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Messenger
Kinds of Messenger Terms modified by Messenger Selected AbstractsMeasuring the plasma environment at Mercury: The fast imaging plasma spectrometerMETEORITICS & PLANETARY SCIENCE, Issue 9 2002P. L. KOEHN Three primary populations of ions exist at Mercury: solar wind, magnetospheric, and pickup ions. These pickup ions are generated through the ionization of Mercury's exosphere or are sputtered particles from the Mercury surface. A comprehensive mission to Mercury, such as MESSENGER (MErcury: Surface, Space ENvironment, GEochemistry, Ranging), should include a sensor that is able to determine the dynamical properties and composition of all these plasma components. An instrument to measure the composition of these ion populations and their three-dimensional velocity distribution functions must be lightweight, fast, and have a very large field of view. The fast imaging plasma spectrometer (FIPS) is an imaging mass spectrometer, part of NASA's MESSENGER mission, the first Mercury orbiter. This versatile instrument has a very small footprint, and has a mass that is ,1 order of magnitude less than other comparable systems. It maintains a nearly full-hemisphere field of view, suitable for either spinning or three-axis-stabilized platforms. The major piece of innovation to enable this sensor is a new deflection system geometry that enables a large instantaneous (,1.5,) field of view. This novel electrostatic analyzer system is then combined with a position sensitive time-of-flight system. We discuss the design and prototype tests of the FIPS deflection system and show how this system is expected to address one key problem in Mercury science, that of the nature of the radar-bright regions at the Hermean poles. [source] Fair Value Accounting and the Financial Crisis: Messenger or Contributor?,ACCOUNTING PERSPECTIVES, Issue 3 2009Michel L. Magnan ABSTRACT This commentary discusses how fair value accounting (FVA) affects the nature of financial reporting, especially for financial institutions that were deeply affected by the 2007-9 financial crisis. Toward that end, I address four questions. First, I review FVA's role in financial reporting, emphasizing its development over time. While the commentary's focus is on the interface between financial instruments and FVA, its reach extends well beyond financial instruments. Thereafter, I discuss the measurement and valuation challenges that arise from the use of FVA in financial reporting. Then, I analyze the evidence, analytical and empirical, on the role that FVA may have played in the financial crisis of 2007-9. Since, to some extent, the crisis is still unfolding, there is limited yet very insightful empirical evidence on this issue. The evidence does suggest that FVA, in combination with its use by regulators, may have severely undermined the financial condition of some institutions. The effect was amplified for institutions holding assets in markets that saw their liquidity dry up during the crisis. In other words, FVA may have amplified the crisis. Finally, I discuss some implications that we can draw from the crisis about the merits and risks underlying FVA. For instance, I conclude that, in a search for relevance, the use of FVA in financial reporting may accelerate its disconnection from a firm's business reality. [source] Configurations of Relationships in Different Media: FtF, Email, Instant Messenger, Mobile Phone, and SMSJOURNAL OF COMPUTER-MEDIATED COMMUNICATION, Issue 4 2007Hyo Kim This study analyzes the configurations of communication relationships in Korea through face-to-face, email, instant messaging, mobile phone, and short message service media. Through a web survey, we asked respondents to identify (1) for each of the five media (2) up to five of their most frequent communication partners, (3) the partner's social role (including colleagues, family, friends), and (4) their own employment category. Individual-level and network-level analyses were used to compare variations in communication relationships and configurations of relationships among social roles overall, within each medium, and for different employment categories, and to identify configurations of relationships across media. IM, SMS, and mobile phone are distinctive media for students, mobile phone for homeworkers, and email for organizational workers. Moreover, mobile phones tend to be used in reinforcing strong social ties, and text-based CMC media tend to be used in expanding relationships with weak ties. Finally, face-to-face (FtF) seems to be a universal medium without significant differences across respondents' employment categories. [source] Messenger Between Two Worlds, 1998JOURNAL OF LATIN AMERICAN & CARIBBEAN ANTHROPOLOGY, Issue 1 2005Joselina Da Silva [source] The Nunawading Messiah: James Fisher and Popular Millenarianism in Nineteenth-Century MelbourneJOURNAL OF RELIGIOUS HISTORY, Issue 1 2002Guy Featherstone James Fisher (1832-1913), known as the "Nunawading Messiah," was the leader of a millenarian sect now virtually forgotten. This article describes the beliefs and practices of the sect, the Church of the Firstborn, which he led for nearly fifty years, first in Nunawading (Vic.) and later Wickepin (W.A.). From limited sources, the development of the sect is