Sample records for second messenger systems

  1. Mechanical forces and their second messengers in stimulating cell growth in vitro

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.

    1992-01-01

    Mechanical forces play an important role in modulating the growth of a number of different tissues including skeletal muscle, smooth muscle, cardiac muscle, bone, endothelium, epithelium, and lung. As interest increases in the molecular mechanisms by which mechanical forces are transduced into growth alterations, model systems are being developed to study these processes in tissue culture. This paper reviews the current methods available for mechanically stimulating tissue cultured cells. It then outlines some of the putative 'mechanogenic' second messengers involved in altering cell growth. Not surprisingly, many mechanogenic second messengers are the same as those involved in growth factor-induced cell growth. It is hypothesized that from an evolutionary standpoint, some second messenger systems may have initially evolved for unicellular organisms to respond to physical forces such as gravity and mechanical perturbation in their environment. As multicellular organisms came into existence, they appropriated these mechanogenic second messenger cascades for cellular regulation by growth factors.

  2. Agonist-specific coupling of a cloned Drosophila octopamine/tyramine receptor to multiple second messenger systems.

    PubMed Central

    Robb, S; Cheek, T R; Hannan, F L; Hall, L M; Midgley, J M; Evans, P D

    1994-01-01

    A cloned seven transmembrane-spanning Drosophila octopamine/tyramine receptor, permanently expressed in a Chinese hamster ovary cell line, both inhibits adenylate cyclase activity and leads to the elevation of intracellular Ca2+ levels by separate G-protein-coupled pathways. Agonists of this receptor (octopamine and tyramine), differing by only a single hydroxyl group in their side chain, may be capable of differentially coupling it to different second messenger systems. Thus, a single receptor may have a different pharmacological profile depending on which second messenger system is used to assay its efficacy. PMID:8137817

  3. Bacterial nucleotide-based second messengers.

    PubMed

    Pesavento, Christina; Hengge, Regine

    2009-04-01

    In all domains of life nucleotide-based second messengers transduce signals originating from changes in the environment or in intracellular conditions into appropriate cellular responses. In prokaryotes cyclic di-GMP has emerged as an important and ubiquitous second messenger regulating bacterial life-style transitions relevant for biofilm formation, virulence, and many other bacterial functions. This review describes similarities and differences in the architecture of the cAMP, (p)ppGpp, and c-di-GMP signaling systems and their underlying signaling principles. Moreover, recent advances in c-di-GMP-mediated signaling will be presented and the integration of c-di-GMP signaling with other nucleotide-based signaling systems will be discussed.

  4. Cyclic Dinucleotides in the Scope of the Mammalian Immune System.

    PubMed

    Mankan, Arun K; Müller, Martina; Witte, Gregor; Hornung, Veit

    2017-01-01

    First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system. In this regard, our main focus is the role of the cGAS-STING axis in the context of microbial infection and sterile inflammation and its implications for therapeutic applications.

  5. A multiplexed fluorescent assay for independent second-messenger systems: decoding GPCR activation in living cells.

    PubMed

    Tewson, Paul H; Quinn, Anne Marie; Hughes, Thomas E

    2013-08-01

    There is a growing need in drug discovery and basic research to measure multiple second-messenger components of cell signaling pathways in real time and in relevant tissues and cell types. Many G-protein-coupled receptors activate the heterotrimeric protein, Gq, which in turn activates phospholipase C (PLC). PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) to produce two second messengers: diacylglycerol (DAG), which remains in the plasma membrane, and inositol triphosphate (IP3), which diffuses through the cytosol to release stores of intracellular calcium ions (Ca(2+)). Our goal was to create a series of multiplex sensors that would make it possible to simultaneously measure two different components of the Gq pathway in living cells. Here we describe new fluorescent sensors for DAG and PIP2 that produce robust changes in green or red fluorescence and can be combined with one another, or with existing Ca(2+) sensors, in a live-cell assay. These assays can detect multiple components of Gq signaling, simultaneously in real time, on standard fluorescent plate readers or live-cell imaging systems.

  6. Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers

    PubMed Central

    Gründling, Angelika; Jenal, Urs; Ryan, Robert; Yildiz, Fitnat

    2015-01-01

    The first International Symposium on c-Di-GMP Signaling in Bacteria (22 to 25 March 2015, Harnack-Haus, Berlin, Germany) brought together 131 molecular microbiologists from 17 countries to discuss recent progress in our knowledge of bacterial nucleotide second messenger signaling. While the focus was on signal input, synthesis, degradation, and the striking diversity of the modes of action of the current second messenger paradigm, i.e., cyclic di-GMP (c-di-GMP), “classics” like cAMP and (p)ppGpp were also presented, in novel facets, and more recent “newcomers,” such as c-di-AMP and c-AMP-GMP, made an impressive appearance. A number of clear trends emerged during the 30 talks, on the 71 posters, and in the lively discussions, including (i) c-di-GMP control of the activities of various ATPases and phosphorylation cascades, (ii) extensive cross talk between c-di-GMP and other nucleotide second messenger signaling pathways, and (iii) a stunning number of novel effectors for nucleotide second messengers that surprisingly include some long-known master regulators of developmental pathways. Overall, the conference made it amply clear that second messenger signaling is currently one of the most dynamic fields within molecular microbiology, with major impacts in research fields ranging from human health to microbial ecology. PMID:26055111

  7. Inhibitors of second messenger pathways and Ca(2+)-induced exposure of phosphatidylserine in red blood cells of patients with sickle cell disease.

    PubMed

    Gbotosho, O T; Cytlak, U M; Hannemann, A; Rees, D C; Tewari, S; Gibson, J S

    2014-07-01

    The present work investigates the contribution of various second messenger systems to Ca(2+)-induced phosphatidylserine (PS) exposure in red blood cells (RBCs) from sickle cell disease (SCD) patients. The Ca(2+) dependence of PS exposure was confirmed using the Ca(2+) ionophore bromo-A23187 to clamp intracellular Ca(2+) over 4 orders of magnitude in high or low potassium-containing (HK or LK) saline. The percentage of RBCs showing PS exposure was significantly increased in LK over HK saline. This effect was reduced by the Gardos channel inhibitors, clotrimazole and charybdotoxin. Nevertheless, although Ca(2+) loading in the presence of an outwardly directed electrochemical gradient for K(+) stimulated PS exposure, substantial exposure still occurred in HK saline. Under the conditions used inhibitors of other second messenger systems (ABT491, quinacrine, acetylsalicylic acid, 3,4-dichloroisocoumarin, GW4869 and zVAD-fmk) did not inhibit the relationship between [Ca(2+)] and PS exposure. Inhibitors of phospholipase A2, cyclooxygenase, platelet-activating factor, sphingomyelinase and caspases, therefore, were without effect on Ca(2+)-induced PS exposure in RBCs, incubated in either HK or LK saline.

  8. MESSENGER and Venus Express Observations of the Near-tail of Venus: Magnetic Flux Transport, Current Sheet Structure, and Flux Rope Formation

    NASA Technical Reports Server (NTRS)

    Slavin, James A.; Boardsen, S. A.; Sarantos, M.; Acuna, M. H.; Anderson, B. J.; Barabash, S.; Benna, M.; Fraenz, M.; Gloeckler, G.; Gold, R. E.; hide

    2008-01-01

    At 23:08 UT on 5 June 2007 the MESSENGER spacecraft reached its closest approach altitude (338 km) during its second flyby of Venus en route to its 2011 orbit insertion at Mercury. Whereas no measurements were collected during MESSENGER'S first Venus flyby in October 2006, the Magnetometer (MAG) and the Energetic Particle and Plasma Spectrometer (EPPS) operated successfully throughout this second encounter. Venus provides the solar system's best example to date of a solar wind - ionosphere planetary interaction. We present MESSENGER observations of the near-tail of Venus with emphasis on determining the time scales for magnetic flux transport, the structure of the cross-tail current sheet at very low altitudes (approx. 300 to 1000 km), and the nature and origin of a magnetic flux rope observed in the current sheet. The availability of the simultaneous Venus Express upstream measurements provides a unique opportunity to examine the influence of solar wind plasma and interplanetary magnetic field conditions on this planet's solar wind interaction at solar minimum.

  9. Thrombin Induces Inositol Trisphosphate-Mediated Spatially Extensive Responses in Lung Microvessels.

    PubMed

    Escue, Rachel; Kandasamy, Kathirvel; Parthasarathi, Kaushik

    2017-04-01

    Activation of plasma membrane receptors initiates compartmentalized second messenger signaling. Whether this compartmentalization facilitates the preferential intercellular diffusion of specific second messengers is unclear. Toward this, the receptor-mediated agonist, thrombin, was instilled into microvessels in a restricted region of isolated blood-perfused mouse lungs. Subsequently, the thrombin-induced increase in endothelial F-actin was determined using confocal fluorescence microscopy. Increased F-actin was evident in microvessels directly treated with thrombin and in those located in adjoining thrombin-free regions. This increase was abrogated by inhibiting inositol trisphosphate-mediated calcium release with Xestospongin C (XeC). XeC also inhibited the thrombin-induced increase in the amplitude of endothelial cytosolic Ca 2+ oscillations. Instillation of thrombin and XeC into adjacent restricted regions increased F-actin in microvessels in the thrombin-treated and adjacent regions but not in those in the XeC-treated region. Thus, inositol trisphosphate, and not calcium, diffused interendothelially to the spatially remote thrombin-free microvessels. Thus, activation of plasma membrane receptors increased the ambit of inflammatory responses via a second messenger different from that used by stimuli that induce cell-wide increases in second messengers. Thrombin however failed to induce the spatially extensive response in microvessels of mice lacking endothelial connexin43, suggesting a role for connexin43 gap junctions. Compartmental second messenger signaling and interendothelial communication define the specific second messenger involved in exacerbating proinflammatory responses to receptor-mediated agonists. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Adenosine receptor activation potentiates phosphoinositide hydrolysis and arachidonic acid release in DDT1-MF2 cells: putative interrelations.

    PubMed

    Schachter, J B; Yasuda, R P; Wolfe, B B

    1995-09-01

    Studies were undertaken in an effort to discern possible mechanisms by which the A1 adenosine receptor agonist cyclopentyladenosine (CPA) enhances the norepinephrine-stimulated (NE-stimulated) hydrolysis of phosphoinositides in DDT1-MF2 cells. Measurements of arachidonic acid release revealed similar behaviours to those observed in measurements of phosphoinositide hydrolysis. In the presence of NE, both second messenger responses were potentiated by the addition of CPA, whereas in the absence of NE, CPA had little or no effect on either second messenger. The stimulation and potentiation of both second messenger responses were enhanced in the presence of extracellular calcium, and in each case these effects were persistent over time. For either second messenger system the stimulation by NE and the potentiation by CPA appeared to utilize separate mechanisms as evidenced by the fact that the potentiations by CPA were selectively antagonized by a cAMP analogue or by pertussis toxin, whereas the stimulations by NE were essentially unaffected by these agents. Inhibition of phospholipase A2 (PLA2) also blocked the potentiation of PLC by CPA, without affecting NE-stimulated phosphoinositide hydrolysis. Furthermore, in the presence of CPA, the exogenous administration of PLA2 was found to stimulate phosphoinositide hydrolysis in these cells. These data are consistent with a hypothesis whereby the apparent potentiation of NE-stimulated phosphoinositide hydrolysis by CPA is actually due to the stimulation by CPA of a second pathway of phospholipase C activity which is additive to that of NE. The activation of PLC and PLA2 by NE produces phospholipid products which may play a permissive role in the pathway coupling adenosine A1 receptors to these phospholipases. The formation of lysophosphatidic acid is suggested as one possible mediator of this permissive effect.

  11. An overview of mechanisms of redox signaling.

    PubMed

    Forman, Henry Jay; Ursini, Fulvio; Maiorino, Matilde

    2014-08-01

    A principal characteristic of redox signaling is that it involves an oxidation-reduction reaction or covalent adduct formation between the sensor signaling protein and second messenger. Non-redox signaling may involve alteration of the second messenger as in hydrolysis of GTP by G proteins, modification of the signaling protein as in farnesylation, or simple non-covalent binding of an agonist or second messenger. The chemistry of redox signaling is reviewed here. Specifically we have described how among the so-called reactive oxygen species, only hydroperoxides clearly fit the role of a second messenger. Consideration of reaction kinetics and cellular location strongly suggests that for hydroperoxides, particular protein cysteines are the targets and that the requirements for redox signaling is that these cysteines are in microenvironments in which the cysteine is ionized to the thiolate, and a proton can be donated to form a leaving group. The chemistry described here is the same as occurs in the cysteine and selenocysteine peroxidases that are generally considered the primary defense against oxidative stress. But, these same enzymes can also act as the sensors and transducer for signaling. Conditions that would allow specific signaling by peroxynitrite and superoxide are also defined. Signaling by other electrophiles, which includes lipid peroxidation products, quinones formed from polyphenols and other metabolites also involves reaction with specific protein thiolates. Again, kinetics and location are the primary determinants that provide specificity required for physiological signaling although enzymatic catalysis is not likely involved. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System". Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. MESSENGER Observations of Mercury's Magnetosphere

    NASA Technical Reports Server (NTRS)

    Slavin, James A.

    2010-01-01

    During MESSENGER's second and third flybys of Mercury on October 6, 2008 and September 29, 2009, respectively, southward interplanetary magnetic field (IMF) produced intense reconnection signatures in the dayside and nightside magnetosphere and markedly different system-level responses. The IMF during the second flyby was continuously southward and the magnetosphere appeared very active, with large magnetic field components normal to the magnetopause and the generation of flux transfer events at the magnetopause and plasmoids in the tail current sheet every 30 to 90 s. However, the strength and direction of the tail magnetic field was stable. In contrast, the IMF during the third flyby varied from north to south on timescales of minutes. Although the MESSENGER measurements were limited during that encounter to the nightside magnetosphere, numerous examples of plasmoid release in the tail were detected, but they were not periodic. Instead, plasmoid release was highly correlated with four large enhancements of the tail magnetic field (i.e. by factors > 2) with durations of approx. 2 - 3 min. The increased flaring of the magnetic field during these intervals indicates that the enhancements were caused by loading of the tail with magnetic flux transferred from the dayside magnetosphere. New analyses of the second and third flyby observations of reconnection and its system-level effects provide a basis for comparison and contrast with what is known about the response of the Earth s magnetosphere to variable versus steady southward IMF.

  13. The role of the actin cytoskeleton in calcium signaling in starfish oocytes.

    PubMed

    Santella, Luigia; Puppo, Agostina; Chun, Jong Tai

    2008-01-01

    Ca2+ is the most universal second messenger in cells from the very first moment of fertilization. In all animal species, fertilized eggs exhibit massive mobilization of intracellular Ca2+ to orchestrate the initial events of development. Echinoderm eggs have been an excellent model system for studying fertilization and the cell cycle due to their large size and abundance. In preparation for fertilization, the cell cycle-arrested oocytes must undergo meiotic maturation. Studies of starfish oocytes have shown that Ca2+ signaling is intimately involved in this process. Our knowledge of the molecular mechanism of meiotic maturation and fertilization has expanded greatly in the past two decades due to the discovery of cell cycle-related kinases and Ca2+-mobilizing second messengers. However, the molecular details of their actions await elucidation of other cellular elements that assist in the creation and transduction of Ca2+ signals. In this regard, the actin cytoskeleton, the receptors for second messengers and the Ca2+-binding proteins also require more attention. This article reviews the physiological significance and the mechanism of intracellular Ca2+ mobilization in starfish oocytes during maturation and fertilization.

  14. Mercury-arc photolysis: a method for examining second messenger regulation of endothelial cell monolayer integrity.

    PubMed

    Patton, W F; Alexander, J S; Dodge, A B; Patton, R J; Hechtman, H B; Shepro, D

    1991-07-01

    Cell-cell apposition in bovine pulmonary endothelial cell monolayers was modulated by inducing transient increases in intracellular adenosine 3':5'-cyclic monophosphate (cAMP) and 1,4,5-inositol triphosphate (IP3). This was accomplished by mercury-arc flash photolysis of o-nitrobenzyl derivatives of the second messengers (caged compounds). Second messenger release by the mercury-arc lamp was determined by radioimmunoassay of cAMP to have a t1/2 of approximately 8 min. Each second messenger induced the phosphorylation of a distinct subset of cytoskeletal proteins; however, both IP3 and cAMP increased vimentin phosphorylation. Actin isoform patterns were not altered by the second messengers. Intracellular pulses of IP3 in pulmonary endothelial cells caused disruption of endothelial monolayer integrity as determined by phase-contrast microscopy and by visualization of actin stress fibers with rhodamine-phalloidin. Intracellular pulses of cAMP increased cell-cell contact, cell surface area, and apposition. IP3 appeared to have its greatest effect on the actin peripheral band. In silicone rubber contractility assays this agent caused contraction of pulmonary microvascular endothelial cells as visualized by an increase in wrinkles beneath the cells. On the other hand, cAMP appeared to effect both the peripheral band and centralized actin domains. Caged cAMP caused relaxation of endothelial cells as visualized by a disappearance of wrinkles beneath the cells.

  15. Calcium in the regulation of gravitropism by light

    NASA Technical Reports Server (NTRS)

    Perdue, D. O.; LaFavre, A. K.; Leopold, A. C.

    1988-01-01

    The red light requirement for positive gravitropism in roots of corn (Zea mays cv "Merit") provides an entry for examining the participation of calcium in gravitropism. Applications of calcium chelators inhibit the light response. Calcium channel blockers (verapamil, lanthanum) can also inhibit the light response, and a calcium ionophore, A23187, can substitute for light. One can substitute for red light by treatments which have elsewhere been shown to trigger Ca2+ influx into the cytosol, e.g. heat or cold shock. Agents which are known to be agonists of the phosphatidylinositol second messenger system (serotonin, 2,4-dichlorophenoxyacetic acid, deoxycholate) can each partially substitute for the red light, and Li+ can inhibit the light effect. These experiments suggest that the induction of positive gravitropism by red light involves a rise in cytoplasmic Ca2+ concentration, and that a contribution to this end may be made by the phosphatidylinositol second messenger system.

  16. Occurrence of Cyclic di-GMP-Modulating Output Domains in Cyanobacteria: an Illuminating Perspective

    PubMed Central

    Agostoni, Marco; Koestler, Benjamin J.; Waters, Christopher M.; Williams, Barry L.; Montgomery, Beronda L.

    2013-01-01

    ABSTRACT Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical role in regulating cellular processes such as biofilm formation and cellular motility. Cyclic di-GMP signaling systems have been largely characterized in pathogenic bacteria; however, proteins that can impact the synthesis or degradation of c-di-GMP are prominent in cyanobacterial species and yet remain largely underexplored. In cyanobacteria, many putative c-di-GMP synthesis or degradation domains are found in genes that also harbor light-responsive signal input domains, suggesting that light is an important signal for altering c-di-GMP homeostasis. Indeed, c-di-GMP-associated domains are often the second most common output domain in photoreceptors—outnumbered only by a histidine kinase output domain. Cyanobacteria differ from other bacteria regarding the number and types of photoreceptor domains associated with c-di-GMP domains. Due to the widespread distribution of c-di-GMP domains in cyanobacteria, we investigated the evolutionary origin of a subset of genes. Phylogenetic analyses showed that c-di-GMP signaling systems were present early in cyanobacteria and c-di-GMP genes were both vertically and horizontally inherited during their evolution. Finally, we compared intracellular levels of c-di-GMP in two cyanobacterial species under different light qualities, confirming that light is an important factor for regulating this second messenger in vivo. PMID:23943760

  17. Evidence for young volcanism on Mercury from the third MESSENGER flyby.

    PubMed

    Prockter, Louise M; Ernst, Carolyn M; Denevi, Brett W; Chapman, Clark R; Head, James W; Fassett, Caleb I; Merline, William J; Solomon, Sean C; Watters, Thomas R; Strom, Robert G; Cremonese, Gabriele; Marchi, Simone; Massironi, Matteo

    2010-08-06

    During its first two flybys of Mercury, the MESSENGER spacecraft acquired images confirming that pervasive volcanism occurred early in the planet's history. MESSENGER's third Mercury flyby revealed a 290-kilometer-diameter peak-ring impact basin, among the youngest basins yet seen, having an inner floor filled with spectrally distinct smooth plains. These plains are sparsely cratered, postdate the formation of the basin, apparently formed from material that once flowed across the surface, and are therefore interpreted to be volcanic in origin. An irregular depression surrounded by a halo of bright deposits northeast of the basin marks a candidate explosive volcanic vent larger than any previously identified on Mercury. Volcanism on the planet thus spanned a considerable duration, perhaps extending well into the second half of solar system history.

  18. Activation of Phosphoinositide Metabolism by Cholinergic Agents.

    DTIC Science & Technology

    1992-03-15

    most notably calcium. Cholinergic agonist-induced seizures; Brain second messenger systems; Neurotransmitter/ Neuromodulator interactions; RAV; Lab...have been described: modulation by protein kinase C and modulation by neurotransmitter (or neuromodulator ) interactions. Agents which stimulate...phosphoinositide hydrolysis that has been identified consists of interactions among neurotransmitter systems or neuromodulators . Perhaps those most widely

  19. Exploring the Inner Solar System During IPA

    NASA Astrophysics Data System (ADS)

    Weir, H. M.; Stockman, S. A.; Carter, B. L.; Bleacher, L. V.

    2008-12-01

    During 2009, the International Year of Astronomy, both the MESSENGER mission to Mercury and the Lunar Reconnaissance Orbiter (LRO) mission to orbit the Moon will use key mission milestones to engage the public. For the MESSENGER mission key millstones will be the release to the public of data from the Oct 6th 2008, flyby and the Sept 29th 2009 third and last Mercury flyby before MESSENGER orbits Mercury in 2011. IYA activities will include participating in 365 Days of Astronomy podcasts, making the second flyby data publicly available and exciting the public with images from the third flyby. The data from the first flyby can be seen in a variety of locations across the country on Science on a Sphere. During IYA, the MESSENGER mission will also be reaching a wide variety of audiences through social media networking such as Facebook and Twitter. Informal education communities will be able to include Mercury data in their IYA programming through the distribution of MESSENGER data through the NASA Museum Alliance. The LRO mission will return the public's attention to our nearest neighbor, the Moon, in 2009. As a result, the public will see high resolution images of the Moon never seen before. LRO will also engage the public in the lunar observation program. Starting in early 2009, LRO and Lunar CRater Observation and Sensing Satellite (LCROSS) will be launched, and will continue their science missions throughout IYA. The public will be encouraged to make observations of the Moon during critical maneuvers for the LRO and LCROSS missions, including the LCROSS encounter, impacting the Moon which will occur in 2009. These events will help shift the public's attention to the Moon, and highlight the role our nearest neighbor plays in helping scientists learn about the early history of our Solar System. In addition to viewing LRO images and observing the Moon, the public can learn about the Moon, LRO, LCROSS, and past lunar missions virtually via the "Return to the Moon Hall" on CoLab Island in Second Life. As with MESSENGER, LRO will also be featured on Facebook, Twitter and the Museum Alliance.

  20. Medicinal Chemistry of the Noncanonical Cyclic Nucleotides cCMP and cUMP.

    PubMed

    Schwede, Frank; Rentsch, Andreas; Genieser, Hans-Gottfried

    2017-01-01

    After decades of intensive research on adenosine-3',5'-cyclic monophosphate (cAMP)- and guanosine-3',5'-cyclic monophosphate (cGMP)-related second messenger systems, also the noncanonical congeners cyclic cytidine-3',5'-monophosphate (cCMP) and cyclic uridine-3',5'-monophosphate (cUMP) gained more and more interest. Until the late 1980s, only a small number of cCMP and cUMP analogs with sometimes undefined purities had been described. Moreover, most of these compounds had been rather synthesized as precursors of antitumor and antiviral nucleoside-5'-monophosphates and hence had not been tested for any second messenger activity. Along with the recurring interest in cCMP- and cUMP-related signaling in the early 2000s, it became evident that well-characterized small molecule analogs with reliable purities would serve as highly valuable tools for the evaluation of a putative second messenger role of cyclic pyrimidine nucleotides. Meanwhile, for this purpose new cCMP and cUMP derivatives have been developed, and already known analogs have been resynthesized and highly purified. This chapter summarizes early medicinal chemistry work on cCMP and cUMP and analogs thereof, followed by a description of recent synthetic developments and an outlook on potential future directions.

  1. Mechanism and control of fluid secretion.

    PubMed

    Oschman, J L

    1977-01-01

    Fluid secretion and reabsorption by a variety of plant and animal tissues appear to be accomplished by osmotic coupling between solute transport and water movement. The local osmosis model suggests that active accumulation of solutes within narrow folds at the cell surface may produce the local gradients that generate water flow. Both micropuncture techniques and electron-probe X-ray microanalysis have established that local osmotic gradients occur in absorptive epithelia, but they have not as yet been detected in secretory tissues.Hormonal control of secretion involves stimulation of solute pumps and adjustments of permeability to non-transported solutes. Since hormone receptors and pumps are often located on opposite surfaces of the cell, intracellular second messengers convey the secretory signal through cytoplasm. Much has been learned by study of insect tissues that are anatomically simple and that function for long periods in vitro. Aspects of hormone-receptor interaction have been explored, including the action of halluninogenic molecules. In insect salivary glands cyclic AMP appears to stimulate cation transport, while calcium increases anion permeability. The various second messengers probably interact with each other in complex feedback loops that stabilize the system and make it quickly responsive to hormone. Cyclic AMP may stimulate release of calcium from mitochondria. Unresolved is the way second messengers alter properties of the cell surface.

  2. 3',5'-cIMP as Potential Second Messenger in the Vascular Wall.

    PubMed

    Leung, Susan W S; Gao, Yuansheng; Vanhoutte, Paul M

    2017-01-01

    Traditionally, only the 3',5'-cyclic monophosphates of adenosine and guanosine (produced by adenylyl cyclase and guanylyl cyclase, respectively) are regarded as true "second messengers" in the vascular wall, despite the presence of other cyclic nucleotides in different tissues. Among these noncanonical cyclic nucleotides, inosine 3',5'-cyclic monophosphate (cIMP) is synthesized by soluble guanylyl cyclase in porcine coronary arteries in response to hypoxia, when the enzyme is activated by endothelium-derived nitric oxide. Its production is associated with augmentation of vascular contraction mediated by stimulation of Rho kinase. Based on these findings, cIMP appears to meet most, if not all, of the criteria required for it to be accepted as a "second messenger," at least in the vascular wall.

  3. MESSENGER Team Presents Latest Science Results

    NASA Image and Video Library

    2009-04-30

    This mosaic was assembled using NAC images acquired as the MESSENGER spacecraft approached the planet during the mission second Mercury flyby The Rembrandt impact basin is seen at the center of the mosaic.

  4. Sphingolipids in macroautophagy.

    PubMed

    Lavieu, Grégory; Scarlatti, Francesca; Sala, Giusy; Carpentier, Stéphane; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

    2008-01-01

    Sphingolipids are constituents of biological membranes. Ceramide and sphingosine 1-phosphate (S1P) also act as second messengers and are part of a rheostat system, in which ceramide promotes cell death and growth arrest, and S1P induces proliferation and maintains cell survival. As macroautophagy is a lysosomal catabolic mechanism involved in determining the duration of the lifetime of cells, we raised the question of its regulation by sphingolipid messengers. Using chemical and genetic methods, we have shown by GFP-LC3 staining and analysis of the degradation of long-lived proteins that both ceramide and S1P stimulate autophagy.

  5. Mobile Immersion: An Experiment Using Mobile Instant Messenger to Support Second-Language Learning

    ERIC Educational Resources Information Center

    Lai, Arthur

    2016-01-01

    Immersion has been an acclaimed approach for second-language acquisition, but is not available to most students. The idea of this study was to create a mobile immersion environment on a smartphone using a mobile instant messenger, WhatsApp™. Forty-five Form-1 (7th grade) students divided into the Mobile Group and Control Group participated in a…

  6. Cyclic nucleotide- and inositol phosphate-gated ion channels in lobster olfactory receptor neurons.

    PubMed Central

    Hatt, H; Ache, B W

    1994-01-01

    The idea of having two second messenger pathways in olfaction, one mediated by cAMP and the other by inositol 1,4,5-trisphosphate, is supported by evidence that both second messengers directly activate distinct ion channels in the outer dendrite of lobster olfactory receptor neurons. Evidence that both types of second messenger-gated channels can occur in the same patch of membrane suggests that channels of both types can be expressed in one neuron. Evidence of more than one type of inositol phosphate-gated channel in this highly specialized region of the neuron furthers the idea that the output of individual olfactory receptor cells is regulated through multiple effectors and allows that effector diversity may contribute to functional diversity among olfactory receptor cells. Images PMID:7517547

  7. Is the Pharmacological Mode of Action of Chromium(III) as a Second Messenger?

    PubMed

    Vincent, John B

    2015-07-01

    Although recent studies have shown that chromium (as the trivalent ion) is not an essential trace element, it has been demonstrated to generate beneficial effects at pharmacologically relevant doses on insulin sensitivity and cholesterol levels of rodent models of insulin insensitivity, including models of type 2 diabetes. The mode of action of Cr(III) at a molecular level is still an area of active debate; however, the movement of Cr(III) in the body, particularly in response to changes in insulin concentration, suggests that Cr(III) could act as a second messenger, amplifying insulin signaling. The evidence for the pharmacological mechanism of Cr(III)'s ability to increase insulin sensitivity by acting as a second messenger is reviewed, and proposals for testing this hypothesis are described.

  8. Mercury's Exosphere During MESSENGER's Second Flyby: Detection of Magnesium and Distinct Distributions of Neutral Species

    NASA Technical Reports Server (NTRS)

    McClintock, William E.; Vervack, Ronald J., Jr.; Bradley, E. Todd; Killen, Rosemary M.; Mouawad, Nelly; Sprague, Ann L.; Burger, Matthew H.; Solomon, Sean C.; Izenberg, Noam R.

    2009-01-01

    During MESSENGER's second Mercury flyby, the Mercury Atmospheric and Surface Composition Spectrometer observed emission from Mercury's neutral exosphere. These observations include the first detection of emission from magnesium. Differing spatial distributions for sodium, calcium, and magnesium were revealed by observations beginning in Mercury's tail region, approximately 8 Mercury radii anti-sunward of the planet, continuing past the nightside, and ending near the dawn terminator. Analysis of these observations, supplemented by observations during the first Mercury flyby as well as those by other MESSENGER instruments, suggests that the distinct spatial distributions arise from a combination of differences in source, transfer, and loss processes.

  9. Regulation of cyclic nucleotide-gated channels and membrane excitability in olfactory receptor cells by carbon monoxide

    NASA Technical Reports Server (NTRS)

    Leinders-Zufall, T.; Shepherd, G. M.; Zufall, F.

    1995-01-01

    1. The effect of the putative neural messenger carbon monoxide (CO) and the role of the cGMP second-messenger system for olfactory signal generation was examined in isolated olfactory receptor neurons (ORNs) of the tiger salamander. 2. With the use of whole cell voltage-clamp recordings in combination with a series of ionic and pharmological tests, it is demonstrated that exogenously applied CO is a potent activator (K1/2 = 2.9 microM) of cyclic nucleotide-gated (CNG) channels previously described to mediate odor transduction. 3. Several lines of evidence suggest that CO mediates its effect through stimulation of a soluble guanylyl cyclase (sGC) leading to formation of the second-messenger cGMP. This conclusion is based on the findings that CO responses show an absolute requirement for guanosine 5'-triphosphate (GTP) in the internal solution, that no direct effect of CO on CNG currents in the absence of GTP is detectable, and that a blocker of sGC activation, LY85383 (10 microM), completely inhibits the CO response. 4. The dose-response curve for cGMP at CNG channels is used as a calibration to provide a quantitative estimate of the CO-stimulated cGMP formation. This analysis implies that CO is a potent activator of olfactory sGC. 5. Perforated patch recordings using amphotericin B demonstrate that low micromolar doses of CO effectively depolarize the membrane potential of ORNs through tonic activation of CNG channels. This effect in turn regulates excitable and adaptive properties of ORNs and modulates neuronal responsiveness. 6. These data argue for an important role of the cGMP pathway in olfactory signaling and support the idea that CO may function as a diffusible messenger in the olfactory system.

  10. Enhanced Color Mercury Map

    NASA Image and Video Library

    2017-12-08

    This colorful view of Mercury was produced by using images from the color base map imaging campaign during MESSENGER's primary mission. These colors are not what Mercury would look like to the human eye, but rather the colors enhance the chemical, mineralogical, and physical differences between the rocks that make up Mercury's surface. This specific color combination places the second principle component in the red channel, the first principle component in the green channel, and the ratio of the 430 nm/1000 nm filters in the blue channel. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. During the first two years of orbital operations, MESSENGER acquired over 150,000 images and extensive other data sets. MESSENGER is capable of continuing orbital operations until early 2015. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  11. 30 CFR 75.705-11 - Use of grounded messenger wires; ungrounded systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Use of grounded messenger wires; ungrounded....705-11 Use of grounded messenger wires; ungrounded systems. Solely for purposes of grounding ungrounded high-voltage power systems, grounded messenger wires used to suspend the cables of such systems...

  12. 30 CFR 75.705-11 - Use of grounded messenger wires; ungrounded systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Use of grounded messenger wires; ungrounded....705-11 Use of grounded messenger wires; ungrounded systems. Solely for purposes of grounding ungrounded high-voltage power systems, grounded messenger wires used to suspend the cables of such systems...

  13. cCMP, cUMP, cTMP, cIMP and cXMP as possible second messengers: development of a hypothesis based on studies with soluble guanylyl cyclase α(1)β(1).

    PubMed

    Beste, Kerstin Y; Seifert, Roland

    2013-02-01

    Adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate are second messengers that regulate multiple physiological functions. The existence of additional cyclic nucleotides in mammalian cells was postulated many years ago, but technical problems hampered development of the field. Using highly specific and sensitive mass spectrometry methods, soluble guanylyl cyclase has recently been shown to catalyze the formation of several cyclic nucleotides in vitro. This minireview discusses the broad substrate-specificity of soluble guanylyl cyclase and the possible second messenger roles of cyclic nucleotides other than adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate. We hope that this article stimulates productive and critical research in an area that has been neglected for many years.

  14. Riboswitches in eubacteria sense the second messenger c-di-AMP

    PubMed Central

    Nelson, James W.; Sudarsan, Narasimhan; Furukawa, Kazuhiro; Weinberg, Zasha; Wang, Joy X.; Breaker, Ronald R.

    2013-01-01

    Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered bacterial second messenger implicated in the control of cell wall metabolism, osmotic stress responses, and sporulation. However, the mechanisms by which c-di-AMP triggers these physiological responses have remained largely unknown. Intriguingly, a candidate riboswitch class called ydaO associates with numerous genes involved in these same processes. Although a representative ydaO motif RNA recently was reported to weakly bind ATP, we report that numerous members of this noncoding RNA class selectively respond to c-di-AMP with sub-nanomolar affinity. Our findings resolve the mystery regarding the primary ligand for this extremely common riboswitch class and expose a major portion of the super-regulon of genes that are controlled by the widespread bacterial second messenger c-di-AMP. PMID:24141192

  15. ALTERATIONS IN CALCIUM ION ACTIVITY BY ELF AND RF ELECTROMAGNETIC FIELDS

    EPA Science Inventory



    Alterations in calcium ion activity by ELF and RF electromagnetic fields

    Introduction

    Calcium ions play many important roles in biological systems. For example, calcium ion activity can be used as an indicator of second-messenger signal-transduction processe...

  16. 30 CFR 77.704-11 - Use of grounded messenger wires; ungrounded systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Use of grounded messenger wires; ungrounded... AREAS OF UNDERGROUND COAL MINES Grounding § 77.704-11 Use of grounded messenger wires; ungrounded systems. Solely for purposes of grounding ungrounded high-voltage power systems, grounded messenger wires...

  17. 30 CFR 77.704-11 - Use of grounded messenger wires; ungrounded systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Use of grounded messenger wires; ungrounded... AREAS OF UNDERGROUND COAL MINES Grounding § 77.704-11 Use of grounded messenger wires; ungrounded systems. Solely for purposes of grounding ungrounded high-voltage power systems, grounded messenger wires...

  18. Brain clock driven by neuropeptides and second messengers

    NASA Astrophysics Data System (ADS)

    Miro-Bueno, Jesus; Sosík, Petr

    2014-09-01

    The master circadian pacemaker in mammals is localized in a small portion of the brain called the suprachiasmatic nucleus (SCN). It is unclear how the SCN produces circadian rhythms. A common interpretation is that the SCN produces oscillations through the coupling of genetic oscillators in the neurons. The coupling is effected by a network of neuropeptides and second messengers. This network is crucial for the correct function of the SCN. However, models that study a possible oscillatory behavior of the network itself have received little attention. Here we propose and analyze a model to examine this oscillatory potential. We show that an intercellular oscillator emerges in the SCN as a result of the neuropeptide and second messenger dynamics. We find that this intercellular clock can produce circadian rhythms by itself with and without genetic clocks. We also found that the model is robust to perturbation of parameters and can be entrained by light-dark cycles.

  19. Brain clock driven by neuropeptides and second messengers.

    PubMed

    Miro-Bueno, Jesus; Sosík, Petr

    2014-09-01

    The master circadian pacemaker in mammals is localized in a small portion of the brain called the suprachiasmatic nucleus (SCN). It is unclear how the SCN produces circadian rhythms. A common interpretation is that the SCN produces oscillations through the coupling of genetic oscillators in the neurons. The coupling is effected by a network of neuropeptides and second messengers. This network is crucial for the correct function of the SCN. However, models that study a possible oscillatory behavior of the network itself have received little attention. Here we propose and analyze a model to examine this oscillatory potential. We show that an intercellular oscillator emerges in the SCN as a result of the neuropeptide and second messenger dynamics. We find that this intercellular clock can produce circadian rhythms by itself with and without genetic clocks. We also found that the model is robust to perturbation of parameters and can be entrained by light-dark cycles.

  20. Termination of second messenger signaling in olfaction.

    PubMed Central

    Boekhoff, I; Breer, H

    1992-01-01

    By using isolated rat olfactory cilia and a fast kinetics methodology, it has been demonstrated that odorant-induced second messenger signaling in the millisecond time range is terminated via phosphorylation reactions catalyzed by specific protein kinases. The cyclic adenosine nucleotide pathway is turned off by kinase A activity, whereas the inositol trisphosphate cascade is terminated by kinase C. The data support the concept that desensitization of odorant responses involves phosphorylation of key elements in the transduction cascade. PMID:1370581

  1. MESSENGER Observations of Reconnection and Its Effects on Mercury's Magnetosphere

    NASA Technical Reports Server (NTRS)

    Slavin, James A.; Anderson, Brian J.; Baker, Daniel N.; Benna, Mehdi; Boardsen, Scott A.; Gloeckler, George; Gold, Robert E.; Ho, George C.; Imber, Suzanne M.; Korth, Haje; hide

    2010-01-01

    During MESSENGER's second and third flybys of Mercury on October 6, 2008 and September 29, 2009, respectively, southward interplanetary magnetic fields produced very intense reconnection signatures in the dayside and nightside magnetosphere and very different systemlevel responses. The IMF during the second flyby was continuously southward and the magnetosphere appeared very active with very large magnetic fields normal to the magnetopause and the generation of flux transfer events at the magnetopause and plasmoids in the tail current sheet every 30 s to 90 s. However, the strength and direction of the tail magnetic field was very stable. In contrast the third flyby experienced a variable IMF with it varying from north to south on timescales of minutes. Although the MESSENGER measurements were limited this time to the nightside magnetosphere, numerous examples of plasmoid release in the tail were detected, but they were not periodic. Rather, plasmoid release was highly correlated with the four large enhancements of the tail magnetic field (i.e. by factors > 2) with durations of approx. 2 - 3 min. The increased flaring of the magnetic field during these intervals indicates that the enhancements were caused by loading of the tail with magnetic flux transferred from the dayside magnetosphere. New analyses of the second and third flyby observations of reconnection and its system-level effects will be presented. The results will be examined in light of what is known about the response of the Earth's magnetosphere to variable versus steady southward IMF.

  2. An Investigation into the Effects of Peptide Neurotransmitters and Intracellular Second Messengers in Rat Central Neurons in Culture.

    DTIC Science & Technology

    1988-02-04

    Purkinje neurons. 3. Neuromodulation of synaptic efficacy in an invertebrate preparation that may be a useful model system for the actions of histamine in...neurotransmitters, neuromodulators , affect brain function. Nerve cells are the functional units of the brain, and changes in neuronal activity are ultimately

  3. Zinc as a second messenger of mitogenic induction. Effects on diadenosine tetraphosphate (Ap4A) and DNA synthesis.

    PubMed

    Grummt, F; Weinmann-Dorsch, C; Schneider-Schaulies, J; Lux, A

    1986-03-01

    DNA synthesis and adenosine(5')tetraphosphate(5')adenosine (Ap4A) levels decrease in cells treated with EDTA. The inhibitory effect of EDTA can be reversed with micromolar amounts of ZnCl2. ZnCl2 in micromolar concentrations also inhibits Ap4A hydrolase and stimulates amino acid-dependent Ap4A synthesis, suggesting that Zn2+ is modulating intracellular Ap4A pools. Serum addition to G1-arrested cells enhances uptake of Zn, whereas serum depletion leads to a fivefold decrease of the rates of zinc uptake. These results are discussed by regarding Zn2+ as a putative 'second messenger' of mitogenic induction and Ap4A as a possible 'third messenger' and trigger of DNA synthesis.

  4. Active site structure and catalytic mechanism of phosphodiesterase for degradation of intracellular second messengers

    NASA Astrophysics Data System (ADS)

    Zhan, Chang-Guo

    2002-03-01

    Phosphodiesterases are clinical targets for a variety of biological disorders, because this superfamily of enzymes regulate intracellular concentration of cyclic nucleotides that serve as the second messengers playing a critical role in a variety of physiological processes. Understanding structure and mechanism of a phosphodiesterase will provide a solid basis for rational design of the more efficient therapeutics. Although a three-dimensional X-ray crystal structure of the catalytic domain of human phosphodiesterase 4B2B was recently reported, it was uncertain whether a critical bridging ligand in the active site is a water molecule or a hydroxide ion. The identity of this bridging ligand has been determined by performing first-principles quantum chemical calculations on models of the active site. All the results obtained indicate that this critical bridging ligand in the active site of the reported X-ray crystal structure is a hydroxide ion, rather than a water molecule, expected to serve as the nucleophile to initialize the catalytic degradation of the intracellular second messengers.

  5. Designing proteins to combat disease: Cardiac troponin C as an example.

    PubMed

    Davis, Jonathan P; Shettigar, Vikram; Tikunova, Svetlana B; Little, Sean C; Liu, Bin; Siddiqui, Jalal K; Janssen, Paul M L; Ziolo, Mark T; Walton, Shane D

    2016-07-01

    Throughout history, muscle research has led to numerous scientific breakthroughs that have brought insight to a more general understanding of all biological processes. Potentially one of the most influential discoveries was the role of the second messenger calcium and its myriad of handling and sensing systems that mechanistically control muscle contraction. In this review we will briefly discuss the significance of calcium as a universal second messenger along with some of the most common calcium binding motifs in proteins, focusing on the EF-hand. We will also describe some of our approaches to rationally design calcium binding proteins to palliate, or potentially even cure cardiovascular disease. Considering not all failing hearts have the same etiology, genetic background and co-morbidities, personalized therapies will need to be developed. We predict designer proteins will open doors for unprecedented personalized, and potentially, even generalized medicines as gene therapy or protein delivery techniques come to fruition. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Creating Order from Chaos: Cellular Regulation by Kinase Anchoring

    PubMed Central

    Scott, John D.; Dessauer, Carmen W.; Tasken, Kjetil

    2012-01-01

    Second messenger responses rely on where and when the enzymes that propagate these signals become active. Spatial and temporal organization of certain signaling enzymes is controlled in part by A-kinase anchoring proteins (AKAPs). This family of regulatory proteins was originally classified on the basis of their ability to compartmentalize the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (also known as protein kinase A, or PKA). However, it is now recognized that AKAPs position G protein–coupled receptors, adenylyl cyclases, G proteins, and their effector proteins in relation to protein kinases and signal termination enzymes such as phosphodiesterases and protein phosphatases. This arrangement offers a simple and efficient means to limit the scope, duration, and directional flow of information to sites deep within the cell. This review focuses on the pros and cons of reagents that define the biological role of kinase anchoring inside cells and discusses recent advances in our understanding of anchored second messenger signaling in the cardiovascular and immune systems. PMID:23043438

  7. Choline acetyltransferase expression during periods of behavioral activity and across natural sleep-wake states in the basal forebrain.

    PubMed

    Greco, M A; McCarley, R W; Shiromani, P J

    1999-01-01

    The present study examined whether the expression of the messenger RNA encoding the protein responsible for acetylcholine synthesis is associated with sleep-wakefulness. Choline acetyltransferase messenger RNA levels were analysed using a semi-quantitative assay in which reverse transcription was coupled to complementary DNA amplification using the polymerase chain reaction. To examine the relationship between steady-state messenger RNA and behavioral activity, rats were killed during the day (4.00 p.m.) or night (4.00 a.m.), and tissue from the vertical and horizontal limbs of the diagonal bands of Broca was analysed. Choline acetyltransferase messenger RNA levels were higher during the day than during the night. The second study examined more closely the association between choline acetyltransferase messenger RNA levels and individual bouts of wakefulness, slow-wave sleep or rapid eye movement sleep. Choline acetyltransferase messenger RNA levels were low during wakefulness, intermediate in slow-wave sleep and high during rapid eye movement sleep. In contrast, protein activity, measured at a projection site of cholinergic neurons of the basal forebrain, was higher during wakefulness than during sleep. These findings suggest that choline acetyltransferase protein and messenger RNA levels exhibit an inverse relationship during sleep and wakefulness. The increased messenger RNA expression during sleep is consistent with a restorative function of sleep.

  8. MESSENGER observations of transient bursts of energetic electrons in Mercury's magnetosphere.

    PubMed

    Ho, George C; Krimigis, Stamatios M; Gold, Robert E; Baker, Daniel N; Slavin, James A; Anderson, Brian J; Korth, Haje; Starr, Richard D; Lawrence, David J; McNutt, Ralph L; Solomon, Sean C

    2011-09-30

    The MESSENGER spacecraft began detecting energetic electrons with energies greater than 30 kilo-electron volts (keV) shortly after its insertion into orbit about Mercury. In contrast, no energetic protons were observed. The energetic electrons arrive as bursts lasting from seconds to hours and are most intense close to the planet, distributed in latitude from the equator to the north pole, and present at most local times. Energies can exceed 200 keV but often exhibit cutoffs near 100 keV. Angular distributions of the electrons about the magnetic field suggest that they do not execute complete drift paths around the planet. This set of characteristics demonstrates that Mercury's weak magnetic field does not support Van Allen-type radiation belts, unlike all other planets in the solar system with internal magnetic fields.

  9. Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger

    PubMed Central

    Galperin, Michael Y.; Gomelsky, Mark

    2013-01-01

    SUMMARY Twenty-five years have passed since the discovery of cyclic dimeric (3′→5′) GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger. PMID:23471616

  10. The Effectiveness of Using WhatsApp Messenger as One of Mobile Learning Techniques to Develop Students' Writing Skills

    ERIC Educational Resources Information Center

    Fattah, Said Fathy El Said Abdul

    2015-01-01

    The present study was an attempt to determine the effectiveness of using a WhatsApp Messenger as one of mobile learning techniques to develop students' writing skills. Participants were 30 second year college students, English department from a private university in Saudi Arabia. The experimental group (N = 15) used WhatsApp technology to develop…

  11. Nucleotide, c-di-GMP, c-di-AMP, cGMP, cAMP, (p)ppGpp signaling in bacteria and implications in pathogenesis.

    PubMed

    Kalia, Dimpy; Merey, Gökçe; Nakayama, Shizuka; Zheng, Yue; Zhou, Jie; Luo, Yiling; Guo, Min; Roembke, Benjamin T; Sintim, Herman O

    2013-01-07

    For an organism to survive, it must be able to sense its environment and regulate physiological processes accordingly. Understanding how bacteria integrate signals from various environmental factors and quorum sensing autoinducers to regulate the metabolism of various nucleotide second messengers c-di-GMP, c-di-AMP, cGMP, cAMP and ppGpp, which control several key processes required for adaptation is key for efforts to develop agents to curb bacterial infections. In this review, we provide an update of nucleotide signaling in bacteria and show how these signals intersect or integrate to regulate the bacterial phenotype. The intracellular concentrations of nucleotide second messengers in bacteria are regulated by synthases and phosphodiesterases and a significant number of these metabolism enzymes had been biochemically characterized but it is only in the last few years that the effector proteins and RNA riboswitches, which regulate bacterial physiology upon binding to nucleotides, have been identified and characterized by biochemical and structural methods. C-di-GMP, in particular, has attracted immense interest because it is found in many bacteria and regulate both biofilm formation and virulence factors production. In this review, we discuss how the activities of various c-di-GMP effector proteins and riboswitches are modulated upon c-di-GMP binding. Using V. cholerae, E. coli and B. subtilis as models, we discuss how both environmental factors and quorum sensing autoinducers regulate the metabolism and/or processing of nucleotide second messengers. The chemical syntheses of the various nucleotide second messengers and the use of analogs thereof as antibiofilm or immune modulators are also discussed.

