respectively. We can estimate elastic moduli of an antigorite single crystal from measured velocities on the assumption of orthorhombic symmetry of elasticity, and then calculate

  20. Dynamics of nanoparticules detected at 1 AU by S/WAVES onboard STEREO spacecraft

    Science.gov (United States)

    Belheouane, Soraya; Issautier, Karine; Meyer-Vernet, Nicole; Le Chat, Gaétan; Czechowski, Andrzej; Zaslavsky, Arnaud; Zouganelis, Yannis; Mann, Ingrid

    In order to interpret in detail the S/WAVES data on the interplanetary nanodust discovered by STEREO at 1 AU [Meyer-Vernet et al., 2009], we study the dynamics of nanoparticles in the inner interplanetary medium as well as the distribution of their velocities and directions of arrival, with a model based on [Czechowski and Mann, 2012]. We deduce the charges released by their impacts on the STEREO spacecraft at 1 AU and their dependence on the position of the spacecraft on their orbits. The model studies nanoparticles of size equal or smaller than about 70 nm, assumed to be created via collisional fragmentation of dust grains of larger size moving on keplerian orbits, and sublimation of dust, meteoroids and comets. The nanoparticles are released near the Sun with initial velocities close to keplerian, and mainly subjected to the Lorentz force calculated with a simple solar wind model. A part of the nanoparticles is accelerated to high speeds of the order of 300 km/s, thereby providing impact charges between 10(-14) and 10(-11) Cb [Belheouane, 2014] which enable them to be detected by S/WAVES, whereas another part is trapped within about 0.2 AU from the Sun. We discuss how the fluxes and direction of arrival at 1 AU are expected to change in function of the solar cycle. These results enable us to interpret in detail the STEREO/WAVES observations [Zaslavsky et al., 2012]; [Pantellini et al., 2013]; [Le Chat et al., 2013]. Belheouane, S. (2014). Nanoparticules dans le vent solaire, observations spatiales et theorie. PhD thesis, Pierre and Marie Curie University UPMC. Czechowski, A. and Mann, I. (2012). Nanodust Dynamics in Interplanetary Space, chapter Nanodust Dynamics in Interplanetary Space. Springer Berlin Heidelberg. Le Chat, G., Zaslavsky, A., Meyer-Vernet, N., Issautier, K., Belheouane, S., Pantellini, F., Maksimovic, M., Zouganelis, I., Bale, S., and Kasper, J. (2013). Interplanetary Nanodust Detection by the Solar Terrestrial Relations Observatory/WAVES Low

  1. Role of iso-receptors in receptor-receptor interactions with a focus on dopamine iso-receptor complexes.

    Science.gov (United States)

    Agnati, Luigi F; Guidolin, Diego; Cervetto, Chiara; Borroto-Escuela, Dasiel O; Fuxe, Kjell

    2016-01-01

    Intercellular and intracellular communication processes consist of signals and recognition/decoding apparatuses of these signals. In humans, the G protein-coupled receptor (GPCR) family represents the largest family of cell surface receptors. More than 30 years ago, it has been proposed that GPCR could form dimers or higher-order oligomers (receptor mosaics [RMs] at the plasma membrane level and receptor-receptor interactions [RRIs] have been proposed as a new integrative mechanism for chemical signals impinging on cell plasma membranes). The basic phenomena involved in RRIs are allostery and cooperativity of membrane receptors, and the present paper provides basic information concerning their relevance for the integrative functions of RMs. In this context, the possible role of iso-receptor RM is discussed (with a special focus on dopamine receptor subtypes and on some of the RMs they form with other dopamine iso-receptors), and it is proposed that two types of cooperativity, namely, homotropic and heterotropic cooperativity, could allow distinguishing two types of functionally different RMs. From a general point of view, the presence of iso-receptors and their topological organization within RMs allow the use of a reduced number of signals for the intercellular communication processes, since the target cells can recognize and decode the same signal in different ways. This theoretical aspect is further analyzed here by means of an analogy with artificial information systems. Thus, it is suggested that the 'multiplexer' and 'demultiplexer' concepts could, at least in part, model the role of RMs formed by iso-receptors in the information handling by the cell. PMID:26418645

  2. Receptor studies in biological psychiatry

    International Nuclear Information System (INIS)

    Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D2) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3H-clonidine binding sites were increased in platelet membranes of depressive patients, 3H-imipramine binding sites were decreased. The GABAA receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D2) and the ion-channel type (GABAA). (J.P.N.)

  3. Increased Accuracy in the Measurement of the Dielectric Constant of Seawater at 1.413 GHz

    Science.gov (United States)

    Zhou, Y.; Lang R.; Drego, C.; Utku, C.; LeVine, D.

    2012-01-01

    This paper describes the latest results for the measurements of the dielectric constant at 1.413 GHz by using a resonant cavity technique. The purpose of these measurements is to develop an accurate relationship for the dependence of the dielectric constant of sea water on temperature and salinity which is needed by the Aquarius inversion algorithm to retrieve salinity. Aquarius is the major instrument on the Aquarius/SAC-D observatory, a NASA/CONAE satellite mission launched in June of20ll with the primary mission of measuring global sea surface salinity to an accuracy of 0.2 psu. Aquarius measures salinity with a 1.413 GHz radiometer and uses a scatterometer to compensate for the effects of surface roughness. The core part of the seawater dielectric constant measurement system is a brass microwave cavity that is resonant at 1.413 GHz. The seawater is introduced into the cavity through a capillary glass tube having an inner diameter of 0.1 mm. The change of resonance frequency and the cavity Q value are used to determine the real and imaginary parts of the dielectric constant of seawater introduced into the thin tube. Measurements are automated with the help of software developed at the George Washington University. In this talk, new results from measurements made since September 2010 will be presented for salinities 30, 35 and 38 psu with a temperature range of O C to 350 C in intervals of 5 C. These measurements are more accurate than earlier measurements made in 2008 because of a new method for measuring the calibration constant using methanol. In addition, the variance of repeated seawater measurements has been reduced by letting the system stabilize overnight between temperature changes. The new results are compared to the Kline Swift and Meissner Wentz model functions. The importance of an accurate model function will be illustrated by using these model functions to invert the Aquarius brightness temperature to get the salinity values. The salinity values

  4. Novel roles of nuclear angiotensin receptors and signaling mechanisms.

    Science.gov (United States)

    Gwathmey, TanYa M; Alzayadneh, Ebaa M; Pendergrass, Karl D; Chappell, Mark C

    2012-03-01

    The renin-angiotensin system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. The dysregulation of the RAS is considered a major influence in the development and progression of cardiovascular disease and other pathologies. Indeed, experimental and clinical evidence indicates that blockade of this system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 1 receptor (AT1R) antagonists is an effective therapy to attenuate hypertension and diabetic renal injury, and to improve heart failure. Originally defined as a circulating system, multiple tissues express a complete RAS, and compelling evidence now favors an intracellular system involved in cell signaling and function. Within the kidney, intracellular expression of the three predominant ANG receptor subtypes is evident in the nuclear compartment. The ANG type 1 receptor (AT1R) is coupled to the generation of reactive oxygen species (ROS) through the activation of phosphoinositol-3 kinase (PI3K) and PKC. In contrast, both ANG type 2 (AT2R) and ANG-(1-7) (AT7R) receptors stimulate nitric oxide (NO) formation, which may involve nuclear endothelial NO synthase (eNOS). Moreover, blockade of either ACE2-the enzyme that converts ANG II to ANG-(1-7)-or the AT7 receptor exacerbates the ANG II-ROS response on renal nuclei. Finally, in a model of fetal programmed hypertension, the nuclear ROS response to ANG II is enhanced, while both AT2 and AT7 stimulation of NO is attenuated, suggesting that an imbalance in the intracellular RAS may contribute to the development of programming events. We conclude that a functional intracellular or nuclear RAS may have important implications in the therapeutic approaches to cardiovascular disease. PMID:22170620

  5. Glucocorticoid receptor mediated the propofol self-administration by dopamine D1 receptor in nucleus accumbens.

    Science.gov (United States)

    Wu, Binbin; Liang, Yuyuan; Dong, Zhanglei; Chen, Zhichuan; Zhang, Gaolong; Lin, Wenxuan; Wang, Sicong; Wang, Benfu; Ge, Ren-Shan; Lian, Qingquan

    2016-07-22

    Propofol, a widely used anesthetic, can cause addictive behaviors in both human and experimental animals. In the present study, we examined the involvement of glucocorticoid receptor (GR) signaling in the molecular process by which propofol may cause addiction. The propofol self-administration model was established by a fixed ratio 1 (FR1) schedule of reinforced dosing over successive 14days in rats. On day 15, the rats were treated with dexamethasone, a GR agonist (10-100μg/kg), or RU486, a GR antagonist (10-100μg/kg) at 1h prior to the last training. The animal behaviors were recorded automatically by the computer. The expression of dopamine D1 receptor in the nucleus accumbens (NAc) was examined by Western blot and the concentrations of plasma corticosterone were measured by enzyme-linked immunosorbent assay (ELISA). To further examine the specificity of GR in the process, mineralocorticoid receptor (MR) antagonist, spironolactone, and dexamethasone plus MR agonist, aldosterone, were also tested. Administration of dexamethasone (100μg/kg) or RU486 (⩾10mg/kg) significantly attenuated the rate of propofol maintained active nose-poke responses and infusions, which were accompanied by reductions in both plasma corticosterone level and the expression of D1 receptor in the NAc. Neither spironolactone alone nor dexamethasone combined with aldosterone affected the propofol-maintaining self-administrative behavior, indicating GR, but not MR, modulates the propofol reward in rats. In addition, neither the food-maintaining sucrose responses under FR1 schedule nor the locomotor activity was affected by any doses of dexamethasone or RU486 tested. These findings provide evidence that GR signaling may play an important role in propofol reward. PMID:27126557

  6. Rotation State of Comet 103P/Hartley 2 from Radio Spectroscopy at 1 mm

    Science.gov (United States)

    Drahus, Michał; Jewitt, David; Guilbert-Lepoutre, Aurélie; Waniak, Wacław; Hoge, James; Lis, Dariusz C.; Yoshida, Hiroshige; Peng, Ruisheng; Sievers, Albrecht

    2011-06-01

    The nuclei of active comets emit molecules anisotropically from discrete vents. As the nucleus rotates, we expect to observe periodic variability in the molecular emission line profiles, which can be studied through millimeter/submillimeter spectroscopy. Using this technique we investigated the HCN atmosphere of comet 103P/Hartley 2, the target of NASA's EPOXI mission, which had an exceptionally favorable apparition in late 2010. We detected short-term evolution of the spectral line profile, which was stimulated by the nucleus rotation, and which provides evidence for rapid deceleration and excitation of the rotation state. The measured rate of change in the rotation period is +1.00 ± 0.15 minutes day-1 and the period itself is 18.32 ± 0.03 hr, both applicable at the epoch of the EPOXI encounter. Surprisingly, the spin-down efficiency is lower by two orders of magnitude than the measurement in comet 9P/Tempel 1 and the best theoretical prediction. This secures rotational stability of the comet's nucleus during the next few returns, although we anticipate a catastrophic disruption from spin-up as its ultimate fate. Based on observations carried out with the IRAM 30 m, JCMT 15 m, and CSO 10.4 m telescopes. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain). JCMT is operated by Joint Astronomy Centre and supported by STFC (UK), NRC (Canada), and NWO (Netherlands). CSO is operated by Caltech and supported through NSF grant AST-0540882 (USA).

  7. Experimental study of radium partitioning between anorthite and melt at 1 atm

    Energy Technology Data Exchange (ETDEWEB)

    Miller, S; Burnett, D; Asimow, P; Phinney, D; Hutcheon, I

    2007-03-08

    We present the first experimental radium mineral/melt partitioning data, specifically between anorthite and a CMAS melt at atmospheric pressure. Ion microprobe measurement of coexisting anorthite and glass phases produces a molar D{sub Ra} = 0.040 {+-} 0.006 and D{sub Ra}/D{sub Ba} = 0.23 {+-} 0.05 at 1400 C. Our results indicate that lattice strain partitioning models fit the divalent (Ca, Sr, Ba, Ra) partition coefficient data of this study well, supporting previous work on crustal melting and magma chamber dynamics that has relied on such models to approximate radium partitioning behavior in the absence of experimentally determined values.

  8. Latitudinal Dependence of Cosmic Rays Modulation at 1 AU and Interplanetary Magnetic Field Polar Correction

    Directory of Open Access Journals (Sweden)

    P. Bobik

    2013-01-01

    Full Text Available The cosmic rays differential intensity inside the heliosphere, for energy below 30 GeV/nuc, depends on solar activity and interplanetary magnetic field polarity. This variation, termed solar modulation, is described using a 2D (radius and colatitude Monte Carlo approach for solving the Parker transport equation that includes diffusion, convection, magnetic drift, and adiabatic energy loss. Since the whole transport is strongly related to the interplanetary magnetic field (IMF structure, a better understanding of his description is needed in order to reproduce the cosmic rays intensity at the Earth, as well as outside the ecliptic plane. In this work an interplanetary magnetic field model including the standard description on ecliptic region and a polar correction is presented. This treatment of the IMF, implemented in the HelMod Monte Carlo code (version 2.0, was used to determine the effects on the differential intensity of Proton at 1 AU and allowed one to investigate how latitudinal gradients of proton intensities, observed in the inner heliosphere with the Ulysses spacecraft during 1995, can be affected by the modification of the IMF in the polar regions.

  9. Biodegradation of dispersed oil in Arctic seawater at -1°C.

    Directory of Open Access Journals (Sweden)

    Kelly M McFarlin

    Full Text Available As offshore oil and gas exploration expands in the Arctic, it is important to expand the scientific understanding of arctic ecology and environmental impact to mitigate operational risks. Understanding the fate of oil in arctic seawater is a key factor for consideration. Here we report the chemical loss due to the biodegradation of Alaska North Slope (ANS crude oil that would occur in the water column following the successful dispersion of a surface oil slick. Primary biodegradation and mineralization were measured in mesocosms containing Arctic seawater collected from the Chukchi Sea, Alaska, incubated at -1°C. Indigenous microorganisms degraded both fresh and weathered oil, in both the presence and absence of Corexit 9500, with oil losses ranging from 46-61% and up to 11% mineralization over 60 days. When tested alone, 14% of 50 ppm Corexit 9500 was mineralized within 60 days. Our study reveals that microorganisms indigenous to Arctic seawater are capable of performing extensive biodegradation of chemically and physically dispersed oil at an environmentally relevant temperature (-1°C without any additional nutrients.

  10. The Galaxy Cluster Mid-Infrared Luminosity Function at 1.3

    CERN Document Server

    Wylezalek, Dominika; De Breuck, Carlos; Stern, Daniel; Brodwin, Mark; Galametz, Audrey; Gonzalez, Anthony H; Jarvis, Matt; Hatch, Nina; Seymour, Nick; Stanford, Spencer A

    2014-01-01

    We present 4.5 {\\mu}m luminosity functions for galaxies identified in 178 candidate galaxy clusters at 1.3 1.3. The luminosity functions are derived for different redshift and richness bins, and the IRAC imaging reaches depths of m*+2, allowing us to measure the faint end slopes of the luminosity functions. We find that {\\alpha} = -1 describes the luminosity function very well in all redshifts bins and does not evolve significantly. This provides evidence that the rate at which the low mass galaxy population grows through star formation, gets quenched and is replenished by in-falling field galaxies does not have a major net effect on the shape of the luminosity function. Our measurements for m* are consistent with passive evolution models and high formation redshifts z_f ~ 3. We find a slight trend towards fainter m* for the richest clusters, implying that the most massive clusters in our sample could contain older stellar populations, yet another example of cosmic downsizing. Modelling shows that a contribu...

  11. Craniopharyngiomas - the utility of contrast medium enhancement for MR imaging at 1.5 T

    International Nuclear Information System (INIS)

    To evaluate the efficacy of i.v. contrast medium administration in MR imaging at 1.5 T in patients with craniopharyngiomas, MR studies of 10 men and 6 women with pathologically proven craniopharyngiomas were made. The MR images were obtained as 3- to 5-mm-thick coronal (n=13) or axial (n=3) T1-weighted images (T1WI) prior to an following i.v. Gd-DTPA administration. Proton density-(PD) and T2-weighted images (T2WI) were also obtained. Conspicuity of tumor margins, cystic versus solid components, size, location and effect upon adjacent structures were separately characterized in all imaging sequences. In 6 patients contrast medium-enhanced T1WI, PD and T2WI demonstrated cystic tumor components not seen on unenhanced T1WI. There were significant differences (p<0.004) on 2-tailed Student's t-test comparing tumor conspicuity on contrast medium-enhanced T1WI with unenhanced T1WI, PD and T2WI. Optimal tumor delineation on MR imaging of patients with craniopharyngiomas justifies the use of i.v. contrast medium. (orig.)

  12. The structure of LpxD from Pseudomonas aeruginosa at 1.3 Å resolution

    International Nuclear Information System (INIS)

    The crystal structure of the bacterial protein LpxD from P. aeruginosa was solved and refined at 1.3 Å resolution. The overall domain architecture and biological assembly are similar to those found in previously solved structures of LpxD from other species. LpxD is a bacterial protein that is part of the biosynthesis pathway of lipid A and is responsible for transferring 3-hydroxymyristic acid from the R-3-hydroxymyristoyl-acyl carrier protein to the 2-OH group of UDP-3-O-(3-hydroxymyristoyl) glucosamine. The crystal structure of LpxD from Pseudomonas aeruginosa has been determined at high resolution (1.3 Å). The crystal belonged to space group H3, with unit-cell parameters a = b = 106.19, c = 93.38 Å, and contained one molecule in the asymmetric unit. The structure was solved by molecular replacement using the known structure of LpxD from Escherichia coli as a search model and was refined to Rwork = 16.4% (Rfree = 18.5%) using 91 655 reflections. The final protein model includes 355 amino-acid residues (including 16 amino acids from a 20 amino-acid N-terminal His tag), one chloride ion and two ethylene glycol molecules

  13. The Deep Diffuse Extragalactic Radio Sky at 1.75 GHz

    CERN Document Server

    Vernstrom, T; Scott, Douglas; Wall, J V

    2014-01-01

    We present a study of diffuse extragalactic radio emission at 1.75 GHz from a portion of the ELAIS-S1 field observed with the Australia Telescope Compact Array. The resulting mosaic covers an area of $2.46$ deg$^2$ with a beam size of $150 \\times60\\,$arcsec and instrumental noise $\\sigma_n= (52\\pm5)$ $\\mu$Jy beam$^{-1}$. Using models of point-source emission obtained from the ATLAS survey, we subtracted the discrete emission in this field to a flux density of 150 $\\mu$Jy beam$^{-1}$. Comparison of the source-subtracted probability distribution with the predicted distribution from the noise and model of unsubtracted discrete emission, we find an excess of (76$\\pm$23) $\\mu$Jy beam$^{-1}$. We take this excess as an upper limit on any possible extended emission and constrain several models of extended emission source counts, assuming source sizes of 2 arcmin or less. The best-fitting models yield extended emission temperature contributions to the radio background of $T_b=(10\\pm7)$mK, giving an upper limit on the ...