outlined, noting the eighteenth-century English background from which it drew inspiration and the Christian Israelite traditions which it followed to some degree. Fisher's attempt to succeed Wroe as an Angelic Messenger is detailed as is the public controversy of 1871 concerning Fisher's prophetic claims and alleged polygamy. An analysis of the reasons why Fisher was able to attract a following and retain it for so long is included. The final years of his life as the leader of a communal settlement in Western Australia is followed by a discus-sion of his place in the millenarian tradition in Australia and his sect is compared with millenarian behaviour generally. [source] Jurors'Evaluations of Expert Testimony: Judging the Messenger and the MessageLAW & SOCIAL INQUIRY, Issue 2 2003Sanja Kutnjak Ivkovi Jurors are laypersons with no specific expert knowledge, yet they are routinely placed in situations in which they need to critically evaluate complex expert testimony. This paper examines jurors'reactions to experts who testify in civil trials and the factors jurors identify as important to expert credibility. Based on in-depth qualitative analyses of interviews with 55 jurors in 7 civil trials, we develop a comprehensive model of the key factors jurors incorporate into the process of evaluating expert witnesses and their testimony. Contrary to the frequent criticism that jurors primarily evaluate expert evidence in terms of its subjective characteristics, the results of our study indicate that jurors consider both the messenger and the message in the course of evaluating the expert's credibility. [source] 2004 Nier Prize for Scott R. MessengerMETEORITICS & PLANETARY SCIENCE, Issue S8 2004Larry R. Nittler [source] Entirely Artificial Signal Transduction with a Primary Messenger,ANGEWANDTE CHEMIE, Issue 43 2009Kai Bernitzki In einem künstlichen System gelingt die Botenstoff-induzierte Signalleitung über eine Membran. Die Zugabe des primären Botenstoffs (DET; siehe Bild) führt zur Bildung eines heterodimeren Komplexes aus Transmembran-Einheiten mit Tryptophan-Donor (Trp) und Dansyl-Akzeptor (Dan), der wiederum einen starken FRET-Effekt auf der Innenseite der Membran induziert (FRET: resonanter Fluoreszenzenergietransfer). [source] 3-Hydroxybenzene 1,2,4-Trisphosphate, a Novel Second Messenger Mimic and unusual Substrate for Type-I myo -Inositol 1,4,5-Trisphosphate 5-Phosphatase: Synthesis and PhysicochemistryCHEMBIOCHEM, Issue 11 2006Stephen J. Mills Dr. Abstract 3-Hydroxybenzene 1,2,4-trisphosphate 4 is a new myo -inositol 1,4,5-trisphosphate analogue based on the core structure of benzene 1,2,4-trisphosphate 2 with an additional hydroxyl group at position-3, and is the first noninositol based compound to be a substrate for inositol 1,4,5-trisphosphate 5-phosphatase. In physicochemical studies on 2, when three equivalents of protons were added, the 31P NMR spectrum displayed monophasic behaviour in which phosphate-1 and phosphate-2 behaved independently in most of the studied pH range. For compound 4, phosphate-2 and phosphate-4 interacted with the 3-OH group, which does not titrate at physiological pH, displaying complex biphasic behaviour which demonstrated co-operativity between these groups. Phosphate-1 and phosphate-2 strongly interacted with each other and phosphate-4 experienced repulsion because of the interaction of the 3-OH group. Benzene 1,2,4-trisphosphate 2 is resistant to inositol 1,4,5-trisphosphate type I 5-phosphatase catalysed dephosphorylation. However, surprisingly, 3-hydroxybenzene 1,2,4-trisphosphate 4 was dephosphorylated by this 5-phosphatase to give the symmetrical 2,3-dihydroxybenzene 1,4-bisphosphate 16. The extra hydroxyl group is shown to form a hydrogen bond with the vicinal phosphate groups at ,15,°C, and 1H NMR titration of the ring and hydroxyl protons in 4 shows the OH proton to be strongly stabilized as soon as the phosphate groups are deprotonated. The effect of the phenolic 3-OH group in compound 4 confirms a critical role for the 6-OH group of the natural messenger in the dephosphorylation mechanism that persists even in radically modified analogues. [source] The Seventh Messenger and Australia 1904,1980: Benjamin Purnell and the House of DavidJOURNAL OF RELIGIOUS HISTORY, Issue 3 2005GUY FEATHERSTONE The Southcottian tradition of the Seven Angelic Messengers of Rev. 10:7 has a long association with millennial belief in Australia. Brought hither by Christian Israelite missionaries in the 1840s, the final three Messengers (Wroe, Jezreel, and Purnell) all journeyed to Australia to win converts. After describing the origins and beliefs of the sects established by these Messengers, this article outlines the impact of Benjamin Purnell's House of David on local Christian Israelites and others. His visit to Melbourne in December 1904 to "ingather" over seventy converts from the Fitzroy congregation is outlined; a comparison is made with J. A. Dowie's missionary tour of the same year. A description of the life the Australians led in Michigan and their attempts to leave the colony and expose Purnell's sexual misconduct are outlined. Despite unfavourable press reports, continuing missionary activity in Melbourne and then in Sydney resulted in further converts leaving for America, and the establishment of a branch community