  12. Nuclease-resistant c-di-AMP derivatives that differentially recognize RNA and protein receptors

    PubMed Central

    Meehan, Robert E.; Torgerson, Chad D.; Gaffney, Barbara L.; Jones, Roger A.; Strobel, Scott A.

    2016-01-01

    The ability of bacteria to sense environmental cues and adapt is essential for their survival. The use of second-messenger signaling molecules to translate these cues into a physiological response is a common mechanism employed by bacteria. The second messenger 3’-5’-cyclic diadenosine monophosphate (c-di-AMP) has been linked to a diverse set of biological processes involved in maintaining cell viability and homeostasis, as well as pathogenicity. A complex network of both protein and RNA receptors inside the cell activate specific pathways and mediate phenotypic outputs in response to c-di-AMP. Structural analysis of these RNA and protein receptors has revealed the different recognition elements employed by these effectors to bind the same small molecule. Herein, using a series of c-di-AMP analogs, we probed the interactions made with a riboswitch and a phosphodiesterase protein to identify the features important for c-di-AMP binding and recognition. We found that the ydaO riboswitch binds c-di-AMP in two discrete sites with near identical affinity and a Hill coefficient of 1.6. The ydaO riboswitch distinguishes between c-di-AMP and structurally related second messengers by discriminating against an amine at the C2 position, more than a carbonyl at the C6 position. We also identified phosphate-modified analogs that bind both the ydaO RNA and GdpP protein with high affinity, while symmetrically-modified ribose analogs exhibited a substantial decrease in ydaO affinity, but retained high affinity for GdpP. These ligand modifications resulted in increased resistance to enzyme-catalyzed hydrolysis by the GdpP enzyme. Together, these data suggest that these c-di-AMP analogs could be useful as chemical tools to specifically target subsections of the second-messenger signaling pathways. PMID:26789423

  13. Mechanism of colon cancer cell apoptosis mediated by pyropheophorbide-a methylester photosensitization.

    PubMed

    Matroule, J Y; Carthy, C M; Granville, D J; Jolois, O; Hunt, D W; Piette, J

    2001-07-05

    Pyropheophorbide-a methylester (PPME) is a second generation of photosensitizers used in photodynamic therapy (PDT). We demonstrated that PPME photosensitization triggered apoptosis of colon cancer cells as measured by using several classical parameters such as DNA laddering, PARP cleavage, caspase activation and mitochondrial release of cytochrome c. Preincubation of cells with N-acetyl cysteine (NAC) or pyrolidine dithiocarbamate (PDTC) protected against apoptosis mediated by PPME photosensitization showing that reactive oxygen species (ROS) are involved as second messengers. On the other hand, photosensitization carried out in the presence of deuterium oxide (D2O) which enhances singlet oxygen (1O2) lifetime only increases necrosis without affecting apoptosis. Since PPME was localized in the endoplasmic reticulum (ER)/Golgi system and lysosomes, other messengers than ROS were tested such as calcium, Bid, Bap31, phosphorylated Bcl-2 and caspase-12 but none was clearly identified as being involved in triggering cytochrome c release from mitochondria. On the other hand, we demonstrated that the transduction pathways leading to NF-kappaB activation and apoptosis were clearly independent although NF-kappaB was shown to counteract apoptosis mediated by PPME photosensitization.

  14. cGMP Signaling in the Cardiovascular System—The Role of Compartmentation and Its Live Cell Imaging

    PubMed Central

    Bork, Nadja I.; Nikolaev, Viacheslav O.

    2018-01-01

    The ubiquitous second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) regulates multiple physiologic processes in the cardiovascular system. Its intracellular effects are mediated by stringently controlled subcellular microdomains. In this review, we will illustrate the current techniques available for real-time cGMP measurements with a specific focus on live cell imaging methods. We will also discuss currently accepted and emerging mechanisms of cGMP compartmentation in the cardiovascular system. PMID:29534460

  15. Caged compounds: tools for illuminating neuronal responses and connections.

    PubMed

    Nerbonne, J M

    1996-06-01

    A number of new 'caged' intracellular second messengers and neurotransmitters have been developed using the photolabile o-nitrobenzyl group. This chemistry has also recently been exploited in novel ways, including the development of caged enzyme substrates and caged proteins. Although caged compounds continue to be used primarily for mechanistic (kinetic) studies of processes mediated by transmitters or second messengers, the spatial resolution afforded by the use of light to effect changes in transmitter concentrations has now been clearly demonstrated. The increased availability of caged compounds and of the technologies required to exploit them provides neurobiologists with powerful tools for probing neuronal response properties and connectivity patterns.

  16. Inhibition of endothelin- and phorbol ester-stimulated tyrosine kinase activity by corticotrophin in the rat adrenal zona glomerulosa.

    PubMed Central

    Kapas, S; Hinson, J P

    1996-01-01

    1. The experiments described in this study were carried out to investigate the role of tyrosine kinase in the acute adrenal response to peptide hormone stimulation, and to determine whether the activity of this kinase may be subject to regulation by other intracellular signalling mechanisms in the adrenal zona glomerulosa. 2. Previous studies from this laboratory have shown that angiotensin II stimulates tyrosine kinase activity in the rat adrenal cortex. This study has shown, for the first time, that endothelin-1 also stimulates tyrosine kinase activity in this tissue. 3. Using the specific inhibitor of protein kinase C (PKC) activity, Ro 31-8220, we have shown that stimulation of tyrosine kinase activity, in response to endothelin-1, angiotensin II or the phorbol ester phorbol 12-myristate 13-acetate, is at least partly dependent on increased PKC activity. 4. The data presented also provide further evidence of cross-talk between signalling systems in the adrenal cortex. Corticotrophin and its intracellular second messenger, cyclic AMP, significantly attenuate the increment in tyrosine kinase activity seen in response to each of the effectors used. 5. The results of this study provide important new evidence for the regulation of protein kinases by other intracellular second messenger systems. PMID:8611168

  17. Exploring the Rays of Debussy

    NASA Image and Video Library

    2017-12-08

    NASA image acquired: March 29, 2011 Bright rays, consisting of impact ejecta and secondary craters, spread across this NAC image and radiate from Debussy crater, located at the top. The image, acquired yesterday during the first orbit for which MDIS was imaging, shows just a small portion of Debussy's large system of rays in greater detail than ever previously seen. Images acquired during MESSENGER's second Mercury flyby showed that Debussy's rays extend for hundreds of kilometers across Mercury's surface. Debussy crater was named in March 2010, in honor of the French composer Claude Debussy (1862-1918). On March 17, 2011 (March 18, 2011, UTC), MESSENGER became the first spacecraft to orbit the planet Mercury. The mission is currently in its commissioning phase, during which spacecraft and instrument performance are verified through a series of specially designed checkout activities. In the course of the one-year primary mission, the spacecraft's seven scientific instruments and radio science investigation will unravel the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the science questions that the MESSENGER mission has set out to answer. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Join us on Facebook

  18. Details of MESSENGER Impact Location

    NASA Image and Video Library

    2015-04-29

    These graphics show the current best prediction of the location and time of NASA MESSENGER impact on Mercury surface. These current best estimates are: Date: 30 April 2015 Time: 3:26:02 pm EDT 19:26:02 UTC Latitude: 54.4° N Longitude: 210.1° E. Traveling at 3.91 kilometers per second (over 8,700 miles per hour), the MESSENGER spacecraft will collide with Mercury's surface, creating a crater estimated to be 16 meters (52 feet) in diameter. View this image to learn about the named features and geology of this region on Mercury. Instruments: Mercury Dual Imaging System (MDIS) and Mercury Laser Altimeter (MLA) Top Image Latitude Range: 49°-59° N Top Image Longitude Range: 204°-217° E Topography in Top Image: Exaggerated by a factor of 5.5. Colors in Top Image: Coded by topography. The tallest regions are colored red and are roughly 3 kilometers (1.9 miles) higher than low-lying areas such as the floors of impact craters, colored blue. Scale in Top Image: The large crater on the left side of the image is Janacek, with a diameter of 48 kilometers (30 miles) http://photojournal.jpl.nasa.gov/catalog/PIA19443

  19. MESSENGER observations of Mercury's exosphere: detection of magnesium and distribution of constituents.

    PubMed

    McClintock, William E; Vervack, Ronald J; Bradley, E Todd; Killen, Rosemary M; Mouawad, Nelly; Sprague, Ann L; Burger, Matthew H; Solomon, Sean C; Izenberg, Noam R

    2009-05-01

    Mercury is surrounded by a tenuous exosphere that is supplied primarily by the planet's surface materials and is known to contain sodium, potassium, and calcium. Observations by the Mercury Atmospheric and Surface Composition Spectrometer during MESSENGER's second Mercury flyby revealed the presence of neutral magnesium in the tail (anti-sunward) region of the exosphere, as well as differing spatial distributions of magnesium, calcium, and sodium atoms in both the tail and the nightside, near-planet exosphere. Analysis of these observations, supplemented by observations during the first Mercury flyby, as well as those by other MESSENGER instruments, suggests that the distinct spatial distributions arise from a combination of differences in source, transfer, and loss processes.

  20. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, workers begin moving NASA’s MESSENGER spacecraft into the building MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - is being taken into a high bay clean room where employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, workers begin moving NASA’s MESSENGER spacecraft into the building MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - is being taken into a high bay clean room where employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  1. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, a lift begins lowering NASA’s MESSENGER spacecraft onto the ground. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, a lift begins lowering NASA’s MESSENGER spacecraft onto the ground. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  2. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, workers check the moveable pallet holding NASA’s MESSENGER spacecraft. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, workers check the moveable pallet holding NASA’s MESSENGER spacecraft. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  3. Monte Carlo Modeling of Sodium in Mercury's Exosphere During the First Two MESSENGER Flybys

    NASA Technical Reports Server (NTRS)

    Burger, Matthew H.; Killen, Rosemary M.; Vervack, Ronald J., Jr.; Bradley, E. Todd; McClintock, William E.; Sarantos, Menelaos; Benna, Mehdi; Mouawad, Nelly

    2010-01-01

    We present a Monte Carlo model of the distribution of neutral sodium in Mercury's exosphere and tail using data from the Mercury Atmospheric and Surface Composition Spectrometer (MASCS) on the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft during the first two flybys of the planet in January and September 2008. We show that the dominant source mechanism for ejecting sodium from the surface is photon-stimulated desorption (PSD) and that the desorption rate is limited by the diffusion rate of sodium from the interior of grains in the regolith to the topmost few monolayers where PSD is effective. In the absence of ion precipitation, we find that the sodium source rate is limited to approximately 10(exp 6) - 10(exp 7) per square centimeter per second, depending on the sticking efficiency of exospheric sodium that returns to the surface. The diffusion rate must be at least a factor of 5 higher in regions of ion precipitation to explain the MASCS observations during the second MESSENGER f1yby. We estimate that impact vaporization of micrometeoroids may provide up to 15% of the total sodium source rate in the regions observed. Although sputtering by precipitating ions was found not to be a significant source of sodium during the MESSENGER flybys, ion precipitation is responsible for increasing the source rate at high latitudes through ion-enhanced diffusion.

  4. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, NASA’s MESSENGER spacecraft from NASA’s Goddard Space Flight Center in Greenbelt, Md., is offloaded. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, NASA’s MESSENGER spacecraft from NASA’s Goddard Space Flight Center in Greenbelt, Md., is offloaded. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  5. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, a lift helps offload NASA’s MESSENGER spacecraft shipped from NASA’s Goddard Space Flight Center in Greenbelt, Md. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, a lift helps offload NASA’s MESSENGER spacecraft shipped from NASA’s Goddard Space Flight Center in Greenbelt, Md. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  6. Reductions of {sup 56}Fe heavy-particle irradiation-induced deficits in striatal muscarinic receptor sensitivity by selective cross-activation/inhibition of second-messenger systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Joseph, J.A.; Villalobos-Molina, R.; Rabin, B.M.

    Recent experiments have revealed radiation-induced losses of sensitivity of rodent neostriatal muscarinic receptors to stimulation by cholinergic agonists that appears as reduction in oxotremorine enhancement of K{sup +}-evoked dopamine release. These losses were postulated to be the result of radiation-induced alterations early in phosphoinositide-mediated signal transduction. Additional findings indicated that if the ligand-receptor-G protein interface was bypassed no radiation deficits were seen. In the present study, radiation-induced deficits in K{sup +}-evoked dopamine release were examined in perifused striatal tissue obtained from rats exposed to 0,0.1 or 1.0 Gy of {sup 56}Fe particles. Results showed that these deficits could be reducedmore » by co-applying combinations of various pharmacological agents that were known to have differential effects on various second messengers such as 1,4,5-inositoltrisphosphate (IP{sub 3}). Combinations included oxotremorine-carbachol, and either oxotremorine or carbachol with arginine vasopressin or arachidonic acid. These results are discussed in terms of putative radiation-induced changes in receptor-containing membranes which alter receptor-G protein coupling/uncoupling. 49 refs., 4 figs.« less

  7. c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria

    PubMed Central

    Fahmi, Tazin; Port, Gary C.

    2017-01-01

    Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an attractive antimicrobial drug target and therefore has been the focus of intensive study in several important pathogens. PMID:28783096

  8. KSC-04pd1347

    NASA Image and Video Library

    2004-06-25

    KENNEDY SPACE CENTER, FLA. - At Astrotech in Titusville, Fla., technicians secure guide wires on the second solar panel to be installed on NASA’s MESSENGER spacecraft. The two large solar panels, supplemented with a nickel-hydrogen battery, will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  9. KSC-04pd1346

    NASA Image and Video Library

    2004-06-25

    KENNEDY SPACE CENTER, FLA. - At Astrotech in Titusville, Fla., technicians check the second solar panel that will be installed on NASA’s MESSENGER spacecraft. The two large solar panels, supplemented with a nickel-hydrogen battery, will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  10. KSC-04pd1345

    NASA Image and Video Library

    2004-06-25

    KENNEDY SPACE CENTER, FLA. - At Astrotech in Titusville, Fla., technicians maneuver a second solar panel to a vertical position to move it toward NASA’s MESSENGER spacecraft for installation. The two large solar panels, supplemented with a nickel-hydrogen battery, will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  11. KSC-04pd1349

    NASA Image and Video Library

    2004-06-25

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech in Titusville, Fla., hold steady the second solar panel being installed on NASA’s MESSENGER spacecraft. At left is the first panel already installed. The two large solar panels, supplemented with a nickel-hydrogen battery, will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  12. Mechanisms of Regulation of Olfactory Transduction and Adaptation in the Olfactory Cilium

    PubMed Central

    Antunes, Gabriela; Sebastião, Ana Maria; Simoes de Souza, Fabio Marques

    2014-01-01

    Olfactory adaptation is a fundamental process for the functioning of the olfactory system, but the underlying mechanisms regulating its occurrence in intact olfactory sensory neurons (OSNs) are not fully understood. In this work, we have combined stochastic computational modeling and a systematic pharmacological study of different signaling pathways to investigate their impact during short-term adaptation (STA). We used odorant stimulation and electroolfactogram (EOG) recordings of the olfactory epithelium treated with pharmacological blockers to study the molecular mechanisms regulating the occurrence of adaptation in OSNs. EOG responses to paired-pulses of odorants showed that inhibition of phosphodiesterases (PDEs) and phosphatases enhanced the levels of STA in the olfactory epithelium, and this effect was mimicked by blocking vesicle exocytosis and reduced by blocking cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and vesicle endocytosis. These results suggest that G-coupled receptors (GPCRs) cycling is involved with the occurrence of STA. To gain insights on the dynamical aspects of this process, we developed a stochastic computational model. The model consists of the olfactory transduction currents mediated by the cyclic nucleotide gated (CNG) channels and calcium ion (Ca2+)-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca2+, and it simulates the EOG results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca2+ response, two second messengers implicated with STA occurrence. The model reproduced the experimental data for each pharmacological treatment and provided a mechanistic explanation for the action of GPCR cycling in the levels of second messengers modulating the levels of STA. All together, these experimental and theoretical results indicate the existence of a mechanism of regulation of STA by signaling pathways that control GPCR cycling and tune the levels of second messengers in OSNs, and not only by CNG channel desensitization as previously thought. PMID:25144232

  13. The Yersinia pestis Rcs phosphorelay inhibits biofilm formation by repressing transcription of the diguanylate cyclase gene hmsT.

    PubMed

    Sun, Yi-Cheng; Guo, Xiao-Peng; Hinnebusch, B Joseph; Darby, Creg

    2012-04-01

    Yersinia pestis, which causes bubonic plague, forms biofilms in fleas, its insect vectors, as a means to enhance transmission. Biofilm development is positively regulated by hmsT, encoding a diguanylate cyclase that synthesizes the bacterial second messenger cyclic-di-GMP. Biofilm development is negatively regulated by the Rcs phosphorelay signal transduction system. In this study, we show that Rcs-negative regulation is accomplished by repressing transcription of hmsT.

  14. KSC-04pd1447

    NASA Image and Video Library

    2004-07-06

    KENNEDY SPACE CENTER, FLA. - The Boeing Delta II Heavy second-stage engine, the Aerojet AJ10-118K, is lifted up the mobile service tower at Pad 17-B, Cape Canaveral Air Force Station. The Delta II is the launch vehicle for the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft, scheduled to lift off Aug. 2. Bound for Mercury, the spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  15. Synthesis and characterization of non-hydrolysable diphosphoinositol polyphosphate second messengers.

    PubMed

    Wu, Mingxuan; Dul, Barbara E; Trevisan, Alexandra J; Fiedler, Dorothea

    2013-01-01

    The diphosphoinositol polyphosphates (PP-IPs) are a central group of eukaryotic second messengers. They regulate numerous processes, including cellular energy homeostasis and adaptation to environmental stresses. To date, most of the molecular details in PP-IP signalling have remained elusive, due to a lack of appropriate methods and reagents. Here we describe the expedient synthesis of methylene-bisphosphonate PP-IP analogues. Their characterization revealed that the analogues exhibit significant stability and mimic their natural counterparts very well. This was further confirmed in two independent biochemical assays, in which our analogues potently inhibited phosphorylation of the protein kinase Akt and hydrolytic activity of the Ddp1 phosphohydrolase. The non-hydrolysable PP-IPs thus emerge as important tools and hold great promise for a variety of applications.

  16. KENNEDY SPACE CENTER, FLA. - Doors are open on the air-conditioned transportation van that carried NASA’s MESSENGER spacecraft from NASA’s Goddard Space Flight Center in Greenbelt, Md., to the Astrotech Space Operations processing facilities near KSC. After offloading, MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - Doors are open on the air-conditioned transportation van that carried NASA’s MESSENGER spacecraft from NASA’s Goddard Space Flight Center in Greenbelt, Md., to the Astrotech Space Operations processing facilities near KSC. After offloading, MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  17. Fluorescence correlation spectroscopy experiments to quantify free diffusion coefficients in reaction-diffusion systems: The case of Ca2 + and its dyes

    NASA Astrophysics Data System (ADS)

    Sigaut, Lorena; Villarruel, Cecilia; Ponce, María Laura; Ponce Dawson, Silvina

    2017-06-01

    Many cell signaling pathways involve the diffusion of messengers that bind and unbind to and from intracellular components. Quantifying their net transport rate under different conditions then requires having separate estimates of their free diffusion coefficient and binding or unbinding rates. In this paper, we show how performing sets of fluorescence correlation spectroscopy (FCS) experiments under different conditions, it is possible to quantify free diffusion coefficients and on and off rates of reaction-diffusion systems. We develop the theory and present a practical implementation for the case of the universal second messenger, calcium (Ca2 +) and single-wavelength dyes that increase their fluorescence upon Ca2 + binding. We validate the approach with experiments performed in aqueous solutions containing Ca2 + and Fluo4 dextran (both in its high and low affinity versions). Performing FCS experiments with tetramethylrhodamine-dextran in Xenopus laevis oocytes, we infer the corresponding free diffusion coefficients in the cytosol of these cells. Our approach can be extended to other physiologically relevant reaction-diffusion systems to quantify biophysical parameters that determine the dynamics of various variables of interest.

  18. Move over protein kinase C, you've got company: alternative cellular effectors of diacylglycerol and phorbol esters.

    PubMed

    Brose, Nils; Rosenmund, Christian

    2002-12-01

    Diacylglycerol is an essential second messenger in mammalian cells. The most prominent intracellular targets of diacylglycerol and of the functionally analogous phorbol esters belong to the protein kinase C (PKC) family. However, at least five alternative types of high-affinity diacylglycerol/phorbol-ester receptor are known: chimaerins, protein kinase D, RasGRPs, Munc13s and DAG kinase gamma. Recent evidence indicates that these have functional roles in diacylglycerol second messenger signalling in vivo and that several cellular processes depend on these targets rather than protein kinase C isozymes. These findings contradict the still prevalent view according to which all diacylglycerol/phorbol-ester effects are caused by the activation of protein kinase C isozymes. RasGRP1 (in Ras/Raf/MEK/ERK signalling) and Munc13-1 (in neurotransmitter secretion) are examples of non-PKC diacylglycerol/phorbol-ester receptors that mediate diacylglycerol and phorbol-ester effects originally thought to be caused by PKC isozymes. In the future, pharmacological studies on PKC must be complemented with alternative experimental approaches to allow the separation of PKC-mediated effects from those caused by alternative targets of the diacylglycerol second messenger pathway. The examples of RasGRP1 and Munc13-1 show that detailed genetic analyses of C(1)-domain-containing non-PKC diacylglycerol/phorbol-ester receptors in mammals are ideally suited to achieve this goal.

  19. KSC-04pd1348

    NASA Image and Video Library

    2004-06-25

    KENNEDY SPACE CENTER, FLA. - At right, technicians at Astrotech in Titusville, Fla., guide into place the second solar panel to be installed on NASA’s MESSENGER spacecraft. At left is the first panel already installed. The two large solar panels, supplemented with a nickel-hydrogen battery, will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  20. KENNEDY SPACE CENTER, FLA. - Shipped in an air-conditioned transportation van from NASA’s Goddard Space Flight Center in Greenbelt, Md., NASA’s MESSENGER spacecraft, the first Mercury orbiter, arrives at the Astrotech Space Operations processing facilities near KSC. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be offloaded and taken into a high bay clean room. After the spacecraft is removed from its shipping container, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - Shipped in an air-conditioned transportation van from NASA’s Goddard Space Flight Center in Greenbelt, Md., NASA’s MESSENGER spacecraft, the first Mercury orbiter, arrives at the Astrotech Space Operations processing facilities near KSC. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be offloaded and taken into a high bay clean room. After the spacecraft is removed from its shipping container, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  1. Synthesis and characterization of non-hydrolysable diphosphoinositol polyphosphate second messengers

    PubMed Central

    Wu, Mingxuan; Dul, Barbara E.; Trevisan, Alexandra J.; Fiedler, Dorothea

    2012-01-01

    The diphosphoinositol polyphosphates (PP-IPs) are a central group of eukaryotic second messengers. They regulate numerous processes, including cellular energy homeostasis and adaptation to environmental stresses. To date, most of the molecular details in PP-IP signalling have remained elusive, due to a lack of appropriate methods and reagents. Here we describe the expedient synthesis of methylene-bisphosphonate PP-IP analogues. Their characterization revealed that the analogues exhibit significant stability and mimic their natural counterparts very well. This was further confirmed in two independent biochemical assays, in which our analogues potently inhibited phosphorylation of the protein kinase Akt and hydrolytic activity of the Ddp1 phosphohydrolase. The non-hydrolysable PP-IPs thus emerge as important tools and hold great promise for a variety of applications. PMID:23378892

  2. KSC-04pd1453

    NASA Image and Video Library

    2004-07-06

    KENNEDY SPACE CENTER, FLA. - Workers in the mobile service tower on Pad 17-B, Cape Canaveral Air Force Station, check the progress of the Boeing Delta II Heavy second-stage engine as it descends toward the first stage. The Delta is the launch vehicle for the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft, scheduled to lift off Aug. 2. Bound for Mercury, the spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  3. KSC-04pd1446

    NASA Image and Video Library

    2004-07-06

    KENNEDY SPACE CENTER, FLA. - The Boeing Delta II Heavy second-stage engine, the Aerojet AJ10-118K, is ready for lifting up the mobile service tower at Pad 17-B, Cape Canaveral Air Force Station. The Delta II is the launch vehicle for the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft, scheduled to lift off Aug. 2. Bound for Mercury, the spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  4. Molecular and cellular aspects of calcium action in plants

    NASA Technical Reports Server (NTRS)

    Poovaiah, B. W.

    1988-01-01

    Calcium is known to be a second messenger in many developmental processes in animal systems, but it has only recently become evident that Ca is an important intracellular messenger in plants as well. The level of free Ca concentration in the cytoplasm is extremely low, and it is influenced by extracellular signals such as light, gravity, and hormones. Investigations from our laboratory indicated that Ca and its binding protein, calmodulin, play an important role in stimulus-response coupling by regulating enzyme activities, especially through protein phosphorylation. In vivo and in vitro protein phosphorylation studies have revealed Ca-dependent changes in various plant tissues. We have also been able to influence various physiological processes such as cell elongation, abscission, senescence, and tuberization by altering extracellular and intracellular Ca levels. Other examples of Ca-mediated processes in plants are as follows: a) cell division, b) geotropism, c) protoplasmic streaming, d) stomatal control, e) chloroplast movement, f) secretion, g) hormone-dependent changes, h) enzyme activation, and i) protein phosphorylation.

  5. MESSENGER Observations of Mercury's Dynamic Magnetosphere During Three Flybys

    NASA Astrophysics Data System (ADS)

    Slavin, James; Krimigis, Stamatios; Anderson, Brian J.; Benna, Mehdi; Gold, Robert E.; Ho, George; McNutt, Ralph; Raines, James; Schriver, David; Solomon, Sean C.

    MESSENGER's 14 January and 6 October 2008 and 29 September 2009 encounters with Mer-cury have provided new measurements of dynamic variations in the planet's coupled atmo-sphere-magnetosphere system. The three flybys took place under very different interplanetary magnetic field (IMF) conditions. Consistent with predictions of magnetospheric models for northward IMF, the neutral atmosphere was observed to have its strongest sources in the high latitude northern hemisphere for the first flyby. The southward IMF for the second encounter revealed a highly dynamic magnetosphere. Reconnection between the interplanetary and plan-etary magnetic fields is known to control the rate of energy transfer from the solar wind and to drive magnetospheric convection. The MESSENGER magnetic field measurements revealed that the rate at which interplanetary magnetic fields were reconnecting to the planetary fields was a factor of 10 greater than is usually observed at Earth. This extremely high reconnection rate results in a large magnetic field component normal to the magnetopause and the formation of flux transfer events that are much larger relative to the size of the forward magnetosphere than is observed at Earth. The resulting magnetospheric configuration allows the solar wind access to much of the dayside surface of Mercury. During MESSENGER's third Mercury flyby, a variable interplanetary magnetic field produced a series of several-minute-long enhancements of the tail magnetic field by factors of 2 to 3.5. The magnetic field flaring during these intervals indicates that they resulted from loading of the tail with magnetic flux transferred from the dayside magnetosphere. The unloading intervals were associated with plasmoids and traveling compression regions, signatures of tail reconnection. The peak tail magnetic flux during the smallest loading events equaled 30

  6. Calcium ion as intracellular messenger and cellular toxin.

    PubMed

    Rasmussen, H; Barrett, P; Smallwood, J; Bollag, W; Isales, C

    1990-03-01

    Ca2+ serves a nearly universal intracellular messenger function in cell activation, but excess Ca2+ is also a cellular toxin. The possibility of Ca2+ intoxication is minimized by an elaborate autoregulatory system in which changes in Ca2+ influx rate across the plasma membrane are rapidly compensated for by parallel changes in Ca2+ efflux rate. By this mean, cellular Ca2+ homestasis is maintained so that minimal changes in total cell calcium and cytosolic Ca2+ concentration occur during sustained Ca2(+)-mediated responses. Rather than a sustained increase in cytosolic Ca2+ concentration, it is the localized cycling of Ca2+ across the plasma membrane that is the critically important Ca2+ messenger during the sustained phase of cellular responses mediated via surface receptors linked to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 hydrolysis gives rise to inositol(1,4,5)trisphosphate (IP3) and diacylglycerol (DAG). The IP3 acts to release Ca2+ from an intracellular pool, thereby causing a transient rise in cytosolic Ca2+ concentration. This transient Ca2+ signal activates calmodulin-dependent protein kinases transiently, and hence, causes the transient phosphorylation of a subset of cellular proteins that mediate the initial phase of the response. The DAG brings about the association of protein kinase C (PKC) with the plasma membrane where a receptor-mediated increase in Ca2+ cycling across the membrane regulates PKC activity. The sustained phosphorylation of a second subset of proteins by PKC mediates the sustained phase of the response. Hence, Ca2+ serves as a messenger during both phases of the cellular response, but its cellular sites of action, its mechanisms of generation, and its molecular targets differ during the initial and sustained phases of the response.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Calcium ion as intracellular messenger and cellular toxin.

    PubMed Central

    Rasmussen, H; Barrett, P; Smallwood, J; Bollag, W; Isales, C

    1990-01-01

    Ca2+ serves a nearly universal intracellular messenger function in cell activation, but excess Ca2+ is also a cellular toxin. The possibility of Ca2+ intoxication is minimized by an elaborate autoregulatory system in which changes in Ca2+ influx rate across the plasma membrane are rapidly compensated for by parallel changes in Ca2+ efflux rate. By this mean, cellular Ca2+ homestasis is maintained so that minimal changes in total cell calcium and cytosolic Ca2+ concentration occur during sustained Ca2(+)-mediated responses. Rather than a sustained increase in cytosolic Ca2+ concentration, it is the localized cycling of Ca2+ across the plasma membrane that is the critically important Ca2+ messenger during the sustained phase of cellular responses mediated via surface receptors linked to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 hydrolysis gives rise to inositol(1,4,5)trisphosphate (IP3) and diacylglycerol (DAG). The IP3 acts to release Ca2+ from an intracellular pool, thereby causing a transient rise in cytosolic Ca2+ concentration. This transient Ca2+ signal activates calmodulin-dependent protein kinases transiently, and hence, causes the transient phosphorylation of a subset of cellular proteins that mediate the initial phase of the response. The DAG brings about the association of protein kinase C (PKC) with the plasma membrane where a receptor-mediated increase in Ca2+ cycling across the membrane regulates PKC activity. The sustained phosphorylation of a second subset of proteins by PKC mediates the sustained phase of the response. Hence, Ca2+ serves as a messenger during both phases of the cellular response, but its cellular sites of action, its mechanisms of generation, and its molecular targets differ during the initial and sustained phases of the response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2190811

  8. Coronal mass ejection hits mercury: A.I.K.E.F. hybrid-code results compared to MESSENGER data

    NASA Astrophysics Data System (ADS)

    Exner, W.; Heyner, D.; Liuzzo, L.; Motschmann, U.; Shiota, D.; Kusano, K.; Shibayama, T.

    2018-04-01

    Mercury is the closest orbiting planet around the sun and is therefore embedded in an intensive and highly varying solar wind. In-situ data from the MESSENGER spacecraft of the plasma environment near Mercury indicates that a coronal mass ejection (CME) passed the planet on 23 November 2011 over the span of the 12 h MESSENGER orbit. Slavin et al. (2014) derived the upstream parameters of the solar wind at the time of that orbit, and were able to explain the observed MESSENGER data in the cusp and magnetopause segments of MESSENGER's trajectory. These upstream parameters will be used for our first simulation run. We use the hybrid code A.I.K.E.F. which treats ions as individual particles and electrons as a mass-less fluid, to conduct hybrid simulations of Mercury's magnetospheric response to the impact of the CME on ion gyro time scales. Results from the simulation are in agreement with magnetic field measurements from the inner day-side magnetosphere and the bow-shock region. However, at the planet's nightside, Mercury's plasma environment seemed to be governed by different solar wind conditions, in conclusion, Mercury's interaction with the CME is not sufficiently describable by only one set of upstream parameters. Therefore, to simulate the magnetospheric response while MESSENGER was located in the tail region, we use parameters obtained from the MHD solar wind simulation code SUSANOO (Shiota et al. (2014)) for our second simulation run. The parameters of the SUSANOO model achieve a good agreement of the data concerning the plasma tail crossing and the night-side approach to Mercury. However, the polar and closest approach are hardly described by both upstream parameters, namely, neither upstream dataset is able to reproduce the MESSENGER crossing of Mercury's magnetospheric cusp. We conclude that the respective CME was too variable on the timescale of the MESSENGER orbit to be described by only two sets of upstream conditions. Our results suggest locally strong and highly variable dynamics of the CME on timescales of 15 min while MESSENGER was near closest approach.

  9. Symptoms, visual function, and mucin expression of eyes with tear film instability.

    PubMed

    Shimazaki-Den, Seika; Dogru, Murat; Higa, Kazunari; Shimazaki, Jun

    2013-09-01

    We examined symptoms, tear stability, visual function, and conjunctival cytology in eyes with an unstable tear film (UTF), expressed as a short tear film breakup time without epithelial damage or low tear secretion, and compared the results with those from eyes with aqueous deficiency (AD) associated with epithelial damage, and healthy eyes. We divided the patients with ocular discomfort into 2 groups according to the breakup time, Schirmer value, and epithelial staining score: UTF group (≤5 seconds, >5 mm, and <3 points; 21 eyes of 21 patients) and AD group (≤5 seconds, ≤5 mm, and ≥3 points; 21 eyes of 21 patients). We examined all patients and 17 healthy subjects for symptoms, tear functions, tear film stability by tear film lipid layer interferometry and tear film analysis system, and functional visual acuity. Conjunctival impression cytology was performed to investigate changes in goblet cell density, squamous metaplasia, and messenger RNA expression of MUC5AC and MUC16. The symptom scores, tear film analysis system index, and functional visual acuity testing were significantly worse in the UTF and AD groups compared with those in the control group (P < 0.05). The messenger RNA expression levels of MUC5AC and MUC16 were significantly lower in UTF and AD eyes compared with those in the control eyes (P < 0.0001). An UTF itself can cause dry eye symptoms and visual disturbance comparable with those of AD dry eyes.

  10. Imaging During MESSENGER's Second Flyby of Mercury

    NASA Astrophysics Data System (ADS)

    Chabot, N. L.; Prockter, L. M.; Murchie, S. L.; Robinson, M. S.; Laslo, N. R.; Kang, H. K.; Hawkins, S. E.; Vaughan, R. M.; Head, J. W.; Solomon, S. C.; MESSENGER Team

    2008-12-01

    During MESSENGER's second flyby of Mercury on October 6, 2008, the Mercury Dual Imaging System (MDIS) will acquire 1287 images. The images will include coverage of about 30% of Mercury's surface not previously seen by spacecraft. A portion of the newly imaged terrain will be viewed during the inbound portion of the flyby. On the outbound leg, MDIS will image additional previously unseen terrain as well as regions imaged under different illumination geometry by Mariner 10. These new images, when combined with images from Mariner 10 and from MESSENGER's first Mercury flyby, will enable the first regional- resolution global view of Mercury constituting a combined total coverage of about 96% of the planet's surface. MDIS consists of both a Wide Angle Camera (WAC) and a Narrow Angle Camera (NAC). During MESSENGER's second Mercury flyby, the following imaging activities are planned: about 86 minutes before the spacecraft's closest pass by the planet, the WAC will acquire images through 11 different narrow-band color filters of the approaching crescent planet at a resolution of about 5 km/pixel. At slightly less than 1 hour to closest approach, the NAC will acquire a 4-column x 11-row mosaic with an approximate resolution of 450 m/pixel. At 8 minutes after closest approach, the WAC will obtain the highest-resolution multispectral images to date of Mercury's surface, imaging a portion of the surface through 11 color filters at resolutions of about 250-600 m/pixel. A strip of high-resolution NAC images, with a resolution of approximately 100 m/pixel, will follow these WAC observations. The NAC will next acquire a 15-column x 13- row high-resolution mosaic of the northern hemisphere of the departing planet, beginning approximately 21 minutes after closest approach, with resolutions of 140-300 m/pixel; this mosaic will fill a large gore in the Mariner 10 data. At about 42 minutes following closest approach, the WAC will acquire a 3x3, 11-filter, full- planet mosaic with an average resolution of 2.5 km/pixel. Two NAC mosaics of the entire departing planet will be acquired beginning about 66 minutes after closest approach, with resolutions of 500-700 m/pixel. About 89 minutes following closest approach, the WAC will acquire a multispectral image set with a resolution of about 5 km/pixel. Following this WAC image set, MDIS will continue to acquire occasional images with both the WAC and NAC until 20 hours after closest approach, at which time the flyby data will begin being transmitted to Earth.

  11. A whole new Mercury: MESSENGER reveals a dynamic planet at the last frontier of the inner solar system

    NASA Astrophysics Data System (ADS)

    Johnson, Catherine L.; Hauck, , Steven A.

    2016-11-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) mission yielded a wealth of information about the innermost planet. For the first time, visible images of the entire planet, absolute altimetry measurements and a global gravity field, measurements of Mercury's surface composition, magnetic field, exosphere, and magnetosphere taken over more than four Earth years are available. From these data, two overarching themes emerge. First, multiple data sets and modeling efforts point toward a dynamic ancient history. Signatures of graphite in the crust suggest solidification of an early magma ocean, image data show extensive volcanism and tectonic features indicative of subsequent global contraction, and low-altitude measurements of magnetic fields reveal an ancient magnetic field. Second, the present-day Mercury environment is far from quiescent. Convective motions in the outer core support a modern magnetic field whose strength and geometry are unique among planets with global magnetic fields. Furthermore, periodic and aperiodic variations in the magnetosphere and exosphere have been observed, some of which couple to the surface and the planet's deep interior. Finally, signatures of geologically recent volatile activity at the surface have been detected. Mercury's early history and its present-day environment have common elements with the other inner solar system bodies. However, in each case there are also crucial differences and these likely hold the key to further understanding of Mercury and terrestrial planet evolution. MESSENGER's exploration of Mercury has enabled a new view of the innermost planet, and more importantly has set the stage for much-needed future exploration.

  12. GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release.

    PubMed

    Filardo, Edward J; Thomas, Peter

    2005-10-01

    Heterotrimeric G proteins and seven-transmembrane-spanning (7TM) receptors are implicated in rapid estrogen signaling. The orphan 7TM receptor GPR30 is linked to estrogen-mediated activation of adenylyl cyclase, release of epidermal growth factor (EGF)-related ligands, and specific estrogen binding. GPR30 acts independently of estrogen receptors, ERalpha and ERbeta, and probably functions as a heptahelical ER. 7TM receptors elicit signals that stimulate second messengers, and convey intracellular signals via EGF receptors. Identification of GPR30 as a Gs-coupled 7TM receptor that triggers release of heparin-binding EGF establishes its role in cell signaling cascades initiated by estrogens, and explains their capacity to activate second messengers and promote EGF-like effects. Thus, estrogen can signal by the same mechanism as various other hormones, through a specific 7TM receptor.

  13. Diadenosine Tetraphosphate Hydrolase Is Part of the Transcriptional Regulation Network in Immunologically Activated Mast Cells▿

    PubMed Central

    Carmi-Levy, Irit; Yannay-Cohen, Nurit; Kay, Gillian; Razin, Ehud; Nechushtan, Hovav

    2008-01-01

    We previously discovered that microphthalmia transcription factor (MITF) and upstream stimulatory factor 2 (USF2) each forms a complex with its inhibitor histidine triad nucleotide-binding 1 (Hint-1) and with lysyl-tRNA synthetase (LysRS). Moreover, we showed that the dinucleotide diadenosine tetraphosphate (Ap4A), previously shown to be synthesized by LysRS, binds to Hint-1, and as a result the transcription factors are released from their suppression. Thus, transcriptional activity is regulated by Ap4A, suggesting that Ap4A is a second messenger in this context. For Ap4A to be unambiguously established as a second messenger, several criteria have to be fulfilled, including the presence of a metabolizing enzyme. Since several enzymes are able to hydrolize Ap4A, we provided here evidence that the “Nudix” type 2 gene product, Ap4A hydrolase, is responsible for Ap4A degradation following the immunological activation of mast cells. The knockdown of Ap4A hydrolase modulated Ap4A accumulation, resulting in changes in the expression of MITF and USF2 target genes. Moreover, our observations demonstrated that the involvement of Ap4A hydrolase in gene regulation is not a phenomenon exclusive to mast cells but can also be found in cardiac cells activated with the β-agonist isoproterenol. Thus, we have provided concrete evidence establishing Ap4A as a second messenger in the regulation of gene expression. PMID:18644867

  14. Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells.

    PubMed

    Carmi-Levy, Irit; Yannay-Cohen, Nurit; Kay, Gillian; Razin, Ehud; Nechushtan, Hovav

    2008-09-01

    We previously discovered that microphthalmia transcription factor (MITF) and upstream stimulatory factor 2 (USF2) each forms a complex with its inhibitor histidine triad nucleotide-binding 1 (Hint-1) and with lysyl-tRNA synthetase (LysRS). Moreover, we showed that the dinucleotide diadenosine tetraphosphate (Ap(4)A), previously shown to be synthesized by LysRS, binds to Hint-1, and as a result the transcription factors are released from their suppression. Thus, transcriptional activity is regulated by Ap(4)A, suggesting that Ap(4)A is a second messenger in this context. For Ap(4)A to be unambiguously established as a second messenger, several criteria have to be fulfilled, including the presence of a metabolizing enzyme. Since several enzymes are able to hydrolyze Ap(4)A, we provided here evidence that the "Nudix" type 2 gene product, Ap(4)A hydrolase, is responsible for Ap(4)A degradation following the immunological activation of mast cells. The knockdown of Ap(4)A hydrolase modulated Ap(4)A accumulation, resulting in changes in the expression of MITF and USF2 target genes. Moreover, our observations demonstrated that the involvement of Ap(4)A hydrolase in gene regulation is not a phenomenon exclusive to mast cells but can also be found in cardiac cells activated with the beta-agonist isoproterenol. Thus, we have provided concrete evidence establishing Ap(4)A as a second messenger in the regulation of gene expression.

  15. MESSENGER Departs Mercury

    NASA Image and Video Library

    2008-01-30

    After NASA MESSENGER spacecraft completed its successful flyby of Mercury, the Narrow Angle Camera NAC, part of the Mercury Dual Imaging System MDIS, took these images of the receding planet. This is a frame from an animation.

  16. KSC-04PD-0428

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. At the Astrotech Space Operations processing facilities near KSC, workers begin moving NASAs MESSENGER spacecraft into the building MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging is being taken into a high bay clean room where employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  17. KSC-04PD-0427

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. At the Astrotech Space Operations processing facilities near KSC, workers check the moveable pallet holding NASAs MESSENGER spacecraft. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be taken into a high bay clean room and employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  18. The effect of 648 nm diode laser irradiation on second messengers in senescent human keratinocytes

    NASA Astrophysics Data System (ADS)

    Hawkins Evans, D.; Abrahamse, H.

    2009-02-01

    Background/purpose: Stress induced premature senescence (SIPS) is defined as the long-term effect of subcytotoxic stress on proliferative cell types. Cells in SIPS display differences at the level of protein expression which affect energy metabolism, defense systems, redox potential, cell morphology and transduction pathways. This study aimed to determine the effect of laser irradiation on second messengers in senescent cells and to establish if that effect can be directly linked to changes in cellular function such as cell viability or proliferation. Materials and Methods: Human keratinocyte cell cultures were modified to induce premature senescence using repeated sub-lethal stresses of 200 uM H2O2 or 5% OH every day for four days with two days recovery. SIPS was confirmed by senescence-associated β-galactosidase staining. Control conditions included normal, repeated stress of 500 uM H2O2 to induce apoptosis and 200 uM PBN as an anti-oxidant or free radical scavenger. Cells were irradiated with 1.5 J/cm2 on day 1 and 4 using a 648 nm diode laser (3.3 mW/cm2) and cellular responses were measured 1 h post irradiation. The affect on second messengers was assessed by measuring cAMP, cGMP, nitric oxide and intracellular calcium (Ca2+) while functional changes were assessed using cell morphology, ATP cell viability, LDH membrane integrity and WST-1 cell proliferation. Results: Results indicate an increase in NO and a decrease in cGMP and Ca2+ in 200 uM H2O2 irradiated cells while PBN irradiated cells showed a decrease in cAMP and an increase in ATP viability and cell proliferation. Conclusion: Laser irradiation influences cell signaling which ultimately changes the biological function of senescent cells. If laser therapy can stimulate the biological function of senescent cells it may be beneficial to conditions such as immune senescence, skin ageing, muscle atrophy, premature ageing of arteries in patients with advanced heart disease, neurodegenerative disorders and chronic renal failure.

  19. Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?

    PubMed

    Lavieu, Gregory; Scarlatti, Francesca; Sala, Giusy; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

    2007-01-01

    Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively.

  20. Whole-cell patch clamp recording of voltage-sensitive Ca²+ channel currents: heterologous expression systems and dissociated brain neurons.

    PubMed

    Hainsworth, Atticus H; Randall, Andrew D; Stefani, Alessandro

    2005-01-01

    Voltage-sensitive Ca(2+) channels (VSCC) play a central role in an extensive array of physiological processes. Their importance in cellular function arises from their ability both to sense membrane voltage and to conduct Ca(2+) ions, two facets that couple membrane excitability to a key intracellular second messenger. Through this relationship, activation of VSCCs is tightly coupled to the gamut of cellular functions dependent on intracellular Ca(2+), including muscle contraction, energy metabolism, gene expression, and exocytotic/endocytotic cycling.

  1. MESSENGER Reveals Mercury in New Detail

    NASA Image and Video Library

    2008-01-16

    As NASA MESSENGER approached Mercury on January 14, 2008, the spacecraft Narrow-Angle Camera on the Mercury Dual Imaging System MDIS instrument captured this view of the planet rugged, cratered landscape illuminated obliquely by the Sun.