  14. Measurements of the cosmic microwave background temperature at 1. 47 GHz

    Energy Technology Data Exchange (ETDEWEB)

    Bensadoun, M.J.

    1991-11-01

    A radiofrequency-gain total power radiometer measured the intensity of the cosmic microwave background (CMB) at a frequency of 1.47 GHz (20.4 cm wavelength) from White Mountain, California, in September 1988 and from the South Pole, Antarctica, in December 1989. The CMB thermodynamic temperature, TCMB, is 2.27 {plus minus} 0.25 K (68% C.L.) measured from White Mountain and 2.26 {plus minus} 0.21 K from the South Pole site. The combined result is 2.27 {plus minus} 0.19 K. The correction for galactic emission has been derived from scaled low-frequency maps and constitutes the main source, of error. The atmospheric signal is found by extrapolation from zenith scan measurements at higher frequencies. The result is consistent with previous low-frequency measurements, including a measurement at 1.41 GHz (Levin et al. 1988) made with an earlier version of this instrument. The result is {approximately}2.5 {sigma} ({approximately}l% probability) from the 2.74 {plus minus} 0.02,K global average CMB temperature.

  15. Measurements of the cosmic microwave background temperature at 1.47 GHz

    Energy Technology Data Exchange (ETDEWEB)

    Bensadoun, M.J.

    1991-11-01

    A radiofrequency-gain total power radiometer measured the intensity of the cosmic microwave background (CMB) at a frequency of 1.47 GHz (20.4 cm wavelength) from White Mountain, California, in September 1988 and from the South Pole, Antarctica, in December 1989. The CMB thermodynamic temperature, TCMB, is 2.27 {plus_minus} 0.25 K (68% C.L.) measured from White Mountain and 2.26 {plus_minus} 0.21 K from the South Pole site. The combined result is 2.27 {plus_minus} 0.19 K. The correction for galactic emission has been derived from scaled low-frequency maps and constitutes the main source, of error. The atmospheric signal is found by extrapolation from zenith scan measurements at higher frequencies. The result is consistent with previous low-frequency measurements, including a measurement at 1.41 GHz (Levin et al. 1988) made with an earlier version of this instrument. The result is {approximately}2.5 {sigma} ({approximately}l% probability) from the 2.74 {plus_minus} 0.02,K global average CMB temperature.

  16. Space VLBI Observations of 3C 279 at 1.6 and 5 GHz

    CERN Document Server

    Piner, B G; Wehrle, A E; Hirabayashi, H; Lovell, J E J; Unwin, S C

    2000-01-01

    We present the first VLBI Space Observatory Programme (VSOP) observations ofthe gamma-ray blazar 3C 279 at 1.6 and 5 GHz. The combination of the VSOP andVLBA-only images at these two frequencies maps the jet structure on scales from1 to 100 mas. On small angular scales the structure is dominated by the quasarcore and the bright secondary component `C4' located 3 milliarcseconds from thecore (at this epoch). On larger angular scales the structure is dominated by ajet extending to the southwest, which at the largest scale seen in these imagesconnects with the smallest scale structure seen in VLA images. We haveexploited two of the main strengths of VSOP: the ability to obtainmatched-resolution images to ground-based images at higher frequencies and theability to measure high brightness temperatures. A spectral index map was madeby combining the VSOP 1.6 GHz image with a matched-resolution VLBA-only imageat 5 GHz from our VSOP observation on the following day. The spectral index mapshows the core to have a highl...

  17. Fourier Analysis of the OMC1 Image at 1.1 mm Wavelength

    CERN Document Server

    Youn, Soyoung

    2012-01-01

    We present a 1.1 mm emission map of the OMC1 region observed with AzTEC, a new large-format array composed of 144 silicon-nitride micromesh bolometers that was in use at the James Clerk Maxwell Telescope (JCMT). The AzTEC observations of the OMC1 region at 1.1 mm reveal dozens of cloud cores and a tail of filaments in a manner that is almost identical to the submillimeter continuum emission of the entire OMC1 region at 450 and 850 micronm. We perform Fourier analysis of the image with a modified periodogram and the density power spectrum which provides the distribution of length scale of the structures is measured. The expected value of the periodogram converges to the resulting power spectrum in the mean squared sense. From the present analysis of the OMC1 filaments at the 1.1 mm emission, the power spectrum steepens at relatively smaller scales. At largest scales, the power spectrum flattens and the large scale power law becomes shallower. The power spectra of the 1.1 mm emission show clear deviations from ...

  18. The source counts of submillimetre galaxies detected at 1.1 mm

    CERN Document Server

    Scott, K S; Aretxaga, I; Austermann, J E; Chapin, E L; Dunlop, J S; Ezawa, H; Halpern, M; Hatsukade, B; Hughes, D H; Kawabe, R; Kim, S; Kohno, K; Lowenthal, J D; Montana, A; Nakanishi, K; Oshima, T; Sanders, D; Scott, D; Scoville, N; Tamura, Y; Welch, D; Yun, M S; Zeballos, M

    2012-01-01

    The source counts of galaxies discovered at sub-millimetre and millimetre wavelengths provide important information on the evolution of infrared-bright galaxies. We combine the data from six blank-field surveys carried out at 1.1 mm with AzTEC, totalling 1.6 square degrees in area with root-mean-square depths ranging from 0.4 to 1.7 mJy, and derive the strongest constraints to date on the 1.1 mm source counts at flux densities S(1100) = 1-12 mJy. Using additional data from the AzTEC Cluster Environment Survey to extend the counts to S(1100) ~ 20 mJy, we see tentative evidence for an enhancement relative to the exponential drop in the counts at S(1100) ~ 13 mJy and a smooth connection to the bright source counts at >20 mJy measured by the South Pole Telescope; this excess may be due to strong lensing effects. We compare these counts to predictions from several semi-analytical and phenomenological models and find that for most the agreement is quite good at flux densities > 4 mJy; however, we find significant d...

  19. Structure Analysis of OMC1 Filaments at 1.1 mm Emission

    CERN Document Server

    Youn, Soyoung

    2011-01-01

    We present a 1.1 mm emission map of the OMC1 region observed with AzTEC, a new large-format array composed of 144 silicon-nitride micromesh bolometers that was in use at the James Clerk Maxwell Telescope (JCMT). The AzTEC observations of the OMC1 region at 1.1 mm reveal dozens of cloud cores and a tail of filaments in a manner that is almost identical to the submillimeter continuum emission of the entire OMC1 region at 450 and 850 micronm. The density power spectrum provides the size distribution of the structures. We find that a single power law might be fitted to the calculated power spectrum of the 1.1 mm emission between 0.3 pc and 0.03 pc. The slope of the best fit power law is \\gamma~-2.6 and is similar to the spectral index of the power spectrum of \\gamma~-2.7 found in numerical simulations. However, there is a distinct spectral break in the power spectrum at a characteristic scale of ~0.3 pc in OMC1. The effects of beam size and noise spectrum on the shape and slope of the power spectrum are also incl...

  20. Photofissility at 1 GeV for nuclei throughout the periodic table

    International Nuclear Information System (INIS)

    A new approach to evaluate nuclear photo fissilities at incident photon energies above the pion photoproduction threshold has been recently developed and proved to describe successfully the fissilities of natPb and 232Th target nuclei at energies ∼ 0.2-4.0 GeV. The method is merely a simple, semiempirical description of the photofission reactions in which fissility, f, is governed by two basic quantities, namely, 1) the first-chance fission probability, f-bar1, for the average cascade residual, and 2) the slope, s-bar, of the chance-fission probability associated with the average evaporative sequence of fissionable residuals. In the present work we have extended this approach to analyse photofission data that have been accumulated over the past forty years or so, measured at 1 GeV, for nearly forty target nuclei extending from Ti up to Np. Results have shown that the variation of fissility with Z2/A could be described quite satisfactorily by the proposed model. (author)

  1. Microcavity Silicon Photodetectors at 1.55 μm

    Directory of Open Access Journals (Sweden)

    M. Casalino

    2011-01-01

    Full Text Available The design, the realization, and the characterization of silicon resonant cavity enhanced (RCE photodetectors, working at 1.55 μm, are reported. The photodetectors are constituted by a Fabry-Perot microcavity incorporating a Schottky diode. The working principle is based on the internal photoemission effect. We investigated two types of structures: top and back-illuminated. Concerning the top-illuminated photodetectors, a theoretical and numerical analysis has been provided and the device quantum efficiency has been calculated. Moreover, a comparison among three different photodetectors, having as Schottky metal: gold, silver, or copper, was proposed. Concerning the back-illuminated devices, two kinds of Cu/p-Si RCE photodetectors, having various bottom-mirror reflectivities, were realized and characterized. Device performances in terms of responsivity, free spectral range, and finesse were theoretically and experimentally calculated in order to prove an enhancement in efficiency due to the cavity effect. The back-illuminated device fabrication process is completely compatible with the standard silicon technology.

  2. 28 MHz swept source at 1.0 μm for ultrafast quantitative phase imaging.

    Science.gov (United States)

    Wei, Xiaoming; Lau, Andy K S; Xu, Yiqing; Tsia, Kevin K; Wong, Kenneth K Y

    2015-10-01

    Emerging high-throughput optical imaging modalities, in particular those providing phase information, necessitate a demanding speed regime (e.g. megahertz sweep rate) for those conventional swept sources; while an effective solution is yet to be demonstrated. We demonstrate a stable breathing laser as inertia-free swept source (BLISS) operating at a wavelength sweep rate of 28 MHz, particularly for the ultrafast interferometric imaging modality at 1.0 μm. Leveraging a tunable dispersion compensation element inside the laser cavity, the wavelength sweep range of BLISS can be tuned from ~10 nm to ~63 nm. It exhibits a good intensity stability, which is quantified by the ratio of standard deviation to the mean of the pulse intensity, i.e. 1.6%. Its excellent wavelength repeatability, <0.05% per sweep, enables the single-shot imaging at an ultrafast line-scan rate without averaging. To showcase its potential applications, it is applied to the ultrafast (28-MHz line-scan rate) interferometric time-stretch (iTS) microscope to provide quantitative morphological information on a biological specimen at a lateral resolution of 1.2 μm. This fiber-based inertia-free swept source is demonstrated to be robust and broadband, and can be applied to other established imaging modalities, such as optical coherence tomography (OCT), of which an axial resolution better than 12 μm can be achieved. PMID:26504636

  3. Gemini K-band NIRI Adaptive Optics Observations of Massive Galaxies at 1 < z < 2

    CERN Document Server

    Carrasco, Eleazar R; Trujillo, I

    2010-01-01

    We present deep K-band adaptive-optics observations of eight very massive (M* ~ 4 x 10^11 Msun) galaxies at 1 < z < 2 utilizing the Gemini NIRI/Altair Laser Guide System. These systems are selected from the Palomar Observatory Wide-Field Infrared (POWIR) survey, and are amongst the most massive field galaxies at these epochs. The depth and high spatial resolution of our images allow us to explore for the first time the stellar mass surface density distribution of massive distant galaxies from 1 to 15 kpc on an individual galaxy basis, rather than on stacked images. We confirm that some of these massive objects are extremely compact with measured effective radii between 0."1 - 0."2, giving sizes which are < 2 kpc, a factor of ~ 7 smaller in effective radii than similar mass galaxies today. Examining stellar mass surface densities as a function of fixed physical aperture, we find an over-density of material within the inner profiles, and an under-density in the outer profile, within these high-z galaxi...

  4. Photofissility at 1 GeV for nuclei throughout the periodic table

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, O.A.P.; Duarte, S.B.; Morcelle, V. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Deppman, A. [Sao Paulo Univ., SP (Brazil). Inst. de Fisica

    2005-08-15

    A new approach to evaluate nuclear photo fissilities at incident photon energies above the pion photoproduction threshold has been recently developed and proved to describe successfully the fissilities of {sup nat}Pb and {sup 232}Th target nuclei at energies {approx} 0.2-4.0 GeV. The method is merely a simple, semiempirical description of the photofission reactions in which fissility, f, is governed by two basic quantities, namely, 1) the first-chance fission probability, f-bar{sub 1}, for the average cascade residual, and 2) the slope, s-bar, of the chance-fission probability associated with the average evaporative sequence of fissionable residuals. In the present work we have extended this approach to analyse photofission data that have been accumulated over the past forty years or so, measured at 1 GeV, for nearly forty target nuclei extending from Ti up to Np. Results have shown that the variation of fissility with Z{sup 2}/A could be described quite satisfactorily by the proposed model. (author)

  5. Comparing generic models for interplanetary shocks and magnetic clouds axis configurations at 1 AU

    CERN Document Server

    Janvier, Miho; Demoulin, Pascal; Masias-Meza, Jimmy; Lugaz, Noe

    2015-01-01

    Interplanetary Coronal Mass Ejections are the manifestation of solar transient eruptions, which can significantly modify the plasma and magnetic conditions in the heliosphere. They are often preceded by a shock, and a magnetic flux rope is detected in situ in a third to half of them. The main aim of this study is to obtain the best quantitative shape for the flux rope axis and for the shock surface from in situ data obtained during spacecraft crossings of these structures. We first compare the orientation of the flux ropes axes and shock normals obtained from independent data analyses of the same events, observed in situ at 1AU from the Sun. Then, we carry out an original statistical analysis of axes/shock normals by deriving the statistical distributions of their orientations. We fit the observed distributions using the distributions derived from several synthetic models describing these shapes. We show that the distributions of axis/shock orientations are very sensitive to their respective shape. One classi...

  6. Radio-loud CMEs from the disk center lacking shocks at 1 AU

    CERN Document Server

    Gopalswamy, N; Akiyama, S; Yashiro, S; Xie, H; MacDowall, R J; Kaiser, M L

    2012-01-01

    A coronal mass ejection (CME) associated with a type II burst and originating close to the center of the solar disk typically results in a shock at Earth in 2-3 days and hence can be used to predict shock arrival at Earth. However, a significant fraction (about 28%) of such CMEs producing type II bursts were not associated with shocks at Earth. We examined a set of 21 type II bursts observed by the Wind/WAVES experiment at decameter-hectometric (DH) wavelengths that had CME sources very close to the disk center (within a central meridian distance of 30 degrees), but did not have a shock at Earth. We find that the near-Sun speeds of these CMEs average to ~644 km/s, only slightly higher than the average speed of CMEs associated with radio-quiet shocks. However, the fraction of halo CMEs is only ~30%, compared to 54% for the radio-quiet shocks and 91% for all radio-loud shocks. We conclude that the disk-center radio-loud CMEs with no shocks at 1 AU are generally of lower energy and they drive shocks only close t...

  7. Dielectron production in 12C+12C collisions at 1 GeV per nucleon

    International Nuclear Information System (INIS)

    This thesis contains the experimental results on dielectron production in 12C+12C collisions at 1 GeV/u recorded with HADES. Within this work, the analysis is demonstrated, showing that leptons are efficiently reconstructed and hadrons very well discriminated. The described pair analysis shows that the combinatorial background is successfully reduced and the amount of true electron-positron pairs is not decreased. After subtracting the combinatorial background, the efficiency-corrected and normalized invariant-mass, transverse momentum and rapidity distributions of the dileptons are investigated. In the invariant-mass region 0.2-0.6 GeV/c2 the measured pair yield shows a strong excess above the contribution expected from hadron decays after freeze-out according to predictions. Together with the results obtained in 12C+12C at 2 GeV/u it becomes evident that the overshoot of the data increases with decreasing beam energy. A detailed analysis shows that the beam energy dependence of the excess yield, i.e. the pair yield above the known eta contribution, integrated over the 0.15-0.5 GeV/c2 mass range, scales like pion production. (orig.)

  8. Disentangling star formation and AGN activity in powerful infrared luminous radio galaxies at 1

    CERN Document Server

    Drouart, Guillaume; De Breuck, Carlos; Fioc, Michel; Lehnert, Matthew; Seymour, Nick; Stern, Dan; Vernet, Joel

    2016-01-01

    High-redshift radio galaxies present signs of both star formation and AGN activity, making them ideal candidates to investigate the connection and coevolution of AGN and star formation in the progenitors of present-day massive galaxies. We make use of a sample of 11 powerful radio galaxies spanning 1at 1

  9. STRUCTURAL BIOLOGY: A moving story of receptors

    OpenAIRE

    Schwartz, Thue W; Hubbell, Wayne L.

    2008-01-01

    Animals sense light and chemical signals through proteins called G-protein-coupled receptors. The crystal structure of one such receptor in complex with a G-protein fragment shows how these receptors are activated.

  10. Genetics Home Reference: leptin receptor deficiency

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions leptin receptor deficiency leptin receptor deficiency Enable Javascript to view the expand/ ... boxes. Print All Open All Close All Description Leptin receptor deficiency is a condition that causes severe ...

  11. Coronavirus spike-receptor interactions

    NARCIS (Netherlands)

    Mou, H.

    2015-01-01

    Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

  12. *601007 LEPTIN RECEPTOR; LEPR [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 601007 FIELD TI 601007 LEPTIN RECEPTOR; LEPR ;;OBR FIELD TX DESCRIPTION Leptin (LEP; 16 ... ession of the OBR gene in hypothalamic tissue from lean ... and obese humans. The tissue was obtained shortly ... ference in the amount of leptin-receptor mRNA in 7 lean ... and 8 obese subjects as determined by RT-PCR. A se ...

  13. 5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists.