at North Ryde. A comparison of its ethos and that prevailing at Benton Harbor is included. Details of the eventual demise of the North Ryde community are followed by a brief analysis of its place in Australia's religious life. This essay is published to mark the centenary of the departure of the Christian Israelites in February 1905. [source] Don't kill the messenger: writing history and warCRITICAL QUARTERLY, Issue 4 2005RICHARD TOBIAS This article explores the effort to invert Edmund Burke's Sublime and the Beautiful to talk about the Hell and the Ugly of warfare. Official histories fall into the 'rotted language' (Wallace Stevens) of ancient heroics. Since the actual experience of warfare is beyond language, irony - a dangerous and difficult force - is the recourse. Since no Thucydides can write our history of the thirty-one-year war between August of 1914 and August of 1945, a few participants have sufficient irony to find language to convey the actual horror of our inhumanity. The public, however, prefers to obliterate this message. [source] Activation of PLA2 isoforms by cell swelling and ischaemia/hypoxiaACTA PHYSIOLOGICA, Issue 1-2 2006I. H. Lambert Abstract Phospholipase A2 (PLA2) activity is increased in mammalian cells in response to numerous stimuli such as osmotic challenge, oxidative stress and exposure to allergens. The increased PLA2 activity is seen as an increased release of free, polyunsaturated fatty acids, e.g. arachidonic acid and membrane-bound lysophospholipids. Even though arachidonic acid acts as a second messenger in its own most mammalian cells seem to rely on oxidation of the fatty acid into highly potent second messengers via, e.g. cytochrome P450, the cyclo-oxygenase, or the lipoxygenase systems for downstream signalling. Here, we review data that illustrates that stress-induced PLA2 activity involves various PLA2 subtypes and that the PLA2 in question is determined by the cell type and the physiological stress condition. [source] Effect of ,-trinositol on secretion induced by Escherichia coli ST-toxin in rat jejunumACTA PHYSIOLOGICA, Issue 4 2003A.-M. Lahti Abstract Aim:,d -myo-inositol-1,2,6-trisphosphate (, -trinositol, PP56), is a synthetic isomer of the intracellular second messenger, d -myo-inositol-1,4,5-trisphospahate. The pharmacological actions of , -trinositol include potent anti-inflammatory properties and inhibition of the secretion induced by cholera toxin and obstructive ileus. In the present study, we investigated whether , -trinositol was able to influence the secretion induced by heat-stable ST-toxin from Escherichia coli in the rat jejunum. Methods:, A midline abdominal incision was performed in anaesthetized male Sprague,Dawley rats and a 6,7 cm long jejunal segment was isolated with intact vascular supply and placed in a chamber suspended from a force displacement transducer connected to a Grass® polygraph. Intestinal net fluid transport was continuously monitored gravimetrically. Crystalline ST-toxin (120 mouse units) was introduced into the intestinal lumen and left there for the rest of the experiment. When a stable secretion was observed, , -trinositol (60 mg kg,1 h,1) or saline were infused during 2 h, followed by a 2-h control period. Results:, , -Trinositol induced a significant (P < 0.001) inhibition of ST-toxin secretion within 30 min, lasting until 2 h after infusion had stopped. The agent also moderately increased (P < 0.05) net fluid absorption in normal jejunum. Mean arterial pressure (P < 0.001) and heart rate (P < 0.001) were reduced by , -trinositol. Conclusion:, The inhibition by , -trinositol of ST-toxin induced intestinal secretion is primarily secondary to inhibition of secretory mechanisms and only to lesser extent due to increased absorption. The detailed mechanisms of action have not been clarified but may involve suppression of inflammation possibly by means of cellular signal transduction. [source] Arachidonic acid as a retrograde signal controlling growth and dynamics of retinotectal arborsDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2008B.H. Leu Abstract In the developing visual system, correlated presynaptic activity between neighboring retinal ganglion cells (RGC) stabilizes retinotopic synapses via a postsynaptic NMDAR (N -methyl- D -aspartate receptor)-dependent mechanism. Blocking NMDARs makes individual axonal arbors larger, which underlies an unsharpened map, and also increases branch turnover, as if a stabilizing factor from the postsynaptic partner is no longer released. Arachidonic acid (AA), a candidate retrograde stabilizing factor, is released by cytoplasmic phospholipase A2 (cPLA2) after Ca2+ entry through activated NMDARs, and can activate presynaptic protein kinase C to phosphorylate various substrates such as GAP43 to regulate cytoskeletal dynamics. To test the role of cPLA2 in the retinotectal system of developing zebrafish, we first used PED6, a fluorescent reporter of cPLA2 activity, to show that 1,3 min of strobe flashes activated tectal cPLA2 by an NMDAR-dependent mechanism. Second, we imaged the dynamic growth of retinal arbors during both local inhibition of tectal cPLA2 by a pharmacological inhibitor, arachidonic tri-fluoromethylketone, and its suppression by antisense oligonucleotides (both injected intraventricularly). Both methods produced larger arbors and faster branch dynamics as occurs with blocking NMDARs. In contrast, intraocular suppression of retinal cPLA2 with large doses of antisense oligos produced none of the effects of tectal cPLA2 inhibition. Finally, if AA is the retrograde messenger, the application of exogenous AA to the tectum should reverse the increased branch turnover caused by blocking either NMDARs or cPLA2. In both cases, intraventricular injection of AA stabilized the overall branch dynamics, bringing rates down below the normal values. The results suggest that AA generated postsynaptically by cPLA2 downstream of Ca2+ entry through NMDARs acts as a retrograde signal to regulate the dynamic growth of retinal arbors. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Urinary excretion of inositol phosphoglycan P-type in gestational diabetes mellitusDIABETIC MEDICINE, Issue 11 2007M. Scioscia Abstract Objective The mechanisms underlying insulin resistance during normal pregnancy, and its further exacerbation in pregnancies complicated by gestational diabetes mellitus (GDM), are generally unknown. Inositolphosphoglycan P-type (P-IPG), a putative second messenger of insulin, correlates with the degree of insulin resistance in diabetic subjects. An increase during normal pregnancy, in maternal and fetal compartments, has recently been reported. Methods A cross-sectional study was carried out in 48 women with GDM and 23 healthy pregnant women. Urinary levels of P-IPG were assessed spectrophotometrically by the activation of pyruvate dehydrogenase phosphatase in urinary specimens and correlated with clinical parameters. Results Urinary excretion of P-IPG was higher in GDM than in control women (312.1 ± 151.0 vs. 210.6 ± 82.7 nmol NADH/min/mg creatinine, P < 0.01) with values increasing throughout pregnancy in control subjects (r2 = 0.34, P < 0.01). P-IPG correlated with blood glucose levels (r2 = 0.39, P < 0.01 for postprandial glycaemia and r2 = 0.18 P < 0.01 for mean glycaemia) and birthweight in the diabetic group (r2 = 0.14, P < 0.01). Conclusions Increased P-IPG urinary excretion occurs in GDM and positively correlates with blood glucose levels. P-IPG may play a role in maternal glycaemic control and, possibly, fetal growth in GDM. [source] Electrochemical Nitric Oxide Sensors for Biological Samples , Principle, Selected Examples and ApplicationsELECTROANALYSIS, Issue 1 2003Fethi Bedioui Abstract The discoveries made in the 1980s that NO could be synthesized by mammalian cells and could act as physiological messenger and cytotoxic agent had elevated the importance of its detection. The numerous properties of NO, that enable it to carry out its diverse functions, also present considerable problems when attempting its detection and quantification in biological systems. Indeed, its total free concentration in physiological conditions has been established to be in nanomolar range. Thus, detection of nitric oxide remains a challenge, pointing out the difficult dual requirements for specificity and sensitivity. Exception made for the electrochemical techniques, most of the approaches (namely UV-visible spectroscopy, fluorescence, electron paramagnetic resonance spectroscopy) use indirect methods for estimating endogenous NO, relying on measurements of secondary species such as nitrite and nitrate or NO-adducts. They also suffer from allowing only ex situ measurements. So, the only strategies that allow a direct and in vivo detection of NO are those based on the use of ultramicroelectrodes. The reality is that surface electrode modification is needed to make the ultramicroelectrode material selective for NO. Therefore, the design of modified electrode surfaces using organized layers is very attractive and provides the ideal strategy. This review addresses a global description of the various approaches that have involved chemically modified microelectrodes specially designed for the electrochemical detection of NO in biological media. Selected significant examples of applications in biological tissues are also reported in order to highlight the importance of this approach in having new insights into the modulatory role of NO in physiology and pathophysiology. [source] Stress for maintaining memory: HSP70 as a mobile messenger for innate and adaptive immunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2010Taoyong Chen Abstract HSP are abundant and conserved proteins present in all cells. Upon temperature shock or other stress stimuli, HSP are synthesized intracellularly, which may protect cells from protein denaturation or from death. Although HSP are synthesized intracellularly, HSP can also be mobilized to the plasma membrane or even be released under stress conditions. Elucidating the roles of cell surface and extracellular HSP in immune regulation has attracted much attention in recent years. Extracellularly, HSP can serve a cytokine function to initiate both innate and adaptive immunity through activation of APC. HSP serves also a chaperone function and facilitates presentation of antigen peptide to T cells. Similarly, cell surface HSP may activate APC and promote antigen presentation through cell,cell contact. A study in this issue of the European Journal of Immunology demonstrates that cell surface HSP70 on DC induced by stress can upregulate membrane-associated