  2. KSC-04pd1451

    NASA Image and Video Library

    2004-07-06

    KENNEDY SPACE CENTER, FLA. - On Pad 17-B, Cape Canaveral Air Force Station, workers move the Boeing Delta II Heavy second-stage engine, the Aerojet AJ10-118K, inside the mobile service tower. The engine will be mated with the first stage of the Delta II, which is the launch vehicle for the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft, scheduled to lift off Aug. 2. Bound for Mercury, the spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  3. KSC-04pd1449

    NASA Image and Video Library

    2004-07-06

    KENNEDY SPACE CENTER, FLA. - - The Boeing Delta II Heavy second-stage engine, the Aerojet AJ10-118K, approaches the top of the mobile service tower on Pad 17-B, Cape Canaveral Air Force Station. The engine will be mated with the first stage of the Delta II, which is the launch vehicle for the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft, scheduled to lift off Aug. 2. Bound for Mercury, the spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  4. MESSENGER Education and Public Outreach Arranges a Ride to the Innermost Planet

    NASA Astrophysics Data System (ADS)

    Weir, H. M.; Chapman, C. R.; Edmonds, J.; Goldstein, J.; Hallau, K. G.; Hirshon, B.; Vanhala, H.; Solomon, S. C.; Messenger Education; Public Outreach Team

    2010-12-01

    Exploration of the mysterious planet Mercury offers an unprecedented opportunity for teachers, students, and citizens to tag along for the ride, and the Education and Public Outreach (EPO) Team for MESSENGER (MErcury Surface, Space ENvironment, GEochemistry, and Ranging) is making sure the public gets quite a show. Since 2004, when MESSENGER was launched, MESSENGER has been gathering intriguing data and information about the Solar System's innermost planet. That journey will continue at a quickened pace after March 18, 2011, when MESSENGER enters into orbit around Mercury for one year of observations of the planet and its environment. The EPO Team - an extensive network of individuals and institutions - has sought to convey the excitement and complexity of the mission as MESSENGER's team overcomes challenges, achieves triumphs, and shares the adventure of space exploration with the American and global public. The EPO Team has developed a broad and comprehensive set of educational and outreach activities, ranging from curricular materials, teacher training, and unique mission-related student investigations to museum displays and special outreach to underserved communities and minority students. One of the most visible aspects of this effort is the MESSENGER Educator Fellows program: master science educators who conduct teacher training workshops throughout the nation for pre-K-12 educators. Educator Fellows train teachers on the EPO Team's MESSENGER Education Modules, which are also relevant to other NASA missions reaching important milestones this year (see http://www.messenger-education.org/teachers/educ_modules.php). By the time MESSENGER goes into orbit, Educator Fellows will have trained an estimated 18,000 teachers, who in turn, facilitate classroom experiences to over 1.8 million students. The EPO Team comprises individuals from the American Association for the Advancement of Science (AAAS); Carnegie Academy for Science Education (CASE); Center for Educational Resources (CERES) at Montana State University (MSU) - Bozeman; National Center for Earth and Space Science Education (NCESSE); Johns Hopkins University Applied Physics Laboratory (JHU/APL); National Air and Space Museum (NASM); Science Systems and Applications, Inc. (SSAI); and Southwest Research Institute (SwRI).

  5. Planetary Ions at Mercury: Unanswered Questions After MESSENGER

    NASA Astrophysics Data System (ADS)

    Raines, J. M.

    2018-05-01

    We will discuss the key open questions relating to planetary ions, including the behavior of recently created photoions, the near absence of Ca+ / K+ in MESSENGER ion measurements, and the role of ion sputtering in the system.

  6. The Molecular Basis of Communication between Cells.

    ERIC Educational Resources Information Center

    Snyder, Solomon H.

    1985-01-01

    Chemical messengers mediate long-range hormonal communication and short-range neural communication between cells. Background information on peptides, steroids, neuropeptides, and specialized enzymes is given. Investigations reveal that the two systems have many common intercellular messenger molecules. (DH)

  7. Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dickinson, G. D.; Ellefsen, K. L.; Dawson, S. P.

    The range of action of intracellular messengers is determined by their rates of diffusion and degradation. Previous measurements in oocyte cytoplasmic extracts indicated that the Ca 2+-liberating second messenger inositol trisphosphate (IP 3) diffuses with a coefficient (~280 μm 2 s -1) similar to that in water, corresponding to a range of action of ~25 μm. Consequently, IP 3 is generally considered a “global” cellular messenger. We also reexamined this issue by measuring local IP 3-evoked Ca 2+ puffs to monitor IP 3 diffusing from spot photorelease in neuroblastoma cells. Fitting these data by numerical simulations yielded a diffusion coefficientmore » (≤10 μm 2 s -1) about 30-fold slower than that previously reported. Here, we propose that diffusion of IP 3 in mammalian cells is hindered by binding to immobile, functionally inactive receptors that were diluted in oocyte extracts. The predicted range of action of IP 3 (<5 μm) is thus smaller than the size of typical mammalian cells, indicating that IP 3 should better be considered as a local rather than a global cellular messenger.« less

  8. Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action

    DOE PAGES

    Dickinson, G. D.; Ellefsen, K. L.; Dawson, S. P.; ...

    2016-11-08

    The range of action of intracellular messengers is determined by their rates of diffusion and degradation. Previous measurements in oocyte cytoplasmic extracts indicated that the Ca 2+-liberating second messenger inositol trisphosphate (IP 3) diffuses with a coefficient (~280 μm 2 s -1) similar to that in water, corresponding to a range of action of ~25 μm. Consequently, IP 3 is generally considered a “global” cellular messenger. We also reexamined this issue by measuring local IP 3-evoked Ca 2+ puffs to monitor IP 3 diffusing from spot photorelease in neuroblastoma cells. Fitting these data by numerical simulations yielded a diffusion coefficientmore » (≤10 μm 2 s -1) about 30-fold slower than that previously reported. Here, we propose that diffusion of IP 3 in mammalian cells is hindered by binding to immobile, functionally inactive receptors that were diluted in oocyte extracts. The predicted range of action of IP 3 (<5 μm) is thus smaller than the size of typical mammalian cells, indicating that IP 3 should better be considered as a local rather than a global cellular messenger.« less

  9. MESSENGER at Mercury: Early Orbital Operations

    NASA Technical Reports Server (NTRS)

    McNutt, Ralph L., Jr; Solomon, Sean C.; Bedini, Peter D.; Anderson, Brian J.; Blewett, David T.; Evans, Larry G.; Gold, Robert E.; Krimigis, Stamatios M.; Murchie, Scott L.; Nittler, Larry R.; hide

    2013-01-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, launched in August 2004 under NASA's Discovery Program, was inserted into orbit about the planet Mercury in March 2011. MESSENGER's three flybys of Mercury in 2008-2009 marked the first spacecraft visits to the innermost planet since the Mariner 10 flybys in 1974-1975. The unprecedented orbital operations are yielding new insights into the nature and evolution of Mercury. The scientific questions that frame the MESSENGER mission led to the mission measurement objectives to be achieved by the seven payload instruments and the radio science experiment. Interweaving the full set of required orbital observations in a manner that maximizes the opportunity to satisfy all mission objectives and yet meet stringent spacecraft pointing and thermal constraints was a complex optimization problem that was solved with a software tool that simulates science observations and tracks progress toward meeting each objective. The final orbital observation plan, the outcome of that optimization process, meets all mission objectives. MESSENGER's Mercury Dual Imaging System is acquiring a global monochromatic image mosaic at better than 90% coverage and at least 250 m average resolution, a global color image mosaic at better than 90% coverage and at least 1 km average resolution, and global stereo imaging at better than 80% coverage and at least 250 m average resolution. Higher-resolution images are also being acquired of targeted areas. The elemental remote sensing instruments, including the Gamma-Ray and Neutron Spectrometer and the X-Ray Spectrometer, are being operated nearly continuously and will establish the average surface abundances of most major elements. The Visible and Infrared Spectrograph channel of MESSENGER's Mercury Atmospheric and Surface Composition Spectrometer is acquiring a global map of spectral reflectance from 300 to 1450 nm wavelength at a range of incidence and emission angles. Targeted areas have been selected for spectral coverage into the ultraviolet with the Ultraviolet and Visible Spectrometer (UVVS). MESSENGER's Mercury Laser Altimeter is acquiring topographic profiles when the slant range to Mercury's surface is less than 1800 km, encompassing latitudes from 20 deg. S to the north pole. Topography over the remainder of the southern hemisphere will be derived from stereo imaging, radio occultations, and limb profiles. MESSENGER's radio science experiment is determining Mercury's gravity field from Doppler signals acquired during frequent downlinks. MESSENGER's Magnetometer is measuring the vector magnetic field both within Mercury's magnetosphere and in Mercury's solar wind environment at an instrument sampling rate of up to 20 samples/s. The UVVS is determining the three-dimensional, time-dependent distribution of Mercury's exospheric neutral and ionic species via their emission lines. During each spacecraft orbit, the Energetic Particle Spectrometer measures energetic electrons and ions, and the Fast Imaging Plasma Spectrometer measures the energies and mass per charge of thermal plasma components, both within Mercury's magnetosphere and in Mercury's solar-wind environment. The primary mission observation sequence will continue for one Earth year, until March 2012. An extended mission, currently under discussion with NASA, would add a second year of orbital observations targeting a set of focused follow-on questions that build on observations to date and take advantage of the more active Sun expected during 2012-2013. MESSENGER's total primary mission cost, projected at $446 M in real-year dollars, is comparable to that of Mariner 10 after adjustment for inflation.

  10. MESSENGER at Mercury: Early Orbital Operations

    NASA Technical Reports Server (NTRS)

    McNutt, Ralph L., Jr.; Solomon, Sean C.; Bedini, Peter D.; Anderson, Brian J.; Blewett, David T.; Evans, Larry G.; Gold, Robert E.; Krimigis, Stamatios M.; Murchie, Scott L.; Nittler, Larry R.; hide

    2012-01-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, launched in August 2004 under NASA's Discovery Program, was inserted into orbit about the planet Mercury in March 2011. MESSENGER's three flybys of Mercury in 2008-2009 marked the first spacecraft visits to the innermost planet since the Mariner 10 flybys in 1974-1975. The unprecedented orbital operations are yielding new insights into the nature and evolution of Mercury. The scientific questions that frame the MESSENGER mission led to the mission measurement objectives to be achieved by the seven payload instruments and the radio science experiment. Interweaving the full set of required orbital observations in a manner that maximizes the opportunity to satisfy all mission objectives and yet meet stringent spacecraft pointing and thermal constraints was a complex optimization problem that was solved with a software tool that simulates science observations and tracks progress toward meeting each objective. The final orbital observation plan, the outcome of that optimization process, meets all mission objectives. MESSENGER's Mercury Dual Imaging System is acquiring a global monochromatic image mosaic at better than 90%coverage and at least 250 m average resolution, a global color image mosaic at better than 90%coverage and at least 1 km average resolution, and global stereo imaging at better than 80%coverage and at least 250 m average resolution. Higher-resolution images are also being acquired of targeted areas. The elemental remote sensing instruments, including the Gamma-Ray and Neutron Spectrometer and the X-Ray Spectrometer, are being operated nearly continuously and will establish the average surface abundances of most major elements. The Visible and Infrared Spectrograph channel of MESSENGER's Mercury Atmospheric and Surface Composition Spectrometer is acquiring a global map of spectral reflectance from 300 to 1450 nm wavelength at a range of incidence and emission angles. Targeted areas have been selected for spectral coverage into the ultraviolet with the Ultraviolet and Visible Spectrometer (UVVS). MESSENGER's Mercury Laser Altimeter is acquiring topographic profiles when the slant range to Mercury's surface is less than 1800 km, encompassing latitudes from 201S to the north pole. Topography over the remainder of the southern hemisphere will be derived from stereo imaging, radio occultations, and limb profiles. MESSENGER's radio science experiment is determining Mercury's gravity field from Doppler signals acquired during frequent downlinks. MESSENGER's Magnetometer is measuring the vector magnetic field both within Mercury's magnetosphere and in Mercury's solar wind environment at an instrument sampling rate of up to 20 samples/s. The UVVS is determining the three-dimensional, time-dependent distribution of Mercury's exospheric neutral and ionic species via their emission lines. During each spacecraft orbit, the Energetic Particle Spectrometer measures energetic electrons and ions, and the Fast Imaging Plasma Spectrometer measures the energies and mass per charge of thermal plasma components, both within Mercury's magnetosphere and in Mercury's solar-wind environment. The primary mission observation sequence will continue for one Earth year, until March 2012. An extended mission, currently under discussion with NASA, would add a second year of orbital observations targeting a set of focused follow-on questions that build on observations to date and take advantage of the more active Sun expected during 2012-2013. MESSENGER's total primary mission cost, projected at $446 M in real-year dollars, is comparable to that of Mariner 10 after adjustment for inflation.

  11. A Tale of Two Comets: ISON

    NASA Image and Video Library

    2013-11-26

    Release Date: November 25, 2013 MESSENGER image of comet C/2012 S1 (ISON) during its closest approach to Mercury. At that time, ISON was approximately 22.5 million miles (36.2 million kilometers) from MESSENGER and 42.1 million miles (67.8 million kilometers) from the Sun. The image is 7° by 4.7° in size and has been slightly magnified and smoothed to enhance the faint tail of the comet. The tail was oriented at an angle to MESSENGER at the time and is foreshortened in this image; however, some faint structure can still be seen. MESSENGER's cameras have been acquiring targeted observations (watch an animation here) of Encke since October 28 and ISON since October 26, although the first faint detections didn't come until early November. During the closest approach of each comet to Mercury, the Mercury Atmospheric and Surface Composition Spectrometer (MASCS) and X-Ray Spectrometer (XRS) instruments also targeted the comets. Observations of ISON conclude on November 26, when the comet passes too close to the Sun, but MESSENGER will continue to monitor Encke with both the imagers and spectrometers through early December. Read this mission news story for more details. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. During the first two years of orbital operations, MESSENGER acquired over 150,000 images and extensive other data sets. MESSENGER is capable of continuing orbital operations until early 2015. Date acquired: 01:54:30 UTC on November 20, 2013 Instrument: Wide Angle Camera (WAC) of the Mercury Dual Imaging System (MDIS) Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington/Southwest Research Institute NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  12. The mechanosensory calcium-selective ion channel: key component of a plasmalemmal control centre?

    NASA Technical Reports Server (NTRS)

    Pickard, B. G.; Ding, J. P.

    1993-01-01

    Mechanosensory calcium-selective ion channels probably serve to detect not only mechanical stress but also electrical, thermal, and diverse chemical stimuli. Because all stimuli result in a common output, most notably a shift in second messenger calcium concentration, the channels are presumed to serve as signal integrators. Further, insofar as second messenger calcium in turn gives rise to mechanical, electrical, and diverse chemical changes, the channels are postulated to initiate regulatory feedbacks. It is proposed that the channels and the feedback loops play a wide range of roles in regulating normal plant function, as well as in mediating disturbance of normal function by environmental stressors and various pathogens. In developing evidence for the physiological performance of the channel, a model for a cluster of regulatory plasmalemmal proteins and cytoskeletal elements grouped around a set of wall-to-membrane and transmembrane linkers has proved useful. An illustration of how the model might operate is presented. It is founded on the demonstration that several xenobiotics interfere both with normal channel behaviour and with gravitropic reception. Accordingly, the first part of the illustration deals with how the channels and the control system within which they putatively operate might initiate gravitropism. Assuming that gravitropism is an asymmetric expression of growth, the activities of the channels and the plasmalemmal control system are extrapolated to account for regulation of both rate and allometry of cell expansion. Finally, it is discussed how light, hormones, redox agents and herbicides could in principle affect growth via the putative plasmalemmal control cluster or centre.

  13. Complex history of the Rembrandt basin and scarp system, Mercury

    NASA Astrophysics Data System (ADS)

    Ferrari, S.; Massironi, M.; Klimczak, C.; Byrne, P. K.; Cremonese, G.; Solomon, S. C.

    2012-09-01

    During its second and third flybys, the MESSENGER spacecraft [1] imaged the wellpreserved Rembrandt basin in Mercury's southern hemisphere. With a diameter of 715 km, Rembrandt is the second largest impact structure recognized on Mercury after the 1550-km-diameter Caloris basin. Rembrandt is also one of the youngest major basins [2] and formed near the end of the Late Heavy Bombardment (~3.8 Ga). Much of the basin interior has been resurfaced by smooth, high-reflectance units interpreted to be of volcanic origin [3]. These units host sets of contractional and extensional landforms generally oriented in directions radial or concentric to the basin, similar to those observed within the Caloris basin [4-6]; these structures are probably products of multiple episodes of deformation [2,7,8]. Of particular note in the Rembrandt area is a 1,000-km-long reverse fault system [9] that cuts the basin at its western rim and bends eastward toward the north, tapering into the impact material. On the basis of its shape, the structure has previously been characterized as a lobate scarp. Its formation and localization have been attributed to the global contraction of Mercury [2]. From MESSENGER flyby and orbital images, we have identified previously unrecognized kinematic indicators of strike-slip motion along the Rembrandt scarp, together with evidence of interaction between the scarp orientation and the concentric basin-related structural pattern described above. Here we show through cross-cutting relationships and scarp morphology that the development of the Rembrandt scarp was strongly influenced by tectonics related to basin formation and evolution.

  14. Endocellular regulation by free radicals and hydrogen peroxide: key determinants of the inflammatory response.

    PubMed

    Vitetta, Luis; Linnane, Anthony W

    2014-04-01

    The formations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been considered as major contributors to the dysregulation of the inflammatory response. Reactive oxygen species and RNS productions often are reported to be associated with the development of chronic diseases and acceleration of the aging process. Mechanistically, this association has linked the phenomena of oxidative stress with the occurrence of random deleterious modifications of macromolecules with progressive development of pro-inflammatory conditions promoting age-associated systemic diseases. On the contrary the so-called random modification of macromolecules is incorrect rather ROS and RNS are molecular regulators (second messengers) and not universal toxins whose overproduction should be annulled by antioxidants. We have previously reviewed the physiological role of superoxide anion (and hydrogen peroxide) and nitric oxide (and peroxynitrite) and concluded that these reactive molecular species behave as pro-oxidant second messengers. Reactive oxygen species and RNS are produced at specific cellular locations and are essential for both the normal physiological function of the metabolome and the regulated inflammatory response. This brings into question the whole concept of the orally administering of antioxidant molecular species to down-regulate or abrogate an overproduction of free radical activity. There are no human clinical trials that demonstrate that small molecules, the so-called antioxidants (e.g., vitamins C, vitamin E and beta-carotene), confer a favorable clinical outcome of long-lasting control of inflammation.

  15. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, NASA’s MESSENGER spacecraft is secure after transfer to the work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, NASA’s MESSENGER spacecraft is secure after transfer to the work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  16. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, NASA’s MESSENGER spacecraft is lifted off the pallet for transfer to a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, NASA’s MESSENGER spacecraft is lifted off the pallet for transfer to a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  17. KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers remove the protective cover from NASA’s MESSENGER spacecraft. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers remove the protective cover from NASA’s MESSENGER spacecraft. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  18. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, workers check the placement of NASA’s MESSENGER spacecraft on a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, workers check the placement of NASA’s MESSENGER spacecraft on a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  19. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, workers move NASA’s MESSENGER spacecraft into a high bay clean room. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities near KSC, workers move NASA’s MESSENGER spacecraft into a high bay clean room. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  20. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, an overhead crane moves NASA’s MESSENGER spacecraft toward a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, an overhead crane moves NASA’s MESSENGER spacecraft toward a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  1. KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, an overhead crane lowers NASA’s MESSENGER spacecraft onto a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - At the Astrotech Space Operations processing facilities, an overhead crane lowers NASA’s MESSENGER spacecraft onto a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  2. KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, NASA’s MESSENGER spacecraft is revealed. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, NASA’s MESSENGER spacecraft is revealed. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  3. A Terminator View from Mercury Flyby 2

    NASA Image and Video Library

    2009-04-21

    This high-resolution NAC image shows a view of Mercury dawn terminator, the division between the sunlit dayside and dark nightside of the planet, as seen as the MESSENGER spacecraft departed the planet during the mission second Mercury flyby.

  4. Effects of ANP receptor antagonists on ANP secretion from adult rat cultured atrial myocytes.

    PubMed

    Nachshon, S; Zamir, O; Matsuda, Y; Zamir, N

    1995-03-01

    Atrial natriuretic peptide (ANP) is a hormone-secreted predominantly by atrial myocytes. ANP exerts many of its actions via activation of the particulate guanylyl cyclase receptor ANPR-A and the formation of guanosine 3',5'-cyclic monophosphate (cGMP), which serves as a second messenger in the target cells. Using membrane-permeable cGMP analogues (8-bromo-cGMP and dibutyryl- cGMP), we first tested the hypothesis that ANP secretion by adult rat cultured atrial myocytes can be modulated through the second messenger cGMP. Second, we examined the effects of two competitive ANPR-A receptor antagonists, namely HS-142-1 and anantin, on cGMP formation and ANP secretion from cultured atrial myocytes. Cultured atrial myocytes secreted large quantities of immunoreactive (ir) ANP under basal conditions. We found that cGMP analogues inhibited basal irANP secretion from cultured atrial myocytes, whereas HS-142-1 and anantin had stimulating effects. HS-142-1 and anantin reduced cGMP formation in cultured atrial myocytes at basal conditions. These results suggest an autoregulatory mechanism of ANP secretion by atrial myocytes in an autocrine/paracrine fashion.

  5. KSC-04pd1448

    NASA Image and Video Library

    2004-07-06

    KENNEDY SPACE CENTER, FLA. - The Boeing Delta II Heavy second-stage engine, the Aerojet AJ10-118K, is lifted up the mobile service tower on Pad 17-B, Cape Canaveral Air Force Station. At right can be seen the first stage of the Delta II and the nine Solid Rocket Boosters surrounding it. The Delta II is the launch vehicle for the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft, scheduled to lift off Aug. 2. Bound for Mercury, the spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  6. Multi-Messenger Astronomy and Dark Matter

    NASA Astrophysics Data System (ADS)

    Bergström, Lars

    This chapter presents the elaborated lecture notes on Multi-Messenger Astronomy and Dark Matter given by Lars Bergström at the 40th Saas-Fee Advanced Course on "Astrophysics at Very High Energies". One of the main problems of astrophysics and astro-particle physics is that the nature of dark matter remains unsolved. There are basically three complementary approaches to try to solve this problem. One is the detection of new particles with accelerators, the second is the observation of various types of messengers from radio waves to gamma-ray photons and neutrinos, and the third is the use of ingenious experiments for direct detection of dark matter particles. After giving an introduction to the particle universe, the author discusses the relic density of particles, basic cross sections for neutrinos and gamma-rays, supersymmetric dark matter, detection methods for neutralino dark matter, particular dark matter candidates, the status of dark matter detection, a detailled calculation on an hypothetical "Saas-Fee Wimp", primordial black holes, and gravitational waves.

  7. Single-cell resolution of intracellular T cell Ca2+ dynamics in response to frequency-based H2O2 stimulation.

    PubMed

    Kniss-James, Ariel S; Rivet, Catherine A; Chingozha, Loice; Lu, Hang; Kemp, Melissa L

    2017-03-01

    Adaptive immune cells, such as T cells, integrate information from their extracellular environment through complex signaling networks with exquisite sensitivity in order to direct decisions on proliferation, apoptosis, and cytokine production. These signaling networks are reliant on the interplay between finely tuned secondary messengers, such as Ca 2+ and H 2 O 2 . Frequency response analysis, originally developed in control engineering, is a tool used for discerning complex networks. This analytical technique has been shown to be useful for understanding biological systems and facilitates identification of the dominant behaviour of the system. We probed intracellular Ca 2+ dynamics in the frequency domain to investigate the complex relationship between two second messenger signaling molecules, H 2 O 2 and Ca 2+ , during T cell activation with single cell resolution. Single-cell analysis provides a unique platform for interrogating and monitoring cellular processes of interest. We utilized a previously developed microfluidic device to monitor individual T cells through time while applying a dynamic input to reveal a natural frequency of the system at approximately 2.78 mHz stimulation. Although our network was much larger with more unknown connections than previous applications, we are able to derive features from our data, observe forced oscillations associated with specific amplitudes and frequencies of stimuli, and arrive at conclusions about potential transfer function fits as well as the underlying population dynamics.

  8. KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers prepare NASA’s MESSENGER spacecraft for transfer to a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers prepare NASA’s MESSENGER spacecraft for transfer to a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  9. KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers get ready to remove the protective cover from NASA’s MESSENGER spacecraft. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers get ready to remove the protective cover from NASA’s MESSENGER spacecraft. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  10. Control Algorithms Charge Batteries Faster

    NASA Technical Reports Server (NTRS)

    2012-01-01

    On March 29, 2011, NASA s Mercury Surface, Space Environment, Geochemistry and Ranging (MESSENGER) spacecraft beamed a milestone image to Earth: the first photo of Mercury taken from orbit around the solar system s innermost planet. (MESSENGER is also the first spacecraft to orbit Mercury.) Like most of NASA s deep space probes, MESSENGER is enabled by a complex power system that allows its science instruments and communications to function continuously as it travels millions of miles from Earth. "Typically, there isn't one particular power source that can support the entire mission," says Linda Taylor, electrical engineer in Glenn Research Center s Power Systems Analysis Branch. "If you have solar arrays and you are in orbit, at some point you re going to be in eclipse." Because of this, Taylor explains, spacecraft like MESSENGER feature hybrid power systems. MESSENGER is powered by a two-panel solar array coupled with a nickel hydrogen battery. The solar arrays provide energy to the probe and charge the battery; when the spacecraft s orbit carries it behind Mercury and out of the Sun s light, the spacecraft switches to battery power to continue operations. Typically, hybrid systems with multiple power inputs and a battery acting alternately as storage and a power source require multiple converters to handle the power flow between the devices, Taylor says. (Power converters change the qualities of electrical energy, such as from alternating current to direct current, or between different levels of voltage or frequency.) This contributes to a pair of major concerns for spacecraft design. "Weight and size are big drivers for any space application," Taylor says, noting that every pound added to a space vehicle incurs significant costs. For an innovative solution to managing power flows in a lightweight, cost-effective manner, NASA turned to a private industry partner.

  11. Neurobiologically Inspired Approaches to Nonlinear Process Control and Modeling

    DTIC Science & Technology

    1999-12-31

    incorporates second messenger reaction kinetics and calcium dynamics to represent the nonlinear dynamics and the crucial role of neuromodulation in local...reflex). The dynamic neuromodulation as a mechanism for the nonlinear attenuation is the novel result of this study. Ear- lier simulations have shown

  12. A Novel Phosphatidic Acid-Protein-tyrosine Phosphatase D2 Axis Is Essential for ERBB2 Signaling in Mammary Epithelial Cells*

    PubMed Central

    Ramesh, Mathangi; Krishnan, Navasona; Muthuswamy, Senthil K.; Tonks, Nicholas K.

    2015-01-01

    We used a loss-of-function screen to investigate the role of classical protein-tyrosine phosphatases (PTPs) in three-dimensional mammary epithelial cell morphogenesis and ERBB2 signaling. The study revealed a novel role for PTPD2 as a positive regulator of ERBB2 signaling. Suppression of PTPD2 attenuated the ERBB2-induced multiacinar phenotype in three-dimensional cultures specifically by inhibiting ERBB2-mediated loss of polarity and lumen filling. In contrast, overexpression of PTPD2 enhanced the ERBB2 phenotype. We also found that a lipid second messenger, phosphatidic acid, bound PTPD2 in vitro and enhanced its catalytic activity. Small molecule inhibitors of phospholipase D (PLD), an enzyme that produces phosphatidic acid in cells, also attenuated the ERBB2 phenotype. Exogenously added phosphatidic acid rescued the PLD-inhibition phenotype, but only when PTPD2 was present. These findings illustrate a novel pathway involving PTPD2 and the lipid second messenger phosphatidic acid that promotes ERBB2 function. PMID:25681440

  13. No Evidence for Ionotropic Pheromone Transduction in the Hawkmoth Manduca sexta.

    PubMed

    Nolte, Andreas; Gawalek, Petra; Koerte, Sarah; Wei, HongYing; Schumann, Robin; Werckenthin, Achim; Krieger, Jürgen; Stengl, Monika

    2016-01-01

    Insect odorant receptors (ORs) are 7-transmembrane receptors with inverse membrane topology. They associate with the conserved ion channel Orco. As chaperon, Orco maintains ORs in cilia and, as pacemaker channel, Orco controls spontaneous activity in olfactory receptor neurons. Odorant binding to ORs opens OR-Orco receptor ion channel complexes in heterologous expression systems. It is unknown, whether this also occurs in vivo. As an alternative to this ionotropic transduction, experimental evidence is accumulating for metabotropic odor transduction, implicating that insect ORs couple to G-proteins. Resulting second messengers gate various ion channels. They generate the sensillum potential that elicits phasic-tonic action potentials (APs) followed by late, long-lasting pheromone responses. Because it is still unclear how and when Orco opens after odor-OR-binding, we used tip recordings to examine in vivo the effects of the Orco antagonist OLC15 and the amilorides MIA and HMA on bombykal transduction in the hawkmoth Manduca sexta. In contrast to OLC15 both amilorides decreased the pheromone-dependent sensillum potential amplitude and the frequency of the phasic AP response. Instead, OLC15 decreased spontaneous activity, increased latencies of phasic-, and decreased frequencies of late, long-lasting pheromone responses Zeitgebertime-dependently. Our results suggest no involvement for Orco in the primary transduction events, in contrast to amiloride-sensitive channels. Instead of an odor-gated ionotropic receptor, Orco rather acts as a voltage- and apparently second messenger-gated pacemaker channel controlling the membrane potential and hence threshold and kinetics of the pheromone response.

  14. The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.

    PubMed

    Khan, Mike; Harms, Jerome S; Marim, Fernanda M; Armon, Leah; Hall, Cherisse L; Liu, Yi-Ping; Banai, Menachem; Oliveira, Sergio C; Splitter, Gary A; Smith, Judith A

    2016-12-01

    Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  15. Sharing Planetary Exploration: The Education and Public Outreach Program for the NASA MESSENGER Mission to Orbit Mercury

    NASA Astrophysics Data System (ADS)

    Solomon, S. C.; Stockman, S.; Chapman, C. R.; Leary, J. C.; McNutt, R. L.

    2003-12-01

    The Education and Public Outreach (EPO) Program of the MESSENGER mission to the planet Mercury, supported by the NASA Discovery Program, is a full partnership between the project's science and engineering teams and a team of professionals from the EPO community. The Challenger Center for Space Science Education (CCSSE) and the Carnegie Academy for Science Education (CASE) are developing sets of MESSENGER Education Modules targeting grade-specific education levels across K-12. These modules are being disseminated through a MESSENGER EPO Website developed at Montana State University, an Educator Fellowship Program managed by CCSSE to train Fellows to conduct educator workshops, additional workshops planned for NASA educators and members of the Minority University - SPace Interdisciplinary Network (MU-SPIN), and existing inner-city science education programs (e.g., the CASE Summer Science Institute in Washington, D.C.). All lessons are mapped to national standards and benchmarks by MESSENGER EPO team members trained by the American Association for the Advancement of Science (AAAS) Project 2061, all involve user input and feedback and quality control by the EPO team, and all are thoroughly screened by members of the project science and engineering teams. At the college level, internships in science and engineering are provided to students at minority institutions through a program managed by MU-SPIN, and additional opportunities for student participation across the country are planned as the mission proceeds. Outreach efforts include radio spots (AAAS), museum displays (National Air and Space Museum), posters and traveling exhibits (CASE), general language books (AAAS), programs targeting underserved communities (AAAS, CCSSE, and MU-SPIN), and a documentary highlighting the scientific and technical challenges involved in exploring Mercury and how the MESSENGER team has been meeting these challenges. As with the educational elements, science and engineering team members are active partners in each of the public outreach efforts. MESSENGER fully leverages other NASA EPO programs, including the Solar System Exploration EPO Forum and the Solar System Ambassadors. The overarching goal of the MESSENGER EPO program is to convey the excitement of planetary exploration to students and the lay public throughout the nation.

  16. MESSENGER, MErcury: Surface, Space ENvironment, GEochemistry, and Ranging; A Mission to Orbit and Explore the Planet Mercury

    NASA Technical Reports Server (NTRS)

    1999-01-01

    MESSENGER is a scientific mission to Mercury. Understanding this extraordinary planet and the forces that have shaped it is fundamental to understanding the processes that have governed the formation, evolution, and dynamics of the terrestrial planets. MESSENGER is a MErcury Surface, Space ENvironment, GEochemistry and Ranging mission to orbit Mercury for one Earth year after completing two flybys of that planet following two flybys of Venus. The necessary flybys return significant new data early in the mission, while the orbital phase, guided by the flyby data, enables a focused scientific investigation of this least-studied terrestrial planet. Answers to key questions about Mercury's high density, crustal composition and structure, volcanic history, core structure, magnetic field generation, polar deposits, exosphere, overall volatile inventory, and magnetosphere are provided by an optimized set of miniaturized space instruments. Our goal is to gain new insight into the formation and evolution of the solar system, including Earth. By traveling to the inner edge of the solar system and exploring a poorly known world, MESSENGER fulfills this quest.

  17. KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers prepare to attach an overhead crane to NASA’s MESSENGER spacecraft. The spacecraft will be moved to a work stand where employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers prepare to attach an overhead crane to NASA’s MESSENGER spacecraft. The spacecraft will be moved to a work stand where employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  18. KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers attach an overhead crane to NASA’s MESSENGER spacecraft. The spacecraft will be moved to a work stand where employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

    NASA Image and Video Library

    2004-03-10

    KENNEDY SPACE CENTER, FLA. - In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers attach an overhead crane to NASA’s MESSENGER spacecraft. The spacecraft will be moved to a work stand where employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  19. Mickey Mouse Spotted on Mercury!

    NASA Image and Video Library

    2012-06-15

    NASA image acquired: June 03, 2012 This scene is to the northwest of the recently named crater Magritte, in Mercury's south. The image is not map projected; the larger crater actually sits to the north of the two smaller ones. The shadowing helps define the striking "Mickey Mouse" resemblance, created by the accumulation of craters over Mercury's long geologic history. This image was acquired as part of MDIS's high-incidence-angle base map. The high-incidence-angle base map is a major mapping activity in MESSENGER's extended mission and complements the surface morphology base map of MESSENGER's primary mission that was acquired under generally more moderate incidence angles. High incidence angles, achieved when the Sun is near the horizon, result in long shadows that accentuate the small-scale topography of geologic features. The high-incidence-angle base map is being acquired with an average resolution of 200 meters/pixel. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MESSENGER acquired 88,746 images and extensive other data sets. MESSENGER is now in a yearlong extended mission, during which plans call for the acquisition of more than 80,000 additional images to support MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  20. Anyone Else Think This Looks Like the Cookie Monster?

    NASA Image and Video Library

    2017-12-08

    NASA image acquired August 29, 2012 Ok, so maybe it's just me. But the superposition of younger craters on older craters (in this case two smaller craters upon the rim of an older crater) can result in landforms that appear to resemble more familiar shapes to human eyes. More generally, the Law of Superposition allows scientists to determine which surface features pre- and postdate others, leading to a better understanding of the geological history of different regions of Mercury's surface. This image was acquired as a high-resolution targeted observation. Targeted observations are images of a small area on Mercury's surface at resolutions much higher than the 200-meter/pixel morphology base map. It is not possible to cover all of Mercury's surface at this high resolution, but typically several areas of high scientific interest are imaged in this mode each week. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MESSENGER acquired 88,746 images and extensive other data sets. MESSENGER is now in a yearlong extended mission, during which plans call for the acquisition of more than 80,000 additional images to support MESSENGER's science goals. Go here to read more about the MESSENGER mission: www.nasa.gov/mission_pages/messenger/main/index.html Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  1. KSC-04pd0600

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, workers secure NASA’s MESSENGER spacecraft on a test stand. Once in place, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  2. KSC-04pd0601

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, workers secure NASA’s MESSENGER spacecraft on a test stand. Once in place, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  3. KSC-04pd0602

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, workers secure NASA’s MESSENGER spacecraft on a test stand. Once in place, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  4. Changes in ion transport in inflammatory disease.

    PubMed

    Eisenhut, Michael

    2006-03-29

    Ion transport is essential for maintenance of transmembranous and transcellular electric potential, fluid transport and cellular volume. Disturbance of ion transport has been associated with cellular dysfunction, intra and extracellular edema and abnormalities of epithelial surface liquid volume. There is increasing evidence that conditions characterized by an intense local or systemic inflammatory response are associated with abnormal ion transport. This abnormal ion transport has been involved in the pathogenesis of conditions like hypovolemia due to fluid losses, hyponatremia and hypokalemia in diarrhoeal diseases, electrolyte abnormalities in pyelonephritis of early infancy, septicemia induced pulmonary edema, and in hypersecretion and edema induced by inflammatory reactions of the mucosa of the upper respiratory tract. Components of membranous ion transport systems, which have been shown to undergo a change in function during an inflammatory response include the sodium potassium ATPase, the epithelial sodium channel, the Cystic Fibrosis Transmembrane Conductance Regulator and calcium activated chloride channels and the sodium potassium chloride co-transporter. Inflammatory mediators, which influence ion transport are tumor necrosis factor, gamma interferon, interleukins, transforming growth factor, leukotrienes and bradykinin. They trigger the release of specific messengers like prostaglandins, nitric oxide and histamine which alter ion transport system function through specific receptors, intracellular second messengers and protein kinases. This review summarizes data on in vivo measurements of changes in ion transport in acute inflammatory conditions and in vitro studies, which have explored the underlying mechanisms. Potential interventions directed at a correction of the observed abnormalities are discussed.

  5. Changes in ion transport in inflammatory disease

    PubMed Central

    Eisenhut, Michael

    2006-01-01

    Ion transport is essential for maintenance of transmembranous and transcellular electric potential, fluid transport and cellular volume. Disturbance of ion transport has been associated with cellular dysfunction, intra and extracellular edema and abnormalities of epithelial surface liquid volume. There is increasing evidence that conditions characterized by an intense local or systemic inflammatory response are associated with abnormal ion transport. This abnormal ion transport has been involved in the pathogenesis of conditions like hypovolemia due to fluid losses, hyponatremia and hypokalemia in diarrhoeal diseases, electrolyte abnormalites in pyelonephritis of early infancy, septicemia induced pulmonary edema, and in hypersecretion and edema induced by inflammatory reactions of the mucosa of the upper respiratory tract. Components of membranous ion transport systems, which have been shown to undergo a change in function during an inflammatory response include the sodium potassium ATPase, the epithelial sodium channel, the Cystic Fibrosis Transmembrane Conductance Regulator and calcium activated chloride channels and the sodium potassium chloride co-transporter. Inflammatory mediators, which influence ion transport are tumor necrosis factor, gamma interferon, interleukins, transforming growth factor, leukotrienes and bradykinin. They trigger the release of specific messengers like prostaglandins, nitric oxide and histamine which alter ion transport system function through specific receptors, intracellular second messengers and protein kinases. This review summarizes data on in vivo measurements of changes in ion transport in acute inflammatory conditions and in vitro studies, which have explored the underlying mechanisms. Potential interventions directed at a correction of the observed abnormalities are discussed. PMID:16571116

  6. MESSENGER observations of magnetic reconnection in Mercury's magnetosphere.

    PubMed

    Slavin, James A; Acuña, Mario H; Anderson, Brian J; Baker, Daniel N; Benna, Mehdi; Boardsen, Scott A; Gloeckler, George; Gold, Robert E; Ho, George C; Korth, Haje; Krimigis, Stamatios M; McNutt, Ralph L; Raines, Jim M; Sarantos, Menelaos; Schriver, David; Solomon, Sean C; Trávnícek, Pavel; Zurbuchen, Thomas H

    2009-05-01

    Solar wind energy transfer to planetary magnetospheres and ionospheres is controlled by magnetic reconnection, a process that determines the degree of connectivity between the interplanetary magnetic field (IMF) and a planet's magnetic field. During MESSENGER's second flyby of Mercury, a steady southward IMF was observed and the magnetopause was threaded by a strong magnetic field, indicating a reconnection rate ~10 times that typical at Earth. Moreover, a large flux transfer event was observed in the magnetosheath, and a plasmoid and multiple traveling compression regions were observed in Mercury's magnetotail, all products of reconnection. These observations indicate that Mercury's magnetosphere is much more responsive to IMF direction and dominated by the effects of reconnection than that of Earth or the other magnetized planets.

  7. Effects of the foliar-applied protein "Harpin(Ea)" (messenger) on tomatoes infected with Phytophthora infestans.

    PubMed

    Fontanilla, M; Montes, M; De Prado, R

    2005-01-01

    The active ingredient in Messenger, is Harpin(Ea), a naturally occurring protein derived from Erwinia amylovora, a causal agent of fire blight. When Messenger is applied to a plant, the protein Harpin(Ea) binds foliar receptors to it. The receptors recognize the presence of Harpin(Ea), sending a signal that a pathogen is present, actually "tricking" the plant into thinking that it is under attack. This binding process triggers a cascade of responses affecting a global change of gene expressions, stimulating several distinct biochemical pathways within the plant responsible for growth and disease and insect resistance. The objective of this work is to characterize the development of an induced resistance against Phytophthora infestans. No effective treatment is currently available against this pathogenic agent, which causes the loss of complete harvests of different crops. Tomato plants with and without Messenger applications were inoculated with Phytophthora infestans in the same way. In addition, some plants with and without Messenger applications were not inoculated. Inoculated plants were symptomatologically checked for local and systemic symptoms. Evaluations of the number of tomatoes produced, with or without damage, and their growth, were also carried out. Based on the data obtained from the assays, significant changes were observed in the parameters measured due to Messenger treatment. The severe damage of this disease was reduced in the plants which received Messenger applications. These results open up new pathways in the control of diseases like Phytophthora infestans, in which effective means to combat them still do not exist, or these means are harmful to the environment.

  8. NASA News Conference on Mercury's Polar Regions

    NASA Image and Video Library

    2017-12-08

    Tune in to NASA's News Conference today, November 29, 2012, at 2 p.m. EST for new findings about Mercury's polar regions. www.nasa.gov/multimedia/nasatv/index.html Due to its nearly vertical spin axis, Mercury's north pole is never fully sunlit. If it were, it might look something like this image, which is an orthographic projection of a global mosaic. The dark area towards the center of the image contains the north pole. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MESSENGER acquired 88,746 images and extensive other data sets. MESSENGER is now in a yearlong extended mission, during which plans call for the acquisition of more than 80,000 additional images to support MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  9. MESSENGER Magnetic Field Observations of Upstream Ultra-Low Frequency Waves at Mercury

    NASA Technical Reports Server (NTRS)

    Le, G.; Chi, P. J.; Boardsen, S.; Blanco-Cano, X.; Anderosn, B. J.; Korth, H.

    2012-01-01

    The region upstream from a planetary bow shock is a natural plasma laboratory containing a variety of wave particle phenomena. The study of foreshocks other than the Earth's is important for extending our understanding of collisionless shocks and foreshock physics since the bow shock strength varies with heliocentric distance from the Sun, and the sizes of the bow shocks are different at different planets. The Mercury's bow shock is unique in our solar system as it is produced by low Mach number solar wind blowing over a small magnetized body with a predominately radial interplanetary magnetic field. Previous observations of Mercury upstream ultra-low frequency (ULF) waves came exclusively from two Mercury flybys of Mariner 10. The MESSENGER orbiter data enable us to study of upstream waves in the Mercury's foreshock in depth. This paper reports an overview of upstream ULF waves in the Mercury's foreshock using high-time resolution magnetic field data, 20 samples per second, from the MESSENGER spacecraft. The most common foreshock waves have frequencies near 2 Hz, with properties similar to the I-Hz waves in the Earth's foreshock. They are present in both the flyby data and in every orbit of the orbital data we have surveyed. The most common wave phenomenon in the Earth's foreshock is the large-amplitude 30-s waves, but similar waves at Mercury have frequencies at near 0.1 Hz and occur only sporadically with short durations (a few wave cycles). Superposed on the "30-s" waves, there are spectral peaks at near 0.6 Hz, not reported previously in Mariner 10 data. We will discuss wave properties and their occurrence characteristics in this paper.

  10. MESSENGER Observations of ULF Waves in Mercury's Foreshock Region

    NASA Technical Reports Server (NTRS)

    Le, Guan; Chi, Peter J.; Bardsen, Scott; Blanco-Cano, Xochitl; Slavin, James A.; Korth, Haje

    2012-01-01

    The region upstream from a planetary bow shock is a natural plasma laboratory containing a variety of wave particle phenomena. The study of foreshocks other than the Earth s is important for extending our understanding of collisionless shocks and foreshock physics since the bow shock strength varies with heliocentric distance from the Sun, and the sizes of the bow shocks are different at different planets. The Mercury s bow shock is unique in our solar system as it is produced by low Mach number solar wind blowing over a small magnetized body with a predominately radial interplanetary magnetic field. Previous observations of Mercury upstream ultra-low frequency (ULF) waves came exclusively from two Mercury flybys of Mariner 10. The MESSENGER orbiter data enable us to study of upstream waves in the Mercury s foreshock in depth. This paper reports an overview of upstream ULF waves in the Mercury s foreshock using high-time resolution magnetic field data, 20 samples per second, from the MESSENGER spacecraft. The most common foreshock waves have frequencies near 2 Hz, with properties similar to the 1-Hz waves in the Earth s foreshock. They are present in both the flyby data and in every orbit of the orbital data we have surveyed. The most common wave phenomenon in the Earth s foreshock is the large-amplitude 30-s waves, but similar waves at Mercury have frequencies at 0.1 Hz and occur only sporadically with short durations (a few wave cycles). Superposed on the "30-s" waves, there are spectral peaks at 0.6 Hz, not reported previously in Mariner 10 data. We will discuss wave properties and their occurrence characteristics in this paper.

  11. Efficient mucociliary transport relies on efficient regulation of ciliary beating.

    PubMed

    Braiman, Alex; Priel, Zvi

    2008-11-30

    The respiratory mucociliary epithelium is a synchronized and highly effective waste-disposal system. It uses mucus as a vehicle, driven by beating cilia, to transport unwanted particles, trapped in the mucus, away from the respiratory system. The ciliary machinery can function in at least two different modes: a low rate of beating that requires only ATP, and a high rate of beating regulated by second messengers. The mucus propelling velocity is linearly dependent on ciliary beat frequency (CBF). The linear dependence implies that a substantial increase in transport efficiency requires an equally substantial rise in CBF. The ability to enhance beating in response to various physiological cues is a hallmark of mucociliary cells. An intricate signaling network controls ciliary activity, which relies on interplay between calcium and cyclic nucleotide pathways.

  12. Mechanically induced alterations in cultured skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

    1991-01-01

    Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

  13. Cellular and molecular pathways of extremely-low-frequency electromagnetic field interactions with living systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tenforde, T.S.

    1992-06-01

    There is growing evidence that environmental electric and magnetic fields in the extremely-low-frequency (ELF) band below 300 Hz can influence biological functions by mechanisms that are only poorly understood at the present time. The primary objectives of this paper are to review the physical properties of ELF fields, their interactions with living systems at the tissue, cellular, and subcellular levels, and the key role of cell membranes ;in the transduction of signals from imposed ELF fields. Topics of discussion include signal-to-noise ratios for single cells and cell aggregates, resonance phenomena involving a combination of static and ELF magnetic fields, andmore » the possible influence of ELF fields on molecular signaling pathways that involve membrane receptors and cytoplasmic second messengers.« less

  14. KSC-04pd0597

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, workers prepare for contact of NASA’s MESSENGER spacecraft with a test stand. Once in place, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  15. KSC-04pd0599

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, workers verify the correct placement of NASA’s MESSENGER spacecraft on a test stand. Once in place, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  16. KSC-04pd0594

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, workers prepare to move NASA’s MESSENGER spacecraft onto a test stand using an overhead crane. There, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  17. KSC-04pd0598

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, workers check for the correct alignment of NASA’s MESSENGER spacecraft as it is lowered onto a test stand. Once in place, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  18. KSC-04pd0595

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, workers lower NASA’s MESSENGER spacecraft onto a test stand using an overhead crane. Once in place, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  19. KSC-04pd0603

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, the attachment of NASA’s MESSENGER spacecraft to a test stand is complete. The spacecraft is now ready for employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, to begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  20. KSC-04pd0596

    NASA Image and Video Library

    2004-03-22

    KENNEDY SPACE CENTER, FLA. -- At the Astrotech Space Operations processing facilities, workers monitor NASA’s MESSENGER spacecraft as it is lowered onto a test stand by an overhead crane. Once in place, employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will begin final processing for launch, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER - short for MErcury Surface, Space ENvironment, GEochemistry and Ranging - will be launched aboard a Boeing Delta II rocket no earlier than July 30 on a six-year mission to study the planet Mercury.

  1. Guidelines for the Use of Protein Domains in Acidic Phospholipid Imaging.

    PubMed

    Platre, Matthieu Pierre; Jaillais, Yvon

    2016-01-01

    Acidic phospholipids are minor membrane lipids but critically important for signaling events. The main acidic phospholipids are phosphatidylinositol phosphates (PIPs also known as phosphoinositides), phosphatidylserine (PS), and phosphatidic acid (PA). Acidic phospholipids are precursors of second messengers of key signaling cascades or are second messengers themselves. They regulate the localization and activation of many proteins, and are involved in virtually all membrane trafficking events. As such, it is crucial to understand the subcellular localization and dynamics of each of these lipids within the cell. Over the years, several techniques have emerged in either fixed or live cells to analyze the subcellular localization and dynamics of acidic phospholipids. In this chapter, we review one of them: the use of genetically encoded biosensors that are based on the expression of specific lipid binding domains (LBDs) fused to fluorescent proteins. We discuss how to design such sensors, including the criteria for selecting the lipid binding domains of interest and to validate them. We also emphasize the care that must be taken during data analysis as well as the main limitations and advantages of this approach.