    Science.gov (United States)

    Harmon, Jennifer L; Wills, Lauren P; McOmish, Caitlin E; Demireva, Elena Y; Gingrich, Jay A; Beeson, Craig C; Schnellmann, Rick G

    2016-04-01

    In acute organ injuries, mitochondria are often dysfunctional, and recent research has revealed that recovery of mitochondrial and renal functions is accelerated by induction of mitochondrial biogenesis (MB). We previously reported that the nonselective 5-HT2 receptor agonist DOI [1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine] induced MB in renal proximal tubular cells (RPTCs). The goal of this study was to determine the role of 5-HT2 receptors in the regulation of mitochondrial genes and oxidative metabolism in the kidney. The 5-HT2C receptor agonist CP-809,101 [2-[(3-chlorophenyl)methoxy]-6-(1-piperazinyl)pyrazine] and antagonist SB-242,084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] were used to examine the induction of renal mitochondrial genes and oxidative metabolism in RPTCs and in mouse kidneys in the presence and absence of the 5-HT2C receptor. Unexpectedly, both CP-809,101 and SB-242,084 increased RPTC respiration and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA expression in RPTCs at 1-10 nM. In addition, CP-809,101 and SB-242,084 increased mRNA expression of PGC-1α and the mitochondrial proteins NADH dehydrogenase subunit 1 and NADH dehydrogenase (ubiquinone) β subcomplex 8 in mice. These compounds increased mitochondrial genes in RPTCs in which the 5-HT2C receptor was downregulated with small interfering RNA and in the renal cortex of mice lacking the 5-HT2C receptor. By contrast, the ability of these compounds to increase PGC-1α mRNA and respiration was blocked in RPTCs treated with 5-HT2A receptor small interfering RNA or the 5-HT2A receptor antagonist eplivanserin. In addition, the 5-HT2A receptor agonist NBOH-2C-CN [4-[2-[[(2-hydroxyphenyl)methyl]amino]ethyl]-2,5-dimethoxybenzonitrile] increased RPTC respiration at 1-100 nM. These results suggest that agonism of the 5-HT2A receptor induces MB and that the classic 5-HT2C receptor agonist CP

  14. Social support portlet

    OpenAIRE

    Aleksieva-Petrova, Adelina; Petrov, Milen

    2009-01-01

    Aleksieva-Petrova, A., & Petrov, M. (2009). Social support portlet. A first implementation of the social support tool as Liferay portlet. Available under the three clause BSD licence, Copyright TENCompetence Foundation.

  15. Supporting breastfeeding poster

    OpenAIRE

    Public Health Agency

    2013-01-01

    This poster shows how grandparents can make a real difference by supporting a daughter or son's partner in their decision to breastfeed and directs them to the leaflet A grandparent's guide to supporting breastfeeding

  16. Dopamine Receptors and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS. In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist.

  17. SUPPORT GROUPS IN ICEHEARTS

    OpenAIRE

    Cacho, Corey

    2016-01-01

    ABSTRACT Cacho, Corey Support groups in Icehearts. 33 p., 0 appendices. Language: English. Spring 2016. Diaconia University of Applied Sciences. Degree Programme in Social Services, Bachelor of Social Services. The purpose of my thesis is to provide a social support group model for the employees of Icehearts. The social support group model covers the mental health and wellbeing of the employees. The aim of the support group model is to give the employees a creative way of ...

  18. Computer Supported Collaborative Research

    OpenAIRE

    Hinze-Hoare, Vita

    2009-01-01

    Although the areas of Human Computer Interaction (HCI), Computer Supported Collaborative Work (CSCW), and Computer Supported Collaborative Learning (CSCL) are now relatively well established, the related field of Computer Supported Collaborative Research (CSCR) is newly proposed here. An analysis of the principles and issues behind CSCR is performed leading to a full definition and specification of the CSCR domain is provided with a view to setting up an e-laboratory designed to support...

  19. Nutrition support in hospitals

    DEFF Research Database (Denmark)

    Kondrup, Jens

    2005-01-01

    Nutrition support in hospitals is becoming an area of focus because of the evidence showing improved clinical outcome with nutrition support, its status as a human rights issue and its integration into quality assurance.......Nutrition support in hospitals is becoming an area of focus because of the evidence showing improved clinical outcome with nutrition support, its status as a human rights issue and its integration into quality assurance....

  20. On rationally supported surfaces

    DEFF Research Database (Denmark)

    Gravesen, Jens; Juttler, B.; Sir, Z.

    2008-01-01

    We analyze the class of surfaces which are equipped with rational support functions. Any rational support function can be decomposed into a symmetric (even) and an antisymmetric (odd) part. We analyze certain geometric properties of surfaces with odd and even rational support functions. In partic...

  1. Culture and Social Support

    Science.gov (United States)

    Kim, Heejung S.; Sherman, David K.; Taylor, Shelley E.

    2008-01-01

    Social support is one of the most effective means by which people can cope with stressful events. Yet little research has examined whether there are cultural differences in how people utilize their social support networks. A review of studies on culture and social support presents evidence that Asians and Asian Americans are more reluctant to…

  2. The galaxy cluster mid-infrared luminosity function at 1.3 < z < 3.2

    Energy Technology Data Exchange (ETDEWEB)

    Wylezalek, Dominika; Vernet, Joël; De Breuck, Carlos [European Southern Observatory, Karl-Schwarzschildstr.2, D-85748 Garching bei München (Germany); Stern, Daniel [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Brodwin, Mark [Department of Physics and Astronomy, University of Missouri, 5110 Rockhill Road, Kansas City, MO 64110 (United States); Galametz, Audrey [INAF-Osservatorio di Roma, Via Frascati 33, I-00040, Monteporzio (Italy); Gonzalez, Anthony H. [Department of Astronomy, University of Florida, Gainesville, FL 32611 (United States); Jarvis, Matt [Astrophysics, Department of Physics, Keble Road, Oxford OX1 3RH (United Kingdom); Hatch, Nina [School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom); Seymour, Nick [CASS, P.O. Box 76, Epping, NSW, 1710 (Australia); Stanford, Spencer A. [Physics Department, University of California, Davis, CA 95616 (United States)

    2014-05-01

    We present 4.5 μm luminosity functions for galaxies identified in 178 candidate galaxy clusters at 1.3 < z < 3.2. The clusters were identified as Spitzer/Infrared Array Camera (IRAC) color-selected overdensities in the Clusters Around Radio-Loud AGN project, which imaged 420 powerful radio-loud active galactic nuclei (RLAGNs) at z > 1.3. The luminosity functions are derived for different redshift and richness bins, and the IRAC imaging reaches depths of m* + 2, allowing us to measure the faint end slopes of the luminosity functions. We find that α = –1 describes the luminosity function very well in all redshift bins and does not evolve significantly. This provides evidence that the rate at which the low mass galaxy population grows through star formation gets quenched and is replenished by in-falling field galaxies does not have a major net effect on the shape of the luminosity function. Our measurements for m* are consistent with passive evolution models and high formation redshifts (z{sub f} ∼ 3). We find a slight trend toward fainter m* for the richest clusters, implying that the most massive clusters in our sample could contain older stellar populations, yet another example of cosmic downsizing. Modeling shows that a contribution of a star-forming population of up to 40% cannot be ruled out. This value, found from our targeted survey, is significantly lower than the values found for slightly lower redshift, z ∼ 1, clusters found in wide-field surveys. The results are consistent with cosmic downsizing, as the clusters studied here were all found in the vicinity of RLAGNs—which have proven to be preferentially located in massive dark matter halos in the richest environments at high redshift—and they may therefore be older and more evolved systems than the general protocluster population.

  3. The galaxy cluster mid-infrared luminosity function at 1.3 < z < 3.2

    International Nuclear Information System (INIS)

    We present 4.5 μm luminosity functions for galaxies identified in 178 candidate galaxy clusters at 1.3 < z < 3.2. The clusters were identified as Spitzer/Infrared Array Camera (IRAC) color-selected overdensities in the Clusters Around Radio-Loud AGN project, which imaged 420 powerful radio-loud active galactic nuclei (RLAGNs) at z > 1.3. The luminosity functions are derived for different redshift and richness bins, and the IRAC imaging reaches depths of m* + 2, allowing us to measure the faint end slopes of the luminosity functions. We find that α = –1 describes the luminosity function very well in all redshift bins and does not evolve significantly. This provides evidence that the rate at which the low mass galaxy population grows through star formation gets quenched and is replenished by in-falling field galaxies does not have a major net effect on the shape of the luminosity function. Our measurements for m* are consistent with passive evolution models and high formation redshifts (zf ∼ 3). We find a slight trend toward fainter m* for the richest clusters, implying that the most massive clusters in our sample could contain older stellar populations, yet another example of cosmic downsizing. Modeling shows that a contribution of a star-forming population of up to 40% cannot be ruled out. This value, found from our targeted survey, is significantly lower than the values found for slightly lower redshift, z ∼ 1, clusters found in wide-field surveys. The results are consistent with cosmic downsizing, as the clusters studied here were all found in the vicinity of RLAGNs—which have proven to be preferentially located in massive dark matter halos in the richest environments at high redshift—and they may therefore be older and more evolved systems than the general protocluster population.

  4. Diffusion tensor imaging of the spinal cord at 1.5 and 3.0 Tesla

    International Nuclear Information System (INIS)

    Purpose: The feasibility of highly resolved diffusion tensor imaging (DTI) of the human cervical spinal cord was tested on a clinical MR unit operating at 3.0 Tesla. DTI parametrical maps and signal-to-noise ratios (SNRs) were compared to results recorded at 1.5 Tesla. Materials and Methods: Eight healthy volunteers and one patient participated in the study. A transverse oriented single-shot ECG-triggered echo-planar imaging (EPI) sequence with double spin-echo diffusion preparation was applied for highly resolved DTI of the spinal cord. The signal yield, fractional anisotropy (FA), and mean diffusivity (MD) were compared for both field strengths. The clinical applicability of the protocol was also tested in one patient with amyotrophic lateral sclerosis (ALS) at 3.0 T. Results: A mean increase in SNR of 95.7 ± 4.6% was found at 3.0 Tesla compared to 1.5 Tesla. Improved quality of the DTI parametrical maps was observed at higher field strength (p < 0.02). Comparable FA and MD (reported in units of 10 - 3 mm2/s) values were computed in the dorsal white matter at both field strengths (1.5 T: FA = 0.75 ± 0.08, MD = 0.84 ± 0.12, 3.0 T: FA 0.74 ± 0.04, MD = 0.93 ± 0.14). The DTI images exhibited diagnostic image quality in the patient. At the site of the diseased corticospinal tract, a decrease of 46.0 ± 3.8% in FA (0.40 ± 0.03) and an increase of 50.3 ± 5.6% in MD (1.40 ± 0.05) were found in the ALS patient. (orig.)

  5. Diffusion tensor imaging of the spinal cord at 1.5 and 3.0 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, C. [Radiologische Universitaetsklinik, Tuebingen (Germany). Sektion fuer Experimentelle Radiologie; CNR-INFM CRS-Soft, La Sapienza-Univ. Roma (Italy); Enrico Fern Center, Roma (Italy); Boss, A.; Martirosian, P.; Steidle, G.; Schick, F. [Radiologische Universitaetsklinik, Tuebingen (Germany). Sektion fuer Experimentelle Radiologie; Lindig, T.M. [Enrico Fern Center, Roma (Italy); Radiologische Universitaetsklinik, Tuebingen (Germany). Sektion fuer Experimentelle Kernspinresonanz des ZNS; Universitaetsklinikum Tuebingen (Germany). Zentrum fuer Neurologie und Hertie-Inst. fuer klinische Hirnforschung; Maetzler, W. [Universitaetsklinikum Tuebingen (Germany). Zentrum fuer Neurologie und Hertie-Inst. fuer klinische Hirnforschung; Claussen, C.D. [Radiologische Universitaetsklinik, Tuebingen (Germany). Abt. fuer Radiologische Diagnostik; Klose, U. [Radiologische Universitaetsklinik, Tuebingen (Germany). Sektion fuer Experimentelle Kernspinresonanz des ZNS

    2007-03-15

    Purpose: The feasibility of highly resolved diffusion tensor imaging (DTI) of the human cervical spinal cord was tested on a clinical MR unit operating at 3.0 Tesla. DTI parametrical maps and signal-to-noise ratios (SNRs) were compared to results recorded at 1.5 Tesla. Materials and Methods: Eight healthy volunteers and one patient participated in the study. A transverse oriented single-shot ECG-triggered echo-planar imaging (EPI) sequence with double spin-echo diffusion preparation was applied for highly resolved DTI of the spinal cord. The signal yield, fractional anisotropy (FA), and mean diffusivity (MD) were compared for both field strengths. The clinical applicability of the protocol was also tested in one patient with amyotrophic lateral sclerosis (ALS) at 3.0 T. Results: A mean increase in SNR of 95.7 {+-} 4.6% was found at 3.0 Tesla compared to 1.5 Tesla. Improved quality of the DTI parametrical maps was observed at higher field strength (p < 0.02). Comparable FA and MD (reported in units of 10 - 3 mm2/s) values were computed in the dorsal white matter at both field strengths (1.5 T: FA = 0.75 {+-} 0.08, MD = 0.84 {+-} 0.12, 3.0 T: FA = 0.74 {+-} 0.04, MD = 0.93 {+-} 0.14). The DTI images exhibited diagnostic image quality in the patient. At the site of the diseased corticospinal tract, a decrease of 46.0 {+-} 3.8% in FA (0.40 {+-} 0.03) and an increase of 50.3 {+-} 5.6% in MD (1.40 {+-} 0.05) were found in the ALS patient. (orig.)

  6. Remote sensing of soil moisture content over bare fields at 1.4 GHz frequency

    Science.gov (United States)

    Wang, J. R.; Choudhury, B. J.

    1980-01-01

    A simple method of estimating moisture content (W) of a bare soil from the observed brightness temperature (T sub B) at 1.4 GHz is discussed. The method is based on a radiative transfer model calculation, which has been successfully used in the past to account for many observational results, with some modifications to take into account the effect of surface roughness. Besides the measured T sub B's, the three additional inputs required by the method are the effective soil thermodynamic temperature, the precise relation between W and the smooth field brightness temperature T sub B and a parameter specifying the surface roughness characteristics. The soil effective temperature can be readily measured and the procedures of estimating surface roughness parameter and obtaining the relation between W and smooth field brightness temperature are discussed in detail. Dual polarized radiometric measurements at an off-nadir incident angle are sufficient to estimate both surface roughness parameter and W, provided that the relation between W and smooth field brightness temperature at the same angle is known. The method of W estimate is demonstrated with two sets of experimental data, one from a controlled field experiment by a mobile tower and the other, from aircraft overflight. The results from both data sets are encouraging when the estimated W's are compared with the acquired ground truth of W's in the top 2 cm layer. An offset between the estimated and the measured W's exists in the results of the analyses, but that can be accounted for by the presently poor knowledge of the relationship between W and smooth field brightness temperature for various types of soils. An approach to quantify this relationship for different soils and thus improve the method of W estimate is suggested.

  7. Imaging appearance of surgical sponges at 1.5 T MRI: An in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Lisa M., E-mail: lisa.ho@duke.edu [Department of Radiology, Box 3808, Duke University Medical Center, 2301 Erwin Road, Durham, NC 27710 (United States); Merkle, Elmar M. [Department of Radiology, Box 3808, Duke University Medical Center, 2301 Erwin Road, Durham, NC 27710 (United States); Kuo, Paul C. [Department of Surgery, Box 3522, Duke University Medical Center, Durham, NC (United States); Paulson, Erik K. [Department of Radiology, Box 3808, Duke University Medical Center, 2301 Erwin Road, Durham, NC 27710 (United States)

    2011-11-15

    Objective: To predict the MR appearance of retained surgical textiles in the acute setting by using an in vitro phantom and body MR imaging protocols. Methods: Three surgical sponges were embedded in clear gelatin. One of these sponges was soaked in fresh human blood and the other two sponges were embedded dry. The following sequences were acquired at 1.5 T: T1W 3D gradient echo with chemical shift saturation (VIBE, volumetric interpolated breath-hold examination), 3D gradient dual echo T1W (in and opposed phase), 2D T2W single shot fast spin echo (HASTE, half-fourier acquisition single shot turbo spin echo), and 3D T2W fast spin echo (SPACE, sampling perfection with application optimized contrast using different flip angle evolutions). Results: The radiopaque marker within the surgical sponge appears as a linear hypointense structure on T1W and T2W images. Slightly increased conspicuity of the radiopaque marker is seen on the in phase gradient dual echo images compared with the opposed phase gradient dual echo images, likely due to magnetic susceptibility effect. The surgical sponge material is invisible on the T1W images and appears hypointense on the T2W images. Owing to the T1W hyperintensity and T2W hypointensity of blood, the radiopaque marker within the blood soaked gauze is visible on the T1W images but obscured on the T2W images. Conclusions: We describe the in vitro MR appearance of retained surgical sponges in order to simulate their appearance in the acute setting prior to the mass-like foreign body reaction which may occur in the chronic phase.

  8. ESTIMATING THE STAR FORMATION RATE AT 1 kpc SCALES IN NEARBY GALAXIES

    International Nuclear Information System (INIS)

    Using combinations of Hα, ultraviolet (UV), and infrared (IR) emission, we estimate the star formation rate (SFR) surface density, ΣSFR, at 1 kpc resolution for 30 disk galaxies that are targets of the IRAM HERACLES CO survey. We present a new physically motivated IR spectral-energy-distribution-based approach to account for possible contributions to 24 μm emission not associated with recent star formation. Considering a variety of 'reference' SFRs from the literature, we revisit the calibration of the 24 μm term in hybrid (UV+IR or Hα+IR) tracers. We show that the overall calibration of this term remains uncertain at the factor of two level because of the lack of wide-field, robust reference SFR estimates. Within this uncertainty, published calibrations represent a reasonable starting point for 1 kpc-wide areas of star-forming disk galaxies, but we re-derive and refine the calibration of the IR term in these tracers to match our resolution and approach to 24 μm emission. We compare a large suite of ΣSFR estimates and find that above ΣSFR ∼ 10–3 M☉ yr–1 kpc–2 the systematic differences among tracers are less than a factor of two across two orders of magnitude dynamic range. We caution that methodology and data both become serious issues below this level. We note from simple model considerations that when focusing on a part of a galaxy dominated by a single stellar population, the intrinsic uncertainty in Hα- and FUV-based SFRs is ∼0.3 and ∼0.5 dex.

  9. MET Receptor Tyrosine Kinase

    Science.gov (United States)

    Faoro, Leonardo; Cervantes, Gustavo M.; El-Hashani, Essam; Salgia, Ravi

    2010-01-01

    MET receptor tyrosine kinase (RTK) and its ligand hepatocyte growth factor (HGF) have become important therapeutic target in oncology, especially lung cancer. MET RTK is involved in cancer cell growth/survival, motility/migration, invasion/metastasis, and in angiogenesis. MET can be overexpressed in lung cancer, sometimes mutated, and sometimes amplified. Not only can MET be overexpressed, there are subsets of lung cancer tumors that have HGF overexpression. The mutations of MET can occur in the semaphorin and/or juxtamembrane domain in a majority of times. Amplification of MET can occur de novo in primary/metastatic tumors, as well arise in the context of therapeutic inhibition. There are a number of clinical inhibitors that have been developed against MET/HGF. Small molecule inhibitors such as XL184 and PF02341066 have come to clinical fruition, as well as antibodies against MET (such as MetMAb). These inhibitors will be discussed. PMID:19861919

  10. Blokáda AT1 receptorov losartanom zvyšuje expresiu renínu v kore ale nie v dreni nadobličky u potkana

    Czech Academy of Sciences Publication Activity Database

    Zórad, Š.; Železná, Blanka; Tybitanclová, K.