IL-15, which in turn promotes the proliferation of CD4+CD45RA memory T cells. Moreover, a DC-CD4+ T-cell interacting circuit formed by CD40L on T cells and CD40 on DC is proposed to play a role in the maintenance of memory homeostasis. This study has widened our view of HSP in adaptive immunity as well as their classical functions such as APC activator and antigen carrier. [source] REVIEW: Norepinephrine and stimulant addictionADDICTION BIOLOGY, Issue 2 2009Mehmet Sofuoglu ABSTRACT No pharmacotherapies are approved for stimulant use disorders, which are an important public health problem. Stimulants increase synaptic levels of the monoamines dopamine (DA), serotonin and norepinephrine (NE). Stimulant reward is attributable mostly to increased DA in the reward circuitry, although DA stimulation alone cannot explain the rewarding effects of stimulants. The noradrenergic system, which uses NE as the main chemical messenger, serves multiple brain functions including arousal, attention, mood, learning, memory and stress response. In pre-clinical models of addiction, NE is critically involved in mediating stimulant effects including sensitization, drug discrimination and reinstatement of drug seeking. In clinical studies, adrenergic blockers have shown promise as treatments for cocaine abuse and dependence, especially in patients experiencing severe withdrawal symptoms. Disulfiram, which blocks NE synthesis, increased the number of cocaine-negative urines in five randomized clinical trials. Lofexidine, an ,2 -adrenergic agonist, reduces the craving induced by stress and drug cues in drug users. In addition, the NE transporter (NET) inhibitor atomoxetine attenuates some of d-amphetamine's subjective and physiological effects in humans. These findings warrant further studies evaluating noradrenergic medications as treatments for stimulant addiction. [source] Soluble guanylyl cyclase appears in a specific subset of periglomerular cells in the olfactory bulbEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2005Maria Gutičrrez-Mecinas Abstract In the brain, nitric oxide acts as an atypical messenger in cellular nonsynaptic transmission. In the olfactory bulb, this gas is produced at the level of the olfactory glomeruli by a subpopulation of periglomerular cells that participates in the first synaptic relay of the olfactory information between the olfactory nerve and the dendritic tufts of principal cells. It has been proposed that nitric oxide modulates intraglomerular synaptic integration of sensory inputs, but its specific role in the glomerular circuitry remains to be understood. In this article, we demonstrate that, in the glomerular circuits, a specific subset of periglomerular cells, most of them expressing the calcium binding protein calbindin D-28 k, expresses the ,1 subunit of the soluble guanylyl cyclase. These cells could be the targets for the action of nitric oxide at the glomerular level via activation of soluble guanylyl cyclase and production of cGMP. [source] Stabilizing effects of extracellular ATP on synaptic efficacy and plasticity in hippocampal pyramidal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Eduardo D. Martķn Abstract The role of adenosine triphosphate (ATP) as a neurotransmitter and extracellular diffusible messenger has recently received considerable attention because of its possible participation in the regulation of synaptic plasticity. However, the possible contribution of extracellular ATP in maintaining and regulating synaptic efficacy during intracellular ATP depletion is understudied. We tested the effects of extracellular ATP on excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by Schaffer collateral stimulation. In the absence of intracellular ATP, EPSC rundown was neutralized when a low concentration of ATP (1 µm) was added to the extracellular solution. Adenosine and ATP analogues did not prevent the EPSC rundown. The P2 antagonists piridoxal-5,-phosphate-azophenyl 2,,4,-disulphonate (PPADS) and reactive blue-2, and the P1 adenosine receptor antagonist 8-cyclopentyltheophylline (CPT) had no detectable effects in cells depleted of ATP. However, the protective action of extracellular ATP on synaptic efficacy was blocked by extracellular application of the protein kinase inhibitors K252b and staurosporine. In contrast, K252b and staurosporine per se did not interfere with synaptic transmission in ATP loaded cells. Without intracellular ATP, bath-applied caffeine induced a transient (< 35 min) EPSC potentiation that was transformed into a persistent long-term potentiation (> 80 min) when 1 µm ATP was added extracellularly. An increased probability of transmitter release paralleled the long-term potentiation induced by caffeine, suggesting that it originated presynaptically. Therefore, we conclude that extracellular ATP may operate to maintain and regulate synaptic efficacy and plasticity in conditions of abnormal intracellular ATP depletion by phosphorylation of a surface protein substrate via activation of ecto-protein kinases. [source] The effects of nitric oxide on magnocellular neurons could involve multiple indirect cyclic GMP-dependent pathwaysEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003C. M. Vacher Abstract Nitric oxide (NO) is known to regulate the release of arginine-vasopressin (AVP) and oxytocin (OT) by the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). The aim of the current study was to identify in these nuclei the NO-producing neurons and the NO-receptive cells in mice. The determination of NO-synthesizing neurons was performed by double immunohistochemistry for the neuronal form of NO synthase (NOS), and AVP or OT. Besides, we visualized the NO-receptive cells by detecting cyclic GMP (cGMP), the major second messenger for NO, by immunohistochemistry on hypothalamus slices. Neuronal NOS was exclusively colocalized with OT in the PVN and the SON, suggesting that NO is mainly synthesized by oxytocinergic neurons in mice. By contrast, cGMP was not observed in magnocellular neurons, but in GABA-, tyrosine hydroxylase- and glutamate-positive fibers, as well as in GFAP-stained cells. The cGMP-immunostaining was abolished by incubating brain slices with a NOS inhibitor (L-NAME). Consequently, we provide the first evidence that NO could regulate the release of AVP and OT indirectly by modulating the activity of the main afferents to magnocellular neurons rather than by acting directly on magnocellular neurons. Moreover, both the NADPH-diaphorase activity and the mean intensity of cGMP-immunofluorescence were increased in monoamine oxidase A knock-out mice (Tg8) compared to control mice (C3H) in both nuclei. This suggests that monoamines could enhance the production of NO, contributing by this way to the fine regulation of AVP and OT release and synthesis. [source] The retrograde inhibition of IPSCs in rat cerebellar Purkinje cells is highly sensitive to intracellular Ca2+EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2000Maike Glitsch Abstract The Ca2+ -dependent retrograde inhibition of inhibitory postsynaptic currents (depolarization-induced-suppression of inhibition; DSI) was investigated using fura-2 Ca2+ measurements and whole-cell patch-clamp recordings in rat cerebellar Purkinje cells. DSI was studied in cells loaded with different concentrations of the Ca2+ chelators BAPTA and EGTA. A concentration of 40 m m BAPTA was required to significantly interfere with DSI, whereas 10 m m BAPTA was almost ineffective. 40 m m EGTA reduced DSI, but was less effective than 40 m m BAPTA. Ratiometric Ca2+ measurements indicated that the extent of DSI depended critically on the changes in intracellular calcium ([Ca2+]i). The relationship between DSI and peak ,[Ca2+]i could be approximated by a hyperbolic function, with apparent half-saturation concentrations of 200 and 40 n m for dendritic and somatic [Ca2+]i, respectively. It is suggested that DSI is due to somatodendritic exocytosis of a retrograde messenger, and that this exocytosis is highly sensitive to [Ca2+]i. [source] ATP allosteric activation of atrial natriuretic factor receptor guanylate cyclaseFEBS JOURNAL, Issue 11 2010Teresa Duda Atrial natriuretic factor receptor guanylate cyclase (ANF-RGC) is the receptor and the signal transducer of two natriuretic peptide hormones: atrial natriuretic factor and brain natriuretic peptide. It is a single transmembrane-spanning protein. It binds these hormones at its extracellular domain and activates its intracellular catalytic domain. This results in the accelerated production of cyclic GMP, a second messenger in controlling blood pressure, cardiac vasculature and fluid secretion. ATP is obligatory for the transduction of this hormonal signal. Two models of ATP action have been proposed. In Model 1, it is a direct allosteric transducer. It binds to the defined regulatory domain (ATP-regulated module) juxtaposed to the C-terminal side of the transmembrane domain of ANF-RGC, induces a cascade of temporal and spatial changes and activates the catalytic module residing at the C-terminus of the cyclase. In Model 2, before ATP can exhibit its allosteric effect, ANF-RGC must first be phosphorylated by an as yet unidentified protein kinase. This initial step is obligatory in atrial natriuretic factor signaling of ANF-RGC. Until now, none of these models has been directly validated because it has not been possible to segregate the allosteric and the phosphorylation effects of ATP in ANF-RGC activation. The present study accomplishes this aim through a novel probe, staurosporine. This unequivocally validates Model 1 and settles the over two-decade long debate on the role of ATP in ANF-RGC signaling. In addition, the present study demonstrates that the mechanisms of allosteric modification of ANF-RGC by staurosporine and adenylyl-imidodiphosphate, a nonhydrolyzable analog of ATP, are almost (or totally) identical. [source] Nucleotide-mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptorsGLIA, Issue 3 2003Marta Fumagalli Abstract ATP is the dominant messenger for astrocyte-to-astrocyte calcium-mediated communication. Definition of the exact ATP/P2 receptors in astrocytes and of their coupling to intracellular calcium ([Ca2+]i) has important implications for brain physiology and pathology. We show that, with the only exception of the P2X6 receptor, primary rat cortical astrocytes express all cloned ligand-gated P2X (i.e., P2X1,5 and P2X7) and G-protein-coupled P2Y receptors (i.e., P2Y1, P2Y2, P2Y4, P2Y6, and P2Y12). These cells also express the P2Y-like UDP-glucose receptor, which has been recently recognized as the P2Y14 