  2. A novel phosphatidic acid-protein-tyrosine phosphatase D2 axis is essential for ERBB2 signaling in mammary epithelial cells.

    PubMed

    Ramesh, Mathangi; Krishnan, Navasona; Muthuswamy, Senthil K; Tonks, Nicholas K

    2015-04-10

    We used a loss-of-function screen to investigate the role of classical protein-tyrosine phosphatases (PTPs) in three-dimensional mammary epithelial cell morphogenesis and ERBB2 signaling. The study revealed a novel role for PTPD2 as a positive regulator of ERBB2 signaling. Suppression of PTPD2 attenuated the ERBB2-induced multiacinar phenotype in three-dimensional cultures specifically by inhibiting ERBB2-mediated loss of polarity and lumen filling. In contrast, overexpression of PTPD2 enhanced the ERBB2 phenotype. We also found that a lipid second messenger, phosphatidic acid, bound PTPD2 in vitro and enhanced its catalytic activity. Small molecule inhibitors of phospholipase D (PLD), an enzyme that produces phosphatidic acid in cells, also attenuated the ERBB2 phenotype. Exogenously added phosphatidic acid rescued the PLD-inhibition phenotype, but only when PTPD2 was present. These findings illustrate a novel pathway involving PTPD2 and the lipid second messenger phosphatidic acid that promotes ERBB2 function. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Single-cell imaging techniques for the real-time detection of IP₃ in live cells.

    PubMed

    Nelson, Carl P

    2013-01-01

    Inositol 1,4,5-trisphosphate (IP(3)) is a ubiquitous second messenger, derived from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP(2)) by enzymes of the phospholipase C (PLC) family. Binding of IP(3) to its cognate receptor in the endoplasmic reticulum membrane leads to release of Ca(2+) into the cytoplasm, which is involved in the regulation of an array of cellular functions. Traditional techniques for the detection of IP(3) have required the extraction of a large number of cells, with limitations in the time resolution of changes in IP(3) and an inability to obtain detailed information on the dynamics of this second messenger in single cells. Recent progress in this field has led to the development of a number of genetically encoded fluorescent biosensors, which upon recombinant expression are able selectively to detect real-time changes in IP(3) in single live cells. In this chapter, I detail protocols for the expression, visualization (by confocol or fluorescence microscopy), and interpretation of data obtained with such biosensors expressed in mammalian cells.

  4. Acute loading and aging effects on myostatin pathway biomarkers in human skeletal muscle after three sequential bouts of resistance exercise.

    PubMed

    Dalbo, Vincent J; Roberts, Michael D; Sunderland, Kyle L; Poole, Chris N; Stout, Jeff R; Beck, Travis W; Bemben, Mike; Kerksick, Chad M

    2011-08-01

    To determine the influence of age and resistance exercise on myostatin pathway-related genes, younger (n = 10; 28 ± 5 years) and older (n = 10; 68 ± 6 years) men underwent four testing conditions (T1-T4). A baseline (T1) muscle sample was obtained, whereas the second and third biopsies were obtained 48 hours following the first and second training sessions (T2, T3), and a final biopsy was taken 24 hours following T3. The training sessions consisted of 3 sets of 10 repetitions (80% of one repetition maximum) on leg press, hack squat, and leg extension exercises. Follistatin (FST) messenger RNA was greater in older compared with younger men at T1 and T2 (p < .05). Follistatin-like 3 (FSTL3) messenger RNA was greater in older compared with younger men at T1 and T4 (p < .05). In older men, there was a significant decrease in myostatin (MSTN) messenger RNA at T4 (p < .05). Older men contained less active (Ser-425 phosphorylated) SMAD3 (p-SMAD3) protein than younger men at T3 and T4 (p < .05).Although it is well known that younger individuals possess a greater hypertrophic potential to resistance exercise, it appears that older individuals may paradoxically possess a more favorable resistance exercise response regarding myostatin pathway-related genes and a protein marker of pathway activity. Future research is warranted to examine the physiological significance of this age-dependent mechanism.

  5. To Be Connected or Not To Be Connected? Mobile Messenger Overload, Fatigue, and Mobile Shunning.

    PubMed

    Shin, Jaewook; Shin, Mincheol

    2016-10-01

    With the increased adoption of mobile devices, mobile communication is all around us and we are connected anywhere, anytime. Mobile communication in general and mobile messenger service in particular make interpersonal communication in Korea so frequent and convenient. However, being connected too much anywhere and anytime via mobile messenger service appears to lead an increasing number of people to feel fatigue and to decrease mobile communication under some conditions. Based on a sample of 334 respondents, this study empirically investigated the relationships among commercial, noncommercial mobile messenger overload, mobile messenger fatigue, relational self-concept, and mobile shunning behavior. The findings show that (a) the effect of noncommercial mobile messenger overload is stronger than that of commercial mobile messenger overload in increasing mobile messenger fatigue although both positively affect mobile messenger fatigue, (b) relational self-concept has moderating effects on the relationship between mobile messenger overload and mobile messenger fatigue, and that (c) mobile messenger fatigue triggers mobile communicators' shunning behavior through which the communicators increase their intention to avoid mobile communication, to change their mobile phone numbers, and to subscribe to dual number service on one mobile device. When confronted with mobile messenger fatigue caused by mobile messenger overload, mobile messaging service users are likely to shun their mobile communication. Being constantly and conveniently connected appears to be a blessing in disguise.

  6. Assessment of Apical Expression of Alpha-2 Integrin, Heat Shock Protein, and Proinflammatory and Immunoregulatory Cytokines in Response to Endodontic Infection.

    PubMed

    Bambirra, Wilson; Maciel, Kamilla Faria; Thebit, Marcela Marçal; de Brito, Luciana Carla Neves; Vieira, Leda Quercia; Sobrinho, Antônio Paulino Ribeiro

    2015-07-01

    The purpose of this study was to examine alpha-2 integrin, molecular mediators, cytokines, and chemokines from cells in periapical interstitial fluid from root canal infections before and after the reduction of the bacterial load using a cleaning procedure. Subjects included 20 patients referred to the School of Dentistry at the Universidade Federal de Minas Gerais (Belo Horizonte, Minas Gerais, Brazil). Clinical samples were taken from teeth with pulp necrosis, and no patients had acute periapical symptoms at the time of the appointments. After cleaning and drying, 3 paper points were introduced into the root canal, passing passively through the root apex (2 mm) into the periapical tissues for 1 minute. The samples were collected immediately after root canal cleaning and 7 days later (restrained root canal bacterial load) to characterize those gene expressions using real-time polymerase chain reaction. Significantly lower levels of tumor necrosis factor alpha, chemokine ligand 5 (CCL5), chemokine ligand 2/monocyte chemotactic protein 1 (CCL2/MCP-1), and interleukin (IL)-8 in teeth with restrained bacterial loads (second collection) compared with the first collection were observed (P < .05). Similarly, the messenger RNA expression of the integrins secreted phosphoprotein 1 (SSP1)/ostepontin and focal adhesion kinase (FAK) decreased in samples from the second collection (P < .05). The messenger RNA for the regulatory cytokine IL-10 was significant higher in samples from the second collection (day 7) compared with the first collection (day 0) (P < .05). Messenger RNA expression of IL-1β, IL-17A, interferon gamma, alpha-2 integrin, and Hsp47/SERPINH1 were similar at both time points (P > .05). These findings suggest that after reducing the root canal bacterial load a decrease in the inflammatory response took place in the periapical lesions. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Compiling Mercury relief map using several data sources

    NASA Astrophysics Data System (ADS)

    Zakharova, Maria; Lazarev, Evgeniy

    2015-04-01

    There are several data of Mercury topography obtained as the result of processing materials collected by two spacecrafts - the Mariner-10 and the MESSENGER during their Mercury flybys. The history of the visual mapping of the Mercury begins at the recent times as the first significant observations were made during the latter half of the 20th century, whereas today we have no data with 100% coverage for the entire surface of the Mercury except the global mosaic composed of the images acquired by MESSENGER. The Mercury relief map has been created with the help of four different types of data: - global mosaic with 100% coverage of Mercury's surface created by using MESSENGER orbital images (30% of the final map); - Digital Terrain Models obtained by the treating stereo images made during the Mariner 10's flybys (10% of the map) (Cook and Robinson, 2000); - Digital Terrain Models obtained from images acquired during the Messenger flybys (20% of the map) (F. Preusker et al., 2011); - the data sets produced by the MESSENGER Mercury Laser Altimeter (MLA) (40 % of the map). The main objective of this work is to collect, combine and process the existing data and then to merge them correctly for one single map compiling. The final map is created in the Lambert azimuthal Equal area projection and mainly shows the hypsometric features of the planet. It represents two hemispheres - western and eastern. In order not to divide data sources the eastern hemisphere takes an interval from 50 degrees east longitude to 130 degrees west longitude and the western one takes respectively the interval from 130 degrees west longitude to 50 degrees east longitude. References: Global mosaics of Mercury's surface. Available mosaics include one created prior to MESSENGER's orbital operations, high resolution versions that use MESSENGER's orbital images that are available in NASA's Planetary Data System (PDS) (http://messenger.jhuapl.edu/the_mission/mosaics.html). Cook, A.C., Robinson, M.S., 2000. Mariner 10 stereo image coverage of Mercury. J. Geophys. Res. 105, 9429-9443. Preusker, F., Oberst, J., Head, J.W., Watters, T.R., Robinson, M.S., Zuber, M.T., Solomon, S.C., 2010. Stereo topographic models of Mercury after three MESSENGER flybys. Planetary and Space Science 59 (2011), 1910-1917. The MLA is a time-of-flight laser rangefinder that uses direct detection and pulse-edge timing to determine precisely the range from the MESSENGER spacecraft to Mercury's surface (http://pds-geosciences.wustl.edu/missions/messenger/mla.htm).

  8. Calcium and signal transduction in plants

    NASA Technical Reports Server (NTRS)

    Poovaiah, B. W.; Reddy, A. S.

    1993-01-01

    Environmental and hormonal signals control diverse physiological processes in plants. The mechanisms by which plant cells perceive and transduce these signals are poorly understood. Understanding biochemical and molecular events involved in signal transduction pathways has become one of the most active areas of plant research. Research during the last 15 years has established that Ca2+ acts as a messenger in transducing external signals. The evidence in support of Ca2+ as a messenger is unequivocal and fulfills all the requirements of a messenger. The role of Ca2+ becomes even more important because it is the only messenger known so far in plants. Since our last review on the Ca2+ messenger system in 1987, there has been tremendous progress in elucidating various aspects of Ca(2+) -signaling pathways in plants. These include demonstration of signal-induced changes in cytosolic Ca2+, calmodulin and calmodulin-like proteins, identification of different Ca2+ channels, characterization of Ca(2+) -dependent protein kinases (CDPKs) both at the biochemical and molecular levels, evidence for the presence of calmodulin-dependent protein kinases, and increased evidence in support of the role of inositol phospholipids in the Ca(2+) -signaling system. Despite the progress in Ca2+ research in plants, it is still in its infancy and much more needs to be done to understand the precise mechanisms by which Ca2+ regulates a wide variety of physiological processes. The purpose of this review is to summarize some of these recent developments in Ca2+ research as it relates to signal transduction in plants.

  9. MESSENGER View of Mercury's Caloris Basin

    NASA Image and Video Library

    2017-12-08

    NASA image acquired October 28, 2011 This stunning, and as of yet unnamed, crater lies within the Caloris basin. Its floor provides another example of the beautiful "hollows" found on Mercury and has an etched appearance similar to that found in the crater Tyagaraja. This image was acquired as a high-resolution targeted observation. Targeted observations are images of a small area on Mercury's surface at resolutions much higher than the 250-meter/pixel (820 feet/pixel) morphology base map or the 1-kilometer/pixel (0.6 miles/pixel) color base map. It is not possible to cover all of Mercury's surface at this high resolution during MESSENGER's one-year mission, but several areas of high scientific interest are generally imaged in this mode each week. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MDIS is scheduled to acquire more than 75,000 images in support of MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  10. Happy Little Crater on Mercury

    NASA Image and Video Library

    2017-12-08

    It looks like even the craters on Mercury have heard of Bob Ross! The central peaks of this complex crater have formed in such a way that it resembles a smiling face. This image is oriented so north is toward the bottom. This image was acquired as a high-resolution targeted observation. Targeted observations are images of a small area on Mercury's surface at resolutions much higher than the 200-meter/pixel morphology base map. It is not possible to cover all of Mercury's surface at this high resolution, but typically several areas of high scientific interest are imaged in this mode each week. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MESSENGER acquired 88,746 images and extensive other data sets. MESSENGER is now in a yearlong extended mission, during which plans call for the acquisition of more than 80,000 additional images to support MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  11. Geodesy at Mercury with MESSENGER

    NASA Technical Reports Server (NTRS)

    Smith, David E.; Zuber, Maria t.; Peale, Stanley J.; Phillips, Roger J.; Solomon, Sean C.

    2006-01-01

    In 2011 the MESSENGER (MErcury Surface, Space ENvironment, GEochemistry, and Ranging) spacecraft will enter Mercury orbit and begin the mapping phase of the mission. As part of its science objectives the MESSENGER mission will determine the shape and gravity field of Mercury. These observations will enable the topography and the crustal thickness to be derived for the planet and will determine the small libration of the planet about its axis, the latter critical to constraining the state of the core. These measurements require very precise positioning of the MESSENGER spacecraft in its eccentric orbit, which has a periapsis altitude as low as 200 km, an apoapsis altitude near 15,000 km, and a closest approach to the surface varying from latitude 60 to about 70 N. The X-band tracking of MESSENGER and the laser altimetry are the primary data that will be used to measure the planetary shape and gravity field. The laser altimeter, which has an expected range of 1000 to 1200 km, is expected to provide significant data only over the northern hemisphere because of MESSENGER's eccentric orbit. For the southern hemisphere, radio occultation measurements obtained as the spacecraft passes behind the planet as seen from Earth and images obtained with the imaging system will be used to provide the long-wavelength shape of the planet. Gravity, derived from the tracking data, will also have greater resolution in the northern hemisphere, but full global models for both topography and gravity will be obtained at low harmonic order and degree. The limiting factor for both gravity and topography is expected to be knowledge of the spacecraft location. Present estimations are that in a combined tracking, altimetry, and occultation solution the spacecraft position uncertainty is likely to be of order 10 m. This accuracy should be adequate for establishing an initial geodetic coordinate system for Mercury that will enable positioning of imaged features on the surface, determination of the planet's obliquity, and detection of the librational motion of the planet about its axis.

  12. False Color View of Mercury

    NASA Image and Video Library

    2017-12-08

    This colorful view of Mercury was produced by using images from the color base map imaging campaign during MESSENGER's primary mission. These colors are not what Mercury would look like to the human eye, but rather the colors enhance the chemical, mineralogical, and physical differences between the rocks that make up Mercury's surface. To watch a movie of this colorful view of Mercury as a spinning globe go here: www.flickr.com/photos/gsfc/8497927473 Young crater rays, extending radially from fresh impact craters, appear light blue or white. Medium- and dark-blue areas are a geologic unit of Mercury's crust known as the "low-reflectance material", thought to be rich in a dark, opaque mineral. Tan areas are plains formed by eruption of highly fluid lavas. The giant Caloris basin is the large circular tan feature located just to the upper right of center of the image. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MESSENGER acquired 88,746 images and extensive other data sets. MESSENGER is now in a yearlong extended mission, during which plans call for the acquisition of more than 80,000 additional images to support MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  13. Mercury's gravity field, orientation, and ephemeris after MESSENGER's Low-Altitude Campaign

    NASA Astrophysics Data System (ADS)

    Genova, Antonio; Mazarico, Erwan; Goossens, Sander J.; Lemoine, Frank G.; Neumann, Gregory A.; Smith, David E.; Zuber, Maria T.; Solomon, Sean C.

    2015-04-01

    In April 2015, the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft will complete more than 4 years of operations in orbit around Mercury. In its last year, as part of MESSENGER's Second Extended Mission (XM2) started in March 2013, the spacecraft has been collecting radio tracking data at unprecedented low altitudes in Mercury's northern hemisphere. During the first two years in orbit, the spacecraft periapsis altitude was kept between 200 and 500 km, while its location drifted slowly northward from 60˚N to 84˚N. The orbital period initially was 12 h, but it was decreased to 8 h in April 2012. The remaining fuel onboard the spacecraft enabled two extended missions, the last of which will end with an impact expected on or before 28 April 2015. During the second extended mission, the periapsis altitude has been as low as 15-25 km. NASA's Deep Space Network (DSN) tracked the spacecraft during periapsis passages from April to October 2014, when the spacecraft periapsis altitude was between 25 and 100 km. In the last six months of the mission, the closest approaches of MESSENGER were occulted by Mercury and were thus not visible from Earth. However, additional radio tracking data have been collected at altitudes (75-100 km) that are still substantially below the initial periapsis altitude. The new low-altitude radio tracking data have enabled an updated model of the gravity field of Mercury. With these data, the resolution of the field in the northern hemisphere has been improved, revealing features that were previously undetectable and that correlate well with topography. The zonal harmonics are in good agreement with those in previous models of the gravity field. We also focused our study on the determination of other geophysical parameters, such as the orientation of Mercury. The new data were acquired not only at lower altitudes but also at latitudes closer to the equator, so they provide important information on tides, the right ascension of the pole, and the physical libration in longitude. The new model of Mercury's gravity field includes the estimation of the declination and the right ascension of the pole, the Love number k2, and the amplitude of the longitudinal libration. We also report an update on the ephemeris of Mercury obtained from MESSENGER range data covering the entire mission period, from the flybys until the end of the mission.

  14. Activation of Exchange Protein Activated by Cyclic-AMP Enhances Long-Lasting Synaptic Potentiation in the Hippocampus

    ERIC Educational Resources Information Center

    Gelinas, Jennifer N.; Banko, Jessica L.; Peters, Melinda M.; Klann, Eric; Weeber, Edwin J.; Nguyen, Peter V.

    2008-01-01

    cAMP is a critical second messenger implicated in synaptic plasticity and memory in the mammalian brain. Substantial evidence links increases in intracellular cAMP to activation of cAMP-dependent protein kinase (PKA) and subsequent phosphorylation of downstream effectors (transcription factors, receptors, protein kinases) necessary for long-term…

  15. From the First to the Last

    NASA Image and Video Library

    2015-04-30

    On March 18, 2011, MESSENGER made history by becoming the first spacecraft ever to orbit Mercury. Eleven days later, the spacecraft captured the first image ever obtained from Mercury orbit, shown here on the left. Originally planned as a one-year orbital mission, the MESSENGER spacecraft orbited Mercury for more than four years, accomplishing technological firsts and making new scientific discoveries about the origin and evolution of the Solar System's innermost planet. Check out the Top 10 Science Results. Dates acquired: March 29, 2011; April 30, 2015 Image IDs: 65056, 8422953 Instrument: Mercury Dual Imaging System (MDIS) Left Image Center Latitude: -53.3° Left Image Center Longitude: 13.0° E Left Image Resolution: 2.7 kilometers/pixel Left Image Scale: The rayed crater Debussy has a diameter of 80 kilometers (50 miles) Right Image Center Latitude: 72.0° Right Image Center Longitude: 223.8° E Right Image Resolution: 2.1 meters/pixel Right Image Scale: This image is about 1 kilometers (0.6 miles) across On April 30, 2015, MESSENGER again made history, becoming the first spacecraft to impact the planet. In total, MESSENGER acquired and returned to Earth more than 277,000 images from orbit about Mercury. The last of those images is shown here on the right. http://photojournal.jpl.nasa.gov/catalog/PIA19449

  16. KSC-04PD-0431

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers remove the protective cover from NASAs MESSENGER spacecraft. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  17. KSC-04PD-0442

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. At the Astrotech Space Operations processing facilities, workers check the placement of NASAs MESSENGER spacecraft on a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  18. KSC-04PD-0432

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers remove the protective cover from NASAs MESSENGER spacecraft. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  19. KSC-04PD-0443

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. At the Astrotech Space Operations processing facilities, workers check the placement of NASAs MESSENGER spacecraft on a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  20. KSC-04PD-0429

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. At the Astrotech Space Operations processing facilities near KSC, workers move NASAs MESSENGER spacecraft into a high bay clean room. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  1. Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense.

    PubMed

    O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark; Alexandre, Gladys

    2017-09-15

    Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense , c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and modulates their contribution to the overall chemotaxis response. Here, we used an optogenetic system to perturb intracellular concentrations of the bacterial second messenger c-di-GMP to show that in some chemotaxis receptors, c-di-GMP functions in a similar feedback loop to connect the metabolic status of the cells to the sensory activity of chemotaxis receptors. Copyright © 2017 American Society for Microbiology.

  2. Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense

    PubMed Central

    O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark

    2017-01-01

    ABSTRACT Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense, c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and modulates their contribution to the overall chemotaxis response. Here, we used an optogenetic system to perturb intracellular concentrations of the bacterial second messenger c-di-GMP to show that in some chemotaxis receptors, c-di-GMP functions in a similar feedback loop to connect the metabolic status of the cells to the sensory activity of chemotaxis receptors. PMID:28264994

  3. Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices.

    PubMed

    Grassi, S; Pettorossi, V E

    2001-08-01

    The analysis of cellular-molecular events mediating synaptic plasticity within vestibular nuclei is an attempt to explain the mechanisms underlying vestibular plasticity phenomena. The present review is meant to illustrate the main results, obtained in vitro, on the mechanisms underlying long-term changes in synaptic strength within the medial vestibular nuclei. The synaptic plasticity phenomena taking place at the level of vestibular nuclei could be useful for adapting and consolidating the efficacy of vestibular neuron responsiveness to environmental requirements, as during visuo-vestibular recalibration and vestibular compensation. Following a general introduction on the most salient features of vestibular compensation and visuo-vestibular adaptation, which are two plastic events involving neuronal circuitry within the medial vestibular nuclei, the second and third sections describe the results from rat brainstem slice studies, demonstrating the possibility to induce long-term potentiation and depression in the medial vestibular nuclei, following high frequency stimulation of the primary vestibular afferents. In particular the mechanisms sustaining the induction and expression of vestibular long-term potentiation and depression, such as the role of various glutamate receptors and retrograde messengers have been described. The relevant role of the interaction between the platelet-activating factor, acting as a retrograde messenger, and the presynaptic metabotropic glutamate receptors, in determining the full expression of vestibular long-term potentiation is also underlined. In addition, the mechanisms involved in vestibular long-term potentiation have been compared with those leading to long-term potentiation in the hippocampus to emphasize the most significant differences emerging from vestibular studies. The fourth part, describes recent results demonstrating the essential role of nitric oxide, another retrograde messenger, in the induction of vestibular potentiation. Finally the fifth part suggests the possible functional significance of different action times of the two retrograde messengers and metabotropic glutamate receptors, which are involved in mediating the presynaptic mechanism sustaining vestibular long-term potentiation.

  4. Students Engaging the Public in Exciting Discoveries by NASA's MESSENGER Mission

    NASA Astrophysics Data System (ADS)

    Hallau, K. G.; Morison, J.; Schuele, H.

    2012-12-01

    In March 2011, NASA's MESSENGER spacecraft entered into orbit around Mercury, the closest planet to the Sun. As the first mission to orbit and study Mercury in depth, MESSENGER sought to answer six primary scientific questions: why is Mercury so dense; what is the geologic history of Mercury; what is the nature of Mercury's magnetic field; what is the structure of Mercury's core; what are the unusual materials at Mercury's poles; and what volatiles are important at Mercury? In the first year of orbit, MESSENGER answered all of these questions, and also made several surprising discoveries. Student interns working with the MESSENGER Education and Public Outreach (EPO) team are using MESSENGER Mosaic Postcards (MPC) in both print and digital formats to present this new information to a broad audience. These MPCs, in conjunction with the rest of the MESSENGER EPO tools, present a unified and global resource for the public. By creating this resource in a variety of media, from printable cards to interactive features on the EPO website (http://www.messenger-education.org/), the EPO team can reach a larger audience, further the goal of the MPC project to share newly discovered features and phenomena with the general public, and thereby generate increased interest in and excitement about science and planetary exploration. One side of each MPC shows a MESSENGER image of a portion of Mercury's surface, and together the postcards can be arranged to form a complete image of the planet. On the reverse side of some cards is information pertaining to an item of interest in view on the image-side. One of us (physics undergraduate JEM) researches interesting features on the surface of Mercury and creates descriptions for the informational side of the postcards, and another (computer science undergraduate HCS) creates the digital versions of cards and associated resources for the Surface Interactive, an interactive tool on the MESSENGER EPO website. Postcards already in distribution address topics such as craters with pyroclastic deposits, rayed craters, crater superposition, dark materials on Mercury, smooth plains, and lobate scarps. As MESSENGER continues its orbital study of Mercury, ever more exciting and surprising data are being returned, and from them new MPCs are being produced. Several of these MPCs focus on specific geologic features of Mercury, including the Caloris basin, one of the largest impact basins in the solar system; Pantheon Fossae, a mysterious set of radial troughs; and Raditladi, a comparatively young, double-ringed impact basin. Moreover, discoveries about Mercury extend beyond geologic features. Newly produced MPCs also explain how MESSENGER used gravity assists of Earth, Venus, and Mercury to succeed in its orbit insertion and how the probe's eccentric orbit protects the spacecraft and instruments from heat re-radiated from Mercury's surface. New information regarding Mercury's magnetic field, magnetosphere, and exosphere are also intriguing topics to be presented in future MPCs.

  5. Cytoplasmic Electric Fields and Electroosmosis: Possible Solution for the Paradoxes of the Intracellular Transport of Biomolecules

    PubMed Central

    Andreev, Victor P.

    2013-01-01

    The objective of the paper is to show that electroosmotic flow might play an important role in the intracellular transport of biomolecules. The paper presents two mathematical models describing the role of electroosmosis in the transport of the negatively charged messenger proteins to the negatively charged nucleus and in the recovery of the fluorescence after photobleaching. The parameters of the models were derived from the extensive review of the literature data. Computer simulations were performed within the COMSOL 4.2a software environment. The first model demonstrated that the presence of electroosmosis might intensify the flux of messenger proteins to the nucleus and allow the efficient transport of the negatively charged phosphorylated messenger proteins against the electrostatic repulsion of the negatively charged nucleus. The second model revealed that the presence of the electroosmotic flow made the time of fluorescence recovery dependent on the position of the bleaching spot relative to cellular membrane. The magnitude of the electroosmotic flow effect was shown to be quite substantial, i.e. increasing the flux of the messengers onto the nucleus up to 4-fold relative to pure diffusion and resulting in the up to 3-fold change in the values of fluorescence recovery time, and therefore the apparent diffusion coefficient determined from the fluorescence recovery after photobleaching experiments. Based on the results of the modeling and on the universal nature of the electroosmotic flow, the potential wider implications of electroosmotic flow in the intracellular and extracellular biological processes are discussed. Both models are available for download at ModelDB. PMID:23613967

  6. Cytoplasmic electric fields and electroosmosis: possible solution for the paradoxes of the intracellular transport of biomolecules.

    PubMed

    Andreev, Victor P

    2013-01-01

    The objective of the paper is to show that electroosmotic flow might play an important role in the intracellular transport of biomolecules. The paper presents two mathematical models describing the role of electroosmosis in the transport of the negatively charged messenger proteins to the negatively charged nucleus and in the recovery of the fluorescence after photobleaching. The parameters of the models were derived from the extensive review of the literature data. Computer simulations were performed within the COMSOL 4.2a software environment. The first model demonstrated that the presence of electroosmosis might intensify the flux of messenger proteins to the nucleus and allow the efficient transport of the negatively charged phosphorylated messenger proteins against the electrostatic repulsion of the negatively charged nucleus. The second model revealed that the presence of the electroosmotic flow made the time of fluorescence recovery dependent on the position of the bleaching spot relative to cellular membrane. The magnitude of the electroosmotic flow effect was shown to be quite substantial, i.e. increasing the flux of the messengers onto the nucleus up to 4-fold relative to pure diffusion and resulting in the up to 3-fold change in the values of fluorescence recovery time, and therefore the apparent diffusion coefficient determined from the fluorescence recovery after photobleaching experiments. Based on the results of the modeling and on the universal nature of the electroosmotic flow, the potential wider implications of electroosmotic flow in the intracellular and extracellular biological processes are discussed. Both models are available for download at ModelDB.

  7. Melatonin: a universal time messenger.

    PubMed

    Erren, Thomas C; Reiter, Russel J

    2015-01-01

    Temporal organization plays a key role in humans, and presumably all species on Earth. A core building block of the chronobiological architecture is the master clock, located in the suprachi asmatic nuclei [SCN], which organizes "when" things happen in sub-cellular biochemistry, cells, organs and organisms, including humans. Conceptually, time messenging should follow a 5 step-cascade. While abundant evidence suggests how steps 1 through 4 work, step 5 of "how is central time information transmitted througout the body?" awaits elucidation. Step 1: Light provides information on environmental (external) time; Step 2: Ocular interfaces between light and biological (internal) time are intrinsically photosensitive retinal ganglion cells [ipRGS] and rods and cones; Step 3: Via the retinohypothalamic tract external time information reaches the light-dependent master clock in the brain, viz the SCN; Step 4: The SCN translate environmental time information into biological time and distribute this information to numerous brain structures via a melanopsin-based network. Step 5: Melatonin, we propose, transmits, or is a messenger of, internal time information to all parts of the body to allow temporal organization which is orchestrated by the SCN. Key reasons why we expect melatonin to have such role include: First, melatonin, as the chemical expression of darkness, is centrally involved in time- and timing-related processes such as encoding clock and calendar information in the brain; Second, melatonin travels throughout the body without limits and is thus a ubiquitous molecule. The chemial conservation of melatonin in all tested species could make this molecule a candidate for a universal time messenger, possibly constituting a legacy of an all-embracing evolutionary history.

  8. The Air Forces on a Model of the Sperry Messenger Airplane Without Propeller

    NASA Technical Reports Server (NTRS)

    Munk, Max M; Diehl, Walter S

    1926-01-01

    This is a report on a scale effect research which was made in the variable-density wind tunnel of the National Advisory Committee for Aeronautics at the request of the Army Air Service. A 1/10 scale model of the sperry messenger airplane with USA-5 wings was tested without a propeller at various Reynolds numbers up to the full scale value. Two series of tests were: the first on the original model which was of the usual simplified construction, and the second on a modified model embodying a great amount of detail. The experimental results show that the scale effect is almost entirely confined to the drag. It was also found that the model should be geometrically similar to the full-scale airplane if the test data are to be directly applicable to full scale.

  9. MESSENGER Observations of Rapid and Impulsive Magnetic Reconnection in Mercury's Magnetotail

    NASA Astrophysics Data System (ADS)

    Zhong, J.; Wei, Y.; Pu, Z. Y.; Wang, X. G.; Wan, W. X.; Slavin, J. A.; Cao, X.; Raines, J. M.; Zhang, H.; Xiao, C. J.; Du, A. M.; Wang, R. S.; Dewey, R. M.; Chai, L. H.; Rong, Z. J.; Li, Y.

    2018-06-01

    The nature of magnetic reconnection in planetary magnetospheres may differ between various planets. We report the first observations of a rapidly evolving magnetic reconnection process in Mercury’s magnetotail by the MESSENGER spacecraft. The reconnection process was initialized in the plasma sheet and then evolved into the lobe region during a ∼35 s period. The tailward reconnection fronts of primary and secondary flux ropes with clear Hall signatures and energetic electron bursts were observed. The reconnection timescale of a few seconds is substantially shorter than that of terrestrial magnetospheric plasmas. The normalized reconnection rate during a brief quasi-steady period is estimated to be ∼0.2 on average. The observations show the rapid and impulsive nature of the exceedingly driven reconnection in Mercury’s magnetospheric plasma that may be responsible for the much more dynamic magnetosphere of Mercury.

  10. Translation of globin messenger RNA by the mouse ovum

    PubMed Central

    Brinster, R. L.; Chen, H. Y.; Trumbauer, M. E.; Avarbock, M. R.

    2016-01-01

    It has been demonstrated that the Xenopus oocyte can translate rabbit haemoglobin messenger RNA (mRNA) following microinjection of the message into the cell1. The Xenopus oocyte has since been shown to be capable of translating a variety of messenger RNAs from different species2–4. This system has proved useful in understanding the mechanism of message translation and has also provided information about the translation capability of the Xenopus oocyte5,6. Several other cell types, including HeLa cells and fibroblasts, can also translate exogenous message injected into the cell7,8. However, there have been no reports of injection of mRNA into oocytes or fertilised one-cell ova of mammalian species. Nevertheless, the latter system could be of considerable use in studying the processing of exogenous messages in a mammalian system undergoing development, as well as providing insight into the way the early embryo processes injected messages and the protein products of such messages. We report here the results of injecting message into the fertilised one-cell mouse ovum and show that both mouse and rabbit globin mRNA are translated in this system. PMID:7352032

  11. redox Signaling by 8-nitro-cyclic guanosine monophosphate: nitric oxide- and reactive oxygen species-derived electrophilic messenger.

    PubMed

    Fujii, Shigemoto; Akaike, Takaaki

    2013-10-10

    Emerging evidence has revealed that nitric oxide (NO)- and reactive oxygen species (ROS)-derived electrophiles formed in cells mediate signal transduction for responses to oxidative stress. The cyclic nucleotide with a nitrated guanine moiety-8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP)-first identified in 2007 as a second messenger for NO and ROS-has certain unique properties that its parental cGMP lacks. For example, it can react with particular protein Cys thiols because of its electrophilicity and can cause unique post-translational modifications of redox-sensor proteins such as Keap1 and H-Ras. Site-specific S-guanylation of Keap1 at Cys434 induced NO- and ROS-mediated adaptive responses to oxidative stress. H-Ras Cys184 S-guanylation was recently found to be involved in activation of mitogen-activated protein kinase cascades as manifested by cellular senescence and heart failure in mouse cardiac hypertrophy models. The latest finding related to the concept of electrophile-based redox signaling is a potent regulatory function of endogenously produced hydrogen sulfide for redox signaling via 8-nitro-cGMP. Electrophile modification of 8-nitro-cGMP, as a second messenger for NO and ROS, by hydrogen sulfide (i.e., electrophile sulfhydration) can most likely effect physiological regulation of cellular redox signaling. Continued investigation of the precise function of cellular hydrogen sulfide that may control electrophile-dependent redox cellular signaling, most typically via 8-nitro-cGMP formation, may provide novel insights into the molecular mechanisms of oxidative stress responses, oxidative stress-related pathology and disease control, and development of therapeutics for various diseases.

  12. Multiple Ion Binding Equilibria, Reaction Kinetics, and Thermodynamics in Dynamic Models of Biochemical Pathways

    PubMed Central

    Vinnakota, Kalyan C.; Wu, Fan; Kushmerick, Martin J.; Beard, Daniel A.

    2009-01-01

    The operation of biochemical systems in vivo and in vitro is strongly influenced by complex interactions between biochemical reactants and ions such as H+, Mg2+, K+, and Ca2+. These are important second messengers in metabolic and signaling pathways that directly influence the kinetics and thermodynamics of biochemical systems. Herein we describe the biophysical theory and computational methods to account for multiple ion binding to biochemical reactants and demonstrate the crucial effects of ion binding on biochemical reaction kinetics and thermodynamics. In simulations of realistic systems, the concentrations of these ions change with time due to dynamic buffering and competitive binding. In turn, the effective thermodynamic properties vary as functions of cation concentrations and important environmental variables such as temperature and overall ionic strength. Physically realistic simulations of biochemical systems require incorporating all of these phenomena into a coherent mathematical description. Several applications to physiological systems are demonstrated based on this coherent simulation framework. PMID:19216922

  13. Calcium and ROS: A mutual interplay

    PubMed Central

    Görlach, Agnes; Bertram, Katharina; Hudecova, Sona; Krizanova, Olga

    2015-01-01

    Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions. The Ca2+ signaling network works in many different ways to regulate cellular processes that function over a wide dynamic range due to the action of buffers, pumps and exchangers on the plasma membrane as well as in internal stores. Calcium signaling pathways interact with other cellular signaling systems such as reactive oxygen species (ROS). Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death. Increasing evidence suggests a mutual interplay between calcium and ROS signaling systems which seems to have important implications for fine tuning cellular signaling networks. However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders. PMID:26296072

  14. WhatsApp Messenger as an Adjunctive Tool for Telemedicine: An Overview

    PubMed Central

    2017-01-01

    Background The advent of telemedicine has allowed physicians to deliver medical treatment to patients from a distance. Mobile apps such as WhatsApp Messenger, an instant messaging service, came as a novel concept in all fields of social life, including medicine. The use of instant messaging services has been shown to improve communication within medical teams by providing means for quick teleconsultation, information sharing, and starting treatment as soon as possible. Objective The aim of this study was to perform a comprehensive systematic review of present literature on the use of the WhatsApp Messenger app as an adjunctive health care tool for medical doctors. Methods Searches were performed in PubMed, EMBASE, and the Cochrane Library using the term “whatsapp*” in articles published before January 2016. A bibliography of all relevant original articles that used the WhatsApp Messenger app was created. The level of evidence of each study was determined according to the Oxford Levels of Evidence ranking system produced by the Oxford Centre for Evidence-Based Medicine. The impact and the indications of WhatsApp Messenger are discussed in order to understand the extent to which this app currently functions as an adjunctive tool for telemedicine. Results The database search identified a total of 30 studies in which the term “whatsapp*” was used. Each article’s list of references was evaluated item-by-item. After literature reviews, letters to the editor, and low-quality studies were excluded, a total of 10 studies were found to be eligible for inclusion. Of these studies, 9 had been published in the English language and 1 had been published in Spanish. Five were published by medical doctors. Conclusions The pooled data presents compelling evidence that the WhatsApp Messenger app is a promising system, whether used as a communication tool between health care professionals, as a means of communication between health care professionals and the general public, or as a learning tool for providing health care information to professionals or to the general population. However, high-quality and properly evaluated research is needed, as are improvements in descriptions of the methodology and the study processes. These improvements will allow WhatsApp Messenger to be categorically defined as an effective telemedicine tool in many different fields of health care. PMID:28733273

  15. Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells

    PubMed Central

    Joshi, Mahesh S.; Ferguson, T. Bruce; Johnson, Fruzsina K.; Johnson, Robert A.; Parthasarathy, Sampath; Lancaster, Jack R.

    2007-01-01

    Arginine contains the guanidinium group and thus has structural similarity to ligands of imidazoline and α-2 adrenoceptors (α-2 AR). Therefore, we investigated the possibility that exogenous arginine may act as a ligand for these receptors in human umbilical vein endothelial cells and activate intracellular nitric oxide (NO) synthesis. Idazoxan, a mixed antagonist of imidazoline and α-2 adrenoceptors, partly inhibited l-arginine-initiated NO formation as measured by a Griess reaction. Rauwolscine, a highly specific antagonist of α-2 AR, at very low concentrations completely inhibited NO formation. Like l-arginine, agmatine (decarboxylated arginine) also activated NO synthesis, however, at much lower concentrations. We found that dexmedetomidine, a specific agonist of α-2 AR was very potent in activating cellular NO, thus indicating a possible role for α-2 AR in l-arginine-mediated NO synthesis. d-arginine also activated NO production and could be inhibited by imidazoline and α-2 AR antagonists, thus indicating nonsubstrate actions of arginine. Pertussis toxin, an inhibitor of G proteins, attenuated l-arginine-mediated NO synthesis, thus indicating mediation via G proteins. l-type Ca2+ channel blocker nifedipine and phospholipase C inhibitor U73122 inhibited NO formation and thus implicated participation of a second messenger pathway. Finally, in isolated rat gracilis vessels, rauwolscine completely inhibited the l-arginine-initiated vessel relaxation. Taken together, these data provide evidence for binding of arginine to membrane receptor(s), leading to the activation of endothelial NO synthase (eNOS) NO production through a second messenger pathway. These findings provide a previously unrecognized mechanistic explanation for the beneficial effects of l-arginine in the cardiovascular system and thus provide new potential avenues for therapeutic development. PMID:17535904

  16. Infrared photodissociation spectroscopy of H(+)(H2O)6·M(m) (M = Ne, Ar, Kr, Xe, H2, N2, and CH4): messenger-dependent balance between H3O(+) and H5O2(+) core isomers.

    PubMed

    Mizuse, Kenta; Fujii, Asuka

    2011-04-21

    Although messenger mediated spectroscopy is a widely-used technique to study gas phase ionic species, effects of messengers themselves are not necessarily clear. In this study, we report infrared photodissociation spectroscopy of H(+)(H(2)O)(6)·M(m) (M = Ne, Ar, Kr, Xe, H(2), N(2), and CH(4)) in the OH stretch region to investigate messenger(M)-dependent cluster structures of the H(+)(H(2)O)(6) moiety. The H(+)(H(2)O)(6), the protonated water hexamer, is the smallest system in which both the H(3)O(+) (Eigen) and H(5)O(2)(+) (Zundel) hydrated proton motifs coexist. All the spectra show narrower band widths reflecting reduced internal energy (lower vibrational temperature) in comparison with bare H(+)(H(2)O)(6). The Xe-, CH(4)-, and N(2)-mediated spectra show additional band features due to the relatively strong perturbation of the messenger. The observed band patterns in the Ar-, Kr-, Xe-, N(2)-, and CH(4)-mediated spectra are attributed mainly to the "Zundel" type isomer, which is more stable. On the other hand, the Ne- and H(2)-mediated spectra are accounted for by a mixture of the "Eigen" and "Zundel" types, like that of bare H(+)(H(2)O)(6). These results suggest that a messenger sometimes imposes unexpected isomer-selectivity even though it has been thought to be inert. Plausible origins of the isomer-selectivity are also discussed.

  17. Petit Petipa

    NASA Image and Video Library

    2017-12-08

    This striking image highlights Petipa crater, which was recently named after Marius Petipa, a French ballet dancer, teacher, and choreographer. The rays eminating from Petipa indicate that it is a relatively fresh crater; over time, these rays will fade as they are subjected to space weathering. North is towards the top of this image. This image was acquired as a high-resolution targeted observation. Targeted observations are images of a small area on Mercury's surface at resolutions much higher than the 200-meter/pixel morphology base map. It is not possible to cover all of Mercury's surface at this high resolution, but typically several areas of high scientific interest are imaged in this mode each week. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MESSENGER acquired 88,746 images and extensive other data sets. MESSENGER is now in a yearlong extended mission, during which plans call for the acquisition of more than 80,000 additional images to support MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  18. Mechanical stimulation of skeletal muscle generates lipid-related second messengers by phospholipase activation

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.; Shansky, Janet; Karlisch, Patricia; Solerssi, Rosa Lopez

    1991-01-01

    Repetitive mechanical stimulation of cultured avian skeletal muscle increases the synthesis of prostaglandins E2 and F2(alpha) which regulate protein turnover rates and muscle cell growth. Mechnical stimulation significantly increases the breakdown rate of (3)H-arachidonic acid labelled phospholipids, releasing free (3)H-arachidonic acid, and the rate-limiting precursor of prostaglandin synthesis. Mechanical stimulation also significantly increases (3)H-arachidonic acid labelled diacylglycerol formation and intracellular levels of inositol phosphates from myo-2-(3)H inositol labelled phospholipids. Phospholipase A2, phosphatidylinositol-specific phospholipase C (PLC), and phospholipase D (PLD) are activated by stretch. The lipase inhibitors bromophenacylbromide and RHC80267 together reduce stretch-induced prostaglandin production by 73-83 percent. The stretch-induced increases in prostaglandin production, (3)H-arachidonic acid labelled phospholipid breakdown, and (3)H-arachidonic acid labelled diacylglycerol formation occur independently of cellular electrical activity (tetrodotoxin insensitive) whereas the formation of inositol phosphates from myo-2-(3)H inositol labelled phospholipids are dependent on cellular electrical activity. These results indicate that mechanical stimulation increases the lipid-related second messengers arachidonic acid, diacylglycerol, and prostaglandins through activation of specific phospholipases such as PLA2 and PLD, but not by activation of phosphatidylinositol-specific PLC.

  19. Second messenger production in avian medullary nephron segments in response to peptide hormones.

    PubMed

    Goldstein, D L; Reddy, V; Plaga, K

    1999-03-01

    We examined the sites of peptide hormone activation within medullary nephron segments of the house sparrow (Passer domesticus) kidney by measuring rates of hormone-induced generation of cyclic nucleotide second messenger. Thin descending limbs, thick ascending limbs, and collecting ducts had baseline activity of adenylyl cyclase that resulted in cAMP accumulation of 207 +/- 56, 147 +/- 31, and 151 +/- 41 fmol. mm-1. 30 min-1, respectively. In all segments, this activity increased 10- to 20-fold in response to forskolin. Activity of adenylyl cyclase in the thin descending limb was stimulated approximately twofold by parathyroid hormone (PTH) but not by any of the other hormones tested [arginine vasotocin (AVT), glucagon, atrial natriuretic peptide (ANP), or isoproterenol, each at 10(-6) M]. Thick ascending limb was stimulated two- to threefold by both AVT and PTH; however, glucagon and isoproterenol had no effect, and ANP stimulated neither cAMP nor cGMP accumulation. Adenylyl cyclase activity in the collecting duct was stimulated fourfold by AVT but not by the other hormones; likewise, ANP did not stimulate cGMP accumulation in this segment. These data support a tubular action of AVT and PTH in the avian renal medulla.

  20. Dual specificity and novel structural folding of yeast phosphodiesterase-1 for hydrolysis of second messengers cyclic adenosine and guanosine 3',5'-Monophosphate

    DOE PAGES

    Tian, Yuanyuan; Cui, Wenjun; Huang, Manna; ...

    2014-08-05

    Cyclic nucleotide phosphodiesterases (PDEs) decompose second messengers cAMP and cGMP that play critical roles in many physiological processes. PDE1 of Saccharomyces cerevisiae has been subcloned and expressed in Escherichia coli. Recombinant yPDE1 has a K M of 110 μM and a k cat of 16.9 s⁻¹ for cAMP and a K M of 105 μM and a k cat of 11.8 s₅⁻¹ for cGMP. Thus, the specificity constant (k cat/K McAMP)/(k cat/K M cGMP) of 1.4 indicates a dual specificity of yPDE1 for hydrolysis of both cAMP and cGMP. The crystal structures of unliganded yPDE1 and its complex with GMPmore » at 1.31 Å resolution reveal a new structural folding that is different from those of human PDEs but is partially similar to that of some other metalloenzymes such as metallo-β-lactamase. In spite of their different structures and divalent metals, yPDE1 and human PDEs may share a common mechanism for hydrolysis of cAMP and cGMP.« less

  1. Mechanical stimulation of skeletal muscle generates lipid-related second messengers by phospholipase activation

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.; Shansky, J.; Karlisch, P.; Solerssi, R. L.

    1993-01-01

    Repetitive mechanical stimulation of cultured avian skeletal muscle increases the synthesis of prostaglandins (PG) E2 and F2 alpha which regulate protein turnover rates and muscle cell growth. These stretch-induced PG increases are reduced in low extracellular calcium medium and by specific phospholipase inhibitors. Mechanical stimulation increases the breakdown rate of 3H-arachidonic acid labelled phospholipids, releasing free 3H-arachidonic acid, the rate-limiting precursor of PG synthesis. Mechanical stimulation also increases 3H-arachidonic acid labelled diacylglycerol formation and intracellular levels of inositol phosphates from myo-[2-3H]inositol labelled phospholipids. Phospholipase A2 (PLA2), phosphatidylinositol-specific phospholipase C (PLC), and phospholipase D (PLD) are all activated by stretch. The stretch-induced increases in PG production, 3H-arachidonic acid labelled phospholipid breakdown, and 3H-arachidonic acid labelled diacylglycerol formation occur independently of cellular electrical activity (tetrodotoxin insensitive) whereas the formation of inositol phosphates from myo-[2-3H]inositol labelled phospholipids is dependent on cellular electrical activity. These results indicate that mechanical stimulation increases the lipid-related second messengers arachidonic acid, diacylglycerol, and PG through activation of specific phospholipases such as PLA2 and PLD, but not by activation of phosphatidylinositol-specific PLC.