    Praha : Galen, 2004 - (Houdek, L.), s. 1 ISBN 80-7262-288-9. [Konference České společnosti pro hypertenzi /21./, Konference pracovní skupiny Preventivní kardiologie ČKS /13./, Konference pracovní skupiny Srdeční selhání ČKS. Lázně Jeseník (CZ), 07.10.2004-09.10.2004] Grant ostatní: VEGA(SK) 2/7213/22 Keywords : AT1 receptor losartan renin Subject RIV: CE - Biochemistry

  11. Supported employment, supported education, and career development.

    Science.gov (United States)

    Mueser, Kim T; Cook, Judith A

    2012-12-01

    Two articles in the current issue of the Psychiatric Rehabilitation Journal bring into focus the important question of the importance of work, and in particular meaningful employment, in people with a serious mental illness. Gewurtz, Cott, Rush, and Kirsh (see record 2012-34112-003) present findings from a change in policy in Canada for the funding of vocational services for people with a serious mental illness from a fee-for-service model to an outcomes-based model, with reimbursement based on successful competitive job placement and retention, irrespective of job type and consumer preference. The results indicated increased rates of competitive work, mainly in entry-level jobs, but they also raised questions as to whether the narrow focus on job attainment may have been at the cost of less career development and ultimately less meaningful work for the consumers. Baksheev, Allott, Jackson, McGorry, and Killackey (see record 2012-34112-002) found that a combined supported employment and education program for people with a first episode of psychosis led to higher rates of employment and class completion than usual services. The analysis presented in this report showed that no individual consumer characteristics other than program assignment (supported employment and education vs. usual services) predicted vocational or educational outcomes. The findings underscore the potency of supported employment, and suggest that combining it with educational services may be fruitful for people who have recently experienced an episode of psychosis. These findings raise several questions that will be touched on in this editorial, including: Why are career development and supported education important? What have we learned about supported education? What are the current gaps in our knowledge about supported education? PMID:23276233

  12. High energy, picosecond regenerative thin disk amplifier at 1 kHz

    Czech Academy of Sciences Publication Activity Database

    Chyla, Michal; Smrž, Martin; Mocek, Tomáš

    Bellingham: SPIE, 2012 - (Clarkson, W.; Shori, R.). (Proceedings of SPIE. 8235). ISBN 978-0-8194-8878-7. ISSN 0277-786X. [Solid State Lasers XXI: Technology and Devices. San Francisco (US), 22.01.2012-25.01.2012] R&D Projects: GA MŠk ED1.1.00/02.0061; GA MŠk ED2.1.00/01.0027 Grant ostatní: ELI Beamlines(XE) CZ.1.05/1.1.00/02.0061; HILASE(XE) CZ.1.05/2.1.00/01.0027 Institutional support: RVO:68378271 Keywords : Yb: YAG * thin-disk * regenerative amplifier * high energy * picosecond pulses * CPA * amplification * lasers Subject RIV: BH - Optics, Masers, Lasers

  13. The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

    DEFF Research Database (Denmark)

    Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja;

    2015-01-01

    We have proposed that lactate is a “volume transmitter” in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes the ...

  14. Troglitazone stimulates β-arrestin-dependent cardiomyocyte contractility via the angiotensin II type 1A receptor

    International Nuclear Information System (INIS)

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists are commonly used to treat cardiovascular diseases, and are reported to have several effects on cardiovascular function that may be due to PPARγ-independent signaling events. Select angiotensin receptor blockers (ARBs) interact with and modulate PPARγ activity, thus we hypothesized that a PPARγ agonist may exert physiologic effects via the angiotensin II type 1A receptor (AT1AR). In AT1AR-overexpressing HEK 293 cells, both angiotensin II (Ang II) and the PPARγ agonist troglitazone (Trog) enhanced AT1AR internalization and recruitment of endogenous β-arrestin1/2 (βarr1/2) to the AT1AR. A fluorescence assay to measure diacylglycerol (DAG) accumulation showed that although Ang II induced AT1AR-Gq protein-mediated DAG accumulation, Trog had no impact on DAG generation. Trog-mediated recruitment of βarr1/2 was selective to AT1AR as the response was prevented by an ARB- and Trog-mediated βarr1/2 recruitment to β1-adrenergic receptor (β1AR) was not observed. In isolated mouse cardiomyocytes, Trog increased both % and rate of cell shortening to a similar extent as Ang II, effects which were blocked with an ARB. Additionally, these effects were found to be βarr2-dependent, as cardiomyocytes isolated from βarr2-KO mice showed blunted contractile responses to Trog. These findings show for the first time that the PPARγ agonist Trog acts at the AT1AR to simultaneously block Gq protein activation and induce the recruitment of βarr1/2, which leads to an increase in cardiomyocyte contractility.

  15. Supported microporous ceramic membranes

    Science.gov (United States)

    Webster, E.; Anderson, M.

    1993-12-14

    A method for the formation of microporous ceramic membranes onto a porous support includes placing a colloidal suspension of metal or metal oxide particles on one side of the porous support and exposing the other side of the porous support to a drying stream of gas or a reactive gas stream so that the particles are deposited on the drying side of the support as a gel. The gel so deposited can be sintered to form a supported ceramic membrane useful for ultrafiltration, reverse osmosis, or molecular sieving having mean pore sizes less than 100 Angstroms. 4 figures.

  16. Synthesis of new PET radiotracer 18F-Fluoro Ethyl Losartan for molecular imaging of AT1R in tumor model

    International Nuclear Information System (INIS)

    Losartan is an antagonist of type 1 angiotensin II receptor (AT1R) and a drug widely used for the treatment of hypertension. Several studies have shown that losartan derivatives radiolabelled beta and gamma detect and quantify the expression of AT1R in some organs such as the heart and kidneys through the use of molecular imaging techniques. Furthermore, an expression of the AT1 receptor has been described in various types of tumors and correlates with an increased proliferation index and angiogenesis. Several groups have confirmed the antitumor effect of losartan potential, for example, in reducing tumor growth of a subtype of breast cancer. In this paper the synthesis of new radiotracer 18F-fluoroethyl Losartan, and its standard compound is described. The standard compound was synthesized via fluoroethyl losartan reaction between losartan and fluoroethyl tosylate potassium in dimethylformamide at 80 ° C for 2 hours under argon. The base used in the reaction was sodium hydride. a complex mixture of products including the desired product fluoroethyl losartan with 14% yield was obtained. This compound was analyzed by HPLC and characterized by widely different spectroscopic techniques: 1H NMR, 13C NMR, 19F NMR, HSQC, HMBC and mass spectroscopy. 18F synthesis losartan-fluoroethyl by indirect labeling of losartan potassium with 18F-fluoroethyl prosthetic group tosylate to 80°C for 20 min under nitrogen is achieved manually, using hydrate of sodium as base. The compound was purified by preparative HPLC semi-(Acetonitrile (A) / agua0,1% TFA (B), 60-80% A for 30 min, 4 mL / min, tR 8.9 min) and was obtained in 8 -21% (n = 5) and higher yield 99% radiochemical purity. The product identity was confirmed by comparison of residence times of the labeled product and the standard compound, HPLC analysis obtained under the same conditions: Acetonitrile (A) / agua0,1% TFA (B), 55:45 A / B , 1 mL / min, tR 9.6 min. The 18F-labeled prosthetic group fluoroethyl tosylate was

  17. The Role of Metabotropic Glutamate Receptor Genes in Schizophrenia.

    Science.gov (United States)

    Maj, Carlo; Minelli, Alessandra; Giacopuzzi, Edoardo; Sacchetti, Emilio; Gennarelli, Massimo

    2016-01-01

    Genomic studies revealed two main components in the genetic architecture of schizophrenia, one constituted by common variants determining a distributed polygenic effect and one represented by a large number of heterogeneous rare and highly disruptive mutations. These gene modifications often affect neural transmission and different studies proved an involvement of metabotropic glutamate receptors in schizophrenia phenotype. Through the combination of literature information with genomic data from public repositories, we analyzed the current knowledge on the involvement of genetic variations of the human metabotropic glutamate receptors in schizophrenia and related endophenotypes. Despite the analysis did not reveal a definitive connection, different suggestive associations have been identified and in particular a relevant role has emerged for GRM3 in affecting specific schizophrenia endophenotypes. This supports the hypothesis that these receptors are directly involved in schizophrenia disorder. PMID:27296644

  18. Electrocatalyst-support interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kinoshita, K.

    1978-01-01

    The maximum utilization of noble metals as heterogeneous catalysts is achieved by dispersing the noble metals as small particles supported on a porous, high surface area powder. In some studies with supported noble metal catalysts, it has been reported that the metal particle interacts with the support material and that the interaction affects the catalytic properties of the metal. Experimental studies on metal-support interactions that are pertinent to electrocatalysis will be discussed. Platinum supported on carbon black is one of the most active electrocatalysts for oxygen reduction in phosphoric acid fuel cells. In the acid environment at 100 to 200/sup 0/C, the Pt surface area decreases with time due to the growth of the supported Pt particles. The effects of a liquid-phase environment on the particle growth mechanism of supported Pt catalysts is discussed. 60 references.

  19. Angiotensin II receptor mRNA expression and vasoconstriction in human coronary arteries

    DEFF Research Database (Denmark)

    Wackenfors, Angelica; Pantev, Emil; Emilson, Malin;

    2004-01-01

    -induced vasoconstriction diminished with increasing age in patients with heart failure (r(2)=0.31, P<0.05). Also, the AT(1) receptor mRNA expression levels decreased with increasing age in patients with heart failure (r(2)=0.74, P<0.05), while no such correlation could be shown in the control group (r(2)=0.04, P......=n.s.). The AT(2) receptor mRNA expression levels did not correlate with age in patients with heart failure or controls. In conclusion, the diminished angiotensin II vasoconstriction with age in heart failure patients is most likely due to a lower density of AT(1) receptors and may result from a longer period...

  20. Strangeness production in Ni+Ni collisions at 1.93 AGeV

    International Nuclear Information System (INIS)

    This work deals with the production of strange particles in Ni + Ni collisions at 1.93 A GeV detected with the Fopi (four pi) detector at the heavy ion synchrotron SIS (GSI - Germany). We have limited our investigation to the study of Λ and Ξ hyperons. The first chapter presents the models used to describe ultra-relativistic heavy ions collisions. In the second chapter we present the main experimental results concerning the production and transport of strange particles in an energy domain ranging from SIS to RHIC (relativistic heavy ion collider) energies. The third chapter is dedicated to the specificities of the Fopi detector. The fourth chapter deals with the production of Λ particles in Ni + Ni collisions. An analysis method based on neuron network has been used in parallel with a more classical method. The production rate and temperature of Λ have been deduced from both methods. The neuron network method gives a statistical gain and allows a better identification of particles with low transverse impulses. The fifth chapter is dedicated to the detection of the doubly strange Ξ- particle. A detailed study about the stability of the signal is presented. In the last chapter all our experimental results are confronted with theoretical predictions. The UrQMD model that uses a hard equation of state, can simulate satisfactorily the production rates of Λ and K+ as well as their dependency on collision centrality despite the fact that this model does not use a potential linked to the medium density. The comparison between experimental results and predictions given by the IQMD model (that is based on a soft equation of state) is better when the version of the model that does not take into account the effects of the media is used. We see that the choices for the nuclear matter compressibility, for the particles involved in Kaon and Λ creation process, or for the interaction potential with dense medium, appear to be degrees of freedom that are difficult to adjust

  1. Discoidin domain receptors in disease.

    Science.gov (United States)

    Borza, Corina M; Pozzi, Ambra

    2014-02-01

    Discoidin domain receptors, DDR1 and DDR2, lie at the intersection of two large receptor families, namely the extracellular matrix and tyrosine kinase receptors. As such, DDRs are uniquely positioned to function as sensors for extracellular matrix and to regulate a wide range of cell functions from migration and proliferation to cytokine secretion and extracellular matrix homeostasis/remodeling. While activation of DDRs by extracellular matrix collagens is required for normal development and tissue homeostasis, aberrant activation of these receptors following injury or in disease is detrimental. The availability of mice lacking DDRs has enabled us to identify key roles played by these receptors in disease initiation and progression. DDR1 promotes inflammation in atherosclerosis, lung fibrosis and kidney injury, while DDR2 contributes to osteoarthritis. Furthermore, both DDRs have been implicated in cancer progression. Yet the mechanisms whereby DDRs contribute to disease progression are poorly understood. In this review we highlight the mechanisms whereby DDRs regulate two important processes, namely inflammation and tissue fibrosis. In addition, we discuss the challenges of targeting DDRs in disease. Selective targeting of these receptors requires understanding of how they interact with and are activated by extracellular matrix, and whether their cellular function is dependent on or independent of receptor kinase activity. PMID:24361528

  2. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [123I]TISCH for D1 dopamine receptors; [123I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [123I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  3. Purinergic receptors in psychiatric disorders.

    Science.gov (United States)

    Krügel, Ute

    2016-05-01

    Psychiatric disorders describe different mental or behavioral patterns, causing suffering or poor coping of ordinary life with manifold presentations. Multifactorial processes can contribute to their development and progression. Purinergic neurotransmission and neuromodulation in the brain have attracted increasing therapeutic interest in the field of psychiatry. Purine nucleotides and nucleosides are well recognized as signaling molecules mediating cell to cell communication. The actions of ATP are mediated by ionotropic P2X and metabotropic P2Y receptor subfamilies, whilst the actions of adenosine are mediated by P1 (A1 or A2) adenosine receptors. Purinergic mechanisms and specific receptor subtypes have been shown to be linked to the regulation of many aspects of behavior and mood and to dysregulation in pathological processes of brain function. In this review the recent knowledge on the role of purinergic receptors in the two most frequent psychiatric diseases, major depression and schizophrenia, as well as on related animal models is summarized. At present the most promising data for therapeutic strategies derive from investigations of the adenosine system emphasizing a unique function of A2A receptors at neurons and astrocytes in these disorders. Among the P2 receptor family, in particular P2X7 and P2Y1 receptors were related to disturbances in major depression and schizophrenia, respectively. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:26518371

  4. Immunisation with Torpedo acetylcholine receptor.

    Science.gov (United States)

    Elfman, L

    1984-01-01

    Acetylcholine mediates the transfer of information between neurons in the electric organ of, for example, Torpedo as well as in vertebrate skeletal muscle. The nicotinic acetylcholine receptor complex translates the binding of acetylcholine into ion permeability changes. This leads to an action potential in the muscle fibre. The nicotinic acetylcholine receptor protein has been purified from Torpedo by use of affinity chromatography. The receptor is an intrinsic membrane glycoprotein composed of five polypeptide chains. When various animals are immunised with the receptor they demonstrate clinical signs of severe muscle weakness coincident with high antibody titres in their sera. The symptoms resemble those found in the autoimmune neuromuscular disease myasthenia gravis in humans. This animal model has constituted a unique model for studying autoimmune diseases. This paper reviews some of the work using Torpedo acetylcholine receptor in order to increase the understanding of the motor nervous system function and myasthenia gravis. It is now known that the nicotinic acetylcholine receptor protein is the antigen involved in myasthenia gravis. The mechanism of immune damage involves a direct block of the receptor function. This depends on the presence of antibodies which crosslink the postsynaptic receptors leading to their degradation. The questions to be answered in the future are; (a) what initiates or triggers the autoimmune response, (b) how do the antibodies cause the symptoms--is there a steric hindrance of the interaction of acetylcholine and the receptor, (c) why is there not a strict relationship between antibody titre and severity of symptoms, and (d) why are some muscles affected and other spared? With help of the experimental model, answers to these questions may result in improved strategies for the treatment of the autoimmune disease myasthenia gravis. PMID:6097937

  5. Hemoglobin and heme scavenger receptors

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Møller, Holger Jon; Moestrup, Søren Kragh

    2010-01-01

    Heme, the functional group of hemoglobin, myoglobin, and other hemoproteins, is a highly toxic substance when it appears in the extracellular milieu. To circumvent potential harmful effects of heme from hemoproteins released during physiological or pathological cell damage (such as hemolysis and......-binding haptoglobin and the receptor CD163, and b) the heme-binding hemopexin and the receptor low density lipoprotein receptor-related protein/CD91. Apart from the disclosure of the molecular basis for these important heme scavenging systems by identifying the functional link between the carrier proteins and the...

  6. Evidence for Newly Initiated Reconnection in the Solar Wind at 1 AU

    Science.gov (United States)

    Xu, Xiaojun; Wong, Hon-Cheng; Ma, Yonghui; Wang, Yi; Zhou, Meng; Zuo, Pingbing; Wei, Fengsi; Feng, Xueshang; Deng, Xiaohua

    2015-08-01

    We report the first evidence for a large-scale reconnection exhaust newly initiated in the solar wind using observations from three spacecraft: ACE, Wind, and ARTEMIS P2. We identified a well-structured X-line exhaust using measurements from ARTEMIS P2 in the downstream solar wind. However, in the upstream solar wind, ACE detected the same current sheet that corresponds to the exhaust identified by ARTEMIS P2 data without showing any reconnection signals. We cannot find any reconnection signals from Wind located between ACE and ARTEMIS P2. Within the exhaust, a magnetic island is identified, which is not consistent with the quasi-steady feature as previously reported and provides further evidence that the reconnection is newly initiated. Our observations show that the entering of energetic particles, probably from Earth's bow shock, makes the crucial difference between the non-reconnecting current sheet and the exhaust. Since no obvious driving factors are responsible for the reconnection initiation, we infer that these energetic particles probably play an important role in the reconnection initiation. Theoretical analysis also shows support for this potential mechanism.