receptor. Single-cell image analysis showed that only some of these receptors are coupled to [Ca2+]i. While ATP induced rapid and transient [Ca2+]i increases (counteracted by the P2 antagonists suramin, pyridoxal-phosphate-6-azophenyl-2,-4,-disulfonic acid and oxidized ATP), the P2X1/P2X3 agonist ,,meATP produced no changes. Conversely, the P2X7 agonist BzATP markedly increased [Ca2+]i; the presence and function of the P2X7 receptor was also confirmed by the formation of the P2X7 pore. ADP and 2meSADP also produced [Ca2+]i increases antagonized by the P2Y1 antagonist MRS2179. Some cells also responded to UTP but not to UDP. Significant responses to sugar-nucleotides were also detected, which represents the first functional response reported for the putative P2Y14 receptor in a native system. Based on agonist preference of known P2 receptors, we conclude that, in rat astrocytes, ATP-induced calcium rises are at least mediated by P2X7 and P2Y1 receptors; additional receptors (i.e., P2X2, P2X4, P2X5, P2Y2, P2Y4, and P2Y14) may also contribute. © 2003 Wiley-Liss, Inc. [source] Stimulation of NMDA and AMPA glutamate receptors elicits distinct concentration dynamics of nitric oxide in rat hippocampal slicesHIPPOCAMPUS, Issue 7 2009J.G. Frade Abstract Nitric oxide (,NO) is an intercellular messenger implicated in memory formation and neurodegeneration in the hippocampus. Owing to its physical and chemical properties, the concentration dynamics of ,NO is a critical issue in determining its bioactivity as a signaling molecule. Its production is closely related to glutamate N -methyl- D -aspartate (NMDA) receptors, following a rise in intracellular calcium levels. However, that dependent on ,-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors remains elusive and controversial, despite reports describing a role for these receptors in other brain regions, largely because of lack of quantitative and dynamic measurements of ,NO. Using a ,NO-selective microsensor inserted in the diffusional spread of ,NO in the CA1 region of rat hippocampal slices, we measured its real-time endogenous production, following activation of ionotropic glutamate receptors and under tissue physiological oxygen tension. Both NMDA and AMPA stimulation resulted in a concentration-dependent ,NO production but encompassing distinct kinetics for lag phases and slower rates of ,NO production were observed for AMPA stimulation. Robustness of the results was achieved instrumentally and pharmacologically, by means of nitric oxide synthase (NOS) inhibitors and antagonists of NMDA (D -(,)-2-amino-5-phosphonopentanoic acid, AP5) and AMPA (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, NBQX) receptors. When using glutamate as a stimulus, ,NO production was of lower magnitude in the presence of AP5 plus NBQX than with AP5 alone, suggesting that even when NMDA receptors are inhibited Ca2+ rises to levels to induce a peak of ,NO from the background. Whereas extracellular Ca2+ was required for the ,NO signals, Philanthotoxin-4,3,3 (PhTX-4,3,3) a toxin used to target Ca2+ -permeable AMPA receptors, attenuated ,NO production. These observations are interpreted on basis of a distinct coupling between the glutamate receptors and neuronal NOS. A role for Ca2+ -permeable AMPA receptors in the Ca2+ activation of neuronal NOS is suggested. © 2008 Wiley-Liss, Inc. [source] Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved puzzleIMMUNOLOGY, Issue 4 2004George Kolios Summary In recent years, nitric oxide (NO), a gas previously considered to be a potentially toxic chemical, has been established as a diffusible universal messenger that mediates cell,cell communication throughout the body. Constitutive and inducible NO production regulate numerous essential functions of the gastrointestinal mucosa, such as maintenance of adequate perfusion, regulation of microvascular and epithelial permeability, and regulation of the immune response. Up-regulation of the production of NO via expression of inducible nitric oxide synthase (iNOS) represents part of a prompt intestinal antibacterial response; however, NO has also been associated with the initiation and maintenance of inflammation in human inflammatory bowel disease (IBD). Recent studies on animal models of experimental IBD have shown that constitutive and inducible NO production seems to be beneficial during acute colitis, but sustained up-regulation of NO is detrimental. This fact is also supported by studies on mice genetically deficient in various NOS isoforms. However, the mechanism by which NO proceeds from being an indispensable homeostatic regulator to a harmful destructor remains unknown. Furthermore, extrapolation of data from animal colitis models to human IBD is questionable. The purpose of this review is to update our knowledge about the role of this universal mediator and the enzymes that generate it in the pathogenesis of IBD. [source] Apis mellifera ultraspiracle: cDNA sequence and rapid up-regulation by juvenile hormoneINSECT MOLECULAR BIOLOGY, Issue 5 2004A. R. Barchuk Abstract Two hormones, 20-hydroxyecdysone (20E) and juvenile hormone (JH) are key regulators of insect development including the differentiation of the alternative caste phenotypes of social insects. In addition, JH plays a different role in adult honey bees, acting as a ,behavioural pacemaker'. The functional receptor for 20E is a heterodimer consisting of the ecdysone receptor and ultraspiracle (USP) whereas the identity of the JH receptor remains unknown. We have cloned and sequenced a cDNA encoding Apis mellifera ultraspiracle (AMUSP) and examined its responses to JH. A rapid, but transient up-regulation of the AMUSP messenger is observed in the fat bodies of both queens and workers. AMusp appears to be a single copy gene that produces two transcripts (,4 and ,5 kb) that are differentially expressed in the animal's body. The predicted AMUSP protein shows greater sequence similarity to its orthologues from the vertebrate,crab,tick,locust group than to the dipteran,lepidopteran group. These characteristics and the rapid up-regulation by JH suggest that some of the USP functions in the honey bee may depend on ligand binding. [source] Dyspnoea after AZD 6140: blaming the messengerINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2007V. L. Serebruany No abstract is available for this article. [source] PDK1 and PKB/Akt: Ideal Targets for Development of New Strategies to Structure-Based Drug DesignIUBMB LIFE, Issue 3 2003Thomas Harris Abstract Growth factor binding events to receptor tyrosine kinases result in activation of phosphatidylinositol 3-kinase (PI3K), and activated PI3K generates the membrane-bound second messengers phosphatidylinositol 3,4-diphosphate [PI(3,4)P2] and PI(3,4,5)P3, which mediate membrane translocation of the phosphoinositide-dependent kinase-1 (PDK1) and protein kinase B (PKB, also known as Akt). In addition to the kinase domain, PDK1 and PKB contain a pleckstrin homology (PH) domain that binds to the second messenger, resulting in the phosphorylation and activation of PKB by PDK1. Recent evidence indicates that constitutive activation of PKB contributes to cancer progression by promoting proliferation and increased cell survival. The indicating of PDK1 and PKB as primary targets for discovery of anticancer drugs, together with the observations that both PDK1 and PKB contain small-molecule regulatory binding sites that may be in proximity to the kinase active site, make PDK1 and PKB ideal targets for the development of new strategies to structure-based drug design. While X-ray structures have been reported for the kinase domains of PDK1 and PKB, no suitable crystals have been obtained for either PDK1 or PKB with their PH domains intact. In this regard, a novel structure-based strategy is proposed, which utilizes segmental isotopic labeling of the PH domain in combination with site-directed spin labeling of the kinase active site. Then, long-range distance restraints between the 15N-labeled backbone amide groups of the PH domain and the unpaired electron of the active site spin label can be determined from magnetic resonance studies of the enhancement effect that the paramagnetic spin label has on the nuclear relaxation rates of the amide protons. The determination of the structure and position of the PH domain with respect to the known X-ray structure of the kinase active site could be useful in the rational design of potent and selective inhibitors of PDK1 and PKB by 'linking' the free energies of binding of substrate (ATP) analogs with analogs of the inositol polar head group of the phospholipid second messenger. The combined use of X-ray crystallography, segmental isotopic and spin labeling, and magnetic resonance studies can be further extended to the study of other dynamic multidomain proteins and targets for structure-based drug design. IUBMB Life, 55: 117-126, 2003 [source] ORIGINAL ARTICLE: The approach to the mechanism of calcitonin gene-related peptide-inducing inhibition of food intakeJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5 2010J.-Y. Sun Summary The aim of this study was to investigate the anorectic mechanism of calcitonin gene-related peptide (CGRP) in rats. Intraperitoneal injection of CGRP (50 ,g/kg) resulted in decline (p < 0.05) in the food intake of rats at 0.5, 1, 2 and 4 h in comparison with saline control. Compared with saline-treated group, the levels of hypothalamic 3,,5,-cyclic adenosine monophosphate (cAMP) and plasma glucagon were increased (p < 0.05) in CGRP-treated group, but insulin level was decreased (p < 0.05). No significant changes (p > 0.05) in the plasma leptin were observed between two treatment groups. Calcitonin gene-related peptide injection down regulated (p < 0.05) both neuropeptide Y (NPY) and melanin-concentrating hormone (MCH) genes at mRNA levels, but up regulated (p < 0.05) the expression of cholecystokinin (CCK) gene. The correlations analysis showed that food intake was negatively correlated (p < 0.05) with CCK mRNA, cAMP and glucagon levels. Moreover, there existed negative correlations (p < 0.05) between MCH mRNA and glucagon levels, and positive correlations (p < 0.05) between insulin and leptin levels. The results showed that cAMP acting as the second messenger may play a vital role in the anorectic effects of CGRP. Calcitonin gene-related peptide could stimulate anorexigenic neuropeptides (i.e. CCK) and/or inhibit orexigenic neuropeptides (i.e. NPY and MCH) expression, and ultimately suppressed food intake that was functionally coupled to cAMP/PKA pathway activation. [source] | ||||||||||||||||||||||||||||||||||||||||||||||