  2. The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

    PubMed Central

    Lahiani, Adi; Yavin, Ephraim; Lazarovici, Philip

    2017-01-01

    An understanding of the molecular mechanisms by which microbial, plant or animal-secreted toxins exert their action provides the most important element for assessment of human health risks and opens new insights into therapies addressing a plethora of pathologies, ranging from neurological disorders to cancer, using toxinomimetic agents. Recently, molecular and cellular biology dissecting tools have provided a wealth of information on the action of these diverse toxins, yet, an integrated framework to explain their selective toxicity is still lacking. In this review, specific examples of different toxins are emphasized to illustrate the fundamental mechanisms of toxicity at different biochemical, molecular and cellular- levels with particular consideration for the nervous system. The target of primary action has been highlighted and operationally classified into 13 sub-categories. Selected examples of toxins were assigned to each target category, denominated as portal, and the modulation of the different portal’s signaling was featured. The first portal encompasses the plasma membrane lipid domains, which give rise to pores when challenged for example with pardaxin, a fish toxin, or is subject to degradation when enzymes of lipid metabolism such as phospholipases A2 (PLA2) or phospholipase C (PLC) act upon it. Several major portals consist of ion channels, pumps, transporters and ligand gated ionotropic receptors which many toxins act on, disturbing the intracellular ion homeostasis. Another group of portals consists of G-protein-coupled and tyrosine kinase receptors that, upon interaction with discrete toxins, alter second messengers towards pathological levels. Lastly, subcellular organelles such as mitochondria, nucleus, protein- and RNA-synthesis machineries, cytoskeletal networks and exocytic vesicles are also portals targeted and deregulated by other diverse group of toxins. A fundamental concept can be drawn from these seemingly different toxins with respect to the site of action and the secondary messengers and signaling cascades they trigger in the host. While the interaction with the initial portal is largely determined by the chemical nature of the toxin, once inside the cell, several ubiquitous second messengers and protein kinases/ phosphatases pathways are impaired, to attain toxicity. Therefore, toxins represent one of the most promising natural molecules for developing novel therapeutics that selectively target the major cellular portals involved in human physiology and diseases. PMID:28300784

  3. KSC-04PD-0430

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers get ready to remove the protective cover from NASAs MESSENGER spacecraft. Employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  4. KSC-04PD-0436

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers prepare NASAs MESSENGER spacecraft for transfer to a work stand. There employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  5. The Morphology of Craters on Mercury: Results from MESSENGER Flybys

    NASA Technical Reports Server (NTRS)

    Barnouin, Oliver S.; Zuber, Maria T.; Smith, David E.; Neumann, Gregory A.; Herrick, Robert R.; Chappelow, John E.; Murchie, Scott L.; Prockter, Louise M.

    2012-01-01

    Topographic data measured from the Mercury Laser Altimeter (MLA) and the Mercury Dual Imaging System (MDIS) aboard the MESSENGER spacecraft were used for investigations of the relationship between depth and diameter for impact craters on Mercury. Results using data from the MESSENGER flybys of the innermost planet indicate that most of the craters measured with MLA are shallower than those previously measured by using Mariner 10 images. MDIS images of these same MLA-measured craters show that they have been modified. The use of shadow measurement techniques, which were found to be accurate relative to the MLA results, indicate that both small bowl-shaped and large complex craters that are fresh possess depth-to-diameter ratios that are in good agreement with those measured from Mariner 10 images. The preliminary data also show that the depths of modified craters are shallower relative to fresh ones, and might provide quantitative estimates of crater in-filling by subsequent volcanic or impact processes. The diameter that defines the transition from simple to complex craters on Mercury based on MESSENGER data is consistent with that reported from Mariner 10 data.

  6. How MESSENGER Meshes Simulations and Games with Citizen Science

    NASA Astrophysics Data System (ADS)

    Hirshon, B.; Chapman, C. R.; Edmonds, J.; Goldstein, J.; Hallau, K. G.; Solomon, S. C.; Vanhala, H.; Weir, H. M.; Messenger Education; Public Outreach (Epo) Team

    2010-12-01

    How MESSENGER Meshes Simulations and Games with Citizen Science In the film The Last Starfighter, an alien civilization grooms their future champion—a kid on Earth—using a video game. As he gains proficiency in the game, he masters the skills he needs to pilot a starship and save their civilization. The NASA MESSENGER Education and Public Outreach (EPO) Team is using the same tactic to train citizen scientists to help the Science Team explore the planet Mercury. We are building a new series of games that appear to be designed primarily for fun, but that guide players through a knowledge and skill set that they will need for future science missions in support of MESSENGER mission scientists. As players score points, they gain expertise. Once they achieve a sufficiently high score, they will be invited to become participants in Mercury Zoo, a new program being designed by Zooniverse. Zooniverse created Galaxy Zoo and Moon Zoo, programs that allow interested citizens to participate in the exploration and interpretation of galaxy and lunar data. Scientists use the citizen interpretations to further refine their exploration of the same data, thereby narrowing their focus and saving precious time. Mercury Zoo will be designed with input from the MESSENGER Science Team. This project will not only support the MESSENGER mission, but it will also add to the growing cadre of informed members of the public available to help with other citizen science projects—building on the concept that engaged, informed citizens can help scientists make new discoveries. The MESSENGER EPO Team comprises individuals from the American Association for the Advancement of Science (AAAS); Carnegie Academy for Science Education (CASE); Center for Educational Resources (CERES) at Montana State University (MSU) - Bozeman; National Center for Earth and Space Science Education (NCESSE); Johns Hopkins University Applied Physics Laboratory (JHU/APL); National Air and Space Museum (NASM); Science Systems and Applications, Inc. (SSAI); and Southwest Research Institute (SwRI).

  7. Patterns of developmental expression of the RNA editing enzyme rADAR2.

    PubMed

    Paupard M-C; O'Connell, M A; Gerber, A P; Zukin, R S

    2000-01-01

    To date, two structurally related RNA-editing enzymes with adenosine deaminase activity have been identified in mammalian tissue: ADAR1 and ADAR2 [Bass B. I. et al. (1997) RNA 3, 947-949]. In rodents, ADAR2 undergoes alternative RNA splicing, giving rise to two splice variants that differ by the presence or absence of a 10-amino-acid insert in the carboxy-terminal catalytic domain. However, the physiological significance of the splicing and its regional and developmental regulation are as yet unknown. The present study examined spatial and temporal patterns of ADAR2 gene transcripts within specific neuronal populations of rat brain. The two rodent ADAR2 isoforms were expressed at comparable levels at all ages examined. rADAR2 messenger RNA expression was first detectable in the thalamic nuclei formation at embryonic day E19. The rADAR2b insert and rADAR2a splice probes produced images similar to that of the rADAR2 pan probe. At birth, rADAR2a messenger RNA splice variants were abundantly expressed in the thalamic nuclei. No signal for any probe was detectable in other brain regions, including neocortex, hippocampus, striatum and cerebellum at this stage of development. During the first week of postnatal life, rADAR2 messenger RNA expression (detected with the pan probe) increased gradually in several brain regions, with low expression detected at postnatal day P7 in the olfactory bulb, inferior colliculus, and within the pyramidal and granule cell layers of the hippocampus. Hybridization patterns of the rADAR2a variant probe reached peak expression at about the second week of life, while peak expression of the rADAR2b probe was reached at about the third week of life. At the end of the first week of life (P7), expression of both splice variants was strongest in the thalamic nuclei. By P14, rADAR2 messenger RNA expression was more consolidated in the deeper structures, including the thalamic nuclei and the granule cell layer of the cerebellum. By P21, maximal levels of rADARb expression were observed in the thalamic nuclei, inferior colliculus, cerebellum and pontine nuclei. In the adult, rADAR2 messenger RNA expression was of highest intensity in the thalamic nuclei, with high levels of expression in the olfactory bulb, inferior colliculus, cerebellum and pontine nuclei. At the level of the hippocampus, positive labelling was restricted to the CA3 region of the Ammon's horn and the dentate gyrus, with weak signals in the CA1 subfield. rADAR2 pan expression was at near background levels throughout the neocortex and caudate putamen. In summary, our study shows that ADAR2 messenger RNA expression is regulated in a cell-specific manner throughout development. At early ages, ADAR2 messenger RNA is expressed only within (and restricted to) the thalamic nuclei. By the third postnatal week, expression of the editase enzyme is more widely distributed throughout the olfactory bulb, CA3 and dentate gyrus of the hippocampus, thalamus, inferior colliculus and the molecular cell layer of the cerebellum. ADAR2 is thought to act at specific nucleotide positions in primary transcripts encoding glutamate receptor subunits, thereby altering gating and ionic permeability properties of AMPA- and kainate-activated channels. ADAR2 also acts at pre-messenger RNA encoding the serotonin 5HT-2C receptor to alter G-protein coupling. Thus, RNA editing may be an important mechanism for fine-tuning of the physiological and pharmacological properties of transmitter receptors of the central nervous system.

  8. Cross talk between cyclic AMP and the polyphosphoinositide signaling cascade in iris sphincter and other nonvascular smooth muscle.

    PubMed

    Abdel-Latif, A A

    1996-02-01

    Nonvascular smooth muscle, such as the iris sphincter, receives double reciprocal innervation: stimulation of the parasympathetic nervous system (cholinergic muscarinic), which functions through the polyphosphoinositide (PPI) signaling pathway, contracts it, while activation of the sympathetic nervous system (beta-adrenergic), which functions through the cAMP system, relaxes it. Interactions between the two second messenger systems are important in regulation of smooth muscle tone and represent an important focal point for pharmacological manipulation. Here, I have summarized the experimental evidence in support of the hypothesis that the cross talk between cAMP and the PPI cascade could constitute a biochemical correlate for this functional antagonism. Recent studies suggest that cAMP inhibition is on Ca2+ mobilization rather than myosin light chain phosphorylation. Thus, cAMP-elevating agents, which inhibit agonist-induced PPI hydrolysis, are effective relaxants. Furthermore, inositol 1,4,5-trisphosphate (IP3) appears to be involved in both Ca2+ release from the sarcoplasmic reticulum and in Ca2+ influx through the plasma membrane, and since a reduction in intracellular Ca2+ ([Ca2+]i) is the underlying mechanism for cAMP-mediated relaxation, an important target for cAMP inhibition would be either to inhibit IP3 production or to stimulate IP3 inactivation. In the iris sphincter and other nonvascular smooth muscle there is reasonable experimental evidence that shows that cAMP inhibits phospholipase C activation and stimulates IP3 3-kinase activity, both of which can result in: [i) reduction in IP3 concentrations and (ii) reduction in IP3-dependent Ca2+ mobilization, which may lead to muscle relaxation. In addition to IP3-induced Ca2+ mobilization, changes in [Ca2+]i are the result of the interplay of many processes which may also serve as potential sites for cAMP inhibition. A great deal of progress has been made on the cross talk between cAMP and the PPI signaling cascade in the past decade, and there will be more on the regulation of the second messenger systems and their involvement in smooth muscle tone in the coming years. Clearly, an understanding of the physiological and pathophysiological regulation of smooth muscle tone is central to the development of novel therapeutic agents for the treatment of diseases such as asthma and glaucoma, where cAMP-elevating drugs are currently employed.

  9. Color Image of Mercury from NASA's MESSENGER Satellite

    NASA Image and Video Library

    2017-12-08

    NASA image acquired September 3, 2011 Dominici crater, the very bright crater to the top of this image, exhibits bright rays and contains hollows. This crater lies upon the peak ring of Homer Basin, a very degraded peak ring basin that has been filled by volcanism. This image contains several examples of craters that have excavated materials from depth that are spectrally distinct from the surface volcanic layers, providing windows into the subsurface. MESSENGER scientists are estimating the approximate depths of these spectrally distinct materials by applying knowledge of how impacts excavate material during the cratering process. The 1000, 750, and 430 nm bands of the Wide Angle Camera are displayed in red, green, and blue, respectively. This image was acquired as a high-resolution targeted observation. Targeted observations are images of a small area on Mercury's surface at resolutions much higher than the 250-meter/pixel (820 feet/pixel) morphology base map or the 1-kilometer/pixel (0.6 miles/pixel) color base map. It is not possible to cover all of Mercury's surface at this high resolution during MESSENGER's one-year mission, but several areas of high scientific interest are generally imaged in this mode each week. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MDIS is scheduled to acquire more than 75,000 images in support of MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  10. Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds.

    PubMed

    Broillet, M C; Firestein, S

    1996-02-01

    The activation of a cyclic nucleotide-gated channel is the final step in sensory transduction in olfaction. Normally, this channel is opened by the intracellular cyclic nucleotide second messenger cAMP or cGMP. However, in single channel recordings we found that donors of nitric oxide, a putative intercellular messenger, could directly activate the native olfactory neuron channel. Its action was independent of the presence of the normal ligand and did not involve the cyclic nucleotide binding site, suggesting an alternate site on the molecule that is critical in channel gating. The biochemical pathway appears to utilize nitric oxide in one of its alternate redox states, the nitrosonium ion, transnitrosylating a free sulfhydryl group belonging to a cysteine residue tentatively identified as being in the region linking the S6 transmembrane domain to the ligand binding domain.

  11. C-fos mediates antipsychotic-induced neurotensin gene expression in the rodent striatum.

    PubMed

    Robertson, G S; Tetzlaff, W; Bedard, A; St-Jean, M; Wigle, N

    1995-07-01

    The ubiquitous inducibility of the immediate-early gene c-fos in the central nervous system has led to the search for downstream genes which are regulated by its product, Fos. Recent evidence suggests that c-fos induction by a single injection of the classical antipsychotic haloperidol may contribute to the subsequent increase in neurotensin gene expression in the rodent striatum. Consistent with this proposal, in the present study haloperidol-induced Fos-like immunoreactivity and neurotensin/neuromedin N messenger RNA were found to be expressed by the same population of striatal neurons. Moreover, inhibition of haloperidol-induced c-fos expression by intrastriatal injection of antisense phosphorothioate oligodeoxynucleotides complimentary either to bases 109-126 or 127-144 of c-fos attenuated the subsequent increase in neurotensin/neuromedin N messenger RNA. However, injection of a sense phosphorothioate oligodeoxynucleotide corresponding to bases 127-144 of c-fos did not reduce haloperidol-induced c-fos or neurotensin/neuromedin N expression. Furthermore, constitutive expression of Jun-like immunoreactivity in the striatum was not reduced by either the sense or antisense phosphorothioate oligodeoxynucleotides. Similarly, the sense and antisense phosphorothioate oligodeoxynucleotide failed to reduce proenkephalin messenger RNA, which is located in the same striatal neurons that express haloperidol-induced neurotensin/neuromedin N messenger RNA, which is located in the same striatal neurons that express haloperidol-induced neurotensin/neuromedin N messenger RNA. Lastly, haloperidol-induced increases in nerve growth factor I-A-, JunB- and FosB-like immunoreactivity and fosB messenger RNA were not decreased by intrastriatal injection of either the sense or antisense phosphorothioate oligodeoxynucleotides. These results indicate that the antisense phosphorothioate oligodeoxynucleotides attenuated haloperidol-induced neurotensin/neuromedin N expression by selectively reducing c-fos expression and emphasize the potential importance of immediate-early gene induction in the mechanism of action of this antipsychotic drug.

  12. Conservation and divergence of the cyclic adenosine monophosphate-protein kinase A (cAMP–PKA) pathway in two plant-pathogenic fungi: Fusarium graminearum and F. verticillioides

    USDA-ARS?s Scientific Manuscript database

    The cyclic AMP (cAMP)-PKA pathway is a central signaling cascade that transmits extracellular stimuli and governs cell responses through the second messenger cAMP. The importance of cAMP signaling in fungal biology has been well documented. Two key conserved components, adenylate cyclase (AC) and ca...

  13. The Role of Membrane-Derived Second Messengers and Bmx/Etk in Response to Radiation Treatment of Prostate Cancer

    DTIC Science & Technology

    2008-01-01

    enhanced HUVEC radiosensitization. Furthermore, pretreatment of HUVEC with a pharmacological inhibitor of Bmx, LFM-A13, produced significant...Prostate cancer, Bmx, tyrosine kinase, kinase inhibitors , angiogenesis, tumor vasculature, radiation 16. SECURITY CLASSIFICATION OF: 17...activation and that a small molecule inhibitor of Bmx modulates the cellular viability of endothelial and prostate cancer cells, particularly with radiation

  14. Distribution of messenger RNAs for D1 dopamine receptors and DARPP-32 in striatum and cerebral cortex of the cynomolgus monkey: relationship to D1 dopamine receptors.

    PubMed

    Brené, S; Hall, H; Lindefors, N; Karlsson, P; Halldin, C; Sedvall, G

    1995-07-01

    Messenger RNAs for the D1 dopamine receptor and dopamine- and cyclic AMP-regulated phosphoprotein of relative mass 32,000 (DARPP-32) were examined by in situ hybridization in the cynomolgus monkey brain. The messenger RNA distribution was compared to the distribution of D1 dopamine receptors using [3H]SCH 23390 autoradiography. In the caudate nucleus and putamen, D1 dopamine receptor messenger RNA-positive cells were unevenly distributed. Clusters of cells with an approximately three-fold higher intensity of labeling, as compared to surrounding regions, were found. Some of these D1 dopamine receptor messenger RNA intensive cell clusters in the caudate nucleus appeared to some extent to be matched to regions of higher intensity of [3H]SCH 23390 binding. The distribution of cells expressing DARPP-32 messenger RNA in the caudate nucleus and putamen was found to be non-clustered. In neocortical regions, cells of different sizes expressing D1 dopamine receptor messenger RNA were present in layers II-VI. D1 dopamine receptor messenger RNA-positive cells were most abundant in layer V. Unexpectedly, no DARPP-32 messenger RNA signal was detected in neocortex. Chronic SCH 23390 administration did not change the relative levels of messenger RNAs for the D1 dopamine receptor and DARPP-32 or [3H]SCH 23390 binding as measured by quantitative image analysis. The clustered distribution of D1 dopamine receptor messenger RNA is in contrast to that of DARPP-32 messenger RNA. This suggests that D1 dopamine receptors may play a more significant role in regulating DARPP-32 function in patch regions as compared to matrix regions. D1 dopamine receptor messenger RNA-expressing cells could also be visualized in several layers of the primate neocortex, implying that dopamine acts through D1 dopamine receptors within functionally different neuronal circuits of the neocortex.

  15. Calcium-stimulated autophosphorylation site of plant chimeric calcium/calmodulin-dependent protein kinase

    NASA Technical Reports Server (NTRS)

    Sathyanarayanan, P. V.; Siems, W. F.; Jones, J. P.; Poovaiah, B. W.

    2001-01-01

    The existence of two molecular switches regulating plant chimeric Ca(2+)/calmodulin-dependent protein kinase (CCaMK), namely the C-terminal visinin-like domain acting as Ca(2+)-sensitive molecular switch and calmodulin binding domain acting as Ca(2+)-stimulated autophosphorylation-sensitive molecular switch, has been described (Sathyanarayanan, P. V., Cremo, C. R., and Poovaiah, B. W. (2000) J. Biol. Chem. 275, 30417-30422). Here we report the identification of Ca(2+)-stimulated autophosphorylation site of CCaMK by matrix-assisted laser desorption ionization time of flight-mass spectrometry. Thr(267) was confirmed as the Ca(2+)-stimulated autophosphorylation site by post-source decay experiments and by site-directed mutagenesis. The purified T267A mutant form of CCaMK did not show Ca(2+)-stimulated autophosphorylation, autophosphorylation-dependent variable calmodulin affinity, or Ca(2+)/calmodulin stimulation of kinase activity. Sequence comparison of CCaMK from monocotyledonous plant (lily) and dicotyledonous plant (tobacco) suggests that the autophosphorylation site is conserved. This is the first identification of a phosphorylation site specifically responding to activation by second messenger system (Ca(2+) messenger system) in plants. Homology modeling of the kinase and calmodulin binding domain of CCaMK with the crystal structure of calcium/calmodulin-dependent protein kinase 1 suggests that the Ca(2+)-stimulated autophosphorylation site is located on the surface of the kinase and far from the catalytic site. Analysis of Ca(2+)-stimulated autophosphorylation with increasing concentration of CCaMK indicates the possibility that the Ca(2+)-stimulated phosphorylation occurs by an intermolecular mechanism.

  16. KSC-04PD-0435

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers attach an overhead crane to NASAs MESSENGER spacecraft. The spacecraft will be moved to a work stand where employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  17. KSC-04PD-0434

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. In the high bay clean room at the Astrotech Space Operations processing facilities near KSC, workers prepare to attach an overhead crane to NASAs MESSENGER spacecraft. The spacecraft will be moved to a work stand where employees of the Johns Hopkins University Applied Physics Laboratory, builders of the spacecraft, will perform an initial state-of-health check. Then processing for launch can begin, including checkout of the power systems, communications systems and control systems. The thermal blankets will also be attached for flight. MESSENGER short for MErcury Surface, Space ENvironment, GEochemistry and Ranging will be launched May 11 on a six-year mission aboard a Boeing Delta II rocket. Liftoff is targeted for 2:26 a.m. EDT on Tuesday, May 11.

  18. G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins from endosomes.

    PubMed

    Tsvetanova, Nikoleta G; Irannejad, Roshanak; von Zastrow, Mark

    2015-03-13

    Some G protein-coupled receptors (GPCRs), in addition to activating heterotrimeric G proteins in the plasma membrane, appear to elicit a "second wave" of G protein activation after ligand-induced internalization. We briefly summarize evidence supporting this view and then discuss what is presently known about the functional significance of GPCR-G protein activation in endosomes. Endosomal activation can shape the cellular response temporally by prolonging its overall duration, and may shape the response spatially by moving the location of intracellular second messenger production relative to effectors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. WhatsApp Messenger as an Adjunctive Tool for Telemedicine: An Overview.

    PubMed

    Giordano, Vincenzo; Koch, Hilton; Godoy-Santos, Alexandre; Dias Belangero, William; Esteves Santos Pires, Robinson; Labronici, Pedro

    2017-07-21

    The advent of telemedicine has allowed physicians to deliver medical treatment to patients from a distance. Mobile apps such as WhatsApp Messenger, an instant messaging service, came as a novel concept in all fields of social life, including medicine. The use of instant messaging services has been shown to improve communication within medical teams by providing means for quick teleconsultation, information sharing, and starting treatment as soon as possible. The aim of this study was to perform a comprehensive systematic review of present literature on the use of the WhatsApp Messenger app as an adjunctive health care tool for medical doctors. Searches were performed in PubMed, EMBASE, and the Cochrane Library using the term "whatsapp*" in articles published before January 2016. A bibliography of all relevant original articles that used the WhatsApp Messenger app was created. The level of evidence of each study was determined according to the Oxford Levels of Evidence ranking system produced by the Oxford Centre for Evidence-Based Medicine. The impact and the indications of WhatsApp Messenger are discussed in order to understand the extent to which this app currently functions as an adjunctive tool for telemedicine. The database search identified a total of 30 studies in which the term "whatsapp*" was used. Each article's list of references was evaluated item-by-item. After literature reviews, letters to the editor, and low-quality studies were excluded, a total of 10 studies were found to be eligible for inclusion. Of these studies, 9 had been published in the English language and 1 had been published in Spanish. Five were published by medical doctors. The pooled data presents compelling evidence that the WhatsApp Messenger app is a promising system, whether used as a communication tool between health care professionals, as a means of communication between health care professionals and the general public, or as a learning tool for providing health care information to professionals or to the general population. However, high-quality and properly evaluated research is needed, as are improvements in descriptions of the methodology and the study processes. These improvements will allow WhatsApp Messenger to be categorically defined as an effective telemedicine tool in many different fields of health care. ©Vincenzo Giordano, Hilton Koch, Alexandre Godoy-Santos, William Dias Belangero, Robinson Esteves Santos Pires, Pedro Labronici. Originally published in the Interactive Journal of Medical Research (http://www.i-jmr.org/), 21.07.2017.

  20. Terminator View of Mercury

    NASA Image and Video Library

    2014-07-02

    Date acquired: May 05, 2014 Today's color image features both Mercury's terminator and limb. The terminator is the striking separation of night and day on Mercury. It is seen in this image with the change from dark, on the left of the image, to light. Mercury's limb is also captured, as we can see the edge between sunlit Mercury and space. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. During the first two years of orbital operations, MESSENGER acquired over 150,000 images and extensive other data sets. MESSENGER is capable of continuing orbital operations until early 2015. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  1. 12 CFR 7.1012 - Messenger service.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Messenger service. 7.1012 Section 7.1012 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY BANK ACTIVITIES AND OPERATIONS Bank Powers § 7.1012 Messenger service. (a) Definition. For purposes of this section, a “messenger...

  2. Boronate-Based Fluorescent Probes: Imaging Hydrogen Peroxide in Living Systems

    PubMed Central

    Lin, Vivian S.; Dickinson, Bryan C.; Chang, Christopher J.

    2014-01-01

    Hydrogen peroxide, a reactive oxygen species with unique chemical properties, is produced endogenously in living systems as a destructive oxidant to ward off pathogens or as a finely tuned second messenger in dynamic cellular signaling pathways. In order to understand the complex roles that hydrogen peroxide can play in biological systems, new tools to monitor hydrogen peroxide in its native settings, with high selectivity and sensitivity, are needed. Knowledge of organic synthetic reactivity provides the foundation for the molecular design of selective, functional hydrogen peroxide probes. A palette of fluorescent and luminescent probes that react chemoselectively with hydrogen peroxide has been developed, utilizing a boronate oxidation trigger. These indicators offer a variety of colors and in cellulo characteristics and have been used to examine hydrogen peroxide in a number of experimental setups, including in vitro fluorometry, confocal fluorescence microscopy, and flow cytometry. In this chapter, we provide an overview of the chemical features of these probes and information on their behavior to help researchers select the optimal probe and application. PMID:23791092

  3. Estrogen-IGF-1 interactions in neuroprotection: Ischemic Stroke as a case study

    PubMed Central

    Sohrabji, Farida

    2014-01-01

    The steroid hormone 17b-estradiol and the peptide hormone insulin-like growth factor (IGF)-1 independently exert neuroprotective actions in neurologic diseases such as stroke. Only a few studies have directly addressed the interaction between the two hormone systems, however, there is a large literature that indicates potentially greater interactions between the 17b-estradiol and IGF-1 systems. The present review focuses on key issues related to this interaction including IGF-1 and sex differences and common activation of second messenger systems. Using ischemic stroke as a case study, this review also focuses on independent and cooperative actions of estrogen and IGF-1 on neuroprotection, blood brain barrier integrity, angiogenesis, inflammation and post-stroke epilepsy. Finally, the review also focuses on the astrocyte, a key mediator of post stroke repair, as a local source of 17b-estradiol and IGF-1. This review thus highlights areas where significant new research is needed to clarify the interactions between these two neuroprotectants. PMID:24882635

  4. The Role of Glucocorticoids and Neuroinflammation in Mediating the Effects of Stress on Drug Abuse

    DTIC Science & Technology

    2013-10-01

    addiction. In the second year of this project, we made pivotal discoveries in how stress sensitizes the pro-inflammatory effects of methamphetamine ...immunophenotypic and functional characteristics. J Neurosci Methods 151, 121- 130. Krasnova et al., 2009. Methamphetamine toxicity and messengers of death...Tocharus et al., 2010. Melatonin attenuates methamphetamine -induced overexpression of pro- inflammatory cytokines in microglial cell lines. J Pineal Res

  5. Distinct Signaling Roles of cIMP, cCMP, and cUMP.

    PubMed

    Seifert, Roland

    2016-10-04

    The cyclic purine nucleotide cIMP and the cyclic pyrimidine nucleotides cCMP and cUMP are emerging second messengers. These cNMPs show different biological effects, but the molecular mechanisms remain elusive. In this issue of Structure, Ng et al. (2016) provide structural evidence for distinct interactions of cIMP, cCMP, and cUMP with ion channels. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The Phospholipase C Isozymes and Their Regulation

    PubMed Central

    Gresset, Aurelie; Sondek, John

    2013-01-01

    The physiological effects of many extracellular neurotransmitters, hormones, growth factors, and other stimuli are mediated by receptor-promoted activation of phospholipase C (PLC) and consequential activation of inositol lipid signaling pathways. These signaling responses include the classically described conversion of phosphatidylinositol(4,5)P2 to the Ca2+-mobilizing second messenger inositol(1,4,5)P3 and the protein kinase C-activating second messenger diacylglycerol as well as alterations in membrane association or activity of many proteins that harbor phosphoinositide binding domains. The 13 mammalian PLCs elaborate a minimal catalytic core typified by PLC-δ to confer multiple modes of regulation of lipase activity. PLC-β isozymes are activated by Gαq- and Gβγ-subunits of heterotrimeric G proteins, and activation of PLC-γ isozymes occurs through phosphorylation promoted by receptor and non-receptor tyrosine kinases. PLC-ε and certain members of the PLC-β and PLC-γ subclasses of isozymes are activated by direct binding of small G proteins of the Ras, Rho, and Rac subfamilies of GTPases. Recent high resolution three dimensional structures together with biochemical studies have illustrated that the X/Y linker region of the catalytic core mediates autoinhibition of most if not all PLC isozymes. Activation occurs as a consequence of removal of this autoinhibition. PMID:22403074

  7. Developmental emergence of different forms of neuromodulation in Aplysia sensory neurons.

    PubMed

    Marcus, E A; Carew, T J

    1998-04-14

    The capacity for neuromodulation and biophysical plasticity is a defining feature of most mature neuronal cell types. In several cases, modulation at the level of the individual neuron has been causally linked to changes in the functional output of a neuronal circuit and subsequent adaptive changes in the organism's behavioral responses. Understanding how such capacity for neuromodulation develops therefore may provide insights into the mechanisms both of neuronal development and learning and memory. We have examined the development of multiple forms of neuromodulation triggered by a common neurotransmitter, serotonin, in the pleural sensory neurons of Aplysia californica. We have found that multiple signaling cascades within a single neuron develop sequentially, with some being expressed only very late in development. In addition, our data suggest a model in which, within a single neuromodulatory pathway, the elements of the signaling cascade are developmentally expressed in a "retrograde" manner with the ionic channel that is modulated appearing early in development, functional elements in the second messenger cascade appearing later, and finally, coupling of the second messenger cascade to the serotonin receptor appearing quite late. These studies provide the characterization of the development of neuromodulation at the level of an identified cell type and offer insights into the potential roles of neuromodulatory processes in development and adult plasticity.

  8. The crucial role of cyclic GMP in the eclosion hormone mediated signal transduction in the silkworm metamorphoses.

    PubMed

    Shibanaka, Y; Hayashi, H; Okada, N; Fujita, N

    1991-10-31

    The signal transduction of the peptide, eclosion hormone, in the silkworm Bombyx mori appears to be mediated via the second messenger cyclic GMP throughout their life cycle. Injection of 8-bromo-cGMP induced the ecdysis behavior in pharate adults with similar latency to eclosion hormone-induced ecdysis; the moulting occurred 50-70 min after the injection. The potency of 8Br-cGMP was 10(2) fold higher than that of cGMP and the efficacy was increased by the co-injection of the phosphodiesterase inhibitor IBMX. On the other hand, in the silkworm pupal ecdysis the eclosion hormone and also 8Br-cGMP induced the moulting behavior in a dose-dependent manner. The adult development of the ability to respond to 8Br-cGMP took place concomitantly with the response to the eclosion hormone. Both the developmental time courses were shifted by a shift of light and dark cycles. Accordingly, the sensitivities to the peptide and cyclic nucleotide developed correspondently under the light and dark circadian rhythm. Thus throughout the silkworm life cycle, eclosion hormone is effective to trigger the ecdysis behavior and cGMP plays a crucial role as the second messenger in the eclosion hormone-mediated signal transduction.

  9. Return to Mercury: a global perspective on MESSENGER's first Mercury flyby.

    PubMed

    Solomon, Sean C; McNutt, Ralph L; Watters, Thomas R; Lawrence, David J; Feldman, William C; Head, James W; Krimigis, Stamatios M; Murchie, Scott L; Phillips, Roger J; Slavin, James A; Zuber, Maria T

    2008-07-04

    In January 2008, the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft became the first probe to fly past the planet Mercury in 33 years. The encounter revealed that Mercury is a dynamic system; its liquid iron-rich outer core is coupled through a dominantly dipolar magnetic field to the surface, exosphere, and magnetosphere, all of which interact with the solar wind. MESSENGER images confirm that lobate scarps are the dominant tectonic landform and record global contraction associated with cooling of the planet. The history of contraction can be related to the history of volcanism and cratering, and the total contractional strain is at least one-third greater than inferred from Mariner 10 images. On the basis of measurements of thermal neutrons made during the flyby, the average abundance of iron in Mercury's surface material is less than 6% by weight.

  10. Fragmented Sleep Enhances Postoperative Neuroinflammation but Not Cognitive Dysfunction.

    PubMed

    Vacas, Susana; Degos, Vincent; Maze, Mervyn

    2017-01-01

    Sleep is integral to biologic function, and sleep disruption can result in both physiological and psychologic dysfunction including cognitive decline. Surgery activates the innate immune system, inducing neuroinflammatory changes that interfere with cognition. Because surgical patients with sleep disorders have an increased likelihood of exhibiting postoperative delirium, an acute form of cognitive decline, we investigated the contribution of perioperative sleep fragmentation (SF) to the neuroinflammatory and cognitive responses of surgery. The effects of 24-hour SF and surgery were explored in adult C57BL/6J male mice. The SF procedure started at 7 AM with cages being placed on a large platform orbital shaker that cycled every 120 seconds (30 seconds on/90 seconds off) for 24 hours. In separate cohorts, stabilized tibial fracture was performed either before or after the 24-hour SF procedure and assessed for systemic and hippocampal inflammation and cognition. SF-induced nonhippocampal memory dysfunction (mean ± standard deviation [SD] of the difference in time spent between novel and familiar object for control was 4.7 ± 1.4 seconds, n = 8 versus SF -0.5 ± 0.2 seconds, n = 11, yielding an estimated treatment effect of 5.2 seconds [95% confidence interval {CI}, 2.6-7.7]; P < .001) and increased systemic interleukin-6 (median [25%-75% quartile] for control 0.0 [0.0-2.4] pg/mL versus 9.7 [6.3-12.9] pg/mL, n = 8/group, yielding an estimated treatment effect of 9.7 pg/mL [95% CI, 5.8-11.8]; P < .0001). SF reduced freezing time in hippocampal-dependent memory test (mean ± SD for control 49.3% ± 5.8% versus for SF 32.9% ± 5.8%, n = 10/group, estimated treatment effect = 16.4% [95% CI, 11.0-21.8]; P < .0001). Although surgery also reduced freezing time (mean ± SD for control 49.3% ± 5.8% versus for surgery 30.3% ± 3.3%, n = 10/group, estimated treatment effect = 19.0% [95% CI, 14.6-23.4]; P < .0001), memory impairment was not further exacerbated by combining SF with surgery. One day after SF, there was an increase in hippocampal messenger RNA expression of tumor necrosis factor-α (relative quantitation [RQ] 5.12-fold, n = 5/group [95% CI, 1.64-15.97]; P < .01), and 1 day after surgery, there was an increase in messenger RNA interleukin-6 (RQ 4.64-fold, n = 5 [95% CI, 1.48-14.56]; P < .05) and tumor necrosis factor-α (RQ 5.54-fold, n = 5 [95% CI, 2.92-10.51]; P < .01). These increments were more pronounced when either pre- or postoperative SF was combined with surgery. Although SF and surgery can independently produce significant memory impairment, perioperative SF significantly increased hippocampal inflammation without further cognitive impairment. The dissociation between neuroinflammation and cognitive decline may relate to the use of a sole memory paradigm that does not capture other aspects of cognition, especially learning.

  11. False Color View of Mercury

    NASA Image and Video Library

    2017-12-08

    This colorful view of Mercury was produced by using images from the color base map imaging campaign during MESSENGER's primary mission. These colors are not what Mercury would look like to the human eye, but rather the colors enhance the chemical, mineralogical, and physical differences between the rocks that make up Mercury's surface. Young crater rays, extending radially from fresh impact craters, appear light blue or white. Medium- and dark-blue areas are a geologic unit of Mercury's crust known as the "low-reflectance material", thought to be rich in a dark, opaque mineral. Tan areas are plains formed by eruption of highly fluid lavas. The crater in the upper right whose rays stretch across the planet is Hokusai. To watch a movie of this colorful view of Mercury as a spinning globe go here: www.flickr.com/photos/gsfc/8497927473 Young crater rays, extending radially from fresh impact craters, appear light blue or white. Medium- and dark-blue areas are a geologic unit of Mercury's crust known as the "low-reflectance material", thought to be rich in a dark, opaque mineral. Tan areas are plains formed by eruption of highly fluid lavas. The giant Caloris basin is the large circular tan feature located just to the upper right of center of the image. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MESSENGER acquired 88,746 images and extensive other data sets. MESSENGER is now in a yearlong extended mission, during which plans call for the acquisition of more than 80,000 additional images to support MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  12. Evolution of the Rembrandt impact basin on Mercury.

    PubMed

    Watters, Thomas R; Head, James W; Solomon, Sean C; Robinson, Mark S; Chapman, Clark R; Denevi, Brett W; Fassett, Caleb I; Murchie, Scott L; Strom, Robert G

    2009-05-01

    MESSENGER's second Mercury flyby revealed a ~715-kilometer-diameter impact basin, the second-largest well-preserved basin-scale impact structure known on the planet. The Rembrandt basin is comparable in age to the Caloris basin, is partially flooded by volcanic plains, and displays a unique wheel-and-spoke-like pattern of basin-radial and basin-concentric wrinkle ridges and graben. Stratigraphic relations indicate a multistaged infilling and deformational history involving successive or overlapping phases of contractional and extensional deformation. The youngest deformation of the basin involved the formation of a approximately 1000-kilometer-long lobate scarp, a product of the global cooling and contraction of Mercury.

  13. Regulation of Brain Muscarinic Receptors by Protein Kinase C

    DTIC Science & Technology

    1991-06-21

    esters or to high concentrations of muscarinic agonists. Neuronal mouse neuroblastoma cells maintained in culture (clone N1E - 115 ) were used as a...E.E. El-Fakahany: Inhibition of Cyclic AMP Formation in N1E - 115 Neuroblastoma Cells is Mediated by a Noncardiac M2 Muscarinic Receptor Subtype...Receptor-Mediated Second Messenger Responses in N1E - 115 Neuroblastoma Cells. Journal of Neurochemistry. 53, 1300-1308, 1989. 15. McKinney, M., D

  14. Hi, Hokusai!

    NASA Image and Video Library

    2017-12-08

    This dramatic image features Hokusai in the foreground, famous for its extensive set of rays, some of which extend for over a thousand kilometers across Mercury's surface. The extensive, bright rays indicate that Hokusai is one of the youngest large craters on Mercury. Check out previously featured images to see high-resolution details of its central peaks, rim and ejecta blanket, and impact melt on its floor. This image was acquired as part of MDIS's high-incidence-angle base map. The high-incidence-angle base map complements the surface morphology base map of MESSENGER's primary mission that was acquired under generally more moderate incidence angles. High incidence angles, achieved when the Sun is near the horizon, result in long shadows that accentuate the small-scale topography of geologic features. The high-incidence-angle base map was acquired with an average resolution of 200 meters/pixel. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. During the first two years of orbital operations, MESSENGER acquired over 150,000 images and extensive other data sets. MESSENGER is capable of continuing orbital operations until early 2015. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  15. Sharing digital micrographs and other data files between computers.

    PubMed

    Entwistle, A

    2004-01-01

    It ought to be easy to exchange digital micrographs and other computer data files with a colleague even on another continent. In practice, this often is not the case. The advantages and disadvantages of various methods that are available for exchanging data files between computers are discussed. When possible, data should be transferred through computer networking. When data are to be exchanged locally between computers with similar operating systems, the use of a local area network is recommended. For computers in commercial or academic environments that have dissimilar operating systems or are more widely spaced, the use of FTPs is recommended. Failing this, posting the data on a website and transferring by hypertext transfer protocol is suggested. If peer to peer exchange between computers in domestic environments is needed, the use of Messenger services such as Microsoft Messenger or Yahoo Messenger is the method of choice. When it is not possible to transfer the data files over the internet, single use, writable CD ROMs are the best media for transferring data. If for some reason this is not possible, DVD-R/RW, DVD+R/RW, 100 MB ZIP disks and USB flash media are potentially useful media for exchanging data files.

  16. Mercury's Reference Frames After the MESSENGER Mission

    NASA Astrophysics Data System (ADS)

    Stark, A.; Oberst, J.; Preusker, F.; Burmeister, S.; Steinbrügge, G.; Hussmann, H.

    2018-05-01

    We provide an overview of Mercury's reference frames based on MESSENGER observations. We discuss the dynamical, the principal-axes, the ellipsoid, as well as the cartographic frame, which was adopted for MESSENGER data products.

  17. MESSENGER's first Mercury flyby: A summary of scientific observations

    NASA Astrophysics Data System (ADS)

    Solomon, Sean C.; McNutt, Ralph L.; Boynton, William V.; Evans, Larry G.; Head, James W.; Krimigis, Stamatios M.; Murchie, Scott; Phillips, Roger J.; Slavin, James A.; Zuber, Maria T.

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, developed under NASA's Discovery Program, will be the first probe to orbit the planet Mercury in March 2011. Launched in August 2004, MESSENGER successfully completed the first of three flybys of Mercury in January 2008. The Mercury Dual Imaging System acquired an 11-color mosaic of part of the hemisphere not seen by Mariner 10, including the entire Caloris basin; several large monochrome mosaics at a range of resolutions; a series of color frames designed for photometric analysis; and inbound and outbound movies. The Mercury Atmospheric and Surface Composition Spectrometer obtained the first high-resolution spectral reflectance measurements (at ultraviolet to near-infrared wavelengths) of surface composition, conducted limb scans of exospheric species, and mapped the composition and structure of the tail region. The Magnetometer measured Mercury's internal field at low latitudes and documented the major plasma boundaries of Mercury's magnetosphere. The Energetic Particle and Plasma Spectrometer made the first measurements of low-energy ions in Mercury's magnetosphere. The Mercury Laser Altimeter carried out the first space altimetric profile of the planet. Other instruments in the payload provided baseline measurements that will aid in the interpretation of data from the mission orbital phase. Together, the MESSENGER flyby observations have begun to advance our understanding of the innermost planet.

  18. Google Mercury: The Launch of a New Planet

    NASA Astrophysics Data System (ADS)

    Hirshon, B.; Chapman, C. R.; Edmonds, J.; Goldstein, J.; Hallau, K. G.; Solomon, S. C.; Vanhala, H.; Weir, H. M.; Messenger Education; Public Outreach Epo Team

    2010-12-01

    The NASA MESSENGER mission’s Education and Public Outreach (EPO) Team, in cooperation with Google, Inc., has launched Google Mercury, an immersive new environment on the Google Earth platform. Google Mercury features hundreds of surface features, most of them newly revealed by the three flybys of the innermost planet by the MESSENGER spacecraft. As with Google Earth, Google Mercury is available on line at no cost. This presentation will demonstrate how our team worked with Google staff, features we incorporated, how games can be developed within the Google Earth platform, and how others can add tours, games, and other educational features. Finally, we will detail new enhancements to be added once MESSENGER enters into orbit about Mercury in March 2011 and begins sending back compelling images and other global data sets on a daily basis. The MESSENGER EPO Team comprises individuals from the American Association for the Advancement of Science (AAAS); Carnegie Academy for Science Education (CASE); Center for Educational Resources (CERES) at Montana State University (MSU) - Bozeman; National Center for Earth and Space Science Education (NCESSE); Johns Hopkins University Applied Physics Laboratory (JHU/APL); National Air and Space Museum (NASM); Science Systems and Applications, Inc. (SSAI); and Southwest Research Institute (SwRI). Screen shot of Google Mercury as a work in progress

  19. Hydrodynamic shear stress and mass transport modulation of endothelial cell metabolism.

    PubMed

    Nollert, M U; Diamond, S L; McIntire, L V

    1991-09-01

    Mammalian cells responds to physical forces by altering their growth rate, morphology, metabolism, and genetic expression. We have studied the mechanism by which these cells detect the presence of mechanical stress and convert this force into intracellular signals. As our model systems, we have studied cultured human endothelial cells, which line the blood vessels and forms the interface between the blood and the vessel wall. These cell responds within minutes to the initiation of flow by increasing their arachidonic acid metabolism and increasing the level of the intracellular second messengers inositol trisphosphate and calcium ion concentration. With continued exposure to arterial levels of wall shear stress for up to 24 h, endothelial cells increase the expression of tissue plasminogen activator (tPA) and tPA messenger RNA (mRNA) and decrease the expression of endothelin peptide and endothelin mRNA. Since the initiation of flow also causes enhanced convective mass transfer to the endothelial cell monolayer, we have investigated the role of enhanced convection of adenosine trisphosphate (ATP) to the cell surface in eliciting a cellular response by monitoring cytosolic calcium concentrations on the single cell level and by computing the concentration profile of ATP in a parallel-plate flow geometry. Our result demonstrate that endothelial cells respond in very specific ways to the initiation of flow and that mass transfer and fluid shear stress can both play a role in the modulation of intracellular signal transduction and metabolism.

  20. Single-Atom Single-Photon Quantum Interface

    NASA Astrophysics Data System (ADS)

    Moehring, David; Bochmann, Joerg; Muecke, Martin; Specht, Holger; Weber, Bernhard; Wilk, Tatjana; Rempe, Gerhard

    2008-05-01

    By combining atom trapping techniques and cavity cooling schemes we are able to trap a single neutral atom inside a high-finesse cavity for several tens of seconds. We show that our coupled atom-cavity system can be used to generate single photons in a controlled way. With our long trapping times and high single-photon production efficiency, the non-classical properties of the emitted light can be shown in the photon correlations of a single atom. In a similar atom-cavity setup, we investigate the interface between atoms and photons by entangling a single atom with a single photon emitted into the cavity and by further mapping the quantum state of the atom onto a second single photon. These schemes are intrinsically deterministic and establish the basic element required to realize a distributed quantum network with individual atoms at rest as quantum memories and single flying photons as quantum messengers. This work was supported by the Deutsche Forschungsgemeinschaft, and the European Union SCALA and CONQUEST programs. D. L. M. acknowledges support from the Alexander von Humboldt Foundation.

  1. Nitric oxide signaling and the cross talk with prostanoids pathways in vascular system.

    PubMed

    Silva, Bruno R; Paula, Tiago D; Paulo, Michele; Bendhack, Lusiane M

    2016-12-28

    This review provides an overview of the cellular signaling of nitric oxide (NO) and prostanoids in vascular cells and the possible cross talk between their pathways, mainly in hypertension, since the imbalance of these two systems has been attributed to development of some cardiovascular diseases. It also deals with the modulation of vasodilation induced by NO donors. NO is a well-known second messenger involved in many cellular functions. In the vascular system, the NO produced by endothelial NO-synthase (eNOS) or released by NO donors acts in vascular smooth muscle cells, the binding of NO to Fe2+-heme of soluble guanylyl-cyclase (sGC) activates sGC and the production of cyclic guanosine-3-5-monophosphate (cGMP). The second messenger (cGMP) activates protein kinase G and the signaling cascade, including K+ channels. Activation of K+ channels leads to cell membrane hyperpolarization and Ca2+ channels blockade, which induce vascular relaxation. Moreover, the enzyme cyclooxygenase (COX) is also an important regulator of the vascular function by prostanoids production such as thromboxane A2 (TXA2) and prostacyclin (PGI2), which classically induce contraction and relaxation, respectively. Additionaly, studies indicate that the activity of both enzymes can be modulated by their products and reactive oxygen species (ROS) in cardiovascular diseases such as hypertension. The interaction of NO with cellular molecules, particularly the reaction of NO with ROS, determines the biological mechanisms of action and short half-life of NO. We have been working on the vascular effects of ruthenium-derived complexes that release NO. Our research group has published works on the vasodilating effects of ruthenium-derived NO donors and the mechanisms of vascular cells involved in the relaxation of the vascular smooth muscle in health and hypertensive rats. In our previous studies, we have compared the new NO donors synthesized by our group to SNP. It shows the cellular signaling of NO in the endothelial and vascular smooth muscle cells. This work focuses on the cellular mechanisms involved in the vasodilation induced by NO and the role of prostanoids in contractile or relaxing vascular responses. Since the NO is produced by NO-synthase (NOS) or released from NO donors we also discussed the perspectives to cross talk between NO and COX pathways on the vascular tone control.