  7. Nursing supports neonatal porcine testicular development.

    Science.gov (United States)

    Rahman, K M; Lovich, J E; Lam, C; Camp, M E; Wiley, A A; Bartol, F F; Bagnell, C A

    2014-07-01

    The lactocrine hypothesis suggests a mechanism whereby milk-borne bioactive factors delivered to nursing offspring affect development of neonatal tissues. The objective of this study was to assess whether nursing affects testicular development in neonatal boars as reflected by: (1) Sertoli cell number and proliferation measured by GATA-4 expression and proliferating cell nuclear antigen immunostaining patterns; (2) Leydig cell development and steroidogenic activity as reflected by insulin-like factor 3 (INSL3), and P450 side chain cleavage (scc) enzyme expression; and (3) expression of estrogen receptor-alpha (ESR1), vascular endothelial growth factor (VEGF) A, and relaxin family peptide receptor (RXFP) 1. At birth, boars were randomly assigned (n = 6-7/group) to nurse ad libitum or to be pan fed porcine milk replacer for 48 h. Testes were collected from boars at birth, before nursing and from nursed and replacer-fed boars at 50 h on postnatal day (PND) 2. Sertoli cell proliferating cell nuclear antigen labeling index increased (P relaxin family peptide receptor 1 (RXFP1) levels increased (P < 0.01) with age and were greater in replacer-fed boars on PND 2. Results suggest that nursing supports neonatal porcine testicular development and provide additional evidence for the importance of lactocrine signaling in pigs. PMID:24906933

  8. Generation of a squeezed state at 1.55 μm with periodically poled LiNbO3

    Institute of Scientific and Technical Information of China (English)

    Liu Qin; Feng Jin-Xia; Li Hong; Jiao Yue-Chun; Zhang Kuan-Shou

    2012-01-01

    We report on the generation of a squeezing vacuum at 1.55 μm using an optical parametric amplifier based on periodically poled LiNbO3.Using three specifically designed narrow linewidth mode cleaners as the spatial mode and noise filter of the laser at 1.55 μm and 775 nm,the squeezed vacuum of up to 3.0 dB below the shot noise level at 1.55 μm is experimentally obtained.This system is compatible with standard telecommunication optical fibers,and will be useful for continuous variable long-distance quantum communication and distributed quantum computing.

  9. Genetic variants at 1q22 and 10q23 reproducibly associated with gastric cancer susceptibility in a Chinese population

    OpenAIRE

    Zhang, Hanze; Jin, Guangfu; Li, Huizhang; Ren, Chuanli; Ding, Yanbing; Zhang, Qin; Deng, Bin; Wang, Jianming; Hu, Zhibin; Xu, Yaochu; Shen, Hongbing

    2011-01-01

    Two recent genome-wide association studies reported significant associations of genetic variants at 1q22, 10q23 and 20p13 with gastric cancer (GC) risk in Chinese populations. However, these findings have not been confirmed in other independent studies. Here, we performed an independent case–control study in a Chinese population by genotyping three loci (rs4072037A>G at 1q22, rs2274223A>G at 10q23 and rs13042395C>T at 20p13) in 1681 GC cases and 1858 controls. We found that rs4072037 at 1q22 ...

  10. Bitter taste receptors for saccharin and acesulfame K.

    Science.gov (United States)

    Kuhn, Christina; Bufe, Bernd; Winnig, Marcel; Hofmann, Thomas; Frank, Oliver; Behrens, Maik; Lewtschenko, Tatjana; Slack, Jay P; Ward, Cynthia D; Meyerhof, Wolfgang

    2004-11-10

    Weight-conscious subjects and diabetics use the sulfonyl amide sweeteners saccharin and acesulfame K to reduce their calorie and sugar intake. However, the intrinsic bitter aftertaste, which is caused by unknown mechanisms, limits the use of these sweeteners. Here, we show by functional expression experiments in human embryonic kidney cells that saccharin and acesulfame K activate two members of the human TAS2R family (hTAS2R43 and hTAS2R44) at concentrations known to stimulate bitter taste. These receptors are expressed in tongue taste papillae. Moreover, the sweet inhibitor lactisole did not block the responses of cells transfected with TAS2R43 and TAS2R44, whereas it did block the response of cells expressing the sweet taste receptor heteromer hTAS1R2-hTAS1R3. The two receptors were also activated by nanomolar concentrations of aristolochic acid, a purely bitter-tasting compound. Thus, hTAS2R43 and hTAS2R44 function as cognate bitter taste receptors and do not contribute to the sweet taste of saccharin and acesulfame K. Consistent with the in vitro data, cross-adaptation studies in human subjects also support the existence of common receptors for both sulfonyl amide sweeteners. PMID:15537898

  11. Vascular hypothesis revisited: Role of stimulating antibodies against angiotensin and endothelin receptors in the pathogenesis of systemic sclerosis.

    Science.gov (United States)

    Cabral-Marques, Otavio; Riemekasten, Gabriela

    2016-07-01

    Systemic sclerosis (SSc) is a connective tissue disorder of unknown etiology characterized by the presence of multiple autoantibodies, including those against angiotensin and endothelin receptors. Patients with SSc can develop heterogeneous clinical manifestations including microvascular damage, the dysregulation of innate and adaptive immunity, and generalized fibrosis of multiple organs. Autoantibodies against angiotensin II type I receptor (AT1R) and endothelin-1 type A receptor (ETAR) play important roles in the pathogenesis of SSc. These autoantibodies regulate physiological processes ranging from production of collagen by skin fibroblasts to angiogenesis modulation. Understanding the mechanisms behind autoantibodies against AT1R and ETAR could provide insight to future novel therapies for SSc patients. In this review, we focus on elucidating the immunopathological mechanisms triggered by anti-AT1R and anti-ETAR autoantibodies to summarize current knowledge about vascular abnormalities resulting in progressive damage of organs seen in patients with SSc. PMID:26970493

  12. Support for heat exchangers

    International Nuclear Information System (INIS)

    The very large heat exchangers which are typical of many nuclear power plants place great demands on their supports. The support here described is for a vertical heat exchanger. A convex Lubrit plate allows a certain amount of transverse and rotational movement of the heat exhanger relative to the foundation. Taps engaging in the support surface of the heat exchanger and between the support box and the concrete foundation ensure that relative movement is restricted to those surfaces where it is intended. A steel box structure embedded in the concrete foundation dissipates heat transferred through the support system and avoids overheating the concrete. Horizontal stays support the heat exchanger against the concrete walls. (JIW)

  13. Editorial: Support (November 2007)

    OpenAIRE

    Dru Lavigne

    2007-01-01

    What is your first thought when you encounter the term "open source support"? A programmer typing the answer to a question using a chat utility? Hours spent scouring the Internet for a working configuration sample? Contacting a support engineer at a commercial call centre? If you find it difficult to think about a support engineer, you're not alone. Actuate's recently published 2007 Open Source Survey of senior personnel from financial services, Telco, and public sector organizations across N...

  14. Decision support basics

    CERN Document Server

    Power, Daniel J

    2009-01-01

    This book is targeted to busy managers and MBA students who need to grasp the basics of computerized decision support. Some of the topics covered include: What is a DSS? What do managers need to know about computerized decision support? And how can managers identify opportunities to create innovative DSS? Overall the book addresses 35 fundamental questions that are relevant to understanding computerized decision support.

  15. Conduction cooled tube supports

    Science.gov (United States)

    Worley, Arthur C.; Becht, IV, Charles

    1984-01-01

    In boilers, process tubes are suspended by means of support studs that are in thermal contact with and attached to the metal roof casing of the boiler and the upper bend portions of the process tubes. The support studs are sufficiently short that when the boiler is in use, the support studs are cooled by conduction of heat to the process tubes and the roof casing thereby maintaining the temperature of the stud so that it does not exceed 1400.degree. F.

  16. Stress and social support

    OpenAIRE

    Shadiya Baqutayan

    2011-01-01

    Background: This is an experimental study and it discusses the effectiveness of social support in managing academic stress among students. Aim: The purpose of this study is to understand the importance of social support in managing stress. Materials and Methods: Simple random sampling was assigned to a number of 120 students, equally divided into an experimental and a control group. Classes on social support as coping mechanisms were given to the experimental group only. The accumulated data ...

  17. New evidence for hominin carcass processing strategies at 1.5 Ma, Koobi Fora, Kenya.

    Science.gov (United States)

    Pobiner, Briana L; Rogers, Michael J; Monahan, Christopher M; Harris, John W K

    2008-07-01

    Reconstruction of early Pleistocene hominin carcass acquisition and processing behaviors are necessarily based at least in part on butchered fossil bones. This paper provides zooarchaeological and taphonomic analyses and behavioral interpretations of three approximately 1.5 million-year-old archaeofaunas from areas 1A and 103 in the Okote Member of the Koobi Fora Formation, northern Kenya: FwJj14A, FwJj14B, and GaJi14. These sites are all located in similar paleoenvironmental contexts, near shallow water with swampy, seasonally flooded areas, and some evidence for more wooded or gallery forest settings. Both individual specimen--and assemblage-level analyses of butchery-marked bones indicate that the hominins appear to have practiced similar butchery strategies at all of these sites, with butchery (defleshing, disarticulation, and marrow extraction) of both high- and low-ranked skeletal elements with no apparent preference for prey size, skeletal region, limb class, or limb portion. Only four tooth-marked specimens, including one likely crocodile-tooth-marked bone, are preserved in all three archaeofaunas. A paucity of limb epiphyses suggests that bone-crunching hyenids may have deleted these portions subsequent to hominin butchery. Strangely, there are no stone tools preserved with the 292 cut-marked and 27 percussion-marked faunal specimens (out of a total of 6,039 specimens), suggesting that raw material availability may have conditioned hominin lithic discard patterns at these locales. These assemblages increase our knowledge of the dietary behavior and ecology of Homo erectus, and provide support for variability in early Pleistocene hominin carcass foraging patterns. PMID:18514259

  18. Psychological distress among adolescents in Chengdu, Sichuan at 1 month after the 2008 Sichuan earthquake.

    Science.gov (United States)

    Lau, Joseph T F; Yu, Xiaonan; Zhang, Jianxin; Mak, Winnie W S; Choi, Kai Chow; Lui, Wacy W S; Zhang, Jianxin; Chan, Emily Y Y

    2010-05-01

    A devastating earthquake occurred on May 12, 2008 in Sichuan, China. This study investigated the prevalence and factors in association with psychological problems among secondary school students living in Chengdu (90 km away from the disaster epicenter) in June 2008. In a cross-sectional survey, 3,324 secondary students self-administered a structured questionnaire in classroom setting. Validated scales were used in this study. Among all respondents, 22.3% reported post-traumatic stress disorder (PTSD); 22.6% were probable depression cases; 10.6% reported suicidal ideation; and 14.1% would like to receive psychological counseling. No gender differences were found. While social/emotional support from teachers or peers (OR from 0.40 to 0.78) and exposure to positive news reports (OR from 0.59 to 0.62) were found protective, prior experience of severe mental distress (OR from 1.60 to 2.68) and corporal punishment (OR from 1.31 to 1.58), worry about future aftershocks (OR from 1.64 to 3.11), absence from school when it was not closed (OR from 1.38 to 1.48), exposures to scary or sorrowful disaster media coverage (OR from 1.39 to 2.07), post-disaster visits to affected sites (OR from 1.51 to 1.59), separation from parents (OR = 1.61), etc., were risk factors predictive of some of the aforementioned psychological problems. Negative mental health impacts were prevalent among the respondents. Teachers, parents, and the mass media are all important in maintaining good mental health among adolescents that are indirectly affected by the severe earthquake. The results have important implications for earthquake preparedness and relief work in the future. PMID:20405226

  19. MSUD Family Support Group

    Science.gov (United States)

    ... Distributing information and raising public awareness of MSUD. Strengthening the liaison between families and professionals. Supporting newborn screening programs and research for MSUD. Visit our MSUD contacts ...

  20. Radioiodinated endothelin-1: a radiotracer for imaging endothelin receptor distribution and occupancy

    International Nuclear Information System (INIS)

    Endothelin (ET) is one of the most potent vasoconstrictors known. Recently, ET has been implicated in various diseases, e.g., acute renal failure and congestive heart failure, which present the possibility of treating such diseases with endothelin receptor antagonists. However, establishing the dosages for these antagonists may be difficult because no convenient physiologic indicator of action exists, and because of complexities in receptor function. Two receptor subtypes have been identified for which selective antagonists have been reported (e.g., BQ-123 for the ETA receptor and BQ-788 for the ETB receptor). Of the three natural peptide hormones (ET-1, ET-2, and ET-3), ET-1 exhibits high affinity for both subtypes of receptor. Using the selective peptide antagonists, and a nonpeptide antagonist with relatively balanced affinity for the two subtypes (L-749,329), we have characterized the interactions of [125I]ET-1 with its receptors in vivo (in rat). BQ-123, BQ-788, and L-749,329 inhibited binding consistent with binding to a single receptor site. However, the sum of inhibition by the selective antagonist was greater than 100% (as defined by inhibition with L-749,329), which suggests (a) lower in vivo selectivity than determined in vitro and/or (b) receptor subtype interactions. The latter explanation is supported, in part, by in vitro autoradiographic studies as well as studies in isolated tissues and cells. We synthesized ET-1 labeled with I-123 and obtained images of receptor distribution in both rat and rhesus monkey and have demonstrated our ability to visualize, via planar, noninvasive imaging, the occupancy of endothelin receptor by antagonists in both kidney and lung. [123I]ET-1 can therefore be used to determine clinical dosages of antagonist needed for receptor saturation

  1. Profiling Epidermal Growth Factor Receptor and Heregulin Receptor 3 Heteromerization Using Receptor Tyrosine Kinase Heteromer Investigation Technology

    OpenAIRE

    Mohammed Akli Ayoub; Heng B See; Seeber, Ruth M.; Armstrong, Stephen P.; Pfleger, Kevin D.G.

    2013-01-01

    Heteromerization can play an important role in regulating the activation and/or signal transduction of most forms of receptors, including receptor tyrosine kinases (RTKs). The study of receptor heteromerization has evolved extensively with the emergence of resonance energy transfer based approaches such as bioluminescence resonance energy transfer (BRET). Here, we report an adaptation of our Receptor-Heteromer Investigation Technology (Receptor-HIT) that has recently been published as the G p...

  2. Renal effects of angiotensin II in the newborn period: role of type 1 and type 2 receptors

    OpenAIRE

    Vinturache, Angela E.; Francine G. Smith

    2016-01-01

    Background Evidence suggests a critical role for the renin-angiotensin system in regulating renal function during postnatal development. However, the physiological relevance of a highly elevated renin-angiotensin system early in life is not well understood, nor which angiotensin receptors might be involved. This study was designed to investigate the roles of angiotensin receptors type 1 (AT1R) and type 2 (AT2R) in regulating glomerular and tubular function during postnatal development. Method...

  3. Design, synthesis, and pharmacological characterization of novel, potent NMDA receptor antagonists

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Grazioso, Giovanni;

    2004-01-01

    The two diastereomeric pairs of acidic amino acids 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid (8A/8B) and 4-(2-amino-2-carboxyethyl)-5,5-dimethyl-4,5-dihydroisoxazole-3-carboxylic acid (10A/10B) were prepared via a strategy based on a 1,3-dipolar cycloaddition. The four amino...... acids were tested at ionotropic and metabotropic glutamate receptors. None of the compounds was active, neither as agonists nor as antagonists, at 1 mM on metabotropic receptors (mGluR1, -2, -4, and -5 expressed in CHO cell lines). Conversely, the pair of stereoisomers 8A/8B showed a remarkable affinity...... in in vivo tests on DBA/2 mice. Derivative 10A was inactive at all ionotropic glutamate receptors, whereas its stereoisomer 10B displayed a seizable binding to both NMDA and AMPA receptors....

  4. Are olfactory receptors really olfactive?

    DEFF Research Database (Denmark)

    Giorgi, Franco; Maggio, Roberto; Bruni, Luis Emilio

    2011-01-01

    consequence of the environmental conditions olfactory receptor genes have explored during evolution. The association of odorant patterns with specific environmental or contextual situations makes their relationship semiotically triadic, due to the emergence of an interpretant capable of perceiving odorants as...

  5. A threading receptor for polysaccharides.

    Science.gov (United States)

    Mooibroek, Tiddo J; Casas-Solvas, Juan M; Harniman, Robert L; Renney, Charles M; Carter, Tom S; Crump, Matthew P; Davis, Anthony P

    2016-01-01

    Cellulose, chitin and related polysaccharides are key renewable sources of organic molecules and materials. However, poor solubility tends to hamper their exploitation. Synthetic receptors could aid dissolution provided they are capable of cooperative action, for example by multiple threading on a single polysaccharide molecule. Here we report a synthetic receptor designed to form threaded complexes (polypseudorotaxanes) with these natural polymers. The receptor binds fragments of the polysaccharides in aqueous solution with high affinities (K(a) up to 19,000 M(-1)), and is shown--by nuclear Overhauser effect spectroscopy--to adopt the threading geometry. Evidence from induced circular dichroism and atomic force microscopy implies that the receptor also forms polypseudorotaxanes with cellulose and its polycationic analogue chitosan. The results hold promise for polysaccharide solubilization under mild conditions, as well as for new approaches to the design of biologically active molecules. PMID:26673266

  6. A threading receptor for polysaccharides

    Science.gov (United States)

    Mooibroek, Tiddo J.; Casas-Solvas, Juan M.; Harniman, Robert L.; Renney, Charles M.; Carter, Tom S.; Crump, Matthew P.; Davis, Anthony P.

    2016-01-01

    Cellulose, chitin and related polysaccharides are key renewable sources of organic molecules and materials. However, poor solubility tends to hamper their exploitation. Synthetic receptors could aid dissolution provided they are capable of cooperative action, for example by multiple threading on a single polysaccharide molecule. Here we report a synthetic receptor designed to form threaded complexes (polypseudorotaxanes) with these natural polymers. The receptor binds fragments of the polysaccharides in aqueous solution with high affinities (Ka up to 19,000 M-1), and is shown—by nuclear Overhauser effect spectroscopy—to adopt the threading geometry. Evidence from induced circular dichroism and atomic force microscopy implies that the receptor also forms polypseudorotaxanes with cellulose and its polycationic analogue chitosan. The results hold promise for polysaccharide solubilization under mild conditions, as well as for new approaches to the design of biologically active molecules.

  7. Nuclear Receptor Signaling Atlas (NURSA)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Nuclear Receptor Signaling Atlas (NURSA) is designed to foster the development of a comprehensive understanding of the structure, function, and role in disease...

  8. Receptor antibodies as novel therapeutics for diabetes

    DEFF Research Database (Denmark)

    Ussar, Siegfried; Vienberg, Sara Gry; Kahn, C Ronald

    2011-01-01

    Antibodies to receptors can block or mimic hormone action. Taking advantage of receptor isoforms, co-receptors, and other receptor modulating proteins, antibodies and other designer ligands can enhance tissue specificity and provide new approaches to the therapy of diabetes and other diseases....