  2. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dissanayake, V.U.; Hughes, J.; Hunter, J.C.

    The specific binding of the selective {mu}-, {delta}-, and {kappa}-opioid ligands (3H)(D-Ala2,MePhe4,Gly-ol5)enkephalin ((3H) DAGOL), (3H)(D-Pen2,D-Pen5)enkephalin ((3H)DPDPE), and (3H)U69593, respectively, to crude membranes of the guinea pig and rat whole kidney, kidney cortex, and kidney medulla was investigated. In addition, the distribution of specific 3H-opioid binding sites in the guinea pig and rat kidney was visualized by autoradiography. Homogenate binding and autoradiography demonstrated the absence of {mu}- and {kappa}-opioid binding sites in the guinea pig kidney. No opioid binding sites were demonstrable in the rat kidney. In the guinea pig whole kidney, cortex, and medulla, saturation studies demonstrated that (3H)DPDPE boundmore » with high affinity (KD = 2.6-3.5 nM) to an apparently homogeneous population of binding sites (Bmax = 8.4-30 fmol/mg of protein). Competition studies using several opioid compounds confirmed the nature of the {delta}-opioid binding site. Autoradiography experiments demonstrated that specific (3H)DPDPE binding sites were distributed radially in regions of the inner and outer medulla and at the corticomedullary junction of the guinea pig kidney. Computer-assisted image analysis of saturation data yielded KD values (4.5-5.0 nM) that were in good agreement with those obtained from the homogenate binding studies. Further investigation of the {delta}-opioid binding site in medulla homogenates, using agonist ((3H)DPDPE) and antagonist ((3H)diprenorphine) binding in the presence of Na+, Mg2+, and nucleotides, suggested that the {delta}-opioid site is linked to a second messenger system via a GTP-binding protein. Further studies are required to establish the precise localization of the {delta} binding site in the guinea pig kidney and to determine the nature of the second messenger linked to the GTP-binding protein in the medulla.« less

  3. Water Ice on Mercury

    NASA Image and Video Library

    2015-04-16

    This orthographic projection view from NASA MESSENGER spacecraft provides a look at Mercury north polar region. The yellow regions in many of the craters mark locations that show evidence for water ice, as detected by Earth-based radar observations from Arecibo Observatory in Puerto Rico. MESSENGER has collected compelling new evidence that the deposits are indeed water ice, including imaging within the permanently shaded interiors of some of the craters, such as Prokofiev and Fuller. Instrument: Mercury Dual Imaging System (MDIS) Arecibo Radar Image: In yellow (Harmon et al., 2011, Icarus 211, 37-50) http://photojournal.jpl.nasa.gov/catalog/PIA19411

  4. Compact, Passively Q-Switched Nd:YAG Laser for the MESSENGER Mission to the Planet Mercury

    NASA Technical Reports Server (NTRS)

    Krebs, Danny J.; Novo-Gradac, Anne-Marie; Li, Steven X.; Lindauer, Steven J.; Afzal, Robert S.; Yu, Antony

    2004-01-01

    A compact, passively Q-switched Nd:YAG laser has been developed for the Mercury Laser Altimeter (MLA) instrument which is an instrument on the MESSENGER mission to the planet Mercury. The laser achieves 5.4 percent efficiency with a near diffraction limited beam. It has passed all space flight environmental tests at system, instrument, and satellite integration. The laser design draws on a heritage of previous laser altimetry missions, specifically ISESAT and Mars Global Surveyor; but incorporates thermal management features unique to the requirements of an orbit of the planet Mercury.

  5. Development of a microcapillary column for detecting targeted messenger RNA molecules.

    PubMed

    Ohnishi, Michihiro

    2006-03-24

    A capillary column in a rapid-flow system has been developed for detecting targeted messenger RNA (mRNA) molecules. The column has a structure made of two beds-one bed of porous microbeads and one bed of microbeads with a polythymidine base sequence. The targeted eukaryotic mRNA molecules are detected by two-step hybridization (sandwich hybridization) composed of polyadenosine selection of mRNA molecules and formation of a probe-target (targeted mRNA) hybrid. The sandwich hybridization, which is accomplished within 1 h, was tested using synthetic polydeoxynucleotides. Ten picomoles of the targeted polydeoxynucleotide were detected.

  6. Flavored gauge mediation with discrete non-Abelian symmetries

    NASA Astrophysics Data System (ADS)

    Everett, Lisa L.; Garon, Todd S.

    2018-05-01

    We explore the model building and phenomenology of flavored gauge-mediation models of supersymmetry breaking in which the electroweak Higgs doublets and the S U (2 ) messenger doublets are connected by a discrete non-Abelian symmetry. The embedding of the Higgs and messenger fields into representations of this non-Abelian Higgs-messenger symmetry results in specific relations between the Standard Model Yukawa couplings and the messenger-matter Yukawa interactions. Taking the concrete example of an S3 Higgs-messenger symmetry, we demonstrate that, while the minimal implementation of this scenario suffers from a severe μ /Bμ problem that is well known from ordinary gauge mediation, expanding the Higgs-messenger field content allows for the possibility that μ and Bμ can be separately tuned, allowing for the possibility of phenomenologically viable models of the soft supersymmetry-breaking terms. We construct toy examples of this type that are consistent with the observed 125 GeV Higgs boson mass.

  7. Modeling the Role of Incisures in Vertebrate Phototransduction

    PubMed Central

    Caruso, Giovanni; Bisegna, Paolo; Shen, Lixin; Andreucci, Daniele; Hamm, Heidi E.; DiBenedetto, Emmanuele

    2006-01-01

    Phototransduction is mediated by a G-protein-coupled receptor-mediated cascade, activated by light and localized to rod outer segment (ROS) disk membranes, which, in turn, drives a diffusion process of the second messengers cGMP and Ca2+ in the ROS cytosol. This process is hindered by disks—which, however, bear physical cracks, known as incisures, believed to favor the longitudinal diffusion of cGMP and Ca2+. This article is aimed at highlighting the biophysical functional role and significance of incisures, and their effect on the local and global response of the photocurrent. Previous work on this topic regarded the ROS as well stirred in the radial variables, lumped the diffusion mechanism on the longitudinal axis of the ROS, and replaced the cytosolic diffusion coefficients by effective ones, accounting for incisures through their total patent area only. The fully spatially resolved model recently published by our group is a natural tool to take into account other significant details of incisures, including their geometry and distribution. Using mathematical theories of homogenization and concentrated capacity, it is shown here that the complex diffusion process undergone by the second messengers cGMP and Ca2+ in the ROS bearing incisures can be modeled by a family of two-dimensional diffusion processes on the ROS cross sections, glued together by other two-dimensional diffusion processes, accounting for diffusion in the ROS outer shell and in the bladelike regions comprised by the stack of incisures. Based on this mathematical model, a code has been written, capable of incorporating an arbitrary number of incisures and activation sites, with any given arbitrary distribution within the ROS. The code is aimed at being an operational tool to perform numerical experiments of phototransduction, in rods with incisures of different geometry and structure, under a wide spectrum of operating conditions. The simulation results show that incisures have a dual biophysical function. On the one hand, since incisures line up from disk to disk, they create vertical cytoplasmic channels crossing the disks, thus facilitating diffusion of second messengers; on the other hand, at least in those species bearing multiple incisures, they divide the disks into lobes like the petals of a flower, thus confining the diffusion of activated phosphodiesterase and localizing the photon response. Accordingly, not only the total area of incisures, but their geometrical shape and distribution as well, significantly influence the global photoresponse. PMID:16714347

  8. [Cognitive Function and Calcium. Structures and functions of Ca2+-permeable channels].

    PubMed

    Kaneko, Shuji

    2015-02-01

    Calcium is essential for living organisms where the increase in intracellular Ca2+ concentration functions as a second messenger for many cellular processes including synaptic transmission and neural plasticity. The cytosolic concentration of Ca2+ is finely controlled by many Ca2+-permeable ion channels and transporters. The comprehensive view of their expression, function, and regulation will advance our understanding of neural and cognitive functions of Ca2+, which leads to the future drug discovery.

  9. Structural Basis of Differential Ligand Recognition by Two Classes of bis-(3-5)-cyclic Dimeric Guanosine Monophosphate-binding Riboswitches

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    K Smith; C Shanahan; E Moore

    2011-12-31

    The bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) signaling pathway regulates biofilm formation, virulence, and other processes in many bacterial species and is critical for their survival. Two classes of c-di-GMP-binding riboswitches have been discovered that bind this second messenger with high affinity and regulate diverse downstream genes, underscoring the importance of RNA receptors in this pathway. We have solved the structure of a c-di-GMP-II riboswitch, which reveals that the ligand is bound as part of a triplex formed with a pseudoknot. The structure also shows that the guanine bases of c-di-GMP are recognized through noncanonical pairings and that the phosphodiester backbonemore » is not contacted by the RNA. Recognition is quite different from that observed in the c-di-GMP-I riboswitch, demonstrating that at least two independent solutions for RNA second messenger binding have evolved. We exploited these differences to design a c-di-GMP analog that selectively binds the c-di-GMP-II aptamer over the c-di-GMP-I RNA. There are several bacterial species that contain both types of riboswitches, and this approach holds promise as an important tool for targeting one riboswitch, and thus one gene, over another in a selective fashion.« less

  10. Ghrelin upregulates the phosphorylation of the GluN2B subunit of the NMDA receptor by activating GHSR1a and Fyn in the rat hippocampus.

    PubMed

    Berrout, Liza; Isokawa, Masako

    2018-01-01

    Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity. However, it depended on the activation of GHSR1a and Fyn as it was blocked by D-Lys3-GHRP-6 and PP2, respectively. Inhibitors for G-protein-regulated second messengers, such as Rp-cAMP, H89, TBB, ryanodine, and thapsigargin, unexpectedly enhanced GluN2B phosphorylation, suggesting that cAMP, PKA, casein kinase II, and cytosolic calcium signaling may oppose to the effect of ghrelin on the phosphorylation of GluN2B. Our findings suggest that 1) GluN2B is likely a molecular target of ghrelin and GHSR1a-driven signaling cascades, and 2) the ghrelin-mediated phosphorylation of GluN2B depends on Fyn activation under complex negative regulation by other second messengers. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Modulation of cGMP in Heart Failure

    PubMed Central

    Boerrigter, Guido; Lapp, Harald; Burnett, John C.

    2009-01-01

    Heart failure (HF) is a common disease that continues to be associated with high morbidity and mortality warranting novel therapeutic strategies. Cyclic guanosine monophosphate (cGMP) is the second messenger of several important signaling pathways based on distinct guanylate cyclases (GCs) in the cardiovascular system. Both the nitric oxide/soluble GC (NO/sGC) as well as the natriuretic peptide/GC-A (NP/GC-A) systems are disordered in HF, providing a rationale for their therapeutic augmentation. Soluble GC activation with conventional nitrovasodilators has been used for more than a century but is associated with cGMP-independent actions and the development of tolerance, actions which novel NO-independent sGC activators now in clinical development lack. Activation of GC-A by administration of naturally occurring or designer natriuretic peptides is an emerging field, as is the inhibition of enzymes that degrade endogenous NPs. Finally, inhibition of cGMP-degrading phosphodiesterases, particularly phosphodiesterase 5 provides an additional strategy to augment cGMP-signaling. PMID:19089342

  12. A Christmas Crater from Mercury

    NASA Image and Video Library

    2017-12-08

    Release Date: December 21, 2011 The crater at the center of this image is named Dickens, after Charles Dickens, the English novelist who lived from 1812 to 1870. Among Dickens' famous works is A Christmas Carol, the story of Bob Cratchit, his family, and horrible boss Mr. Scrooge. Scientists studying Mercury might consider the Mariner 10 mission to be Christmas Past, MESSENGER to be Christmas Present, and the European Bepi-Colombo mission to be Christmas Yet To Come. This image was acquired as part of MDIS's high-resolution surface morphology base map. The surface morphology base map will cover more than 90% of Mercury's surface with an average resolution of 250 meters/pixel (0.16 miles/pixel or 820 feet/pixel). Images acquired for the surface morphology base map typically have off-vertical Sun angles (i.e., high incidence angles) and visible shadows so as to reveal clearly the topographic form of geologic features. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MDIS is scheduled to acquire more than 75,000 images in support of MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  13. From Orbit, Looking toward Mercury's Horizon

    NASA Image and Video Library

    2017-12-08

    NASA image acquired: March 29, 2011 MESSENGER acquired this image of Mercury's horizon as the spacecraft was moving northward along the first orbit during which MDIS was turned on. Bright rays from Hokusai can be seen running north to south in the image. MDIS frequently acquired images that contained Mercury's horizon during the mission's three Mercury flybys. (Visit these links to see examples of horizon images from Mercury flyby 1, Mercury flyby 2, and Mercury flyby 3.) However, now that MESSENGER is in orbit about Mercury, views of Mercury's horizon in the images will be much less common. The field of view for MDIS will generally be filled with Mercury's surface as the instrument maps out the planet's geology in high resolution, stereo, and color. Occasionally, in order to obtain images of a certain portion of Mercury's surface, the horizon will also be visible. On March 17, 2011 (March 18, 2011, UTC), MESSENGER became the first spacecraft to orbit the planet Mercury. The mission is currently in its commissioning phase, during which spacecraft and instrument performance are verified through a series of specially designed checkout activities. In the course of the one-year primary mission, the spacecraft's seven scientific instruments and radio science investigation will unravel the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the science questions that the MESSENGER mission has set out to answer. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Join us on Facebook

  14. The Terminator is Here

    NASA Image and Video Library

    2017-12-08

    NASA release date June 21, 2011 The terminator of Mercury, shown here in color, is the line between light and dark, or day and night. On Mercury, three days are equivalent to two years, or in other words, the planet spins around its axis three times for every two orbits around the Sun. The first Mercury year of the MESSENGER mission ended on Monday, June 13, 2011. This image was acquired as part of MDIS's color base map. The color base map is composed of WAC images taken through eight different narrow-band color filters and will cover more than 90% of Mercury's surface with an average resolution of 1 kilometer/pixel (0.6 miles/pixel). The highest-quality color images are obtained for Mercury's surface when both the spacecraft and the Sun are overhead, so these images typically are taken with viewing conditions of low incidence and emission angles. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MDIS is scheduled to acquire more than 75,000 images in support of MESSENGER's science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  15. Keeping Cool Close to the Sun

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hazi, A

    The germanium detector in the gamma-ray spectrometer (GRS) aboard the MESSENGER spacecraft is only the size and weight of a can of peaches but will play a critical role in investigating Mercury, the planet closest to the Sun. The MESSENGER (MErcury Surface, Space ENvironment, GEochemistry, and Ranging) spacecraft travels at about 38 kilometers per second and is named after the scientific goals of the mission. It is the first spacecraft to visit Mercury since 1975. MESSENGER must take an oblique route to approach Mercury so that it does not fly past the planet and fall directly into the Sun. Themore » spacecraft will travel 7.9 billion kilometers, flying by Earth once, Venus twice, and Mercury three times before settling into orbit around this mysterious planet. Of all the terrestrial planets, which include Venus, Earth, and Mars, Mercury is the smallest and the densest; its days are 176 Earth days long, two complete orbits of the planet around the Sun. Temperatures range from a high of 450 C on the Sun side during its long day to a low of -185 C on its night side. By studying this extreme planet, scientists hope to better understand how Earth formed and evolved. The GRS, one of the seven lightweight scientific instruments on MESSENGER, will be used to help scientists determine the abundance of elements in Mercury's crust, including the materials that might be ice at its poles. Livermore engineer Norman Madden led the West Coast team effort to design and build the GRS in a collaboration led by Johns Hopkins University Applied Physics Laboratory (JHUAPL). The team included Lawrence Berkeley and Lawrence Livermore national laboratories as well as University of California at Berkeley (UCB) Space Sciences Laboratory (SSL). The JHUAPL MESSENGER project is a National Aeronautics and Space Administration (NASA) Discovery Mission. Because the detector needs to operate at very low temperatures and MESSENGER is close to the Sun, the thermal design to protect the detector was critical. The detector is kept cool by an electromechanical cryocooler attached to the outside of the device. However, the cryocooler has a limited cooling capacity because of size and weight constraints. To ensure the cryocooler would sufficiently cool the detector, Livermore scientists used SINDA/FLUINT, a commercial program originally developed by NASA, to model the thermal environments that the spectrometer was expected to encounter--during liftoff, in space while en route to Mercury, and in orbit around the planet. Using the data from the model, scientists from Lawrence Livermore and Lawrence Berkeley developed a design that included three closely spaced and highly reflective thermal shields held in place with DuPont KEVLAR{reg_sign} fiber.« less

  16. KSC-04pd1470

    NASA Image and Video Library

    2004-07-14

    KENNEDY SPACE CENTER, FLA. - The MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft, mated to the Delta II third stage Payload Assist Module, is ready for presentation to the media at Astrotech Space Operations in Titusville, Fla. Spokespersons for the event are Dr. Robert Gold, MESSENGER payload manager with The Johns Hopkins University Applied Physics Laboratory (APL); and Ted Hartka, MESSENGER lead mechanical engineer, APL. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla.

  17. KSC-04pd1471

    NASA Image and Video Library

    2004-07-14

    KENNEDY SPACE CENTER, FLA. - The MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft, mated to the Delta II third stage Payload Assist Module, is on display at Astrotech Space Operations in Titusville, Fla., for the media. Spokespersons for the event are Dr. Robert Gold, MESSENGER payload manager with The Johns Hopkins University Applied Physics Laboratory (APL); and Ted Hartka, MESSENGER lead mechanical engineer, APL. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla.

  18. KSC-04PD-1539

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. Inside the environmental curtain suspended around the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft while in the mobile service tower at Launch Complex 17-B, Cape Canaveral Air Force Station, a worker removes the protective material wrapped around MESSENGER. Visible at right is the sunshade that will protect MESSENGERs instruments during exposure to the sun as it orbits Mercury. Scheduled to launch Aug. 2, MESSENGER will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. It is expected to enter Mercury orbit in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md. Processing is being done at Astrotech Space Operations in Titusville, Fla.

  19. MESSENGER Observations of Extreme Space Weather in Mercury's Magnetosphere

    NASA Astrophysics Data System (ADS)

    Slavin, J. A.

    2013-09-01

    Increasing activity on the Sun is allowing MESSENGER to make its first observations of Mercury's magnetosphere under extreme solar wind conditions. At Earth interplanetary shock waves and coronal mass ejections produce severe "space weather" in the form of large geomagnetic storms that affect telecommunications, space systems, and ground-based power grids. In the case of Mercury the primary effect of extreme space weather in on the degree to which this it's weak global magnetic field can shield the planet from the solar wind. Direct impact of the solar wind on the surface of airless bodies like Mercury results in space weathering of the regolith and the sputtering of atomic species like sodium and calcium to high altitudes where they contribute to a tenuous, but highly dynamic exosphere. MESSENGER observations indicate that during extreme interplanetary conditions the solar wind plasma gains access to the surface of Mercury through three main regions: 1. The magnetospheric cusps, which fill with energized solar wind and planetary ions; 2. The subsolar magnetopause, which is compressed and eroded by reconnection to very low altitudes where the natural gyro-motion of solar wind protons may result in their impact on the surface; 3. The magnetotail where hot plasma sheet ions rapidly convect sunward to impact the surface on the nightside of Mercury. The possible implications of these new MESSENGER observations for our ability to predict space weather at Earth and other planets will be described.

  20. Biomechanical force in blood development: extrinsic physical cues drive pro-hematopoietic signaling

    PubMed Central

    Lee, Hyun Jung; Li, Nan; Evans, Siobahn M.; Diaz, Miguel F.; Wenzel, Pamela L.

    2013-01-01

    The hematopoietic system is dynamic during development and in adulthood, undergoing countless spatial and temporal transitions during the course of one’s life. Microenvironmental cues in the many unique hematopoietic niches differ, characterized by distinct soluble molecules, membrane-bound factors, and biophysical features that meet the changing needs of the blood system. Research from the last decade has revealed the importance of substrate elasticity and biomechanical force in determination of stem cell fate. Our understanding of the role of these factors in hematopoiesis is still relatively poor; however, the developmental origin of blood cells from the endothelium promts a model for comparison. Many endothelial mechanical sensors and second messenger systems may also determine hematopoietic stem cell fate, self renewal, and homing behaviors. Further, the intimate contact of hematopoietic cells with mechanosensitive cell types, including osteoblasts, endothelial cells, mesenchymal stem cells, and pericytes, places them in close proximity to paracrine signaling downstream of mechanical signals. The objective of this review is to present an overview of the sensors and intracellular signaling pathways activated by mechanical cues and highlight the role of mechanotransductive pathways in hematopoiesis. PMID:23850217

  1. On the Edge of Mercury

    NASA Image and Video Library

    2015-02-04

    In this image, Mercury's horizon cuts a striking edge against the stark blackness of space. On the right, sunlight harshly brings the landscape into relief while on the left, the surface is shrouded in the darkness of night. This image was acquired as part of MDIS's limb imaging campaign. Once per week, MDIS captures images of Mercury's limb, with an emphasis on imaging the southern hemisphere limb. These limb images provide information about Mercury's shape and complement measurements of topography made by the Mercury Laser Altimeter (MLA) of Mercury's northern hemisphere. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. In the mission's more than three years of orbital operations, MESSENGER has acquired over 250,000 images and extensive other data sets. MESSENGER is capable of continuing orbital operations until early 2015. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  2. [The role of inositol deficiency in the etiology of polycystic ovary syndrome disorders].

    PubMed

    Jakimiuk, Artur J; Szamatowicz, Jacek

    2014-01-01

    Inositol acts as a second messenger in insulin signaling pathway Literature data suggest inositol deficiency in insulin-resistant women with the polycystic ovary syndrome. Supplementation of myo-inisitol decreases insulin resistance as it works as an insulin sensitizing agent. The positive role of myo-inositol in the treatment of polycystic ovary syndrome has been of increased evidence recently The present review presents the effects of myo-inositol on the ovarian, hormonal and metabolic parameters in women with PCOS.

  3. The Role of Membrane-Derived Second Messengers and Bmx/Etk in Response to Radiation Treatment of Prostate Cancer

    DTIC Science & Technology

    2009-01-01

    promising pharmacologic target for radiation enhancement. Although LMF- A13 is clinically used as a Btk inhibitor , many groups have used LFM-A13 as a Bmx... inhibitor due to the high homology between Bmx and Btk . Because Btk is only found in bone marrow–derived cells, we felt that LFM-A13 could be used...discovered a number of selective irreversible Btk inhibitors aimed at treating rheumatoid arthritis. Moreover, CGI Pharmaceuticals, Inc. has been developing

  4. Hypergravity signal transduction in HeLa cells with concomitant phosphorylation of proteins immunoprecipitated with anti-microtubule-associated protein antibodies

    NASA Technical Reports Server (NTRS)

    Kumei, Yasuhiro; Whitson, Peggy A.; Sato, Atsushige; Cintron, Nitza M.

    1991-01-01

    It is shown that hypergravity (35g) stimulates the production of inositol 1,4,5-trisphosphate (IP3) and decreases adenosine 3-prime,5-prime-cyclic monophosphate (cAMP) levels in HeLa cells. It is proposed that IP3 and cAMP may act as second messengers in hypergravity signal transduction. Phosphorylation of microtubule-associated proteins in both the detergent-soluble and -insoluble fractions suggests that cytoskeletal structures may be influenced by gravity.

  5. MESSENGER: The Discovery Mission to Mercury

    NASA Astrophysics Data System (ADS)

    McNutt, R. L.; Solomon, S. C.; Gold, R. E.; Domingue, D. L.

    2004-12-01

    NASA's MErcury, Surface, Space ENvironment, GEochenistry, and Ranging (MESSENGER) spacecraft, launched on 3 August 2004, has begun its voyage to initiate a new era in our understanding of the terrestrial planets. The mission, spacecraft, and payload are designed to answer six fundamental questions regarding the innermost planet: What planetary formational processes led to Mercury's high metal/silicate ratio? What is the geological history of Mercury? What are the nature and origin of Mercury's magnetic field? What are the structure and state of Mercury's core? What are the radar-reflective materials at Mercury's poles? What are the important volatile species and their sources and sinks on and near Mercury? Planet formational hypotheses will be tested by measuring the surface abundances of major elements by X-ray and gamma-ray spectrometry. The geological history will be determined from high-resolution color imaging of the heavily cratered highlands, intercrater plains, and smooth plains. MESSENGER will provide detailed views of both the Caloris basin and its antipodal terrain. Topographic, mineralogical, and elemental abundance data will be used to seek evidence of volcanic features and units. Measurement of Mercury's magnetic field and its interaction with the solar wind will distinguish the intrinsic dipole and quadrupole components while separating these from the current systems driven by solar-wind-induced convection. The structure of the internal field will put constraints on dynamo models. Such models will also be constrained by measuring Mercury's libration to determine the extent of a fluid outer core. Both water ice and sulfur have been postulated as major constituents of the high-radar-backscatter polar deposits. MESSENGER will combine gamma-ray and neutron spectrometry of the surface with ultraviolet spectrometry and in situ particle measurements to detect both neutral and charged species originating from the surface. Such measurements will address the sources and sinks of volatiles and their couplings with the surface on a global basis as well as the nature of the polar deposits. To broaden scientific participation in the mission, the MESSENGER project is working with NASA to establish a Participating Scientist Program. The MESSENGER team is also continuing its informal interaction with members of the BepiColombo project to maximize the overall scientific return from both missions.

  6. Signal-dependent Hydrolysis of Phosphatidylinositol 4,5-Bisphosphate without Activation of Phospholipase C

    PubMed Central

    Lev, Shaya; Katz, Ben; Tzarfaty, Vered; Minke, Baruch

    2012-01-01

    In Drosophila, a phospholipase C (PLC)-mediated signaling cascade, couples photo-excitation of rhodopsin to the opening of the transient receptor potential (TRP) and TRP-like (TRPL) channels. A lipid product of PLC, diacylglycerol (DAG), and its metabolites, polyunsaturated fatty acids (PUFAs) may function as second messengers of channel activation. However, how can one separate between the increase in putative second messengers, change in pH, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) depletion when exploring the TRPL gating mechanism? To answer this question we co-expressed the TRPL channels together with the muscarinic (M1) receptor, enabling the openings of TRPL channels via G-protein activation of PLC. To dissect PLC activation of TRPL into its molecular components, we used a powerful method that reduced plasma membrane-associated PI(4,5)P2 in HEK cells within seconds without activating PLC. Upon the addition of a dimerizing drug, PI(4,5)P2 was selectively hydrolyzed in the cell membrane without producing DAG, inositol trisphosphate, or calcium signals. We show that PI(4,5)P2 is not an inhibitor of TRPL channel activation. PI(4,5)P2 hydrolysis combined with either acidification or application of DAG analogs failed to activate the channels, whereas PUFA did activate the channels. Moreover, a reduction in PI(4,5)P2 levels or inhibition of DAG lipase during PLC activity suppressed the PLC-activated TRPL current. This suggests that PI(4,5)P2 is a crucial substrate for PLC-mediated activation of the channels, whereas PUFA may function as the channel activator. Together, this study defines a narrow range of possible mechanisms for TRPL gating. PMID:22065576

  7. Signal-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate without activation of phospholipase C: implications on gating of Drosophila TRPL (transient receptor potential-like) channel.

    PubMed

    Lev, Shaya; Katz, Ben; Tzarfaty, Vered; Minke, Baruch

    2012-01-06

    In Drosophila, a phospholipase C (PLC)-mediated signaling cascade, couples photo-excitation of rhodopsin to the opening of the transient receptor potential (TRP) and TRP-like (TRPL) channels. A lipid product of PLC, diacylglycerol (DAG), and its metabolites, polyunsaturated fatty acids (PUFAs) may function as second messengers of channel activation. However, how can one separate between the increase in putative second messengers, change in pH, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) depletion when exploring the TRPL gating mechanism? To answer this question we co-expressed the TRPL channels together with the muscarinic (M1) receptor, enabling the openings of TRPL channels via G-protein activation of PLC. To dissect PLC activation of TRPL into its molecular components, we used a powerful method that reduced plasma membrane-associated PI(4,5)P(2) in HEK cells within seconds without activating PLC. Upon the addition of a dimerizing drug, PI(4,5)P(2) was selectively hydrolyzed in the cell membrane without producing DAG, inositol trisphosphate, or calcium signals. We show that PI(4,5)P(2) is not an inhibitor of TRPL channel activation. PI(4,5)P(2) hydrolysis combined with either acidification or application of DAG analogs failed to activate the channels, whereas PUFA did activate the channels. Moreover, a reduction in PI(4,5)P(2) levels or inhibition of DAG lipase during PLC activity suppressed the PLC-activated TRPL current. This suggests that PI(4,5)P(2) is a crucial substrate for PLC-mediated activation of the channels, whereas PUFA may function as the channel activator. Together, this study defines a narrow range of possible mechanisms for TRPL gating.

  8. Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

    DOE PAGES

    Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine; ...

    2015-12-28

    Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ 54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response tomore » cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.« less

  9. Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine

    Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ 54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response tomore » cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.« less

  10. Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

    PubMed Central

    Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine; Harwood, Caroline S.; Sondermann, Holger; Navarro, Marcos V. A. S.

    2016-01-01

    Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs. PMID:26712005

  11. One Small Collection of Images, Many Giant Strides Forward for MESSENGER

    NASA Image and Video Library

    2012-07-23

    This image compilation shows some of the most exciting images taken thus far on the MESSENGER mission. A mural-sized copy hangs next to the MESSENGER Science Operations Center at the Johns Hopkins University Applied Physics Laboratory. http://photojournal.jpl.nasa.gov/catalog/PIA16364

  12. Imaging Live Drosophila Brain with Two-Photon Fluorescence Microscopy

    NASA Astrophysics Data System (ADS)

    Ahmed, Syeed Ehsan

    Two-photon fluorescence microscopy is an imaging technique which delivers distinct benefits for in vivo cellular and molecular imaging. Cyclic adenosine monophosphate (cAMP), a second messenger molecule, is responsible for triggering many physiological changes in neural system. However, the mechanism by which this molecule regulates responses in neuron cells is not yet clearly understood. When cAMP binds to a target protein, it changes the structure of that protein. Therefore, studying this molecular structure change with fluorescence resonance energy transfer (FRET) imaging can shed light on the cAMP functioning mechanism. FRET is a non-radiative dipole-dipole coupling which is sensitive to small distance change in nanometer scale. In this study we have investigated the effect of dopamine in cAMP dynamics in vivo. In our study two-photon fluorescence microscope was used for imaging mushroom bodies inside live Drosophila melanogaster brain and we developed a method for studying the change in cyclic AMP level.

  13. Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose.

    PubMed

    Tsuzuki, Takayoshi; Takano, Satoshi; Sakaguchi, Natsumi; Kudoh, Takashi; Murayama, Takashi; Sakurai, Takashi; Hashii, Minako; Higashida, Haruhiro; Weber, Karin; Guse, Andreas H; Kameda, Tomoshi; Hirokawa, Takatsugu; Kumaki, Yasuhiro; Arisawa, Mitsuhiro; Potter, Barry V L; Shuto, Satoshi

    2014-01-01

    Here we describe the successful synthesis of cyclic ADP-4-thioribose (cADPtR, 3 ), designed as a stable mimic of cyclic ADP-ribose (cADPR, 1 ), a Ca 2+ -mobilizing second messenger, in which the key N1-β-thioribosyladenosine structure was stereoselectively constructed by condensation between the imidazole nucleoside derivative 8 and the 4-thioribosylamine 7 via equilibrium in 7 between the α-anomer ( 7α ) and the β-anomer ( 7β ) during the reaction course. cADPtR is, unlike cADPR, chemically and biologically stable, while it effectively mobilizes intracellular Ca 2+ like cADPR in various biological systems, such as sea urchin homogenate, NG108-15 neuronal cells, and Jurkat T-lymphocytes. Thus, cADPtR is a stable equivalent of cADPR, which can be useful as a biological tool for investigating cADPR-mediated Ca 2+ -mobilizing pathways.

  14. TGF-β in tolerance, development and regulation of immunity

    PubMed Central

    Johnston, Chris J.C.; Smyth, Danielle J.; Dresser, David W.; Maizels, Rick M.

    2016-01-01

    The TGF-β superfamily is an ancient metazoan protein class which cuts across cell and tissue differentiation, developmental biology and immunology. Its many members are regulated at multiple levels from intricate control of gene transcription, post-translational processing and activation, and signaling through overlapping receptor structures and downstream intracellular messengers. We have been interested in TGF-β homologues firstly as key players in the induction of immunological tolerance, the topic so closely associated with Ray Owen. Secondly, our interests in how parasites may manipulate the immune system of their host has also brought us to study the TGF-β pathway in infections with longlived, essentially tolerogenic, helminth parasites. Finally, within the spectrum of mammalian TGF-β proteins is an exquisitely tightly-regulated gene, anti-Müllerian hormone (AMH), whose role in sex determination underpins the phenotype of freemartin calves that formed the focus of Ray’s seminal work on immunological tolerance. PMID:26617281

  15. Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients.

    PubMed

    Stoll, A L; Sachs, G S; Cohen, B M; Lafer, B; Christensen, J D; Renshaw, P F

    1996-09-01

    This study examined choline augmentation of lithium for rapid-cycling bipolar disorder. Choline bitartrate was given openly to 6 consecutive lithium-treated outpatients with rapid-cycling bipolar disorder. Five patients also underwent brain proton magnetic resonance spectroscopy. Five of 6 rapid-cycling patients had a substantial reduction in manic symptoms, and 4 patients had a marked reduction in all mood symptoms during choline therapy. The patients who responded to choline all exhibited a substantial rise in the basal ganglia concentration of choline-containing compounds. Choline was well tolerated in all cases. Choline, in the presence of lithium, was a safe and effective treatment for 4 of 6 rapid-cycling patients in our series. A hypothesis is suggested to explain both lithium refractoriness in patients with bipolar disorder and the action of choline in mania, which involves the interaction between phosphatidylinositol and phosphatidylcholine second-messenger systems.

  16. Novel PDE4 Inhibitors Derived from Chinese Medicine Forsythia

    PubMed Central

    Coon, Tiffany A.; McKelvey, Alison C.; Weathington, Nate M.; Birru, Rahel L.; Lear, Travis; Leikauf, George D.; Chen, Bill B.

    2014-01-01

    Cyclic adenosine monophosphate (cAMP) is a crucial intracellular second messenger molecule that converts extracellular molecules to intracellular signal transduction pathways generating cell- and stimulus-specific effects. Importantly, specific phosphodiesterase (PDE) subtypes control the amplitude and duration of cAMP-induced physiological processes and are therefore a prominent pharmacological target currently used in a variety of fields. Here we tested the extracts from traditional Chinese medicine, Forsythia suspense seeds, which have been used for more than 2000 years to relieve respiratory symptoms. Using structural-functional analysis we found its major lignin, Forsynthin, acted as an immunosuppressant by inhibiting PDE4 in inflammatory and immune cell. Moreover, several novel, selective small molecule derivatives of Forsythin were tested in vitro and in murine models of viral and bacterial pneumonia, sepsis and cytokine-driven systemic inflammation. Thus, pharmacological targeting of PDE4 may be a promising strategy for immune-related disorders characterized by amplified host inflammatory response. PMID:25549252

  17. Zinc in Cellular Regulation: The Nature and Significance of "Zinc Signals".

    PubMed

    Maret, Wolfgang

    2017-10-31

    In the last decade, we witnessed discoveries that established Zn 2+ as a second major signalling metal ion in the transmission of information within cells and in communication between cells. Together with Ca 2+ and Mg 2+ , Zn 2+ covers biological regulation with redox-inert metal ions over many orders of magnitude in concentrations. The regulatory functions of zinc ions, together with their functions as a cofactor in about three thousand zinc metalloproteins, impact virtually all aspects of cell biology. This article attempts to define the regulatory functions of zinc ions, and focuses on the nature of zinc signals and zinc signalling in pathways where zinc ions are either extracellular stimuli or intracellular messengers. These pathways interact with Ca 2+ , redox, and phosphorylation signalling. The regulatory functions of zinc require a complex system of precise homeostatic control for transients, subcellular distribution and traffic, organellar homeostasis, and vesicular storage and exocytosis of zinc ions.

  18. Contributions of 5-HT neurons to respiratory control: neuromodulatory and trophic effects.

    PubMed

    Hodges, Matthew R; Richerson, George B

    2008-12-10

    Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter produced by a small number of neurons in the midbrain, pons and medulla. These neurons project widely throughout the neuraxis, where they release 5-HT and co-localized neuropeptides such as substance P (SP) and thyrotropin-releasing hormone (TRH). Each of these chemicals produce effects largely through G protein-coupled receptors, second messenger systems and subsequent neuromodulatory effects on target neurons. Emerging evidence suggests that 5-HT has additional modes of action during development and in adult mammals, including trophic effects (neurogenesis, cell differentiation, proliferation, migration and maturation) and influences on synaptic plasticity. Here, we discuss some of the neuromodulatory and trophic roles of 5-HT in general and in the context of respiratory control, as well as the regulation of release of modulatory neurotransmitters from 5-HT neurons. Future directions of study are also discussed.

  19. Distinct Perceptual Grouping Pathways Revealed By Temporal Carriers and Envelopes

    PubMed Central

    Rainville, Stéphane; Clarke, Aaron

    2014-01-01

    Guttman et al. [2005, Vis. Res., 45(8), 1021-1030] investigated whether observers could perform temporal grouping in multi-element displays where each local element was stochastically modulated over time along one of several potential dimensions – or “messenger types” – such as contrast, position, orientation, or spatial scale. Guttman et al.’s data revealed that grouping discards messenger type and therefore support a single-pathway model that groups elements with similar temporal waveforms. In the current study, we carried out three experiments in which temporal-grouping information resided either in the carrier, the envelope, or the combined carrier and envelope of each messenger’s timecourse. Results revealed that grouping is highly specific for messenger type if carrier envelopes lack grouping information but largely messenger nonspecific if carrier envelopes contain grouping information. The imply that temporal grouping is mediated by several messenger-specific carrier pathways as well as by a messenger-nonspecific envelope pathways. Findings also challenge simple temporal-filtering accounts of perceptual grouping [Adelson & Farid, 1999, Science, 286, 2231a]. PMID:19146293

  20. Extracellular calcium acts as a “third messenger” to regulate enzyme and alkaline secretion

    PubMed Central

    Caroppo, Rosa; Gerbino, Andrea; Fistetto, Gregorio; Colella, Matilde; Debellis, Lucantonio; Hofer, Aldebaran M.; Curci, Silvana

    2004-01-01

    It is generally assumed that the functional consequences of stimulation with Ca2+-mobilizing agonists are derived exclusively from the second messenger action of intracellular Ca2+, acting on targets inside the cells. However, during Ca2+ signaling events, Ca2+ moves in and out of the cell, causing changes not only in intracellular Ca2+, but also in local extracellular Ca2+. The fact that numerous cell types possess an extracellular Ca2+ “sensor” raises the question of whether these dynamic changes in external [Ca2+] may serve some sort of messenger function. We found that in intact gastric mucosa, the changes in extracellular [Ca2+] secondary to carbachol-induced increases in intracellular [Ca2+] were sufficient and necessary to elicit alkaline secretion and pepsinogen secretion, independent of intracellular [Ca2+] changes. These findings suggest that extracellular Ca2+ can act as a “third messenger” via Ca2+ sensor(s) to regulate specific subsets of tissue function previously assumed to be under the direct control of intracellular Ca2+. PMID:15240573

  1. Prediction of Fetal Growth Restriction by Analyzing the Messenger RNAs of Angiogenic Factor in the Plasma of Pregnant Women.

    PubMed

    Takenaka, Shin; Ventura, Walter; Sterrantino, Anna Freni; Kawashima, Akihiro; Koide, Keiko; Hori, Kyoko; Farina, Antonio; Sekizawa, Akihiko

    2015-06-01

    To predict the occurrence of fetal growth restriction (FGR) by analyzing messenger RNA (mRNA) expression levels of vascular endothelial growth factor receptor 1 (fms-like tyrosine kinase 1 [Flt-1]) in maternal blood. Eleven women with FGR were matched with 88 controls. Plasma samples were obtained during each trimester. The Flt-1 mRNA expression levels were compared between groups. Predicted probabilities were calculated, and sensitivity-specificity (receiver-operating characteristic [ROC]) curves were assessed based on regression models for each trimester measurement and possible combinations of measurements. The mRNA levels of the FGR group during all trimesters were significantly higher than those of the control group. The ROC curve of combined first and second trimester data yielded a detection rate of 60% at a 10% false-positive rate, with an area under curve of 0.79. The Flt-1 mRNA expression in maternal blood can be used as a marker to predict the development of FGR, long before a clinical diagnosis is made. © The Author(s) 2014.

  2. Argonaute, Dicer, and Drosha are up-regulated along tumor progression in serous ovarian carcinoma.

    PubMed

    Vaksman, Olga; Hetland, Thea Eline; Trope', Claes G; Reich, Reuven; Davidson, Ben

    2012-11-01

    MicroRNAs are posttranscriptional regulators of messenger RNA synthesis that are intracellularly processed and transferred by the microRNA-regulating machinery consisting of Drosha, Dicer, and Argonaute. The present study analyzed the expression and clinical role of the microRNA-regulating machinery in advanced-stage ovarian carcinoma. Drosha, Dicer, Argonaute 1, and Argonaute 2 messenger RNA levels were analyzed in 144 specimens (82 effusions, 33 primary carcinomas, and 29 solid metastases) using quantitative polymerase chain reaction. Dicer, Argonaute 1, and Argonaute 2 protein levels were analyzed in 103 of the above specimens by Western blotting. Argonaute 1, Argonaute 2, and Drosha messenger RNAs were overexpressed in effusions compared with primary carcinomas and solid metastases (P<.001), whereas Argonaute 1 protein expression was highest in solid metastases (P=.004). Significantly higher expression of all 4 messenger RNAs was found in effusions compared with primary carcinomas (P<.001 to P=.006), whereas Argonaute 2 messenger RNA (P=.002), Drosha messenger RNA (P=.009), and Dicer protein (P=.006) were overexpressed in solid metastases compared with primary carcinomas. Drosha, Dicer, Argonaute 1, and Argonaute 2 messenger RNAs and protein levels in effusions were unrelated to clinicopathologic parameters. In primary carcinomas, higher levels of 3 messenger RNAs were significantly associated with high-grade histology (P=.003 for Dicer and P=.01 for Drosha and Argonaute 1). Higher Argonaute 2 messenger RNA levels in prechemotherapy effusions were related to shorter progression-free survival (P=.049), a finding that retained its significance in multivariate Cox analysis (P=.046). In conclusion, Drosha, Dicer, Argonaute 1, and Argonaute 2 are differentially expressed at different metastatic sites in ovarian carcinoma compared with primary carcinomas, suggesting a role for these molecules in tumor progression. Their clinical role in metastatic ovarian carcinoma merits further research. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Calcium and cAMP directly modulate the speed of the Drosophila circadian clock.

    PubMed

    Palacios-Muñoz, Angelina; Ewer, John

    2018-06-01

    Circadian clocks impose daily periodicities to animal behavior and physiology. At their core, circadian rhythms are produced by intracellular transcriptional/translational feedback loops (TTFL). TTFLs may be altered by extracellular signals whose actions are mediated intracellularly by calcium and cAMP. In mammals these messengers act directly on TTFLs via the calcium/cAMP-dependent transcription factor, CREB. In the fruit fly, Drosophila melanogaster, calcium and cAMP also regulate the periodicity of circadian locomotor activity rhythmicity, but whether this is due to direct actions on the TTFLs themselves or are a consequence of changes induced to the complex interrelationship between different classes of central pacemaker neurons is unclear. Here we investigated this question focusing on the peripheral clock housed in the non-neuronal prothoracic gland (PG), which, together with the central pacemaker in the brain, controls the timing of adult emergence. We show that genetic manipulations that increased and decreased the levels of calcium and cAMP in the PG caused, respectively, a shortening and a lengthening of the periodicity of emergence. Importantly, knockdown of CREB in the PG caused an arrhythmic pattern of eclosion. Interestingly, the same manipulations directed at central pacemaker neurons caused arrhythmicity of eclosion and of adult locomotor activity, suggesting a common mechanism. Our results reveal that the calcium and cAMP pathways can alter the functioning of the clock itself. In the PG, these messengers, acting as outputs of the clock or as second messengers for stimuli external to the PG, could also contribute to the circadian gating of adult emergence.

  4. KSC-04pd1483

    NASA Image and Video Library

    2004-07-19

    KENNEDY SPACE CENTER, FLA. - Workers from the Johns Hopkins University Applied Physics Laboratory in Laurel, Md. get ready to “bag” the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft in the background at Astrotech Space Operations in Titusville, Fla. Placing a protective cover around the Mercury-bound MESSENGER precedes its placement in a transportation canister for the journey to Launch Pad 17-B at Cape Canaveral Air Force Station, Fla. Liftoff of MESSENGER aboard a Boeing Delta II Heavy rocket is scheduled for Aug. 2. The spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by APL.

  5. KSC-04pd1486

    NASA Image and Video Library

    2004-07-19

    KENNEDY SPACE CENTER, FLA. - After bagging the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft, Boeing workers at Astrotech Space Operations in Titusville, Fla., place the first part of a transportation canister around the Delta II upper stage booster. MESSENGER will be transferred to Launch Pad 17-B at Cape Canaveral Air Force Station, Fla. Liftoff of MESSENGER aboard a Boeing Delta II Heavy rocket is scheduled for Aug. 2. The spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  6. KSC-04pd1484

    NASA Image and Video Library

    2004-07-19

    KENNEDY SPACE CENTER, FLA. - Workers from the Johns Hopkins University Applied Physics Laboratory in Laurel, Md., begin placing a protective cover around the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft at Astrotech Space Operations in Titusville, Fla. Bagging the Mercury-bound MESSENGER precedes its placement in a transportation canister for the journey to Launch Pad 17-B at Cape Canaveral Air Force Station, Fla. Liftoff of MESSENGER aboard a Boeing Delta II Heavy rocket is scheduled for Aug. 2. The spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by APL.

  7. KSC-04pd1485

    NASA Image and Video Library

    2004-07-19

    KENNEDY SPACE CENTER, FLA. - Workers at Astrotech Space Operations in Titusville, Fla., place a protective cover around the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft at Astrotech Space Operations in Titusville, Fla. Bagging the Mercury-bound MESSENGER precedes its placement in a transportation canister for the journey to Launch Pad 17-B at Cape Canaveral Air Force Station, Fla. Liftoff of MESSENGER aboard a Boeing Delta II Heavy rocket is scheduled for Aug. 2. The spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  8. Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems.

    PubMed

    Watson, Andrew D

    2006-10-01

    Lipids are water-insoluble molecules that have a wide variety of functions within cells, including: 1) maintenance of electrochemical gradients; 2) subcellular partitioning; 3) first- and second-messenger cell signaling; 4) energy storage; and 5) protein trafficking and membrane anchoring. The physiological importance of lipids is illustrated by the numerous diseases to which lipid abnormalities contribute, including atherosclerosis, diabetes, obesity, and Alzheimer's disease. Lipidomics, a branch of metabolomics, is a systems-based study of all lipids, the molecules with which they interact, and their function within the cell. Recent advances in soft-ionization mass spectrometry, combined with established separation techniques, have allowed the rapid and sensitive detection of a variety of lipid species with minimal sample preparation. A "lipid profile" from a crude lipid extract is a mass spectrum of the composition and abundance of the lipids it contains, which can be used to monitor changes over time and in response to particular stimuli. Lipidomics, integrated with genomics, proteomics, and metabolomics, will contribute toward understanding how lipids function in a biological system and will provide a powerful tool for elucidating the mechanism of lipid-based disease, for biomarker screening, and for monitoring pharmacologic therapy.

  9. Dissecting blue light signal transduction pathway in leaf epidermis using a pharmacological approach.

    PubMed

    Živanović, Branka D; Shabala, Lana I; Elzenga, Theo J M; Shabala, Sergey N

    2015-10-01

    Blue light signalling pathway in broad bean leaf epidermal cells includes key membrane transporters: plasma- and endomembrane channels and pumps of H (+) , Ca (2+) and K (+) ions, and plasma membrane redox system. Blue light signalling pathway in epidermal tissue isolated from the abaxial side of fully developed Vicia faba leaves was dissected by measuring the effect of inhibitors of second messengers on net K(+), Ca(2+) and H(+) fluxes using non-invasive ion-selective microelectrodes (the MIFE system). Switching the blue light on-off caused transient changes of the ion fluxes. The effects of seven groups of inhibitors were tested in this study: CaM antagonists, ATPase inhibitors, Ca(2+) anatagonists or chelators, agents affecting IP3 formation, redox system inhibitors, inhibitors of endomembrane Ca(2+) transport systems and an inhibitor of plasma membrane Ca(2+)-permeable channels. Most of the inhibitors had a significant effect on steady-state (basal) net fluxes, as well as on the magnitude of the transient ion flux responses to blue light fluctuations. The data presented in this study suggest that redox signalling and, specifically, plasma membrane NADPH oxidase and coupled Ca(2+) and K(+) fluxes play an essential role in blue light signal transduction.

  10. Effect of salinity on regulation mechanism of neuroendocrine-immunoregulatory network in Litopenaeus vannamei.

    PubMed

    Zhao, Qun; Pan, Luqing; Ren, Qin; Wang, Lin; Miao, Jingjing

    2016-02-01

    The effects of low salinity (transferred from 31‰ to 26‰, 21‰, and 16‰) on the regulation pathways of neuroendocrine-immunoregulatory network were investigated in Litopenaeus vannamei. The results showed that the hormones (corticotrophin-releasing hormone, adrenocorticotropic hormone) and biogenic amines (dopamine, noradrenaline, 5-hydroxytryptamine) concentrations in lower salinity groups increased significantly within 12 h. The gene expression of biogenic amine receptors showed that dopamine receptor D4 and α2 adrenergic receptor in lower salinity groups decreased significantly within 12 h, whereas the 5-HT7 receptor significantly increased within 1d. The second messenger synthetases (adenylyl cyclase, phospholipase C) and the second messengers (cyclic adenosine monophosphate, cyclic guanosine monophosphate) of lower salinity groups shared a similar trend in which adenylyl cyclase and cyclic adenosine monophosphate reached the maximum at 12 h, whereas phospholipase C and cyclic guanosine monophosphate reached the minimum. The immune parameters (total hemocyte count, phenoloxidase activity, phagocytic activity, crustin expression, antibacterial activity, C-type lectin expression, hemagglutinating activity) in lower salinity groups decreased significantly within 12 h. Except for the total hemocyte count, all the parameters recovered to the control levels afterwards. Therefore, it may be concluded that the neuroendocrine-immunoregulatory network plays a principal role in adapting to salinity changes as the main center for sensing the stress and causes immune response in L. vannamei. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Mechanisms Mediating Vibration-induced Chronic Musculoskeletal Pain Analyzed in the Rat

    PubMed Central

    Dina, Olayinka A.; Joseph, Elizabeth K.; Levine, Jon D.; Green, Paul G.

    2009-01-01

    While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and re-exposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60–80 Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a pro-inflammatory cytokine or re-exposure to vibration. Exposure of a hind limb to vibration produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for ~2 weeks. When nociceptive thresholds had returned to baseline, exposure to a pro-inflammatory cytokine or re-exposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia induced by vibration was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cε, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-α (TNFα) receptor. Finally, in TNFα-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. Perspective These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFα and the second messenger PKCε as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. PMID:19962353

  12. Mechanisms mediating vibration-induced chronic musculoskeletal pain analyzed in the rat.

    PubMed

    Dina, Olayinka A; Joseph, Elizabeth K; Levine, Jon D; Green, Paul G

    2010-04-01

    While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and reexposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a proinflammatory cytokine or reexposure to vibration. Exposure of a hind limb to vibration-produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for approximately 2 weeks. When nociceptive thresholds had returned to baseline, exposure to a proinflammatory cytokine or reexposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cepsilon, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-alpha (TNFalpha) receptor. Finally, in TNFalpha-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFalpha and the second messenger protein kinase Cepsilon as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. Copyright 2010 American Pain Society. All rights reserved.

  13. 29 CFR 520.410 - How long does a messenger, learner, or apprentice certificate remain in effect?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... certificate remain in effect? 520.410 Section 520.410 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS EMPLOYMENT UNDER SPECIAL CERTIFICATE OF MESSENGERS... effect? (a) Messenger and/or learner certificates may be issued for a period of not longer than one year...

  14. Insights into the Nature of Mercury's Exosphere: Early Results from the MESSENGER Orbital Mission Phase

    NASA Technical Reports Server (NTRS)

    McClintock, William E.; Burger, Matthew H.; Killen, Rosemary M.; Merkel, Aimee W.; Sarantos, Menelaos; Sprague, Ann L.; Solomon, Sean C.; Vervack, Ronald J., Jr.

    2011-01-01

    The Ultraviolet and Visible Spectrometer aboard the MESSENGER spacecraft has been making routine observations of Mercury's exosphere since March 29, 2011. Correlations of the spatial distributions of Ca, Mg, and Na with MESSENGER magnetic field and energetic particle distribution data provide insight into the processes that populate the neutral exosphere

  15. Optical System Design and Integration of the Mercury Laser Altimeter

    NASA Technical Reports Server (NTRS)

    Ramos-Izquierdo, Luis; Scott, V. Stanley, III; Schmidt, Stephen; Britt, Jamie; Mamakos, William; Trunzo, Raymond; Cavanaugh, John; Miller, Roger

    2005-01-01

    The Mercury Laser Altimeter (MLA). developed for the 2004 MESSENGER mission to Mercury, is designed to measure the planet's topography via laser ranging. A description of the MLA optical system and its measured optical performance during instrument-level and spacecraft-level integration and testing are presented.

  16. 78 FR 59725 - Construction Fall Protection Systems Criteria and Practices, and Training Requirements; Extension...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-27

    ...- 1648. Mail, hand delivery, express mail, messenger, or courier service: When using this method, you... DEPARTMENT OF LABOR Occupational Safety and Health Administration [Docket No. OSHA-2010-0008] Construction Fall Protection Systems Criteria and Practices, and Training Requirements; Extension of the Office...

  17. Calcium pathway machinery at fertilization in echinoderms

    PubMed Central

    Ramos, Isabela; Wessel, Gary M.

    2016-01-01

    Calcium signaling in cells directs diverse physiological processes. The calcium waves triggered by fertilization is a highly conserved calcium signaling event essential for egg activation, and has been documented in every egg tested. This activity is one of the few highly conserved events of egg activation through the course of evolution. Echinoderm eggs, as well as many other cell types, have three main intracellular Ca2+ mobilizing messengers – IP3, cADPR and NAADP. Both cADPR and NAADP were identified as Ca2+ mobilizing messengers using the sea urchin egg homogenate, and this experimental system, along with the intact urchin and starfish oocyte/egg, continues to be a vital tool for investigating the mechanism of action of calcium signals. While many of the major regulatory steps of the IP3 pathway are well resolved, both cADPR and NAADP remain understudied in terms of our understanding of the fundamental process of egg activation at fertilization. Recently, NAADP has been shown to trigger Ca2+ release from acidic vesicles, separately from the ER, and a new class of calcium channels, the two-pore channels (TPCs), was identified as the likely targets for this messenger. Moreover, it was found that both cADPR and NAADP can be synthesized by the same family of enzymes, the ADP-rybosyl cyclases (ARCs). In this context of increasing amount of information, the potential coupling and functional roles of different messengers, intracellular stores and channels in the formation of the fertilization calcium wave in echinoderms will be critically evaluated. PMID:23218671

  18. Studying the surface of Mercury with BepiColombo

    NASA Astrophysics Data System (ADS)

    Helbert, J.; Benkhoff, J.

    2015-12-01

    The payload of the ESA-JAXA mission BepiColombo had been proposed long before the NASA MESSENGER mission provided us with new insights into the innermost of the terrestrial planets. The discoveries of the MESSENGER fundamentally changed our view of Mercury. It revealed a surface that has been reshaped by volcanism over large parts of geological history. Volatile elements like sulfur have been detected with unexpectedly high abundances of up to 4%. MESSENGER imagined structures that are most likely formed by pyroclastic eruptions in recent geologic history. Among the most exciting discoveries of MESSENGER are hollows - bright irregularly shaped depressions that show sign of ongoing loss of material. BepiColombo will be building on what has been learned from the MESSENGER mission and extend the knowledge. Due to its more circular orbit BepiColombo will provide good spatial resolution for both hemispheres of Mercury. The mission will give us the first good look at the southern hemisphere of the planet. All spectral instruments are imaging and cover a wider spectral range than the instruments on MESSENGER. Some instruments will provide us datasets that have not been obtained by MESSENGER in any form. MERTIS will for example provide the first temperature map of Mercury and will map the surface composition of the planet for the first time in the thermal infrared. The telescopic imaging channel of the XRS instrument will provide elemental composition at an unprecedented spatial resolution. The MESSENGER results will be key to formulate the observation plan for the surface instruments on BepiColombo. They also have motivated a wide range of laboratory experiments that will help to better understand the results returned by the suite of instruments.

  19. Using an Instant Messenger to Learn a Foreign Language in a Peer-Tutoring Environment

    ERIC Educational Resources Information Center

    Baek, Joeun; Yoo, Yungtai; Lee, Kyungsuk; Jung, Bokmoon; Baek, Youngkyun

    2017-01-01

    This study explores useful ways of using an instant messenger in a peer-tutoring environment when two students exchange their mother languages. Seven learners of Korean and seven Korean students learning English were paired randomly to conduct language exchange via an instant messenger, KakaoTalk. The pairs (five of male and female pair and two of…

  20. Ridges and Cliffs on Mercury Surface

    NASA Image and Video Library

    2008-01-20

    A complex history of geological evolution is recorded in this frame from the Narrow Angle Camera NAC, part of the Mercury Dual Imaging System MDIS instrument, taken during NASA MESSENGER close flyby of Mercury on January 14, 2008.

  1. Current Status of Messenger RNA Delivery Systems.

    PubMed

    Stanton, Matthew G

    2018-06-01

    Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results. The use of mRNA for prolonged and repeated expression of proteins and enzymes to treat rare, typically monogenic disease is nearing clinical entry. These uses of mRNA require delivery solutions, and the application of and improvement to existing nanoparticle nucleic acid delivery systems have jump started the pace of development and reenergized the field of particle based nucleic acid delivery. The current status of mRNA delivery is reviewed in this article with an eye toward clinical tractability.

  2. Carbon Solubility in Silicon-Iron-Bearing Metals during Core Formation on Mercury

    NASA Technical Reports Server (NTRS)

    Vander Kaaden, Kathleen E.; McCubbin, Francis M.; Ross, D. Kent; Rapp, Jennifer F.; Danielson, Lisa R.; Keller, Lindsay P.; Righter, Kevin

    2016-01-01

    Recent results obtained from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft showed the surface of Mercury has high S abundances (approximately 4 wt%) and low Iron(II) Oxide abundances (less than 2 wt%). Based on these extreme values, the oxygen fugacity of Mercury's surface materials was estimated to be approximately 3 to 7 log(sub 10) units below the IW buffer (Delta IW-3 to Delta IW-7). This highly reducing nature of the planet has resulted in a large core and relatively thin mantle, extending to only approximately 420 km depth (corresponding to a core-mantle boundary pressure of approximately 4-7 GPa) within the planet. Furthermore, MESSENGER results have suggested the presence of carbon on the surface of the planet. Previous experimental results from have also suggested the possibility of a primary floatation crust on Mercury composed of graphite, produced after a global magma ocean event. With these exotic conditions of this compositional end-member planet, it begs the question, what is the core composition of Mercury? Although no definitive conclusion has been reached, previous studies have made advances towards answering this question. Riner et al. and Chen et al. looked at iron sulfide systems and implemented various crystallization and layered core scenarios to try and determine the composition and structure of Mercury's core. Malavergne et al. examined core crystallization scenarios in the presence of sulfur and silicon. Hauck et al. used the most recent geophysical constraints from the MESSENGER spacecraft to model the internal structure of Mercury, including the core, in a iron-sulfur-silicon system. More recently, Chabot et al. conducted a series of metal-silicate partitioning experiments in a iron-sulfur-silicon system. These results showed the core of Mercury has the potential to contain more than 15 wt% silicon. However, with the newest results from MESSENGER's low altitude campaign, carbon is another potential light element that could be incorporated into Mercury's core. The goal of this study is to determine the carbon concentration at graphite saturation in various silicon-iron bearing metals relevant to possible mercurian core compositions. Future experiments will include the addition of sulfur into these metals.

  3. Smooth Plains in Mercury's North

    NASA Image and Video Library

    2017-12-08

    NASA acquired: March 29, 2011 As the MESSENGER spacecraft passed low over Mercury's north polar region, MDIS used its pivot to capture this image, showing terrain that had not been previously seen by spacecraft. The newly imaged surface is located in Mercury's north polar region, to the north of the bright, rayed crater Hokusai. Looking from the bottom of the image toward the top is looking southward, just as MDIS was doing when this image was acquired. This newly seen terrain shows craters with long shadows, as expected at this high northern latitude. Understanding the interiors of the craters in Mercury's polar regions and any ices they may contain is one of the main science goals of the MESSENGER mission. The long shadows also accentuate the topography of the surface, which includes a number of ridges that resemble those seen on the expansive smooth plains imaged during Mercury flyby 3. On March 17, 2011 (March 18, 2011, UTC), MESSENGER became the first spacecraft ever to orbit the planet Mercury. The mission is currently in its commissioning phase, during which spacecraft and instrument performance are verified through a series of specially designed checkout activities. In the course of the one-year primary mission, the spacecraft's seven scientific instruments and radio science investigation will unravel the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the science questions that the MESSENGER mission has set out to answer. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Join us on Facebook

  4. The MESSENGER Earth Flyby: Results from the Mercury Dual Imaging System

    NASA Astrophysics Data System (ADS)

    Prockter, L. M.; Murchie, S. L.; Hawkins, S. E.; Robinson, M. S.; Shelton, R. G.; Vaughan, R. M.; Solomon, S. C.

    2005-12-01

    The MESSENGER (MErcury Surface, Space ENvironment, Geochemistry, and Ranging) spacecraft was launched from Cape Canaveral Air Force Station, Fla., on 3 August 2004. It returned to Earth for a gravity assist on 2 August 2005, providing an exceptional opportunity for the Science Team to perform instrument calibrations and to test some of the data acquisition sequences that will be used to meet Mercury science goals. The Mercury Dual Imaging System (MDIS), one of seven science instruments on MESSENGER, consists of a wide-angle and a narrow-angle imager that together can map landforms, track variations in surface color, and carry out stereogrammetry. The two imagers are mounted on a pivot platform that enables the instrument to point in a different direction from the spacecraft boresight, allowing great flexibility and increased imaging coverage. During the week prior to the closest approach to Earth, MDIS acquired a number of images of the Moon for radiometric calibration and to test optical navigation sequences that will be used to target planetary flybys. Twenty-four hours before closest approach, images of the Earth were acquired with 11 filters of the wide-angle camera. After MDIS flew over the nightside of the Earth, additional color images centered on South America were obtained at sufficiently high resolution to discriminate small-scale features such as the Amazon River and Lake Titicaca. During its departure from Earth, MDIS acquired a sequence of images taken in three filters every 4 minutes over a period of 24 hours. These images have been assembled into a movie of a crescent Earth that begins as South America slides across the terminator into darkness and continues for one full Earth rotation. This movie and the other images have provided a successful test of the sequences that will be used during the MESSENGER Mercury flybys in 2008 and 2009 and have demonstrated the high quality of the MDIS wide-angle camera.

  5. Gaseotransmitters: New Frontiers for Translational Science

    PubMed Central

    Szabo, Csaba

    2011-01-01

    Research into the biology of the endogenous gaseous mediators nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) has significantly expanded over the last decade. A number of drugs (already in clinical use) and drug candidates (in preclinical or clinical trials) exert their effects via donation of these mediators and/or via modulation of their intracellular second messenger pathways. Due to their important biological roles, gaseotransmitters offer many therapeutic opportunities. However, their unique chemical and pharmacological properties can also represent unusual challenges for translational science. PMID:21106939

  6. Hunt for infrared photons from the first binary neutron star merger

    NASA Astrophysics Data System (ADS)

    Kasliwal, Mansi; Growth Collaboration [Global Relay Of Observatories Watching Transients

    2017-10-01

    Yesterday, within two seconds of 2017 August 17 12:41:04 GMT, both LIGO interferometers and the Fermi satellite detected gravitational waves from a neutron star merger and a short contemporaneous gamma ray burst! We now have a promising optical and infrared counterpart. This may very well be a historic moment in multi-messenger astronomy, and may even prove to be of the same league as neutrinos from SN,1987A. Here, we request the Spitzer Space Telescope to engage in the hunt for infrared photons.

  7. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nomura, S.; Enna, S.J.

    Tricyclic antidepressants (TCAs) have anticholinergic and ..cap alpha..-adrenergic blocking properties. The present study was undertaken to examine the effects of amitriptyline, imipramine, and desipramine on inositol phosphate accumulation, a brain second messenger system associated with cholinergic and adrenergic receptors. Whereas the TCAs were 28 to 400-fold weaker than atropine as inhibitors of /sup 3/H-QNB binding to brain cholinergic receptors, they were 600 to 2000-fold less active than atropine as inhibitors of carbachol-stimulated IP accumulation in brain. In contrast, the relative potencies of the TCAs and prazosin to inhibit norepinephrine-stimulated IP accumulation and /sup 3/H-prazosin binding appeared to be similar inmore » the two assays. The results suggest pharmacological differences between the cholinergic receptors labeled in the ONB binding assay and those mediating the IP response, whereas the ..cap alpha../sub 1/-adrenergic receptors appear to be similar in the two systems. Since atropine is considered a nonselective muscarinic antagonist, it is possible that the TCAs may differentiate between cholinergic receptor subtypes, which may be an important component of their clinical response.« less

  8. Taxonomic applicability of inflammatory cytokines in adverse outcome pathway (AOP) development

    EPA Science Inventory

    Cytokines, low-molecular-weight messenger proteins that act as intercellular immunomodulatory signals, have become a mainstream preclinical marker for assessing the systemic inflammatory response to external stressors. The challenge is to quantitate from healthy subjects cytokine...

  9. Sweet Spot Supersymmetry and Composite Messengers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ibe, Masahiro; Kitano, Ryuichiro

    2007-10-30

    Sweet spot supersymmetry is a phenomenologically and cosmologically perfect framework to realize a supersymmetric world at short distance. We discuss a class of dynamical models of supersymmetry breaking and its mediation whose low-energy effective description falls into this framework. Hadron fields in the dynamical models play a role of the messengers of the supersymmetry breaking. As is always true in the models of the sweet spot supersymmetry, the messenger scale is predicted to be 10{sup 5} GeV {approx}< M{sub mess} {approx}< 10{sup 10} GeV. Various values of the effective number of messenger fields N{sub mess} are possible depending on themore » choice of the gauge group.« less

  10. Mercury MESSENGER Stamp Unveiling

    NASA Image and Video Library

    2011-05-03

    United States Postal Service Vice President of Finance Steve Masse, left, and NASA Mercury Astronaut Scott Carpenter, unveil two USPS stamps to commemorate and celebrate 50 years of US Spaceflight and the MESSENGER program during an event, Wednesday, May 4, 2011 at the NASA Kennedy Space Center in Cape Canaveral, Fla. One stamp commemorates NASA’s Project Mercury, America’s first manned spaceflight program, and NASA astronaut Alan Shepard’s historic flight on May 5, 1961, aboard spacecraft Freedom 7. The other stamp draws attention to NASA’s unmanned MESSENGER mission, a scientific investigation of the planet Mercury. On March 17, 2011, MESSENGER became the first spacecraft to enter into orbit around Mercury. Photo Credit: (NASA/Bill Ingalls)

  11. Mercury MESSENGER Stamp Unveiling

    NASA Image and Video Library

    2011-05-03

    Daughters of NASA astronaut Alan Shepard, Laura Shepard Churchley, left, Alice Wackermann and Julie Jenkins, right, speak during an unveiling ceremony of two USPS stamps that commemorate and celebrate 50 years of US Spaceflight and the MESSENGER program during an event, Wednesday, May 4, 2011 at the NASA Kennedy Space Center in Cape Canaveral, Fla. One stamp commemorates NASA’s Project Mercury, America’s first manned spaceflight program, and NASA astronaut Alan Shepard’s historic flight on May 5, 1961, aboard spacecraft Freedom 7. The other stamp draws attention to NASA’s unmanned MESSENGER mission, a scientific investigation of the planet Mercury. On March 17, 2011, MESSENGER became the first spacecraft to enter into orbit around Mercury. Photo Credit: (NASA/Bill Ingalls)

  12. Cosmic Microwave Background Mapmaking with a Messenger Field

    NASA Astrophysics Data System (ADS)

    Huffenberger, Kevin M.; Næss, Sigurd K.

    2018-01-01

    We apply a messenger field method to solve the linear minimum-variance mapmaking equation in the context of Cosmic Microwave Background (CMB) observations. In simulations, the method produces sky maps that converge significantly faster than those from a conjugate gradient descent algorithm with a diagonal preconditioner, even though the computational cost per iteration is similar. The messenger method recovers large scales in the map better than conjugate gradient descent, and yields a lower overall χ2. In the single, pencil beam approximation, each iteration of the messenger mapmaking procedure produces an unbiased map, and the iterations become more optimal as they proceed. A variant of the method can handle differential data or perform deconvolution mapmaking. The messenger method requires no preconditioner, but a high-quality solution needs a cooling parameter to control the convergence. We study the convergence properties of this new method and discuss how the algorithm is feasible for the large data sets of current and future CMB experiments.

  13. Intercellular and intracellular signalling systems that globally control the expression of virulence genes in plant pathogenic bacteria.

    PubMed

    Ham, Jong Hyun

    2013-04-01

    Plant pathogenic bacteria utilize complex signalling systems to control the expression of virulence genes at the cellular level and within populations. Quorum sensing (QS), an important intercellular communication mechanism, is mediated by different types of small molecules, including N-acyl homoserine lactones (AHLs), fatty acids and small proteins. AHL-mediated signalling systems dependent on the LuxI and LuxR family proteins play critical roles in the virulence of a wide range of Gram-negative plant pathogenic bacteria belonging to the Alphaproteobacteria, Betaproteobacteria and Gammaproteobacteria. Xanthomonas spp. and Xylella fastidiosa, members of the Gammaproteobacteria, however, possess QS systems that are mediated by fatty acid-type diffusible signal factors (DSFs). Recent studies have demonstrated that Ax21, a 194-amino-acid protein in Xanthomonas oryzae pv. oryzae, plays dual functions in activating a rice innate immune pathway through binding to the rice XA21 pattern recognition receptor and in regulating bacterial virulence and biofilm formation as a QS signal molecule. In xanthomonads, DSF-mediated QS systems are connected with the signalling pathways mediated by cyclic diguanosine monophosphate (c-di-GMP), which functions as a second messenger for the control of virulence gene expression in these bacterial pathogens. © 2012 BSPP AND BLACKWELL PUBLISHING LTD.

  14. Sigma receptors: biology and therapeutic potential.

    PubMed

    Guitart, Xavier; Codony, Xavier; Monroy, Xavier

    2004-07-01

    More than 20 years after the identification of the sigma receptors as a unique binding site in the brain and in the peripheral organs, several questions regarding this receptor are still open. Only one of the subtypes of the receptor has been cloned to date, but the endogenous ligand still remains unknown, and the possible association of the receptor with a conventional second messenger system is controversial. From the very beginning, the sigma receptors were associated with various central nervous system disorders such as schizophrenia or movement disorders. Today, after hundreds of papers dealing with the importance of sigma receptors in brain function, it is widely accepted that sigma receptors represent a new and different avenue in the possible pharmacological treatment of several brain-related disorders. In this review, what is known about the biology of the sigma receptor regarding its putative structure and its distribution in the central nervous system is summarized first. The role of sigma receptors regulating cellular functions and other neurotransmitter systems is also addressed, as well as a short overview of the possible endogenous ligands. Finally, although no specific sigma ligand has reached the market, different pharmacological approaches to the alleviation and treatment of several central nervous system disorders and deficits, including schizophrenia, pain, memory deficits, etc., are discussed, with an overview of different compounds and their potential therapeutic use.

  15. Bioinformatics prediction and experimental validation of microRNA-20a targeting Cyclin D1 in hepatocellular carcinoma.

    PubMed

    Karimkhanloo, Hamzeh; Mohammadi-Yeganeh, Samira; Ahsani, Zeinab; Paryan, Mahdi

    2017-04-01

    Hepatocellular carcinoma is the major form of primary liver cancer, which is the second and sixth leading cause of cancer-related death in men and women, respectively. Extensive research indicates that Wnt/β-catenin signaling pathway, which plays a pivotal role in growth, development, and differentiation of hepatocellular carcinoma, is one of the major signaling pathways that is dysregulated in hepatocellular carcinoma. Cyclin D1 is a proto-oncogene and is one of the major regulators of Wnt signaling pathway, and its overexpression has been detected in various types of cancers including hepatocellular carcinoma. Using several validated bioinformatic databases, we predicted that the microRNAs are capable of targeting 3'-untranslated region of Cyclin D1 messenger RNA. According to the results, miR-20a was selected as the highest ranking microRNA targeting Cyclin D1 messenger RNA. Luciferase assay was recruited to confirm bioinformatic prediction results. Cyclin D1 expression was first assessed by quantitative real-time polymerase chain reaction in HepG2 cell line. Afterward, HepG2 cells were transduced by lentiviruses containing miR-20a. Then, the expression of miR-20a and Cyclin D1 was evaluated. The results of luciferase assay demonstrated targeting of 3'-untranslated region of Cyclin D1 messenger RNA by miR-20a. Furthermore, 238-fold decline in Cyclin D1 expression was observed after lentiviral induction of miR-20a in HepG2 cells. The results highlighted a considerable effect of miRNA-20a induction on the down-regulation of Cyclin D1 gene. Our results suggest that miR-20a can be used as a novel candidate for therapeutic purposes and a biomarker for hepatocellular carcinoma diagnosis.

  16. Control of protein synthesis in Escherichia coli: strain differences in control of translational initiation after energy source shift-down.

    PubMed Central

    Jacobson, L A; Jen-Jacobson, L

    1980-01-01

    We have studied the parameters of protein synthesis in a number of Escherichia coli strains after a shift-down from glucose-minimal to succinate-minimal medium. One group of strains, including K-12(lambda) (ATCC 10798) and NF162, showed a postshift translational yield of 50 to 65% and a 2- to 2.5-fold increase in the functional lifetime of general messenger ribonucleic acid. There was no change in the lag time for beta-galactosidase induction in these strains after the shift-down. A second group, including W1 and W2, showed no reduction in translational yield, no change in the functional lifetime of messenger ribonucleic acid, and a 50% increase in the lag time for beta-galactosidase induction. Evidence is presented which indicates that this increased lag time is not the result of a decreased rate of polypeptide chain propagation. A third group of strains, including NF161, CP78, and NF859, showed an intermediate pattern: translational yield was reduced to about 75% of normal, and the messenger ribonucleic acid functional lifetime was increased by about 50%. Calculation of the relative postshift rates of translational initiation gave about 0.2, 1.0, and 0.5, respectively, for the three groups. There was no apparent correlation between the ability to control translation and the genotypes of these strains at the relA, relX, or spoT loci. Measurements of the induction lag for beta-galactosidase during short-term glucose starvation or after a down-shift induced by alpha-methylglucoside indicated that these regimens elicit responses that are physiologically distinct from those elicited by a glucose-to-succinate shift-down. PMID:6155375

  17. Control of protein synthesis in Escherichia coli: strain differences in control of translational initiation after energy source shift-down.

    PubMed

    Jacobson, L A; Jen-Jacobson, L

    1980-06-01

    We have studied the parameters of protein synthesis in a number of Escherichia coli strains after a shift-down from glucose-minimal to succinate-minimal medium. One group of strains, including K-12(lambda) (ATCC 10798) and NF162, showed a postshift translational yield of 50 to 65% and a 2- to 2.5-fold increase in the functional lifetime of general messenger ribonucleic acid. There was no change in the lag time for beta-galactosidase induction in these strains after the shift-down. A second group, including W1 and W2, showed no reduction in translational yield, no change in the functional lifetime of messenger ribonucleic acid, and a 50% increase in the lag time for beta-galactosidase induction. Evidence is presented which indicates that this increased lag time is not the result of a decreased rate of polypeptide chain propagation. A third group of strains, including NF161, CP78, and NF859, showed an intermediate pattern: translational yield was reduced to about 75% of normal, and the messenger ribonucleic acid functional lifetime was increased by about 50%. Calculation of the relative postshift rates of translational initiation gave about 0.2, 1.0, and 0.5, respectively, for the three groups. There was no apparent correlation between the ability to control translation and the genotypes of these strains at the relA, relX, or spoT loci. Measurements of the induction lag for beta-galactosidase during short-term glucose starvation or after a down-shift induced by alpha-methylglucoside indicated that these regimens elicit responses that are physiologically distinct from those elicited by a glucose-to-succinate shift-down.

  18. The Architect and His Temple

    NASA Image and Video Library

    2015-04-16

    One of the most captivating views acquired during NASA MESSENGER first Mercury flyby was of the crater Apollodorus surrounded by the radiating troughs of Pantheon Fossae. The team nicknamed the combined feature as "the spider." Since then, MESSENGER has acquired many other striking views of this unique feature located near the center of Caloris basin. Although Apollodorus of Damascus (the namesake of the crater) is thought to be the architect of the Pantheon in Rome (the namesake of the fossae), the crater Apollodorus is thought to be unrelated to the creation of Pantheon Fossae. Instrument: Mercury Dual Imaging System (MDIS) Center Latitude: 39.1° Center Longitude: 164.3° E Scale: Apollodorus has a diameter of 42 kilometers (26 miles) http://photojournal.jpl.nasa.gov/catalog/PIA19410

  19. Modeling MESSENGER Observations of Calcium in Mercury's Exosphere

    NASA Technical Reports Server (NTRS)

    Burger, Matthew Howard; Killen, Rosemary M.; McClintock, William E.; Vervack, Ronald J., Jr.; Merkel, Aimee W.; Sprague, Ann L.; Sarantos, Menelaos

    2012-01-01

    The Mercury Atmospheric and Surface Composition Spectrometer (MASCS) on the MESSENGER spacecraft has made the first high-spatial-resolution observations of exospheric calcium at Mercury. We use a Monte Carlo model of the exosphere to track the trajectories of calcium atoms ejected from the surface until they are photoionized, escape from the system, or stick to the surface. This model permits an exploration of exospheric source processes and interactions among neutral atoms, solar radiation, and the planetary surface. The MASCS data have suggested that a persistent, high-energy source of calcium that was enhanced in the dawn, equatorial region of Mercury was active during MESSENGER's three flybys of Mercury and during the first seven orbits for which MASCS obtained data. The total Ca source rate from the surface varied between 1.2x10(exp 23) and 2.6x10(exp 23) Ca atoms/s, if its temperature was 50,000 K. The origin of this high-energy, asymmetric source is unknown, although from this limited data set it does not appear to be consistent with micrometeoroid impact vaporization, ion sputtering, electron-stimulated desorption, or vaporization at dawn of material trapped on the cold nightside.

  20. Calcium signaling in plant cells in altered gravity

    NASA Astrophysics Data System (ADS)

    Kordyum, E. L.

    2003-10-01

    Changes in the intracellular Ca 2+ concentration in altered gravity (microgravity and clinostating) evidence that Ca 2+ signaling can play a fundamental role in biological effects of microgravity. Calcium as a second messenger is known to play a crucial role in stimulus - response coupling for many plant cellular signaling pathways. Its messenger functions are realized by transient changes in the cytosolic ion concentration induced by a variety of internal and external stimuli such as light, hormones, temperature, anoxia, salinity, and gravity. Although the first data on the changes in the calcium balance in plant cells under the influence of altered gravity have appeared in 80 th, a review highlighting the performed research and the possible significance of such Ca 2+ changes in the structural and metabolic rearrangements of plant cells in altered gravity is still lacking. In this paper, an attempt was made to summarize the available experimental results and to consider some hypotheses in this field of research. It is proposed to distinguish between cell gravisensing and cell graviperception; the former is related to cell structure and metabolism stability in the gravitational field and their changes in microgravity (cells not specialized to gravity perception), the latter is related to active use of a gravitational stimulus by cells presumebly specialized to gravity perception for realization of normal space orientation, growth, and vital activity (gravitropism, gravitaxis) in plants. The main experimental data concerning both redistribution of free Ca 2+ ions in plant cell organelles and the cell wall, and an increase in the intracellular Ca 2+ concentration under the influence of altered gravity are presented. Based on the gravitational decompensation hypothesis, the consequence of events occurring in gravisensing cells not specialized to gravity perception under altered gravity are considered in the following order: changes in the cytoplasmic membrane surface tension → alterations in the physicochemical properties of the membrane → changes in membrane permeability, ion transport, membrane-bound enzyme activity, etc. → metabolism rearrangements → physiological responses. An analysis of data available on biological effects of altered gravity at the cellular level allows one to conclude that microgravity environment appears to affect cytoskeleton, carbohydrate and lipid metabolism, cell wall biogenesis via changes in enzyme activity and protein expression, with involvement of regulatory Ca 2+ messenger system. Changes in Ca 2+ influx/efflux and possible pathways of Ca 2+ signaling in plant cell biochemical regulation in altered gravity are discussed.

  1. Calcium signaling in plant cells in microgravity

    NASA Astrophysics Data System (ADS)

    Kordyum, E.

    Changes in the intracellular Ca 2 + concentration in altered gravity (microgravity and clinostating) evidence that Ca2 + signaling can play a fundamental role in biological effects of microgravity. Calcium as a second messenger is known to play a crucial role in stimulus - response coupling for many plant cellular signaling pathways. Its messenger functions are realized by transient changes in the cytosolic ion concentration induced by a variety of internal and external stimuli such as light, hormones, temperature, anoxia, salinity, and gravity. Although the first data on the changes in the calcium balance in plant cells under the influence of altered gravity have appeared in eighties, a review highlighting the performed research and the possible significance of such Ca 2 + changes in the structural and metabolic rearrangements of plant cells in altered gravity is still lacking. In this paper, an attempt was made to summarize the available experimental results and to consider some hypotheses in this field of research. It is proposed to distinguish between cell gravisensing and cell graviperception; the former is related to cell structure and metabolism stability in the gravitational field and their changes in microgravity (cells not specialized to gravity perception), the latter is related to active use of a gravitational stimulus by cells presumably specialized to gravity perception for realization of normal space orientation, growth, and vital activity (gravitropism, gravitaxis) in plants. The main experimental data concerning both redistribution of free Ca 2 + ions in plant cell organelles and the cell wall, and an increase in the intracellular Ca 2+ concentration under the influence of altered gravity are presented. Based on the gravitational decompensation hypothesis, the consequence of events occurring in gravis ensing cells not specialized to gravity perception under altered gravity are considered in the following order: changes in the cytoplasmic membrane surface tensionalterations in the physicochemical properties of the membranechanges in membrane permeability, ion transport, membrane-bound enzyme activity, etc.metabolism rearrangementsphysiological responses. An analysis of data available on biological effects of altered gravity at the cellular level allows one to conclude that microgravity environment appears to affect, in the first place, cytoskeleton, carbohydrate and lipid metabolism, cell wall biogenesis via changes in enzyme activity and protein expression, with involvement of regulatory Ca 2 + messenger system. Changes in Ca 2 + influx/efflux and possible pathways of Ca 2 + signaling in plant cell biochemical regulation in altered gravity are discussed.

  2. Opening a Window on ICME Evolution and GCR Modulation During Propagation in the Innermost Heliosphere

    NASA Astrophysics Data System (ADS)

    Winslow, R. M.; Lugaz, N.; Schwadron, N.; Farrugia, C. J.; Guo, J.; Wimmer-Schweingruber, R. F.; Wilson, J. K.; Joyce, C.; Jordan, A.; Lawrence, D. J.

    2017-12-01

    We use multipoint spacecraft observations to study interplanetary coronal mass ejection (ICME) evolution and subsequent galactic cosmic ray (GCR) modulation during propagation in the inner heliosphere. We illustrate ICME propagation effects through two different case studies. The first ICME was launched from the Sun on 29 December 2011 and was observed in near-perfect longitudinal conjunction at MESSENGER and STEREO A. Despite the close longitudinal alignment, we infer from force-free field modeling that the orientation of the underlying flux rope rotated ˜80o in latitude and ˜65o in longitude. Based on both spacecraft measurements as well as ENLIL model simulations of the steady state solar wind, we find that interactions involving magnetic reconnection with corotating structures in the solar wind dramatically alter the ICME magnetic field. In particular, we observed at STEREO A a highly turbulent region with distinct properties within the flux rope that was not observed at MESSENGER; we attribute this region to interaction between the ICME and a heliospheric plasma sheet/current sheet. This is a concrete example of a sequence of events that can increase the complexity of ICMEs during propagation and should serve as a caution on using very distant observations to predict the geoeffectiveness of large interplanetary transients. Our second case study investigates changes with heliospheric distance in GCR modulation by an ICME event (launched on 12 February 2014) observed in near-conjunction at all four of the inner solar system planets. The ICME caused Forbush decreases (FDs) in the GCR count rates at Mercury (MESSENGER), Earth/Moon (ACE/LRO), and Mars (MSL). At all three locations, the pre-ICME background GCR rate was well-matched, but the depth of the FD of GCR fluxes with similar energy ranges diminished with distance from the Sun. A larger difference in FD size was observed between Mercury and Earth than between Earth and Mars, partly owing to the much larger drop in the ICME magnetic field magnitude between Mercury and Earth, and to the faster ICME speed decrease closer to the Sun. The results from these case studies give both a direct and indirect view of how ICMEs evolve during propagation as well as a glimpse of the inner heliosphere environment about to be explored by the Parker Solar Probe and Solar Orbiter.

  3. Evaluation of a Salmonella Strain Lacking the Secondary Messenger C-di-GMP and RpoS as a Live Oral Vaccine

    PubMed Central

    García, Begoña; Gil, Carmen; García-Ona, Enrique; Burgui, Saioa; Casares, Noelia; Hervás-Stubbs, Sandra; Lasarte, Juan José; Lasa, Iñigo

    2016-01-01

    Salmonellosis is one of the most important bacterial zoonotic diseases transmitted through the consumption of contaminated food, with chicken and pig related products being key reservoirs of infection. Although numerous studies on animal vaccination have been performed in order to reduce Salmonella prevalence, there is still a need for an ideal vaccine. Here, with the aim of constructing a novel live attenuated Salmonella vaccine candidate, we firstly analyzed the impact of the absence of cyclic-di-GMP (c-di-GMP) in Salmonella virulence. C-di-GMP is an intracellular second messenger that controls a wide range of bacterial processes, including biofilm formation and synthesis of virulence factors, and also modulates the host innate immune response. Our results showed that a Salmonella multiple mutant in the twelve genes encoding diguanylate cyclase proteins that, as a consequence, cannot synthesize c-di-GMP, presents a moderate attenuation in a systemic murine infection model. An additional mutation of the rpoS gene resulted in a synergic attenuating effect that led to a highly attenuated strain, referred to as ΔXIII, immunogenic enough to protect mice against a lethal oral challenge of a S. Typhimurium virulent strain. ΔXIII immunogenicity relied on activation of both antibody and cell mediated immune responses characterized by the production of opsonizing antibodies and the induction of significant levels of IFN-γ, TNF-α, IL-2, IL-17 and IL-10. ΔXIII was unable to form a biofilm and did not survive under desiccation conditions, indicating that it could be easily eliminated from the environment. Moreover, ΔXIII shows DIVA features that allow differentiation of infected and vaccinated animals. Altogether, these results show ΔXIII as a safe and effective live DIVA vaccine. PMID:27537839

  4. Early MESSENGER Results for Less Abundant or Weakly Emitting Species in Mercury's Exosphere

    NASA Technical Reports Server (NTRS)

    Vervack, Ronald J., Jr.; McClintock, William E.; Killen, Rosemary M.; Sprague, Ann L.; Burger, Matthew H.; Merkel, Aimee W.; Sarantos, Menelaos

    2011-01-01

    Now that the Messenger spacecraft is in orbit about Mercury, the extended observing time enables searches for exospheric species that are less abundant or weakly emitting compared with those for which emission has previously been detected. Many of these species cannot be observed from the ground because of terrestrial atmospheric absorption. We report here on the status of MESSENGER orbital-phase searches for additional species in Mercury's exosphere.

  5. Mercury MESSENGER Stamp Unveiling

    NASA Image and Video Library

    2011-05-03

    Daughters of NASA astronaut Alan Shepard, Laura Shepard Churchley, standing left, Alice Wackermann and Julie Jenkins, standing right, speak during an unveiling ceremony of two USPS stamps that commemorate and celebrate 50 years of US Spaceflight and the MESSENGER program during an event, Wednesday, May 4, 2011 at the NASA Kennedy Space Center in Cape Canaveral, Fla. One stamp commemorates NASA’s Project Mercury, America’s first manned spaceflight program, and NASA astronaut Alan Shepard’s historic flight on May 5, 1961, aboard spacecraft Freedom 7. The other stamp draws attention to NASA’s unmanned MESSENGER mission, a scientific investigation of the planet Mercury. On March 17, 2011, MESSENGER became the first spacecraft to enter into orbit around Mercury. Photo Credit: (NASA/Bill Ingalls)

  6. Morphological differentiation of N1E-115 neuroblastoma cells by dimethyl sulfoxide activation of lipid second messengers.

    PubMed

    Clejan, S; Dotson, R S; Wolf, E W; Corb, M P; Ide, C F

    1996-04-10

    Quantitative changes in the lipid second messenger diacylglycerol (DAG) were studied in the rat neuroblastoma N1E-115 following exposure to the differentiating agent dimethylsulfoxide (DMSO). Relatively high basal levels of DAG are present in these cells, and addition of 2% DMSO elicited a biphasic increase in DAG levels, dependent on the presence of extracellular Ca2+. Exposure to DMSO also elicited a rapid increase in inositol phosphate and a slight increase in phosphatidic acid (PA), trailing that of DAG. The molecular species (MS) of DAG were analyzed. Within 60 s of DMSO application there were transient increases of DAG representative of phosphatidylinositol (PI) hydrolysis. At longer intervals, more DAG originated from phosphatidylcholine. The MS composition of newly formed PA resembled that of PI and native DAG. Inhibition studies indicated that DAG is formed in the DMSO-treated cells by phospholipases C and that PA formed later is a result of DAG phosphorylation and not activity of phospholipase D (PLD). Undifferentiated cells exhibited an active PLD pathway. In contrast, PLD in DMSO-differentiated cells was not active. In examining the involvement of the sphingomyelin pathway, DMSO exposure was found to increase ceramide levels with a concomitant decrease in sphingomyelin. Addition of the exogenous, soluble analog C6-ceramide to undifferentiated cells resulted in dramatic reductions in DAG and PA levels and PLD activity. These results indicate that DMSO treatment inactivates PLD while activating phospholipases C and the sphingomyelin pathway, suggesting a "switch" between signal transduction pathways in the undifferentiated and differentiated states of N1E-115.

  7. Regulated traffic of anion transporters in mammalian Brunner's glands: a role for water and fluid transport.

    PubMed

    Collaco, Anne M; Jakab, Robert L; Hoekstra, Nadia E; Mitchell, Kisha A; Brooks, Amos; Ameen, Nadia A

    2013-08-01

    The Brunner's glands of the proximal duodenum exert barrier functions through secretion of glycoproteins and antimicrobial peptides. However, ion transporter localization, function, and regulation in the glands are less clear. Mapping the subcellular distribution of transporters is an important step toward elucidating trafficking mechanisms of fluid transport in the gland. The present study examined 1) changes in the distribution of intestinal anion transporters and the aquaporin 5 (AQP5) water channel in rat Brunner's glands following second messenger activation and 2) anion transporter distribution in Brunner's glands from healthy and disease-affected human tissues. Cystic fibrosis transmembrane conductance regulator (CFTR), AQP5, sodium-potassium-coupled chloride cotransporter 1 (NKCC1), sodium-bicarbonate cotransporter (NBCe1), and the proton pump vacuolar ATPase (V-ATPase) were localized to distinct membrane domains and in endosomes at steady state. Carbachol and cAMP redistributed CFTR to the apical membrane. cAMP-dependent recruitment of CFTR to the apical membrane was accompanied by recruitment of AQP5 that was reversed by a PKA inhibitor. cAMP also induced apical trafficking of V-ATPase and redistribution of NKCC1 and NBCe1 to the basolateral membranes. The steady-state distribution of AQP5, CFTR, NBCe1, NKCC1, and V-ATPase in human Brunner's glands from healthy controls, cystic fibrosis, and celiac disease resembled that of rat; however, the distribution profiles were markedly attenuated in the disease-affected duodenum. These data support functional transport of chloride, bicarbonate, water, and protons by second messenger-regulated traffic in mammalian Brunner's glands under physiological and pathophysiological conditions.

  8. Integration of the Second Messenger c-di-GMP into the Chemotactic Signaling Pathway

    PubMed Central

    Russell, Matthew H.; Bible, Amber N.; Fang, Xin; Gooding, Jessica R.; Campagna, Shawn R.; Gomelsky, Mark; Alexandre, Gladys

    2013-01-01

    ABSTRACT Elevated intracellular levels of the bacterial second messenger c-di-GMP are known to suppress motility and promote sessility. Bacterial chemotaxis guides motile cells in gradients of attractants and repellents over broad concentration ranges, thus allowing bacteria to quickly adapt to changes in their surroundings. Here, we describe a chemotaxis receptor that enhances, as opposed to suppresses, motility in response to temporary increases in intracellular c-di-GMP. Azospirillum brasilense’s preferred metabolism is adapted to microaerophily, and these motile cells quickly navigate to zones of low oxygen concentration by aerotaxis. We observed that changes in oxygen concentration result in rapid changes in intracellular c-di-GMP levels. The aerotaxis and chemotaxis receptor, Tlp1, binds c-di-GMP via its C-terminal PilZ domain and promotes persistent motility by increasing swimming velocity and decreasing swimming reversal frequency, which helps A. brasilense reach low-oxygen zones. If c-di-GMP levels remain high for extended periods, A. brasilense forms nonmotile clumps or biofilms on abiotic surfaces. These results suggest that association of increased c-di-GMP levels with sessility is correct on a long-term scale, while in the short-term c-di-GMP may actually promote, as opposed to suppress, motility. Our data suggest that sensing c-di-GMP by Tlp1 functions similar to methylation-based adaptation. Numerous chemotaxis receptors contain C-terminal PilZ domains or other sensory domains, suggesting that intracellular c-di-GMP as well as additional stimuli can be used to modulate adaptation of bacterial chemotaxis receptors. PMID:23512960

  9. Is inositol (1,3,4,5)-tetrakisphosphate a new second messenger

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hansen, C.A.; Williamson, J.R.

    1986-05-01

    Hormone-stimulated hydrolysis of inositol (Ins) lipids results in the rapid formation of Ins(1,4,5)P/sub 3/, the second messenger for intracellular Ca/sup 2 +/ mobilization. Recently, a more polar inositol phosphate, Ins(1,3,4,5)P/sub 4/ as well as its probable hydrolysis product Ins(1,3,4)P/sub 3/ have been reported to accumulate in carbachol-stimulated brain slices. Vasopressin addition to hepatocytes prelabeled with (/sup 3/H)-Ins also showed a rapid increase of Ins(1,3,4,5)P/sub 4/, which was similar to that of Ins(1,4,5)P/sub 3/, while the accumulation of Ins(1,3,4)P/sub 3/ was slower. In order to examine whether Ins(1,3,4,5)P/sub 4/ has any functional effects on Ca/sup 2 +/ homeostasis, it was synthesizedmore » enzymatically from (/sup 3/H)-Ins(1,4,5)P/sub 3/ using a partially purified phosphoinositol kinase activity from rat brain cortex. (/sup 3/H)-labeled inositol phosphates were separated by anion exchange chromatography and analyzed by HPLC using ammonium formate/phosphoric acid gradient elution. Preliminary experiments indicate that Ins(1,3,4,5)P/sub 4/ up to 10 ..mu..M does not release Ca/sup 2 +/ from vesicular pools in saponin-permeabilized hepatocytes. It has a slight inhibitory effect on Ins(1,4,5)P/sub 3/-induced Ca/sup 2 +/ release. The effect of Ins(1,3,4,5)P/sub 4/ on plasma membrane Ca/sup 2 +/ fluxes are presently being investigated.« less

  10. Phospholipase D and the Maintenance of Phosphatidic Acid Levels for Regulation of Mammalian Target of Rapamycin (mTOR)*

    PubMed Central

    Foster, David A.; Salloum, Darin; Menon, Deepak; Frias, Maria A.