  9. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    International Nuclear Information System (INIS)

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy

  10. Branching ratios and correlations in antiproton-proton annihilations at 1.6GeV/c

    International Nuclear Information System (INIS)

    The preliminary results on branching ratios and correlations, obtained from the antiproton-proton annihilation experiment in Gargamelle at 1.6GeV/c, are compared with the predictions of two statistical models and of a thermodynamical model

  11. Glycine receptors and brain development

    OpenAIRE

    Avila, Ariel; Nguyen, Laurent; Rigo, Jean-Michel

    2013-01-01

    Glycine receptors (GlyRs) are ligand-gated chloride ion channels that mediate fast inhibitory neurotransmission in the spinal cord and the brainstem. There, they are mainly involved in motor control and pain perception in the adult. However, these receptors are also expressed in upper regions of the central nervous system, where they participate in different processes including synaptic neurotransmission. Moreover, GlyRs are present since early stages of brain development and might influence ...

  12. Dopamine D4 Receptors in Psychostimulant Addiction

    OpenAIRE

    Di Ciano, Patricia; Grandy, David; Le Foll, Bernard

    2014-01-01

    Since the cloning of the D4 receptor in the 1990s, interest has been building in the role of this receptor in drug addiction, given the importance of dopamine in addiction. Like the D3 receptor, the D4 receptor has limited distribution within the brain suggesting it may have a unique role in drug abuse. However, compared to the D3 receptor, few studies have evaluated the importance of the D4 receptor. This may be due, in part, to the relative lack of compounds selective for the D4 receptor; t...

  13. Nuclear Receptors, RXR, and the Big Bang.

    Science.gov (United States)

    Evans, Ronald M; Mangelsdorf, David J

    2014-03-27

    Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the "Big Bang" of molecular endocrinology. This Review provides a personal perspective on nuclear receptors and explores their integrated and coordinated signaling networks that are essential for multicellular life, highlighting the RXR heterodimer and its associated ligands and transcriptional mechanism. PMID:24679540

  14. Thermostabilisation of the neurotensin receptor NTS1

    OpenAIRE

    Shibata, Yoko; White, Jim F.; Serrano-Vega, Maria J.; Magnani, Francesca; Aloia, Amanda L.; Grisshammer, Reinhard; Tate, Christopher G.

    2009-01-01

    Structural studies on G protein-coupled receptors (GPCRs) have been hampered for many years by their instability in detergent solution and by the number of potential conformations that receptors can adopt. Recently, the structures of the β1 and β2 adrenergic receptors and the adenosine A2a receptor were determined with antagonist bound, a receptor conformation that is thought to be more stable than the agonist-bound state. In contrast to these receptors, the neurotensin receptor NTS1 is much ...

  15. 16,20,21,23O-12C reaction cross sections at 1 GeV/nucleon

    International Nuclear Information System (INIS)

    In the present work, we analyze the reaction cross sections of 16,20,21,23O-12C at 1 GeV/nucleon within the framework of conventional Glauber theory. We analyze the reaction cross section of 16,20,21,23O from 12C at 1 GeV/nucleon using the uncorrelated part of the Glauber amplitude. The inputs needed in the theory are the elementary NN amplitude, and the density distributions for the colliding nuclei

  16. Evaluating Ecological Risk to Invertebrate Receptors from PAHs in Sediments at Hazardous Waste Sites (External Review Draft)

    Science.gov (United States)

    In March 2004, ORD's Ecological Risk Assessment Support Center (ERASC) received a request from the Ecological Risk Assessment Forum (ERAF) relating to the evaluation of ecological risk to vertebrate and benthic invertebrate receptors from polycyclic aromatic hydrocarbon compounds...

  17. Direct angiotensin II type 2 receptor stimulation decreases dopamine synthesis in the rat striatum.

    Science.gov (United States)

    Mertens, Birgit; Vanderheyden, Patrick; Michotte, Yvette; Sarre, Sophie

    2010-06-01

    A relationship between the central renin angiotensin system and the dopaminergic system has been described in the striatum. However, the role of the angiotensin II type 2 (AT(2)) receptor in this interaction has not yet been established. The present study examined the outcome of direct AT(2) receptor stimulation on dopamine (DA) release and synthesis by means of the recently developed nonpeptide AT(2) receptor agonist, compound 21 (C21). The effects of AT(2) receptor agonism on the release of DA and its major metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and on the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in the catecholamine biosynthesis, were investigated using in vivo microdialysis. Local administration of C21 (0.1 and 1 microM) resulted in a decrease of the extracellular DOPAC levels, whereas extracellular DA concentrations remained unaltered, suggesting a reduced synthesis of DA. This effect was mediated by the AT(2) receptor since it could be blocked by the AT(2) receptor antagonist PD123319 (1 microM). A similar effect was observed after local striatal (10 nM) as well as systemic (0.3 and 3 mg/kg i.p.) administration of the AT(1) receptor antagonist, candesartan. TH activity as assessed by accumulation of extracellular levels of L-DOPA after inhibition of amino acid decarboxylase with NSD1015, was also reduced after local administration of C21 (0.1 and 1 microM) and candesartan (10 nM). Together, these data suggest that AT(1) and AT(2) receptors in the striatum exert an opposite effect on the modulation of DA synthesis rather than DA release. PMID:20097214

  18. Arterial stiffness in insulin resistance: The role of nitric oxide and angiotensin II receptors

    Directory of Open Access Journals (Sweden)

    Divina G Brillante

    2008-12-01

    Full Text Available Divina G Brillante1, Anthony J O’Sullivan1, Laurence G Howes21St. George Clinical School, University of New South Wales, Kogarah, NSW, Australia; 2Department of Pharmacology and Therapeutics and Department of Cardiology, Griffith and Bond University, Gold Coast Hospital, Southport, QLD, AustraliaAbstract: The insulin resistance syndrome (INSR is associated with increased cardiovascular risk, and affects up to 25% of the Australian population aged >20 years. Increased arterial stiffness has been proposed as a common pathway by which INSR leads to increased cardiovascular risk. We have reviewed the role of nitric oxide (NO and angiotensin II receptors in the modulation of arterial stiffness in the setting of insulin resistance. There is emerging evidence that early stages of INSR may be characterized by increased basal nitric oxide activity and increased activity of non-NO vasodilators such as endothelial derived hyperpolarization factor (EDHF which is manifest by reduced arterial stiffness. Depletion of NO or ineffectiveness of NO mediated vasodilator mechanisms associated with the progression of INSR to type 2 diabetes may result in increased arterial stiffness, which predicts the development of cardiovascular disease. Thus in the early stages of INSR, increased NO and EDHF activity may represent compensatory mechanisms to early vascular damage. The renin-angiotensin system is activated in diseased vascular beds, with up regulation of the two known angiotensin II receptors: the angiotensin II type 1 receptor (AT1R and the angiotensin II type 2 receptor (AT2R. Increased AT1R mediated activity in the vasculature is central to the development of increased arterial stiffness and is enhanced in INSR states. AT2R activity is increased in early in INSR and may contribute to the apparent increase in basal NO activity. AT1R blockade may therefore be valuable treatment for early INSR as antagonism of AT1 receptors would allow angiotensin II to act

  19. Expression of GABAergic receptors in mouse taste receptor cells.

    Directory of Open Access Journals (Sweden)

    Margaret R Starostik

    Full Text Available BACKGROUND: Multiple excitatory neurotransmitters have been identified in the mammalian taste transduction, with few studies focused on inhibitory neurotransmitters. Since the synthetic enzyme glutamate decarboxylase (GAD for gamma-aminobutyric acid (GABA is expressed in a subset of mouse taste cells, we hypothesized that other components of the GABA signaling pathway are likely expressed in this system. GABA signaling is initiated by the activation of either ionotropic receptors (GABA(A and GABA(C or metabotropic receptors (GABA(B while it is terminated by the re-uptake of GABA through transporters (GATs. METHODOLOGY/PRINCIPAL FINDINGS: Using reverse transcriptase-PCR (RT-PCR analysis, we investigated the expression of different GABA signaling molecules in the mouse taste system. Taste receptor cells (TRCs in the circumvallate papillae express multiple subunits of the GABA(A and GABA(B receptors as well as multiple GATs. Immunocytochemical analyses examined the distribution of the GABA machinery in the circumvallate papillae. Both GABA(A-and GABA(B- immunoreactivity were detected in the peripheral taste receptor cells. We also used transgenic mice that express green fluorescent protein (GFP in either the Type II taste cells, which can respond to bitter, sweet or umami taste stimuli, or in the Type III GAD67 expressing taste cells. Thus, we were able to identify that GABAergic receptors are expressed in some Type II and Type III taste cells. Mouse GAT4 labeling was concentrated in the cells surrounding the taste buds with a few positively labeled TRCs at the margins of the taste buds. CONCLUSIONS/SIGNIFICANCE: The presence of GABAergic receptors localized on Type II and Type III taste cells suggests that GABA is likely modulating evoked taste responses in the mouse taste bud.

  20. Cable Supported Bridges

    DEFF Research Database (Denmark)

    Gimsing, Niels Jørgen

    Cable supported bridges in the form of suspension bridges and cable-stayed bridges are distinguished by their ability to overcome large spans.The book concentrates on the synthesis of cable supported bridges, covering both design and construction aspects. The analytical part covers simple methods...

  1. Indications for nutritional support.

    OpenAIRE

    Carpentier, Y A

    1986-01-01

    In this review different types of patients who usually require nutritional support are considered and recommendations made as to when nutritional support should be started, how long it should be continued, and which substrates should be preferentially used by which route.

  2. Supporting Inclusive Practice

    Science.gov (United States)

    Knowles, Gianna

    2006-01-01

    Written to support all teaching and learning staff in developing good inclusive practice, this book provides knowledge and understanding about a range of inclusion issues, such as what an inclusive school might look like and practical guidance on supporting the development of such a school. It also explores issues surrounding: (1) Ethnicity; (2)…

  3. Structure, function, and regulation of adrenergic receptors.

    OpenAIRE

    Strosberg, A.D.

    1993-01-01

    Adrenergic receptors for adrenaline and noradrenaline belong to the large multigenic family of receptors coupled to GTP-binding proteins. Three pharmacologic types have been identified: alpha 1-, alpha 2-, and beta-adrenergic receptors. Each of these has three subtypes, characterized by both structural and functional differences. The alpha 2 and beta receptors are coupled negatively and positively, respectively, to adenylyl cyclase via Gi or Gs regulatory proteins, and the alpha 1 receptors m...

  4. Toll-like receptors in neonatal sepsis.

    LENUS (Irish Health Repository)

    O'Hare, Fiona M

    2013-06-01

    Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

  5. Pharmacology of benzodiazepine receptors: an update.

    OpenAIRE

    Sieghart, W.

    1994-01-01

    Benzodiazepine receptors are allosteric modulatory sites on GABAA receptors. GABAA receptors are probably composed of five protein subunits, at least some of which belong to different subunit classes. So far six alpha-, four beta-, three gamma-, and delta- and two rho = p subunits of GABAA receptors have been identified. A large number of different subunit combinations, each of which will result in a GABAA receptor with distinct electrophysiological and pharmacological properties, are therefo...

  6. Contrasting effects of different cannabinoid receptor ligands on mouse ingestive behaviour.

    Science.gov (United States)

    Grey, Jonathan; Terry, Phil; Higgs, Suzanne

    2012-09-01

    This study characterized the effects of seven diverse cannabinoid receptor agonists (and one antagonist) on ingestive behaviour in nondeprived adult, male CD1 mice. Microstructural analysis of licking for a range of concentrations of condensed milk (10, 15 and 20%) was carried out following administration of vehicle or: Δ⁹-tetrahydrocannabinol (Δ⁹-THC) at 1, 3 or 6 mg/kg; CP55,940 at 10, 30 or 50 µg/kg; Win 55,212-2 at 0.5, 1 or 3 mg/kg; HU-210 at 0.01, 0.03 or 0.1 mg/kg; methanandamide at 1, 3 or 6 mg/kg; arachidonyl-2'-chloroethylamide at 1, 3 or 6 mg/kg and JWH133 at 1, 3 or 6 mg/kg. The cannabinoid receptor antagonist/inverse agonist rimonabant was also tested at 0.3, 1 or 3 mg/kg. Test sessions comprised three 30 s presentations of the milk concentrations separated by 10 s interpresentation intervals. The nonselective CB1 receptor agonists Δ⁹-THC, CP55,940 and Win 55,212-2 increased the number of licks for condensed milk, primarily by a significant increase in bout number. The potent and nonselective CB1 receptor agonist HU-210 and the selective CB1 receptor agonists methanandamide and arachidonyl-2'-chloroethylamide did not significantly affect licking behaviour but did significantly increase the latency to start licking. The CB1 receptor antagonist rimonabant produced effects that were opposite in direction to those produced by Δ⁹-THC, CP55,940 and Win 55,212-2. Finally, the selective CB2 receptor agonist JWH133 had no significant effects on behaviour. These data add to reports that cannabinoid agonists can enhance the appetitive aspects of feeding, but they also demonstrate that not all CB1 receptor agonists do this, and therefore the relationship between action at CB1 receptors and appetitive feeding effects is not straightforward. PMID:22772336

  7. Binding of polychlorinated biphenyls to the aryl hydrocarbon receptor.

    OpenAIRE

    Kafafi, S A; Afeefy, H Y; A. H. Ali; Said, H K; Kafafi, A G

    1993-01-01

    A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that ...

  8. Outline of therapeutic interventions with muscarinic receptor-mediated transmission

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; Šantrůčková, Eva; Randáková, Alena; Janíčková, Helena; Zimčík, Pavel; Rudajev, Vladimír; Michal, Pavel; El-Fakahany, E. E.; Doležal, Vladimír

    2014-01-01

    Roč. 63, Suppl.1 (2014), S177-S189. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/09/0681; GA ČR(CZ) GAP304/12/0259; GA MŠk(CZ) 7E10060 Institutional support: RVO:67985823 Keywords : cholinergic transmission * muscarinic receptors * therapy * Alzheimer 's disease, * schizophrenia Subject RIV: ED - Physiology Impact factor: 1.293, year: 2014

  9. Estrogen receptor beta (ERβ) in reproductive tract of male mice

    Czech Academy of Sciences Publication Activity Database

    Elzeinová, Fatima; Dostálová, Pavla; Děd, Lukáš; Dorosh, Andriy; Pěknicová, Jana

    Hoboken: American Journal of Reproductive Immunology, 2015 - (Mor, G.). s. 44 ISSN 1600-0897. [14th International Symposium for Immunology of Reproduction "progress in Reproductive Immunology". 22.05.2015-24.05.2015, Varna] R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA ČR GA14-05547S Institutional support: RVO:86652036 Keywords : estrogen receptor * testes * spermatozoa * monoclonal antibody Subject RIV: CE - Biochemistry

  10. Towards predictive docking at aminergic G-protein coupled receptors

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; El-Fakahany, E. E.; Doležal, Vladimír

    2015-01-01

    Roč. 21, č. 11 (2015), s. 284. ISSN 1610-2940 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA14-05696S; GA ČR(CZ) GA305/09/0681 Institutional support: RVO:67985823 Keywords : induced-fit docking * pose scoring * molecular dynamics * ligand-receptor interaction Subject RIV: FH - Neurology Impact factor: 1.736, year: 2014

  11. Angiotensin II Type 1 Receptor Signaling Regulates Feeding Behavior through Anorexigenic Corticotropin-releasing Hormone in Hypothalamus*

    OpenAIRE

    Yamamoto, Rie; Akazawa, Hiroshi; Fujihara, Hiroaki; Ozasa, Yukako; Yasuda, Noritaka; Ito, Kaoru; Kudo, Yoko; Qin, Yingjie; Ueta, Yoichi; Komuro, Issei

    2011-01-01

    The activation of renin-angiotensin system contributes to the development of metabolic syndrome and diabetes as well as hypertension. However, it remains undetermined how renin-angiotensin system is implicated in feeding behavior. Here, we show that angiotensin II type 1 (AT1) receptor signaling regulates the hypothalamic neurocircuit that is involved in the control of food intake. Compared with wild-type Agtr1a+/+ mice, AT1 receptor knock-out (Agtr1a−/−) mice were hyperphagic and obese with ...

  12. Deficiency of Angiotensin Type 1a Receptors in Adipocytes Reduces Differentiation and Promotes Hypertrophy of Adipocytes in Lean Mice

    OpenAIRE

    Putnam, Kelly; Batifoulier-Yiannikouris, Frederique; Bharadwaj, Kalyani G.; Lewis, Eboni; Karounos, Michael; Daugherty, Alan; Cassis, Lisa A.

    2012-01-01

    Adipocytes express angiotensin receptors, but the direct effects of angiotensin II (AngII) stimulating this cell type are undefined. Adipocytes express angiotensin type 1a receptor (AT1aR) and AT2R, both of which have been implicated in obesity. In this study, we determined the effects of adipocyte AT1aR deficiency on adipocyte differentiation and the development of obesity in mice fed low-fat (LF) or high-fat (HF) diets. Mice expressing Cre recombinase under the control of the aP2 promoter w...

  13. Polo-like kinase 2 gene expression is regulated by the orphan nuclear receptor estrogen receptor-related receptor gamma (ERRγ)

    International Nuclear Information System (INIS)

    Estrogen receptor-related receptor gamma (ERRγ) is a member of the nuclear receptor family of transcriptional activators. To date, the target genes and physiological functions of ERRγ are not well understood. In the current study, we identify that Plk2 is a novel target of ERRγ. Northern blot analysis showed that overexpression of ERRγ induced Plk2 expression in cancer cell lines. ERRγ activated the Plk2 gene promoter, and deletion and mutational analysis of the Plk2 promoter revealed that the ERRγ-response region is located between nucleotides (nt) -2327 and -2229 and -441 and -432 (relative to the transcriptional start site at +1). Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis demonstrated that ERRγ binds directly to the Plk2 promoter. Overexpression of ERRγ in the presence of the mitotic inhibitor nocodazole significantly decreased apoptosis, and induced S-phase cell cycle progression through the induction of Plk2 expression. Taken together, these results demonstrated that Plk2 is a novel target of ERRγ, and suggest that this interaction is crucial for cancer cell proliferation

  14. On homology modeling of the M-2 muscarinic acetylcholine receptor subtype

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; Randáková, Alena; Doležal, Vladimír

    2013-01-01

    Roč. 27, č. 6 (2013), s. 525-538. ISSN 0920-654X R&D Projects: GA ČR(CZ) GA305/09/0681; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : muscarinic acetylcholine receptor * G-protein coupled receptor * homology energy estimation * MM-GBSA Subject RIV: ED - Physiology Impact factor: 2.782, year: 2013

  15. Activation of the Farnesoid X Receptor Provides Protection against Acetaminophen-Induced Hepatic Toxicity

    OpenAIRE

    Lee, Florence Ying; de Aguiar Vallim, Thomas Quad; Chong, Hansook Kim; Zhang, Yanqiao; Liu, Yaping; Jones, Stacey A.; Osborne, Timothy F.; Edwards, Peter A.

    2010-01-01

    The nuclear receptor, farnesoid X receptor (FXR, NR1H4), is known to regulate cholesterol, bile acid, lipoprotein, and glucose metabolism. In the current study, we provide evidence to support a role for FXR in hepatoprotection from acetaminophen (APAP)-induced toxicity. Pharmacological activation of FXR induces the expression of several genes involved in phase II and phase III xenobiotic metabolism in wild-type, but not Fxr−/− mice. We used chromatin immunoprecipitation-based genome-wide resp...

  16. Systemic blockade of the Hyaluronan Receptor for Endocytosis (HARE) prevents lymph node metastasis of prostate cancer

    OpenAIRE

    Simpson, Melanie A.; Weigel, Janet A.; Weigel, Paul H.

    2012-01-01

    Tumor progression and metastasis are promoted by the remodeling of organized tissue architecture and engagement of molecular interactions that support tumor cell passage through endothelial barriers. Prostate tumor cells that secrete and turn over excessive quantities of pericellular hyaluronan (HA) exhibit accelerated growth kinetics and spontaneous lymph node metastasis in mice. The HA Receptor for Endocytosis (HARE) is an endocytic clearance receptor for HA in the liver that is also highly...

  17. The emerging role of CXC chemokines and their receptors in cancer.

    Science.gov (United States)

    Vinader, Victoria; Afarinkia, Kamyar

    2012-05-01

    Chemokines and their receptors have a multifaceted role in tumor biology and are implicated in nearly all aspects of cancer growth, survival and dissemination. Modulation of the interaction between chemokines and their cell surface receptor is, therefore, a promising area for the development of new cancer medicines. In this review, we look at the compelling evidence that is emerging to support targeting CXC chemokines, also known as family α chemokines, as novel therapeutic strategies in the treatment of cancer. PMID:22571611

  18. Genetic Contributions to Avoidance-Based Decisions: Striatal D2 receptor Polymorphisms

    OpenAIRE

    Frank, Michael J.; Hutchison, Kent

    2009-01-01

    Individuals differ in their tendencies to seek positive decision outcomes or to avoid negative ones. At the neurobiological level, our model suggests that phasic changes in dopamine support learning to reinforce good decisions via striatal D1 receptors, and to avoid maladaptive choices via striatal D2 receptors. Accordingly, in a previous study individual differences in positive and negative learning were strongly modulated by two genetic polymorphisms factors related to striatal D1 and D2 fu...

  19. Effect of ghrelin receptor agonist and antagonist on the activity of arcuate nucleus tyrosine hydroxylase containing neurons in C57BL/6 male mice exposed to normal or high fat diet

    Czech Academy of Sciences Publication Activity Database

    Pirník, Z.; Majerčíková, Z.; Holubová, Martina; Pirník, R.; Železná, Blanka; Maletínská, Lenka; Kiss, A.

    2014-01-01

    Roč. 65, č. 4 (2014), s. 477-486. ISSN 0867-5910 Institutional support: RVO:61388963 Keywords : growth hormone secretagogue receptor * ghrelin receptor agonist * ghrelin receptor antagonist * high fat diet * tyrosine hydroxylase * arcuate nucleus * food intake Subject RIV: CE - Biochemistry Impact factor: 2.386, year: 2014

  20. Cross-adaptation to odor stimulation of olfactory receptor cells in the box turtle, Terrapene carolina.

    Science.gov (United States)

    Tonosaki, K

    1993-01-01

    Electrical recording from small twigs of olfactory nerve and electro-olfactogram (EOG) from olfactory epithelium in a turtle shows that olfactory receptors in the nose are responsive to various odors. I have used the effects of cross-adaptation to odor stimulation on the olfactory receptors to investigate the stimulus-specific components of these responses and to provide information about the responsiveness of cells. The results of the cross-adaptation experiments strongly support the hypothesis that different categories of receptor cells exist in the olfactory epithelium. PMID:8386588

  1. MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction

    DEFF Research Database (Denmark)

    Kocerha, Jannet; Faghihi, Mohammad Ali; Lopez-Toledano, Miguel A;

    2009-01-01

    significantly modulated behavioral responses associated with disrupted NMDA receptor transmission. Furthermore, pretreatment with the antipsychotic drugs haloperidol and clozapine prevented dizocilpine-induced effects on miR-219. Taken together, these data support an integral role for miR-219 in the expression......N-methyl-D-aspartate (NMDA) glutamate receptors are regulators of fast neurotransmission and synaptic plasticity in the brain. Disruption of NMDA-mediated glutamate signaling has been linked to behavioral deficits displayed in psychiatric disorders such as schizophrenia. Recently, noncoding RNA...... of behavioral aberrations associated with NMDA receptor hypofunction....

  2. Studies on insulin receptor, 2

    International Nuclear Information System (INIS)

    The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

  3. HANARO user support

    International Nuclear Information System (INIS)

    The purpose of this project is to support external user for the promotion of HANARO common utilization effectively. To do this, external manpower was recruited and trained. Also, in order to find out and cultivate HANARO user, practice-oriented education was done. The total number of project selected as the promotion of HANARO common utilization was 31 in this year. These composed of four fields such as neutron beam utilization, materials/nuclear materials irradiation test, neutron activation analysis and radioisotope production. In each field, the numbers of project were 17, 7, 4 and 3 respectively. At first, from a selected project of view, supporting ratio by external manpower was reached to the 58%, that is, 18 out of 31 project was supported. In each field, it was 82% for neutron beam utilization and 100% for neutron activation analysis. Also, from the utilization time point of view, supporting ratio of external manpower was reached to 30% for neutron beam utilization and 59% for neutron activation analysis. Otherwise, supporting ratio by manpower in KAERI was reached to 97%, that is, 30 out of 31 project was supported. Also, from the utilization time point of view, total supporting ratio was reached to 15%. In each field, it was 20% for neutron beam utilization, 18% for materials/nuclear materials irradiation test, 20% for neutron activation analysis and 6% for radioisotope production. In order to contribute finding and cultivating of HANARO potential user and increase utilization ratio of HANARO experimental facility, practice-oriented HANARO user education has been done. At first, 32 participants from industries, universities, institutes were educated and practiced on HRPD/SANS instrument in the field of neutron beam utilization. Otherwise, in order to support external user effectively, external manpower were trained. Also, more effective support for external user could be possible through the grasping difficulty and problem on the performance of project

  4. Patient support systems

    International Nuclear Information System (INIS)

    A patient support system for use in computerized tomography (CT) is described. The system is particularly useful for CT scanning of the brain and also of the abdominal area. The support system consists of two moveable tables which may be translated into position for X-ray scanning of the patient's body and which may be translated incrementally and automatically to obtain scans at adjacent locations. For use with brain scans, the second table is replaced by a detachable restraint assembly which is described in detail. The support system is so designed that only a small volume of low density material will intercept the X-ray beam. (UK)

  5. Supported metals in catalysis

    CERN Document Server

    Anderson, James A

    2011-01-01

    With contributions from experts in supported metal catalysis from both the industry and academia, this book presents the latest developments in characterization and application of supported metals in heterogeneous catalysis. In addition to thorough and updated coverage of the traditional aspects of heterogeneous catalysis such as preparation, characterization and use in well-established technologies such as vehicle emission control, the book also includes emerging areas where supported metal catalysis will make significant contributions to future developments, such as fuel cells and fine chemi

  6. The integrated decision support system

    International Nuclear Information System (INIS)

    This paper has introduced development history, present situation, popular decision support technology of decision support system, and discussed the integrated decision support system form with technical foundation. (authors)

  7. A complex pattern of chemokine receptor expression is seen in osteosarcoma

    International Nuclear Information System (INIS)

    Osteosarcoma is the most frequent bone tumor in childhood and adolescence. Patients with primary metastatic disease have a poor prognosis. It is therefore important to better characterize the biology of this tumor to define new prognostic markers or therapeutic targets for tailored therapy. Chemokines and their receptors have been shown to be involved in the development and progression of malignant tumors. They are thought to be active participants in the biology of osteosarcoma. The function of specific chemokines and their receptors is strongly associated with the biological context and microenvironment of their expression. In this report we characterized the expression of a series of chemokine receptors in the complex environment that defines osteosarcoma. The overall level of chemokine receptor mRNA expression was determined using TaqMan RT-PCR of microdissected archival patient biopsy samples. Expression was then verified at the protein level by immunohistochemistry using a series of receptor specific antibody reagents to elucidate the cellular association of expression. Expression at the RNA level was found for most of the tested receptors. CCR1 expression was found on infiltrating mononuclear and polynuclear giant cells in the tumor. Cells associated with the lining of intratumoral vessels were shown to express CCR4. Infiltrating mononuclear cells and tumor cells both showed expression of the receptor CCR5, while CCR7 was predominantly expressed by the mononuclear infiltrate. CCR10 was only very rarely detected in few scattered infiltrating cells. Our data elucidate for the first time the cellular context of chemokine receptor expression in osteosarcoma. This is an important issue for better understanding potential chemokine/chemokine receptor function in the complex biologic processes that underlie the development and progression of osteosarcoma. Our data support the suggested involvement of chemokines and their receptors in diverse aspects of the biology

  8. The Effects of Histamine H3 Receptors on Contractile Responses on Rat Gastric Fundus

    Directory of Open Access Journals (Sweden)

    Aşkın Hekimoğlu

    2006-01-01

    Full Text Available The aim of this study is to determine the effects of histamine receptors on the gastrointestinal system smooth muscle contractions and the role of histamine H3 receptors on these effects. İsolated rat gastric fundus preparations were hanged on isolated organ bath and histamine receptor agonist and anthagonists were added to the bath solution and the electrical field stimulation-induced contractile responses were evaluated. In our study groups after blocking one of the histamine receptors H1, H2,H3; contractile responses were observed. Then, other two receptors were blocked one by one or combination of them to observe the changes on the contractile responses given to the electrical stimulation .To blocke histamine receptors pyrilamine (10-6м as H1 receptor blocker, famotidine (10-6м as H2 receptor blocker and thioperamide (10-5м as H3 receptor blocker and various combination of them were used. All groups were treated with H3 receptor anthagonist thioperamide (10-5м and agonist (R-α-methylhistamine (RMHA on 10-8, 10-7, 10-6 ve 10-5 molar concentrations cumulatively to observe its mediator effects on contractile responses. We suggested that (R-α-methylhistamine mediates the inhibition on the contractile effects of rat gastric fundus. This conclusion was supported by these findings: a the selective agonists (RMHA caused a dumping of the contractile effect of acetylcholine; b the effect of (RMHA was prevented by the selective H3 receptor antagonist thioperamide.

  9. Identification and mechanism of ABA receptor antagonism

    Energy Technology Data Exchange (ETDEWEB)

    Melcher, Karsten; Xu, Yong; Ng, Ley-Moy; Zhou, X. Edward; Soon, Fen-Fen; Chinnusamy, Viswanathan; Suino-Powell, Kelly M; Kovach, Amanda; Tham, Fook S.; Cutler, Sean R.; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Xu, H. Eric (NU Sinapore); (Van Andel); (UCR)

    2010-11-11

    The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands.

  10. Pelvic Support Problems

    Science.gov (United States)

    ... nonsurgical ways to obtain symptom relief? • What are Kegel exercises? • Can surgery correct pelvic support problems? • Glossary ... your overall health and possibly your prolapse symptoms. • Kegel exercises—These exercises strengthen the muscles that surround ...

  11. IT Supporting Strategy Formulation

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.

    2005-01-01

    This overview approaches information and communication technology (ICT) for competitive intelligence from the perspective of strategy formulation. It provides an ICT architecture for supporting the knowledge processes producing relevant knowledge for strategy formulation. To determine what this arch

  12. Editorial: Support (November 2007

    Directory of Open Access Journals (Sweden)

    Dru Lavigne

    2007-11-01

    Full Text Available What is your first thought when you encounter the term "open source support"? A programmer typing the answer to a question using a chat utility? Hours spent scouring the Internet for a working configuration sample? Contacting a support engineer at a commercial call centre? If you find it difficult to think about a support engineer, you're not alone. Actuate's recently published 2007 Open Source Survey of senior personnel from financial services, Telco, and public sector organizations across North America and Europe indicates that 46.3% of respondents cite the lack of availability of long term support as a major barrier to their company's adoption of open source technologies.

  13. Stop smoking support programs

    Science.gov (United States)

    Smokeless tobacco - stop smoking programs; Stop smoking techniques; Smoking cessation programs; Smoking cessation techniques ... It is hard to quit smoking if you are acting alone. Smokers may have a ... of quitting with a support program. Stop smoking programs ...

  14. Hemodynamic Support in Sepsis

    Directory of Open Access Journals (Sweden)

    Fatih Yildiz

    2014-04-01

    Full Text Available Sepsis is called systemic inflammatory response syndrome due to infection. When added to organs failure and perfusion abnormality is defined in severe sepsis, Hypotension that do not respond to fluid therapy is as defined septic shock. Fluid resuscitation is a most important parts of the treatment in patients with septic shock. Ongoing hypotension that despite of the adequate fluid therapy, vasopressor support initiation is required. Sepsis and septic shock, hemodynamic support is often understood as the hemodynamic support. The different approaches to the development of methods to track and objective comes up. Patients with severe sepsis and septic shock should be follow in the intensive care unit and rapid fluid replacement and effectual hemodynamic support should be provided.

  15. Dancing with the dead: Eph receptors and their kinase-null partners.

    Science.gov (United States)

    Truitt, Luke; Freywald, Andrew

    2011-04-01

    Eph receptor tyrosine kinases and their ligands, ephrins, are membrane proteins coordinating a wide range of biological functions both in developing embryos and in adult multicellular organisms. Numerous studies have implicated Eph receptors in the induction of opposing responses, including cell adhesion or repulsion, support or inhibition of cell proliferation and cell migration, and progression or suppression of multiple malignancies. Similar to other receptor tyrosine kinases, Eph receptors rely on their ability to catalyze tyrosine phosphorylation for signal transduction. Interestingly, however, Eph receptors also actively utilize three kinase-deficient receptor tyrosine kinases, EphB6, EphA10, and Ryk, in their signaling network. The accumulating evidence suggests that the unusual flexibility of the Eph family, allowing it to initiate antagonistic responses, might be partially explained by the influence of the kinase-dead participants and that the exact outcome of an Eph-mediated action is likely to be defined by the balance between the signaling of catalytically potent and catalytically null receptors. We discuss in this minireview the emerging functions of the kinase-dead EphB6, EphA10, and Ryk receptors both in normal biological responses and in malignancy, and analyze currently available information related to the molecular mechanisms of their action in the context of the Eph family. PMID:21455264

  16. Insulin action is blocked by a monoclonal antibody that inhibits insulin receptor kinase

    International Nuclear Information System (INIS)

    Thirty-six monoclonal antibodies to the human insulin receptor were produced. Thirty-four bound the intracellular domain of the receptor β subunit, the domain containing the tyrosine-specific kinase activity. Of these 34 antibodies, 33 recognized the rat receptor and 1 was shown to precipitate the receptors from mice, chickens and frogs with high affinity. Another of the antibodies inhibited the kinase activities of the human and frog receptors with equal potencies. This antibody inhibited the kinase activities of these receptors by more than 90%, whereas others had no effect on either kinase activity. Microinjection of the inhibiting antibody into Xenopus oocytes blocked the ability of insulin to stimulate oocyte maturation. In contrast, this inhibiting antibody did not block the ability of progesterone to stimulate the same response. Furthermore, control immunoglobulin and a noninhibiting antibody to the receptor β subunit did not block this response to insulin. These results strongly support a role for the tyrosine-specific kinase activity of the insulin receptor in mediating this biological effect of insulin

  17. Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

    Science.gov (United States)

    Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

    2016-01-01

    The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

  18. Distinct angiotensin II receptor in primary cultures of glial cells from rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raizada, M.K.; Phillips, M.I.; Crews, F.T.; Sumners, C.

    1987-07-01

    Angiotensin II (Ang-II) has profound effects on the brain. Receptors for Ang-II have been demonstrated on neurons, but no relationship between glial cells and Agn-II has been established. Glial cells (from the hypothalamus and brain stem of 1-day-old rat brains) in primary culture have been used to demonstrate the presence of specific Ang-II receptors. Binding of /sup 125/I-Ang-II to glial cultures was rapid, reversible, saturable, and specific for Ang-II. The rank order of potency of /sup 125/I-Ang-II binding was determined. Scatchard analysis revealed a homogeneous population of high-affinity binding sites with a B/sub max/ of 110 fmol/mg of protein. Light-microscopic autoradiography of /sup 125/I-Ang-II binding supported the kinetic data, documenting specific Ang-II receptors on the glial cells. Ang-II stimulated a dose-dependent hydrolysis of phosphatidylinositols in glial cells, an effect mediated by Ang-II receptors. However, Ang-II failed to influence (/sup 3/H) norepinephrine uptake, and catecholamines failed to regulate Ang-II receptors, effects that occur in neurons. These observations demonstrate the presence of specific Ang-II receptors on the glial cells in primary cultures derived from normotensive rat brain. The receptors are kinetically similar to, but functionally distinct from, the neuronal Ang-II receptors.

  19. Purinergic Receptors in Ocular Inflammation

    Directory of Open Access Journals (Sweden)

    Ana Guzman-Aranguez

    2014-01-01

    Full Text Available Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A, and P1,P5-diadenosine pentaphosphate (Ap5A are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl-5′-N-methylcarboxamidoadenosine (CF101 have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

  20. Morbillivirus receptors and tropism: multiple pathways for infection

    Directory of Open Access Journals (Sweden)

    ChiekoKai

    2012-03-01

    Full Text Available Morbilliviruses, which include measles virus (MeV, canine distemper virus, and rinderpest virus, are among the most important pathogens in their respective hosts and cause severe syndromes. Morbilliviruses are enveloped viruses with 2 envelope proteins, one of which is hemagglutinin (H protein, which plays a role in binding to cellular receptors. During morbillivirus infection, the virus initially targets lymphoid cells and replicates efficiently in the lymph nodes. The principal cellular receptor for morbillivirus is signaling lymphocyte activation molecule (SLAM, also called CD150, which is exclusively expressed on immune cells. This feature reflects the strong lymphoid cell tropism and viral spread in the infected body. Morbillivirus infection, however, affects various tissues in the body, including the lung, kidney, gastrointestinal tract, vascular endothelium, and brain. Thus, other receptors for morbilliviruses in addition to SLAM might exist. Recently, nectin-4 has been identified as a novel epithelial cell receptor for MeV. The expression of nectin-4 is localized to polarized epithelial cells, and this localization supports the notion of cell tropism since MeV also grows well in the epithelial cells of the respiratory tract. Although 2 major receptors for lymphoid and epithelial cells in natural infection have been identified, morbillivirus can still infect many other types of cells with low infectivity, suggesting the existence of inefficient but ubiquitously expressed receptors. We have identified other molecules that are implicated in morbillivirus infection of SLAM-negative cells by alternative mechanisms. These findings indicate that morbillivirus utilizes multiple pathways for establishment of infection. These studies will advance our understanding of morbillivirus tropism and pathogenesis.

  1. Allosteric activation mechanism of the cys-loop receptors

    Institute of Scientific and Technical Information of China (English)

    Yong-chang CHANG; Wen WU; Jian-liang ZHANG; Yao HUANG

    2009-01-01

    Binding of a neurotransmitter to its ionotropic receptor opens a distantly located ion channel, a process termed allosteric activation. Here we review recent advances in the molecular mechanism by which the cys-loop receptors are activated with emphasis on the best studied nicotinic acetylcholine receptors (nAChRs). With a combination of affinity labeling, mutagenesis, electrophysiology, kinetic modeling, electron microscopy (EM), and crystal structure analysis, the allosteric activation mechanism is emerging. Specifically, the binding domain and gating domain are interconnected by an allosteric activation network. Agonist binding induces conformational changes, resulting in the rotation of a β sheet of amino-terminal domain and outward movement of loop 2, loop F, and cys-loop, which are coupled to the M2-M3 linker to pull the channel to open. However, there are still some controversies about the movement of the channel-lining domain M2. Nine angstrom resolution EM structure of a nAChR imaged in the open state suggests that channel opening is the result of rotation of the M2 domain. In contrast, recent crystal structures of bacterial homologues of the cys-loop receptor family in apparently open state have implied an M2 tilting model with pore dilation and quaternary twist of the whole pentameric receptor. An elegant study of the nAChR using protonation scanning of M2 domain supports a similar pore dilation activation mechanism with minimal rotation of M2. This remains to be validated with other approaches including high resolution structure determination of the mammalian cys-loop receptors in the open state.

  2. ATLAS support rails

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    These supports will hold the 7000 tonne ATLAS detector in its cavern at the LHC. The huge toroid will be assembled from eight coils that will house some of the muon chambers. Supported within the toroid will be the inner detector, containing tracking devices, as well as devices to measure the energies of the particles produced in the 14 TeV proton-proton collisions at the LHC.

  3. Support vector machines applications

    CERN Document Server

    Guo, Guodong

    2014-01-01

    Support vector machines (SVM) have both a solid mathematical background and good performance in practical applications. This book focuses on the recent advances and applications of the SVM in different areas, such as image processing, medical practice, computer vision, pattern recognition, machine learning, applied statistics, business intelligence, and artificial intelligence. The aim of this book is to create a comprehensive source on support vector machine applications, especially some recent advances.

  4. Hemodynamic Support in Sepsis

    OpenAIRE

    Fatih Yildiz; Emre Karakoc

    2014-01-01

    Sepsis is called systemic inflammatory response syndrome due to infection. When added to organs failure and perfusion abnormality is defined in severe sepsis, Hypotension that do not respond to fluid therapy is as defined septic shock. Fluid resuscitation is a most important parts of the treatment in patients with septic shock. Ongoing hypotension that despite of the adequate fluid therapy, vasopressor support initiation is required. Sepsis and septic shock, hemodynamic support is often under...

  5. STATE SUPPORT IN FISHERY

    Directory of Open Access Journals (Sweden)

    Irena Jahutka

    2004-06-01

    Full Text Available By passing the law on state support in agriculture, fishery and forestry the former support system has been changed. Fishery support beneficiaries can use several kinds of support and help. Former financial stimulations for fishery regulated by law from 1995 to 1st January 2003 were settled by the production stimulation model. Besides that well received model, there are the capital investment model, the support in production insurance, the right to use blue diesel, and granting credit for production of freshwater and saltwater fry, adult fish and shells. These five models of support and help can be used by freshwater and saltwater fish and shell breeders, while for fishing the marine fish the production stimulation model is applied (fishing of small pelagic fish, as well as the capital investment model and right to use blue diesel. Marine and freshwater processors can use the production stimulation and the capital investment model. All these models have in common the fact that all physical and legal entities registered for fishing activities (having licence for commercial fishery, aquaculture (the licence for aquaculture or the one for fish and other marine organisam breeding and processing (having the regulated veterinarian and sanitary conditions, the registration document and having been registered in the List of approved facilities have the right to use them.

  6. Calcification of intervertebral discs in the dachshund: a radiographic study of 115 dogs at 1 and 5 years of age

    International Nuclear Information System (INIS)

    The vertebral columns of 115 dachshunds were x-rayed at 1 and 5 years of age. This sample represented 5.7% of all dachshunds registered with the Norwegian Kennel Club in the period 1986-1988. All dogs were clinically normal at the commencement of the study. At 1 year of age calcified intervertebral discs were identified in 34 (29.6%) of the dogs and the number of calcified discs in each individual varied from 1 to 7 with a mean of 2.7. At 5 years of age calcified discs were identified in 66 (57.4%) of the dogs and the number of calcified discs in each individual varied from 1 to 11 with a mean of 3.2. Of all dogs in which calcified discs were identified at 1 year of age, 33 (97.1%) were found to have calcified discs also at 5 years of age. Of 92 calcified discs identified in the dogs at 1 year of age, 29 (31.5%) were not calcified 4 years later. Of 211 calcified discs identified in the dogs at 5 years of age, 148 (70.1%) were not calcified 4 years before. From 1 to 5 years of age, signs of spinal disease were registered in 12 (35.3%) of the dogs in which calcified discs were identified at 1 year of age, and in 7 (8.6%) of the dogs in which calcified discs were not identified at 1 year of age. Of all dogs in which one or more calcified discs had disappeared during the study-period, signs of spinal disease were registered in 9 (75.0%)

  7. How calcium makes endocytic receptors attractive

    DEFF Research Database (Denmark)

    Andersen, Christian B F; Moestrup, Søren K

    2014-01-01

    receptor. Endosomal acidification and calcium efflux lead to the essential ligand-receptor affinity switch and separation. Recent data, including crystal structures of receptor-ligand complexes, now reveal how calcium, in different types of domain scaffolds, functions in a common way as a removable...... 'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect the...... receptor calcium sites....

  8. Host receptors for bacteriophage adsorption.

    Science.gov (United States)

    Bertozzi Silva, Juliano; Storms, Zachary; Sauvageau, Dominic

    2016-02-01

    The adsorption of bacteriophages (phages) onto host cells is, in all but a few rare cases, a sine qua non condition for the onset of the infection process. Understanding the mechanisms involved and the factors affecting it is, thus, crucial for the investigation of host-phage interactions. This review provides a survey of the phage host receptors involved in recognition and adsorption and their interactions during attachment. Comprehension of the whole infection process, starting with the adsorption step, can enable and accelerate our understanding of phage ecology and the development of phage-based technologies. To assist in this effort, we have established an open-access resource--the Phage Receptor Database (PhReD)--to serve as a repository for information on known and newly identified phage receptors. PMID:26755501

  9. Monoallelic expression of olfactory receptors.

    Science.gov (United States)

    Monahan, Kevin; Lomvardas, Stavros

    2015-01-01

    The sense of smell collects vital information about the environment by detecting a multitude of chemical odorants. Breadth and sensitivity are provided by a huge number of chemosensory receptor proteins, including more than 1,400 olfactory receptors (ORs). Organizing the sensory information generated by these receptors so that it can be processed and evaluated by the central nervous system is a major challenge. This challenge is overcome by monogenic and monoallelic expression of OR genes. The single OR expressed by each olfactory sensory neuron determines the neuron's odor sensitivity and the axonal connections it will make to downstream neurons in the olfactory bulb. The expression of a single OR per neuron is accomplished by coupling a slow chromatin-mediated activation process to a fast negative-feedback signal that prevents activation of additional ORs. Singular OR activation is likely orchestrated by a network of interchromosomal enhancer interactions and large-scale changes in nuclear architecture. PMID:26359778

  10. Defining the functional binding sites of interleukin 12 receptor β1 and interleukin 23 receptor to Janus kinases.

    Science.gov (United States)

    Floss, Doreen M; Klöcker, Tobias; Schröder, Jutta; Lamertz, Larissa; Mrotzek, Simone; Strobl, Birgit; Hermanns, Heike; Scheller, Jürgen

    2016-07-15

    The interleukin (IL)-12-type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor β1 (IL-12Rβ1) as one component of their receptor signaling complexes, with IL-12Rβ2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12Rβ1, whereas Jak2 binds to IL-23R and also to IL-12Rβ2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12Rβ1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12- and IL-23-induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12Rβ1 and Jak2 by IL‑23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable. PMID:27193299

  11. STUDIES ON THE HDL RECEPTORS I:EVIDENCE FOR THE EXISTENCE OF HDL RECEPTORS IN BEIJING DUCK LIVER

    Institute of Scientific and Technical Information of China (English)

    武须军; 王克勤

    1994-01-01

    It hab been found that Beijing ducks (BD)have a high level of HDL(70%),high LCAT but very low CETP activity and will not develop atheroscletosis on an atherogenic diet,suggesting that cholesterol ester is mainly carried by HDL and metabolized through an HDL receptor pathway in the liver.However,evidence of this recep-tor′s existence in the liver is not yet complete.In this paper,the HDL receptor in BD liver has been studied.Our experiments showed:1)ApoE-free 125I-HDL could bind specifically to duck hepatic cell membrane with high affinity (Kd=9.6 μg/ml)and was saturable(Bmax=8.9μg/mg cell membrane protein)at room temperature.2)Competitive inhibition studies with unlabelled duck,human,rat and chick HDL and duck apo AI and its lipo-somes formed with PC or DMPC could inhibit the binding of 125I-HDL to duck hepatic cell membranes,but LDL,apo Eand their liposomes with PC or DMPC could not with the exception of duck LDL.3)The receptor could rec-ognize apo AI but not apo B or E.4)Both phosphorase A2 and pronase could inhibit the binding activity.The above results give strong evidence for the existence of a specific HLD receptor pathway in the duck liver,support-ing our hypothesis that CE in Beijing ducks is metabolized directly through the hepatic HDL receptor instead of be-ing transfered back to VLDL and LDL,then through the LDL receptor pathway.This unique way of metabolizing CE may be behind the Beijing duck′s antiatherogenicity.

  12. Acute liver failure-induced death of rats is delayed or prevented by blocking NMDA receptors in brain.

    Science.gov (United States)

    Cauli, Omar; Rodrigo, Regina; Boix, Jordi; Piedrafita, Blanca; Agusti, Ana; Felipo, Vicente

    2008-09-01

    Developing procedures to delay the mechanisms of acute liver failure-induced death would increase patients' survival by allowing time for liver regeneration or to receive a liver for transplantation. Hyperammonemia is a main contributor to brain herniation and mortality in acute liver failure (ALF). Acute ammonia intoxication in rats leads to N-methyl-D-aspartate (NMDA) receptor activation in brain. Blocking these receptors prevents ammonia-induced death. Ammonia-induced activation of NMDA receptors could contribute to ALF-induced death. If this were the case, blocking NMDA receptors could prevent or delay ALF-induced death. The aim of this work was to assess 1) whether ALF leads to NMDA receptors activation in brain in vivo and 2) whether blocking NMDA receptors prevents or delays ALF-induced death of rats. It is shown, by in vivo brain microdialysis, that galactosamine-induced ALF leads to NMDA receptors activation in brain. Blocking NMDA receptors by continuous administration of MK-801 or memantine through miniosmotic pumps affords significant protection against ALF-induced death, increasing the survival time approximately twofold. Also, when liver injury is not 100% lethal (1.5 g/kg galactosamine), blocking NMDA receptors increases the survival rate from 23 to 62%. This supports that blocking NMDA receptors could have therapeutic utility to improve survival of patients with ALF. PMID:18599589

  13. Regulation of retinal endothelial cell apoptosis through activation of the IGFBP-3 receptor

    OpenAIRE

    Zhang, Qiuhua; Soderland, Carl; Steinle, Jena J.

    2013-01-01

    The goal of this study was to investigate whether insulin-like growth factor binding protein-3 receptor (IGFBP-3 receptor) is required for IGFBP-3 to inhibit retinal endothelial cell (REC) apoptosis. REC were grown in normal glucose (5 mM) or high glucose medium (25 mM) for 3 days. Once cells reached confluence, they were transfected with an endothelial- specific IGFBP-3 plasmid DNA (non-IGF binding; IGFBP-3 NB) at 1 μg/ml for 24 h. Cell proteins were extracted and analyzed for IGFBP-3 recept...

  14. Receptor Proteins in Selective Autophagy

    Directory of Open Access Journals (Sweden)

    Christian Behrends

    2012-01-01

    Full Text Available Autophagy has long been thought to be an essential but unselective bulk degradation pathway. However, increasing evidence suggests selective autophagosomal turnover of a broad range of substrates. Bifunctional autophagy receptors play a key role in selective autophagy by tethering cargo to the site of autophagosomal engulfment. While the identity of molecular components involved in selective autophagy has been revealed at least to some extent, we are only beginning to understand how selectivity is achieved in this process. Here, we summarize the mechanistic and structural basis of receptor-mediated selective autophagy.

  15. Effects of Combined Endothelin A Receptor and Renin-Angiotensin System Blockade on the Course of End-Organ Damage in 5/6 Nephrectomized Ren-2 Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

    Vaněčková, Ivana; Kujal, P.; Husková, Z.; Vaňourková, Z.; Vernerová, Z.; Čertíková; Chábová, V.; Škaroupková, P.; Kramer, H. J.; Tesař, V.; Červenka, L.

    2012-01-01

    Roč. 35, č. 5 (2012), s. 382-392. ISSN 1420-4096 Institutional research plan: CEZ:AV0Z50110509 Keywords : 5/6 nephrectomy * Endothelin receptor type A * AT1 receptor blocker * end-organ damage * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.596, year: 2012

  16. The discovery of a cannabinoid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Devane, W.A.

    1989-01-01

    A tritiated form of CP-55,940, a Pfizer cannabinoid analog that is 20- to 100-fold more potent than {Delta}{sup 9}-tetrahydrocannabinol in various in vivo and in vitro models of cannabimimetric activity, was used as the tool with which to probe for a cannabinoid receptor in rat cortical membranes. The bound and free ligand were successfully separated using a centrifugation assay. Specific binding was saturable, rapidly attained, and completely reversible. The K{sub D}'s derived from kinetic analysis of binding agreed well with the K{sub D}'s derived from saturation and displacement analysis. The ({sup 3}H)CP-55,940 binding site exhibited high affinity with a K{sub D} of 68 pM as determined by LIGAND analysis of homologous displacement studies. The ability of other cannabinoid drugs to displace ({sup 3}H)CP-55,940 binding correlated well with the potency of these drugs in in vivo and in vitro models of cannabimimetic activity. The K{sub i} of {Delta}{sup 9}-THC was 1.6 nM. Cannabidiol and cannabigerol, which both lack psychoactivity in man, displaced specific binding by less than 50% at 1 {mu}M.

  17. Transcriptional Corepressor SMILE Recruits SIRT1 to Inhibit Nuclear Receptor Estrogen Receptor-related Receptor γ Transactivation*

    OpenAIRE

    Xie, Yuan-Bin; Park, Jeong-Hoh; Kim, Don-Kyu; Hwang, Jung Hwan; Oh, Sangmi; Park, Seung Bum; Shong, Minho; Lee, In-Kyu; Choi, Hueng-Sik

    2009-01-01

    SMILE (small heterodimer partner interacting leucine zipper protein) has been identified as a corepressor of the glucocorticoid receptor, constitutive androstane receptor, and hepatocyte nuclear factor 4α. Here we show that SMILE also represses estrogen receptor-related receptor γ (ERRγ) transactivation. Knockdown of SMILE gene expression increases ERRγ activity. SMILE directly interacts with ERRγ in vitro and in vivo. Domain mapping analysis showed that SMILE binds to the AF2 domain of ERRγ....

  18. In vivo 1H spectroscopy of the human brain at 1.5 tesla. Preliminary experience at a clinical installation

    DEFF Research Database (Denmark)

    Henriksen, O; Larsson, H; Jensen, K M

    1990-01-01

    In vivo localized water suppressed proton spectroscopy of human brain was carried out on 15 healthy volunteers and 2 patients suffering from a brain tumour and an infarction, respectively. The measurements were performed on a whole body MR system, operating at 1.5 tesla using the stimulated echo...

  19. Health Care and Satellite Radio Communication in Village Alaska. Final Report of the ATS-1 Biomedical Satellite: Experiment Evaluation.

    Science.gov (United States)

    Kreimer, Osvaldo; And Others

    The executive summary is the first section of this final report of the evaluation of the ATS-1 medical communication system in Alaska. The second section introduces the background of these studies and the sociogeographic setting and health situation of the Alaska natives. The third section presents the main research findings about both the…

  20. Polarization maintaining highly nonlinear photonic crystal fiber for supercontinuum generation at 1.55 μm

    Science.gov (United States)

    Hossain, M. A.; Namihira, Y.; Islam, M. A.; Hirako, Y.

    2012-07-01

    A polarization maintaining highly nonlinear Germanium (Ge) doped photonic crystal fiber (HNL-GePCF) is proposed for supercontinuum (SC) generation at 1.55 μm as polarization maintaining properties in a fiber enhance nonlinear interactions to generate SC using less optical power. By designing 3% higher refractive index Ge-doped core with core ellipticity ɛ=0.9 inside silica, nonlinear coefficient γ and birefringence B are increased as large as 83 W-1 km-1 and 2.82×10-4 respectively at 1.55 μm. Using finite element method (FEM) with a circular perfectly matched boundary layer (PML), it is shown through simulations that the proposed HNL-GePCF offers an efficient SC generation at 1.55 μm. By propagating sech2 picosecond optical pulses having 2.5 ps and 1.0 ps pulsewidth at a full width at half maximum (FWHM) through the proposed HNL-GePCF, output optical pulses are analyzed by the split-step Fourier method to obtain the spectral contents. The highest 10 dB bandwidth spectra at 1.55 μm are observed as 100 nm and 150 nm for 2.5 ps input optical pulse and for 1.0 ps input optical pulse respectively.