    2014-01-01

    Phosphatidic acid (PA) is a critical metabolite at the heart of membrane phospholipid biosynthesis. However, PA also serves as a critical lipid second messenger that regulates several proteins implicated in the control of cell cycle progression and cell growth. Three major metabolic pathways generate PA: phospholipase D (PLD), diacylglycerol kinase (DGK), and lysophosphatidic acid acyltransferase (LPAAT). The LPAAT pathway is integral to de novo membrane phospholipid biosynthesis, whereas the PLD and DGK pathways are activated in response to growth factors and stress. The PLD pathway is also responsive to nutrients. A key target for the lipid second messenger function of PA is mTOR, the mammalian/mechanistic target of rapamycin, which integrates both nutrient and growth factor signals to control cell growth and proliferation. Although PLD has been widely implicated in the generation of PA needed for mTOR activation, it is becoming clear that PA generated via the LPAAT and DGK pathways is also involved in the regulation of mTOR. In this minireview, we highlight the coordinated maintenance of intracellular PA levels that regulate mTOR signals stimulated by growth factors and nutrients, including amino acids, lipids, glucose, and Gln. Emerging evidence indicates compensatory increases in one source of PA when another source is compromised, highlighting the importance of being able to adapt to stressful conditions that interfere with PA production. The regulation of PA levels has important implications for cancer cells that depend on PA and mTOR activity for survival. PMID:24990952

  11. Phospholipase D and the maintenance of phosphatidic acid levels for regulation of mammalian target of rapamycin (mTOR).

    PubMed

    Foster, David A; Salloum, Darin; Menon, Deepak; Frias, Maria A

    2014-08-15

    Phosphatidic acid (PA) is a critical metabolite at the heart of membrane phospholipid biosynthesis. However, PA also serves as a critical lipid second messenger that regulates several proteins implicated in the control of cell cycle progression and cell growth. Three major metabolic pathways generate PA: phospholipase D (PLD), diacylglycerol kinase (DGK), and lysophosphatidic acid acyltransferase (LPAAT). The LPAAT pathway is integral to de novo membrane phospholipid biosynthesis, whereas the PLD and DGK pathways are activated in response to growth factors and stress. The PLD pathway is also responsive to nutrients. A key target for the lipid second messenger function of PA is mTOR, the mammalian/mechanistic target of rapamycin, which integrates both nutrient and growth factor signals to control cell growth and proliferation. Although PLD has been widely implicated in the generation of PA needed for mTOR activation, it is becoming clear that PA generated via the LPAAT and DGK pathways is also involved in the regulation of mTOR. In this minireview, we highlight the coordinated maintenance of intracellular PA levels that regulate mTOR signals stimulated by growth factors and nutrients, including amino acids, lipids, glucose, and Gln. Emerging evidence indicates compensatory increases in one source of PA when another source is compromised, highlighting the importance of being able to adapt to stressful conditions that interfere with PA production. The regulation of PA levels has important implications for cancer cells that depend on PA and mTOR activity for survival. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Structural and Biochemical Determinants of Ligand Binding by the c-di-GMP Riboswitch

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smith, K.; Lipchock, S; Livingston,

    2010-01-01

    The bacterial second messenger c-di-GMP is used in many species to control essential processes that allow the organism to adapt to its environment. The c-di-GMP riboswitch (GEMM) is an important downstream target in this signaling pathway and alters gene expression in response to changing concentrations of c-di-GMP. The riboswitch selectively recognizes its second messenger ligand primarily through contacts with two critical nucleotides. However, these two nucleotides are not the most highly conserved residues within the riboswitch sequence. Instead, nucleotides that stack with c-di-GMP and that form tertiary RNA contacts are the most invariant. Biochemical and structural evidence reveals that themore » most common natural variants are able to make alternative pairing interactions with both guanine bases of the ligand. Additionally, a high-resolution (2.3 {angstrom}) crystal structure of the native complex reveals that a single metal coordinates the c-di-GMP backbone. Evidence is also provided that after transcription of the first nucleotide on the 3{prime}-side of the P1 helix, which is predicted to be the molecular switch, the aptamer is functional for ligand binding. Although large energetic effects occur when several residues in the RNA are altered, mutations at the most conserved positions, rather than at positions that base pair with c-di-GMP, have the most detrimental effects on binding. Many mutants retain sufficient c-di-GMP affinity for the RNA to remain biologically relevant, which suggests that this motif is quite resilient to mutation.« less

  13. Limits to Mercury's Magnesium Exosphere from MESSENGER Second Flyby Observations

    NASA Technical Reports Server (NTRS)

    Sarantos, Menelaos; Killen, Rosemary M.; McClintock, William E.; Bradley, E. Todd; Vervack, Ronald J., Jr.; Benna, Mehdi; Slavin, James A.

    2011-01-01

    The discovery measurements of Mercury's exospheric magnesium, obtained by the MErcury Surface. Space ENvironment, GEochemistry. and Ranging (MESSENGER) probe during its second Mercury flyby, are modeled to constrain the source and loss processes for this neutral species. Fits to a Chamberlain exosphere reveal that at least two source temperatures are required to reconcile the distribution of magnesium measured far from and near the planet: a hot ejection process at the equivalent temperature of several tens of thousands of degrees K, and a competing, cooler source at temperatures as low as 400 K. For the energetic component, our models indicate that the column abundance that can be attributed to sputtering under constant southward interplanetary magnetic field (IMF) conditions is at least a factor of five less than the rate dictated by the measurements, Although highly uncertain, this result suggests that another energetic process, such as the rapid dissociation of exospheric MgO, may be the main source of the distant neutral component. If meteoroid and micrometeoroid impacts eject mainly molecules, the total amount of magnesium at altitudes exceeding approximately 100 km is found to be consistent with predictions by impact vaporization models for molecule lifetimes of no more than two minutes. Though a sharp increase in emission observed near the dawn terminator region can be reproduced if a single meteoroid enhanced the impact vapor at equatorial dawn, it is much more likely that observations in this region, which probe heights increasingly near the surface, indicate a reservoir of volatile Mg being acted upon by lower-energy source processes.

  14. Optimizing low latency LIGO-Virgo localization

    NASA Astrophysics Data System (ADS)

    Chen, Hsin-Yu; Holz, Daniel

    2015-04-01

    Fast and effective localization of gravitational wave (GW) events could play a crucial role in identifying possible electromagnetic counterparts, and thereby help usher in an era of GW multi-messenger astronomy. We discuss an algorithm for accurate and very low latency (<< 1 second) localization of GW sources using only the time of arrival and signal-to-noise ratio at each detector. The algorithm is independent of distances, masses, and waveform templates of the sources to leading order, and applies to all discrete sources detected by ground-based detector networks. For the two detector configuration (LIGO Hanford+Livingston) expected in late 2015 we find a median 50% localization of 150 deg2 for binary neutron stars (for SNR threshold of 12), consistent with previous findings. We explore the improvement in localization resulting from high SNR events, finding that the loudest out of the first four events reduces the median sky localization area by a factor of 1.8. We also discuss some strategies to optimize electromagnetic follow-up of GW events. We specifically explore the case of multi-messenger joint detections coming from independent (and possibly highly uncertain) localizations, such as for short gamma-ray bursts observed by Fermi GBM and neutrinos captured by IceCube.

  15. PDT-treated apoptotic cells induce macrophage synthesis NO

    NASA Astrophysics Data System (ADS)

    Song, S.; Xing, D.; Zhou, F. F.; Chen, W. R.

    2009-11-01

    Nitric oxide (NO) is a biologically active molecule which has multi-functional in different species. As a second messenger and neurotransmitter, NO is not only an important regulatory factor between cells' information transmission, but also an important messenger in cell-mediated immunity and cytotoxicity. On the other side, NO is involving in some diseases' pathological process. In pathological conditions, the macrophages are activated to produce a large quantity of nitric oxide synthase (iNOS), which can use L-arginine to produce an excessive amount of NO, thereby killing bacteria, viruses, parasites, fungi, tumor cells, as well as in other series of the immune process. In this paper, photofrin-based photodynamic therapy (PDT) was used to treat EMT6 mammary tumors in vitro to induce apoptotic cells, and then co-incubation both apoptotic cells and macrophages, which could activate macrophage to induce a series of cytotoxic factors, especially NO. This, in turn, utilizes macrophages to activate a cytotoxic response towards neighboring tumor cells. These results provided a new idea for us to further study the immunological mechanism involved in damaging effects of PDT, also revealed the important function of the immune effect of apoptotic cells in PDT.

  16. Exploring Mercury Tail

    NASA Image and Video Library

    2008-08-26

    As the MESSENGER spacecraft approached Mercury, the UVVS field of view was scanned across the planet's exospheric "tail," which is produced by the solar wind pushing Mercury's exosphere (the planet's extremely thin atmosphere) outward. This figure, recently published in Science magazine, shows a map of the distribution of sodium atoms as they stream away from the planet (see PIA10396); red and yellow colors represent a higher abundance of sodium than darker shades of blue and purple, as shown in the colored scale bar, which gives the brightness intensity in units of kiloRayleighs. The escaping atoms eventually form a comet-like tail that extends in the direction opposite that of the Sun for many planetary radii. The small squares outlined in black correspond to individual measurements that were used to create the full map. These measurements are the highest-spatial-resolution observations ever made of Mercury's tail. In less than six weeks, on October 6, 2008, similar measurements will be made during MESSENGER's second flyby of Mercury. Comparing the measurements from the two flybys will provide an unprecedented look at how Mercury's dynamic exosphere and tail vary with time. Date Acquired: January 14, 2008. http://photojournal.jpl.nasa.gov/catalog/PIA11076

  17. Mineralogy of the Mercurian Surface

    NASA Technical Reports Server (NTRS)

    Vander Kaaden, Kathleen E.; McCubbin, Francis M.; Nittler, Larry R.; Peplowski, Patrick N.; Weider, Shoshana Z.; Evans, Larry R.; Frank, Elizabeth A.; McCoy, Timothy

    2016-01-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft orbited Mercury for four years until April 2015, revealing its structure, chemical makeup, and compositional diversity. Data from the mission have confirmed that Mercury is a compositional end-member among the terrestrial planets. The X-Ray Spectrometer (XRS) and Gamma-Ray Spectrometer (GRS) on board MESSENGER provided the first detailed geochemical analyses of Mercury's surface. These instruments have been used in conjunction with the Neutron Spectrometer and the Mercury Dual Imaging System to classify numerous geological and geochemical features on the surface of Mercury that were previously unknown. Furthermore, the data have revealed several surprising characteristics about Mercury's surface, including elevated S abundances (up to 4 wt%) and low Fe abundances (less than 2.5 wt%). The S and Fe abundances were used to quantify Mercury's highly reduced state, i.e., between 2.6 and 7.3 log10 units below the Iron-Wustite (IW) buffer. This fO2 is lower than any of the other terrestrial planets in the inner Solar System and has important consequences for the thermal and magmatic evolution of Mercury, its surface mineralogy and geochemistry, and the petrogenesis of the planet's magmas. Although MESSENGER has revealed substantial geochemical diversity across the surface of Mercury, until now, there have been only limited efforts to understand the mineralogical and petrological diversity of the planet. Here we present a systematic and comprehensive study of the potential mineralogical and petrological diversity of Mercury.

  18. An Annotated Guide to the First Orbital Image

    NASA Image and Video Library

    2017-12-08

    NASA image acquired: March 29, 2011 This historic first orbital image of Mercury was acquired 37 years to the day after Mariner 10’s historic first flyby of the innermost planet. Labels have been added to indicate several craters that were named based on Mariner 10 images, as well as Debussy, Matabei, and Berkel, which were named based on MESSENGER flyby images. The surface contained in the white lines is terrain previously unseen by spacecraft, and the star indicates the location of the south pole. On March 17, 2011 (March 18, 2011, UTC), MESSENGER became the first spacecraft to orbit the planet Mercury. The mission is currently in its commissioning phase, during which spacecraft and instrument performance are verified through a series of specially designed checkout activities. In the course of the one-year primary mission, the spacecraft's seven scientific instruments and radio science investigation will unravel the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the science questions that the MESSENGER mission has set out to answer. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Join us on Facebook

  19. Highs and Lows of Goethe

    NASA Image and Video Library

    2017-12-08

    Scale: The width of this image is about 250 kilometers (150 miles) Topographic information from the Mercury Laser Altimeter (MLA) is used to colorize a image mosaic of Goethe basin, located in Mercury's northern region. The purple colors are low and white is the highest; the total range of heights shown in this view is about 1 kilometer. Goethe basin is home to a variety of interesting features, including ghost craters with graben, wrinkle ridges that outline the basin, and dark craters that host radar-bright materials. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the key science questions that the MESSENGER mission is addressing. During the one-year primary mission, MDIS acquired 88,746 images and extensive other data sets. MESSENGER is now in a yearlong extended mission, during which plans call for the acquisition of more than 80,000 additional images to support MESSENGER’s science goals. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington/Brown University NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  20. Multi-Messenger Astronomy: White Dwarf Binaries, LISA and GAIA

    NASA Astrophysics Data System (ADS)

    Bueno, Michael; Breivik, Katelyn; Larson, Shane L.

    2017-01-01

    The discovery of gravitational waves has ushered in a new era in astronomy. The low-frequency band covered by the future LISA detector provides unprecedented opportunities for multi-messenger astronomy. With the Global Astrometric Interferometer for Astrophysics (GAIA) mission, we expect to discover about 1,000 eclipsing binary systems composed of a WD and a main sequence star - a sizeable increase from the approximately 34 currently known binaries of this type. In advance of the first GAIA data release and the launch of LISA within the next decade, we used the Binary Stellar Evolution (BSE) code simulate the evolution of White Dwarf Binaries (WDB) in a fixed galaxy population of about 196,000 sources. Our goal is to assess the detectability of a WDB by LISA and GAIA using the parameters from our population synthesis, we calculate GW strength h, and apparent GAIA magnitude G. We can then use a scale factor to make a prediction of how many multi- messenger sources we expect to be detectable by both LISA and GAIA in a galaxy the size of the Milky Way. We create binaries 10 times to ensure randomness in distance assignment and average our results. We then determined whether or not astronomical chirp is the difference between the total chirp and the GW chirp. With Astronomical chirp and simulations of mass transfer and tides, we can gather more information about the internal astrophysics of stars in ultra-compact binary systems.

  1. Investigating Mercury's South Polar Deposits with High-Resolution Determination of Illumination Conditions

    NASA Astrophysics Data System (ADS)

    Shread, E. E.; Chabot, N. L.

    2018-05-01

    High-resolution images acquired by MESSENGER's Mercury Dual Imaging System were used to investigate the illumination conditions of Mercury's south polar deposits and to map the areas of permanent shadow in the region to compare with radar imaging.

  2. MERTIS on BepiColombo: seeing Mercury in a new light

    NASA Astrophysics Data System (ADS)

    Helbert, Jorn; Hiesinger, Harald; D'Amore, Mario; Walter, Ingo; Peter, Gisbert; Säuberlich, Thomas; Arnold, Gabriele; Maturilli, Alessandro; D'Incecco, Piero

    2013-09-01

    The MErcury Radiometer and Thermal infrared Imaging Spectrometer (MERTIS) is part of the payload of the Mercury Planetary Orbiter spacecraft of the ESA-JAXA BepiColombo mission. MERTIS's scientific goals are to infer rockforming minerals, to map surface composition, and to study surface temperature variations on Mercury. To achieve these science goals MERTIS combines a imaging spectrometer covering the wavelength range from 7-14 microns with a radiometer covering the wavelength range from 7-40 microns. MERTIS will map the whole surface of Mercury with a spatial resolution of 500m for the spectrometer channel and 2km for the radiometer channel. The MERTIS instrument had been proposed long before the NASA MESSENGER mission provided us with new insights into the innermost of the terrestrial planets. The discoveries of the MESSENGER fundamentally changed our view of Mercury. It revealed a surface that has been reshaped by volcanism over large parts of geological history. Volatile elements like sulfur have been detected with unexpectedly high abundances of up to 4%. MESSENGER imagined structures that are most likely formed by pyroclastic eruptions in recent geologic history. Among the most exciting discoveries of MESSENGER are hollows - bright irregularly shaped depressions that show sign of ongoing loss of material. Despite all this new results the MERTIS dataset remains unique and is now more important than ever. None of the instruments on the NASA MESSENGER mission covers the same spectral range or provides a measurement of the surface temperature. The MERTIS will complement the results of MESSENGER. MERTIS will for example be able to provide spatially resolved compositional information on the hollows and pyroclastic deposits - both among the most exciting discoveries by the MESSENGER mission for which the NASA mission can not provide compositional information.

  3. The gravity field and orientation of Mercury after the MESSENGER mission

    NASA Astrophysics Data System (ADS)

    Mazarico, E.; Genova, A.; Goossens, S. J.; Lemoine, F. G.; Neumann, G. A.; Zuber, M. T.; Smith, D. E.; Solomon, S. C.

    2015-12-01

    After more than four years in orbit about Mercury, the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft impacted the planet's surface north of Shakespeare crater (54.44° N, 210.12° E,) on 30 April 2015. One of the main goals of the mission was to determine the gravity field of Mercury in order to learn about Mercury's interior. Together with ground-based radar measurements of the obliquity and forced librations, MESSENGER-derived gravity models helped revise models of Mercury's interior. Nevertheless, the refinement of Mercury's orientation with the latest data from MESSENGER can further improve the interior modeling of the planet. The last eight months of the mission provided a special opportunity to conduct low-altitude measurements, with extensive radio tracking coverage below 200 km altitude north of ~30°N. MESSENGER's Mercury Laser Altimeter (MLA) mapped the topography of Mercury's northern hemisphere with a sub-meter vertical precision, an along-track sampling of ~500 m, and a longitudinal resolution (~0.1°) limited by the number of spacecraft orbits (~4,000). The combination of gravity and topography helps determine crustal thickness and interior properties. Altimetric ranges provide geodetic constraints to improve the spacecraft orbit determination, and thus the gravity field model. In particular, whereas the MESSENGER spacecraft was not tracked at each periapsis passage, MLA operated nearly continuously (outside of thermally challenging periods). From an analysis of the entire radiometric and altimetric datasets acquired by MESSENGER, a new gravity field to degree and order 100 has been obtained, resolving features down to ~75 km horizontal scale. The altimetric data help reduce the uncertainties in the determination of the pole position. A reanalysis of the Mercury flybys also constrains the spin rate over the longest available time span.

  4. KSC-04PD-1472

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. Ted Hartka, MESSENGER lead mechanical engineer, with The Johns Hopkins University Applied Physics Laboratory (APL), talks about the MESSENGER spacecrafts mission to Mercury for the media at a special presentation at Astrotech Space Operations in Titusville, Fla. The spacecraft, mated to the Delta II third stage Payload Assist Module, is in the background. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla.

  5. KSC-04pd1472

    NASA Image and Video Library

    2004-07-14

    KENNEDY SPACE CENTER, FLA. - Ted Hartka, MESSENGER lead mechanical engineer, with The Johns Hopkins University Applied Physics Laboratory (APL), talks about the MESSENGER spacecraft’s mission to Mercury for the media at a special presentation at Astrotech Space Operations in Titusville, Fla. The spacecraft, mated to the Delta II third stage Payload Assist Module, is in the background. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla.

  6. KSC-04pd1531

    NASA Image and Video Library

    2004-07-21

    KENNEDY SPACE CENTER, FLA. - MESSENGER, a NASA Discovery mission. The MESSENGER (MErcury Surface, Space ENvironment, GEochemistry, and Ranging) mission is a scientific investigation of the planet Mercury. MESSENGER will be launched in the summer of 2004 and will enter Mercury orbit in March of 2011, after one Earth flyby, two flybys of Venus, and three of Mercury along the way. The flyby and orbital phases of the mission will provide global mapping and detailed characterization of the planet's surface, interior, atmosphere and magnetosphere.

  7. Interobserver Variability of Radiographic Assessment Using a Mobile Messaging Application as a Teleconsultation Tool

    PubMed Central

    Özkan, Sezai; Mellema, Jos J.; Ring, David; Chen, Neal C.

    2017-01-01

    Background: To examine whether interobserver reliability, decision-making, and confidence in decision-making in the treatment of distal radius fractures changes if radiographs are viewed on a messenger application on a mobile phone compared to a standard DICOM viewer. Methods: Radiographs of distal radius fractures were presented to surgeons on either a smart phone using a mobile messenger application or a laptop using a DICOM viewer application. Twenty observers participated: 10 (50%) were randomly assigned to the DICOM viewer group and 10 (50%) to the mobile messenger group. Each observer was asked to evaluate the cases and (1) classify the fracture type according to the AO classification, (2) recommend operative or conservative treatment and (3) rate their confidence about this decision. Results: There was no significant difference in interobserver reliability for AO classification and recommendation for surgery for distal radius fractures in both groups. The percentage of recommendation for surgery was significantly higher in the messenger application group compared to the DICOM viewer group (89% versus 78%, P=0.019) and the confidence for treatment decision was significantly higher in the mobile messenger group compared to the DICOM viewer group (8.9 versus 7.9, P=0.026). Conclusion: Messenger applications on mobile phones could facilitate remote decision-making for patients with distal radius fractures, but should be used with caution. PMID:29226202

  8. Comparing Strategies for Health Information Dissemination: Messengers That Can Help or Hinder.

    PubMed

    Fishman, Jessica; Greenberg, Patricia; Bagga, Margy Barbieri; Casarett, David; Propert, Kathleen

    2018-05-01

    To test the effects of different messengers on the dissemination of health information. An experimental study exposed participants to 12 news articles pertaining to 1 of 3 health topics framed from the perspective of 4 generic messengers: religious figures, doctors, celebrity patients, or ordinary patients. Participants select as many of the 12 articles as desired. A cancer clinic within a large, urban hospital serving a sociodemographically diverse patient population. Eighty-nine patients with a history of cancer. The primary outcome was the frequency with which each news story was selected. Summary statistics and a general estimating equation model. For each health topic, news articles using celebrity messengers were the least likely to be selected; almost half of the participants (36 [41.4%] of 87) rejected all such articles. Articles linked to religious figures were equally unpopular ( P = .59). Articles that used doctors or ordinary patients as the messenger were very likely to be selected: Nearly all women (84 [96.6%] of 87) selected at least one of these. Furthermore, the odds of choosing articles linked to celebrities or religious leaders were statistically significantly lower than the odds of choosing those linked to ordinary patients or doctors ( P < .01). Commonly used generic messengers had large effects on the dissemination of information. Health materials linked to celebrities or religious figures were consistently less likely to be selected than those linked to ordinary patients, or doctors.

  9. MESSENGER soft X-ray observations of the quiet solar corona

    NASA Astrophysics Data System (ADS)

    Schwartz, Richard A.; Hudson, Hugh S.; Tolbert, Anne K; Dennis, Brian R.

    2014-06-01

    In a remarkable result from their "SphinX" experiment, Sylwester et al. (2012) found a non-varying base level of soft X-ray emission at the quietest times in 2009. We describe comparable data from the soft X-ray monitor on board MESSENGER (en route to Mercury) which had excellent coverage both in 2009 and during the true solar minimum of 2008. These observations overlap SphinX's and also are often exactly at Sun-MESSENGER-Earth conjunctions. During solar minimum the Sun-MESSENGER distance varied substantially, allowing us to use the inverse-square law to help distinguish the aperture flux (ie, solar X-rays) from that due to sources of background in the 2-5 keV range. The MESSENGER data show a non-varying background level for many months in 2008 when no active regions were present. We compare these data in detail with those from SphinX. Both sets of data reveal a different behavior when magnetic active regions are present on the Sun, and when they are not.Reference: Sylwester et al., ApJ 751, 111 (2012)

  10. The EAL-domain protein FcsR regulates flagella, chemotaxis and type III secretion system in Pseudomonas aeruginosa by a phosphodiesterase independent mechanism.

    PubMed

    Rossello, Jessica; Lima, Analía; Gil, Magdalena; Rodríguez Duarte, Jorge; Correa, Agustín; Carvalho, Paulo C; Kierbel, Arlinet; Durán, Rosario

    2017-08-31

    The second messenger c-di-GMP regulates the switch between motile and sessile bacterial lifestyles. A general feature of c-di-GMP metabolism is the presence of a surprisingly large number of genes coding for diguanylate cyclases and phosphodiesterases, the enzymes responsible for its synthesis and degradation respectively. However, the physiological relevance of this apparent redundancy is not clear, emphasizing the need for investigating the functions of each of these enzymes. Here we focused on the phosphodiesterase PA2133 from Pseudomonas aeruginosa, an important opportunistic pathogen. We phenotypically characterized P. aeruginosa strain K overexpressing PA2133 or its inactive mutant. We showed that biofilm formation and motility are severely impaired by overexpression of PA2133. Our quantitative proteomic approach applied to the membrane and exoprotein fractions revealed that proteins involved in three processes were mostly affected: flagellar motility, type III secretion system and chemotaxis. While inhibition of biofilm formation can be ascribed to the phosphodiesterase activity of PA2133, down-regulation of flagellar, chemotaxis, and type III secretion system proteins is independent of this enzymatic activity. Based on these unexpected effects of PA2133, we propose to rename this gene product FcsR, for Flagellar, chemotaxis and type III secretion system Regulator.

  11. SOCE and cancer: Recent progress and new perspectives.

    PubMed

    Xie, Jiansheng; Pan, Hongming; Yao, Junlin; Zhou, Yubin; Han, Weidong

    2016-05-01

    Ca(2+) acts as a universal and versatile second messenger in the regulation of a myriad of biological processes, including cell proliferation, differentiation, migration and apoptosis. Store-operated Ca(2+) entry (SOCE) mediated by ORAI and the stromal interaction molecule (STIM) constitutes one of the major routes of calcium entry in nonexcitable cells, in which the depletion of intracellular Ca(2+) stores triggers activation of the endoplasmic reticulum (ER)-resident Ca(2+) sensor protein STIM to gate and open the ORAI Ca(2+) channels in the plasma membrane (PM). Accumulating evidence indicates that SOCE plays critical roles in cancer cell proliferation, metastasis and tumor neovascularization, as well as in antitumor immunity. We summarize herein the recent advances in our understanding of the function of SOCE in various types of tumor cells, vascular endothelial cells and cells of the immune system. Finally, the therapeutic potential of SOCE inhibitors in the treatment of cancer is also discussed. © 2015 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  12. Nitric Oxide-Dependent Posttranslational Modification in Plants: An Update

    PubMed Central

    Astier, Jeremy; Lindermayr, Christian

    2012-01-01

    Nitric oxide (NO) has been demonstrated as an essential regulator of several physiological processes in plants. The understanding of the molecular mechanism underlying its critical role constitutes a major field of research. NO can exert its biological function through different ways, such as the modulation of gene expression, the mobilization of second messengers, or interplays with protein kinases. Besides this signaling events, NO can be responsible of the posttranslational modifications (PTM) of target proteins. Several modifications have been identified so far, whereas metal nitrosylation, the tyrosine nitration and the S-nitrosylation can be considered as the main ones. Recent data demonstrate that these PTM are involved in the control of a wide range of physiological processes in plants, such as the plant immune system. However, a great deal of effort is still necessary to pinpoint the role of each PTM in plant physiology. Taken together, these new advances in proteomic research provide a better comprehension of the role of NO in plant signaling. PMID:23203119

  13. A Perspective on Studying G-Protein–Coupled Receptor Signaling with Resonance Energy Transfer Biosensors in Living Organisms

    PubMed Central

    van Unen, Jakobus; Woolard, Jeanette; Rinken, Ago; Hoffmann, Carsten; Hill, Stephen J.; Goedhart, Joachim; Bruchas, Michael R.; Bouvier, Michel

    2015-01-01

    The last frontier for a complete understanding of G-protein–coupled receptor (GPCR) biology is to be able to assess GPCR activity, interactions, and signaling in vivo, in real time within biologically intact systems. This includes the ability to detect GPCR activity, trafficking, dimerization, protein-protein interactions, second messenger production, and downstream signaling events with high spatial resolution and fast kinetic readouts. Resonance energy transfer (RET)–based biosensors allow for all of these possibilities in vitro and in cell-based assays, but moving RET into intact animals has proven difficult. Here, we provide perspectives on the optimization of biosensor design, of signal detection in living organisms, and the multidisciplinary development of in vitro and cell-based assays that more appropriately reflect the physiologic situation. In short, further development of RET-based probes, optical microscopy techniques, and mouse genome editing hold great potential over the next decade to bring real-time in vivo GPCR imaging to the forefront of pharmacology. PMID:25972446

  14. Sunlit Terraces

    NASA Image and Video Library

    2015-02-09

    The exterior of this unnamed crater is in shadow, while the inner wall and terraces bask in the sunshine. Terraces form just after the crater has been excavated, when oversteepened slopes slump back down. This image was acquired as part of the MDIS low-altitude imaging campaign. During MESSENGER's second extended mission, the spacecraft makes a progressively closer approach to Mercury's surface than at any previous point in the mission, enabling the acquisition of high-spatial-resolution data. For spacecraft altitudes below 350 kilometers, NAC images are acquired with pixel scales ranging from 20 meters to as little as 2 meters. Date acquired: January 23, 2015 Image Mission Elapsed Time (MET): 64352478 Image ID: 7849599 Instrument: Narrow Angle Camera (NAC) of the Mercury Dual Imaging System (MDIS) Center Latitude: 31.48° Center Longitude: 81.89° E Resolution: 6 meters/pixel Scale: This scene is approximately 6.3 km (3.9 miles) from top to bottom Incidence Angle: 82.6° Emission Angle: 0.1° Phase Angle: 82.7° http://photojournal.jpl.nasa.gov/catalog/PIA19196

  15. Mercury MESSENGER Stamp Unveiling

    NASA Image and Video Library

    2011-05-03

    Patty Carpenter, wife of NASA Mercury Astronaut Scott Carpenter, left, Daughters of NASA astronaut Alan Shepard, Laura Shepard Churchley, and, Alice Wackermann, right, sing the National Anthem during an unveiling ceremony of two USPS stamps that commemorate and celebrate 50 years of US Spaceflight and the MESSENGER program during an event, Wednesday, May 4, 2011 at the NASA Kennedy Space Center in Cape Canaveral, Fla. One stamp commemorates NASA’s Project Mercury, America’s first manned spaceflight program, and NASA astronaut Alan Shepard’s historic flight on May 5, 1961, aboard spacecraft Freedom 7. The other stamp draws attention to NASA’s unmanned MESSENGER mission, a scientific investigation of the planet Mercury. On March 17, 2011, MESSENGER became the first spacecraft to enter into orbit around Mercury. Photo Credit: (NASA/Bill Ingalls)

  16. KSC-04pd1465

    NASA Image and Video Library

    2004-07-12

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech Space Operations in Titusville, Fla., work on the back side of the MESSENGER spacecraft, mating it with the Payload Assist Module, the Boeing Delta II third stage, below. The white panel seen here is the heat-resistant, ceramic cloth sunshade that will enable MESSENGER to operate at room temperature. MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. It is expected to enter Mercury orbit in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  17. Twins Image

    NASA Image and Video Library

    2005-08-02

    NASA MESSENGER Earth flyby on Aug. 2, 2005, not only adjusted the spacecraft path to Mercury - the gravity assist maneuver allowed the spacecraft team to test several MESSENGER science instruments by observing its home planet.

  18. Probing the Milky Way electron density using multi-messenger astronomy

    NASA Astrophysics Data System (ADS)

    Breivik, Katelyn; Larson, Shane

    2015-04-01

    Multi-messenger observations of ultra-compact binaries in both gravitational waves and electromagnetic radiation supply highly complementary information, providing new ways of characterizing the internal dynamics of these systems, as well as new probes of the galaxy itself. Electron density models, used in pulsar distance measurements via the electron dispersion measure, are currently not well constrained. Simultaneous radio and gravitational wave observations of pulsars in binaries provide a method of measuring the average electron density along the line of sight to the pulsar, thus giving a new method for constraining current electron density models. We present this method and assess its viability with simulations of the compact binary component of the Milky Way using the public domain binary evolution code, BSE. This work is supported by NASA Award NNX13AM10G.

  19. A Test of General Relativity with MESSENGER Mission Data

    NASA Astrophysics Data System (ADS)

    Genova, A.; Mazarico, E.; Goossens, S. J.; Lemoine, F. G.; Neumann, G. A.; Nicholas, J. B.; Rowlands, D. D.; Smith, D. E.; Zuber, M. T.; Solomon, S. C.

    2016-12-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft initiated collection of scientific data from the innermost planet during its first flyby of Mercury in January 2008. After two additional Mercury flybys, MESSENGER was inserted into orbit around Mercury on 18 March 2011 and operated for more than four Earth years through 30 April 2015. Data acquired during the flyby and orbital phases have provided crucial information on the formation and evolution of Mercury. The Mercury Laser Altimeter (MLA) and the radio science system, for example, obtained geodetic observations of the topography, gravity field, orientation, and tides of Mercury, which helped constrain its surface and deep interior structure. X-band radio tracking data collected by the NASA Deep Space Network (DSN) allowed the determination of Mercury's gravity field to spherical harmonic degree and order 100, as well as refinement of the planet's obliquity and estimation of the tidal Love number k2. These geophysical parameters are derived from the range-rate observables that measure precisely the motion of the spacecraft in orbit around the planet. However, the DSN stations acquired two other kinds of radio tracking data, range and delta-differential one-way ranging, which also provided precise measurements of Mercury's ephemeris. The proximity of Mercury's orbit to the Sun leads to a significant perihelion precession, which was used by Einstein as confirmation of general relativity (GR) because of its inconsistency with the effects predicted from classical Newtonian theory. MESSENGER data allow the estimation of the GR parameterized post-Newtonian (PPN) coefficients γ and β. Furthermore, determination of Mercury's orbit also allows estimation of the gravitational parameter (GM) and the flattening (J2) of the Sun. We modified our orbit determination software, NASA GSFC's GEODYN II, to enable simultaneous orbit integration of both MESSENGER and the planet Mercury. The combined estimation of both orbits leads to a more accurate estimation of Mercury's gravity field, orientation, and tides. Results for these geophysical parameters, GM and J2 for the Sun, and the PPN parameters constitute updates for all of these quantities.

  20. KSC-04PD-1601

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. On Launch Pad 17-B at Cape Canaveral Air Force Station, the Mobile Service Tower begins to roll back from the pad, revealing the MESSENGER (MErcury Surface, Space ENvironment, GEochemistry and Ranging) spacecraft aboard a Delta II rocket, Model 7925-H with heavy lift capability. MESSENGER is ready for liftoff on Aug. 2 at 2:16 a.m. EDT and is expected to enter Mercury orbit in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  1. KSC-04PD-1603

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. On Launch Pad 17-B at Cape Canaveral Air Force Station, the Mobile Service Tower rolls back revealing the MESSENGER (MErcury Surface, Space ENvironment, GEochemistry and Ranging) spacecraft aboard a Delta II rocket, model 7925-H with heavy lift capability. MESSENGER is ready for liftoff on Aug. 2 at 2:16 a.m. EDT and is expected to enter Mercury orbit in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  2. KSC-04pd1433

    NASA Image and Video Library

    2004-07-02

    KENNEDY SPACE CENTER, FLA. - A worker (left) at Astrotech Space Operations in Titusville, Fla., questions another worker about the oxygen connection in his protective suit before spacecraft propellant loading of the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft. Liftoff of MESSENGER aboard a Boeing Delta II Heavy rocket, bound for Mercury, is scheduled for Aug. 2. The spacecraft is expected to reach orbit around the planet in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  3. KSC-04pd1473

    NASA Image and Video Library

    2004-07-14

    KENNEDY SPACE CENTER, FLA. - At Astrotech Space Operations in Titusville, Fla., members of the media, wearing clean room suits, gather around Ted Hartka, MESSENGER lead mechanical engineer, with The Johns Hopkins University Applied Physics Laboratory (APL). Hartka is talking about the MESSENGER spacecraft’s mission to Mercury. The spacecraft, mated to the Delta II third stage Payload Assist Module, is in the background. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla.

  4. Mission provides new findings about Mercury

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2011-06-01

    Mercury once was considered by even some planetary scientists as “an example, to use a phrase coined by a very famous scientist, as ‘one of the burnt-out cinders of the solar system.’ And it is anything but that,” Sean Solomon, who is principal investigator of NASA's Mercury Surface, Space Environment, Geochemistry and Ranging (MESSENGER) spacecraft, said at a 16 June briefing at NASA headquarters in Washington, D. C. Scientists at the briefing announced significant new findings about the planet's chemical composition, topography, magnetic field, and other features. MESSENGER has now logged more than 1 Mercurian year (about 88 Earth days) as the first satellite in orbit around the closest planet to the Sun, and new understandings are being gleaned from the spacecraft's imaging system, which has already taken more than 20,000 images of Mercury. In addition, the laser altimeter has operated more than 2 million times from orbit thus far, and other instruments are also gathering extensive data about the planet.

  5. A minimalist biosensor: Quantitation of cyclic di-GMP using the conformational change of a riboswitch aptamer.

    PubMed

    Kellenberger, Colleen A; Sales-Lee, Jade; Pan, Yuchen; Gassaway, Madalee M; Herr, Amy E; Hammond, Ming C

    2015-01-01

    Cyclic di-GMP (c-di-GMP) is a second messenger that is important in regulating bacterial physiology and behavior, including motility and virulence. Many questions remain about the role and regulation of this signaling molecule, but current methods of detection are limited by either modest sensitivity or requirements for extensive sample purification. We have taken advantage of a natural, high affinity receptor of c-di-GMP, the Vc2 riboswitch aptamer, to develop a sensitive and rapid electrophoretic mobility shift assay (EMSA) for c-di-GMP quantitation that required minimal engineering of the RNA.

  6. KSC-2011-3302

    NASA Image and Video Library

    2011-05-04

    CAPE CANAVERAL, Fla. -- In the Rocket Garden at NASA's Kennedy Space Center Visitor Complex in Florida, a United States Postal Service poster reveals the two new stamps that commemorate the 50th anniversary of human spaceflight. One stamp commemorates NASA's Project Mercury and Alan Shepard's historic launch on May 5, 1961, aboard the spacecraft Freedom 7. The second stamp honors NASA's MESSENGER, which reached Mercury in March to become the first spacecraft to orbit the planet. The two missions frame a remarkable 50-year period in which America advanced space exploration through more than 1,500 crewed and uncrewed flights. Photo credit: NASA/Kim Shiflett

  7. 60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH.

    PubMed

    Gallo-Payet, Nicole

    2016-05-01

    The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo-pituitary-adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH. © 2016 Society for Endocrinology.

  8. Mapping the Topography of Mercury with MESSENGER Laser Altimetry

    NASA Technical Reports Server (NTRS)

    Sun, Xiaoli; Cavanaugh, John F.; Neumann, Gregory A.; Smith, David E..; Zubor, Maria T.

    2012-01-01

    The Mercury Laser Altimeter onboard MESSENGER involves unique design elements that deal with the challenges of being in orbit around Mercury. The Mercury Laser Altimeter (MLA) is one of seven instruments on NASA's MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft. MESSENGER was launched on 3 August 2004, and entered into orbit about Mercury on 18 March 2011 after a journey through the inner solar system. This involved six planetary flybys, including three of Mercury. MLA is designed to map the topography and landforms of Mercury's surface. It also measures the planet's forced libration (motion about the spin axis), which helps constrain the state of the core. The first science measurements from orbit taken with MLA were made on 29 March 2011 and continue to date. MLA had accumulated about 8.3 million laser ranging measurements to Mercury's surface, as of 31 July 2012, i.e., over six Mercury years (528 Earth days). Although MLA is the third planetary lidar built at the NASA Goddard Space Flight Center (GSFC), MLA must endure a much harsher thermal environment near Mercury than the previous instruments on Mars and Earth satellites. The design of MLA was derived in part from that of the Mars Orbiter Laser Altimeter on Mars Global Surveyor. However, MLA must range over greater distances and often in off-nadir directions from a highly eccentric orbit. In MLA we use a single-mode diode-pumped Nd:YAG (neodymium-doped yttrium aluminum garnet) laser that is highly collimated to maintain a small footprint on the planet. The receiver has both a narrow field of view and a narrow spectral bandwidth to minimize the amount of background light detected from the sunlit hemisphere of Mercury. We achieve the highest possible receiver sensitivity by employing the minimum receiver detection threshold.

  9. Petrology and Geochemistry of Mercury

    NASA Astrophysics Data System (ADS)

    Weider, Shoshana Z.

    2018-04-01

    Although having knowledge of a terrestrial planet's chemistry is fundamental to understanding the origin and composition of its rocks, until recently, the geochemistry of Mercury—the Solar System's innermost planet—was largely unconstrained. Without the availability of geological specimens from Mercury, studying the planet's surface and bulk composition relies on remote sensing techniques. Moreover, Mercury's proximity to the Sun makes it difficult to study with Earth/space-based telescopes, or with planetary probes. Indeed, to date, only NASA's Mariner 10 and MESSENGER missions have been sent to Mercury. The former made three "flyby" encounters of Mercury between 1974 and 1975, but did not carry any instrument to make geochemical or mineralogical measurements of the surface. Until the MESSENGER flyby and orbital campaigns (2008–2015), therefore, knowledge of Mercury's chemical composition was severely limited and consisted of only a few facts. For example, it has long been known that Mercury has the highest uncompressed density of all the terrestrial planets (and thus a disproportionately large iron core). In addition, Earth-based spectral reflectance observations indicated a dark surface, largely devoid of iron within silicate minerals. To improve understanding of Mercury's geochemistry, the MESSENGER payload included a suite of geochemical sensing instruments: namely the X-Ray Spectrometer, Gamma-Ray Spectrometer, and Neutron Spectrometer. Indeed, the datasets obtained from these instruments (as well as from other complementary instruments) during MESSENGER's 3.5-year orbital mission allow a much more complete picture of Mercury's geochemistry to be drawn, and quantitative abundance estimates for several major rock-forming elements in Mercury's crust are now available. Overall, the MESSENGER data reveal a surface that is rich in Mg, but poor in Al and Ca, compared with typical terrestrial and lunar crustal materials. Mercury's surface also contains high concentrations of the volatile elements Na, S, K, and Cl. Furthermore, the total surface Fe abundance is now known to be <2 wt%, and the planet's low reflectance is thought to be primarily caused by the presence of C (in graphite) at a level of >1 wt%. Such data are key to constraining models for Mercury's formation and early evolution. Large-scale spatial variations in the MESSENGER geochemical datasets have also led to the designation of several geochemical "terrains" across Mercury's surface, which do not always align to otherwise mapped geological regions. Based on the MESSENGER geochemical results, several recent petrological experiments and calculations have been, and continue to be, performed to study Mercury's surface mineralogy. The results show that there are substantial differences in the precise mineral compositions and abundances among the different terrains, but Mercury's surface appears to be dominated by Mg-rich olivines and pyroxenes, as well as plagioclase and sulphide phases. Depending on the classification scheme used, Mercury's ultramafic surface rocks can thus be described as similar in nature to terrestrial boninites, andesites, norites, or gabbros.

  10. Genetics Home Reference: myotonic dystrophy

    MedlinePlus

    ... mutated gene produces an expanded version of messenger RNA , which is a molecular blueprint of the gene ... the production of proteins. The abnormally long messenger RNA forms clumps inside the cell that interfere with ...

  11. It's All About That Basin

    NASA Image and Video Library

    2015-02-26

    This mosaic of Caloris basin is an enhanced-color composite overlain on a monochrome mosaic featured in a previous post. The color mosaic is made up of WAC images obtained when both the spacecraft and the Sun were overhead, conditions best for discerning variations in albedo, or brightness. The monochrome mosaic is made up of WAC and NAC images obtained at off-vertical Sun angles (i.e., high incidence angles) and with visible shadows so as to reveal clearly the topographic form of geologic features. The combination of the two datasets allows the correlation of geologic features with their color properties. In portions of the scene, color differences from image to image are apparent. Ongoing calibration efforts by the MESSENGER team strive to minimize these differences. Caloris basin has been flooded by lavas that appear orange in this mosaic. Post-flooding craters have excavated material from beneath the surface. The larger of these craters have exposed low-reflectance material (blue in this mosaic) from beneath the surface lavas, likely giving a glimpse of the original basin floor material. Analysis of these craters yields an estimate of the thickness of the volcanic layer: 2.5–3.5 km (1.6–2.2 mi.). The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. In the mission's more than three years of orbital operations, MESSENGER has acquired over 250,000 images and extensive other data sets. MESSENGER is capable of continuing orbital operations until early 2015. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  12. Intense energetic electron flux enhancements in Mercury's magnetosphere: An integrated view with high-resolution observations from MESSENGER.

    PubMed

    Baker, Daniel N; Dewey, Ryan M; Lawrence, David J; Goldsten, John O; Peplowski, Patrick N; Korth, Haje; Slavin, James A; Krimigis, Stamatios M; Anderson, Brian J; Ho, George C; McNutt, Ralph L; Raines, Jim M; Schriver, David; Solomon, Sean C

    2016-03-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) mission to Mercury has provided a wealth of new data about energetic particle phenomena. With observations from MESSENGER's Energetic Particle Spectrometer, as well as data arising from energetic electrons recorded by the X-Ray Spectrometer and Gamma-Ray and Neutron Spectrometer (GRNS) instruments, recent work greatly extends our record of the acceleration, transport, and loss of energetic electrons at Mercury. The combined data sets include measurements from a few keV up to several hundred keV in electron kinetic energy and have permitted relatively good spatial and temporal resolution for many events. We focus here on the detailed nature of energetic electron bursts measured by the GRNS system, and we place these events in the context of solar wind and magnetospheric forcing at Mercury. Our examination of data at high temporal resolution (10 ms) during the period March 2013 through October 2014 supports strongly the view that energetic electrons are accelerated in the near-tail region of Mercury's magnetosphere and are subsequently "injected" onto closed magnetic field lines on the planetary nightside. The electrons populate the plasma sheet and drift rapidly eastward toward the dawn and prenoon sectors, at times executing multiple complete drifts around the planet to form "quasi-trapped" populations.

  13. KSC-04pd1337

    NASA Image and Video Library

    2004-06-24

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech in Titusville, Fla., look over a solar panel ready to be installed on NASA’s MESSENGER spacecraft. It is one of two large solar panels, supplemented with a nickel-hydrogen battery, that will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  14. KSC-04pd1366

    NASA Image and Video Library

    2004-06-28

    KENNEDY SPACE CENTER, FLA. - At Astrotech in Titusville, Fla., technicians with The Johns Hopkins University Applied Physics Laboratory (APL) prepare one of two solar array panels on the MESSENGER spacecraft for deployment. The panels will provide MESSENGER’s power on its journey to Mercury. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by APL in Laurel, Md.

  15. KSC-04pd1368

    NASA Image and Video Library

    2004-06-28

    KENNEDY SPACE CENTER, FLA. - At Astrotech in Titusville, Fla., a technician with The Johns Hopkins University Applied Physics Laboratory (APL) watches as one of the solar array panels on the MESSENGER spacecraft is deployed. The two panels will provide MESSENGER’s power on its journey to Mercury. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by APL in Laurel, Md.

  16. KSC-04pd1339

    NASA Image and Video Library

    2004-06-24

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech in Titusville, Fla., carry a solar panel toward NASA’s MESSENGER spacecraft for installation. It is one of two large solar panels, supplemented with a nickel-hydrogen battery, that will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  17. KSC-04pd1370

    NASA Image and Video Library

    2004-06-28

    KENNEDY SPACE CENTER, FLA. - At Astrotech in Titusville, Fla., technicians with The Johns Hopkins University Applied Physics Laboratory (APL) check one of two solar panels on the MESSENGER spacecraft after a deployment test. The other panel is at right, undeployed. The solar arrays will provide MESSENGER’s power on its journey to Mercury. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by APL in Laurel, Md.

  18. KSC-04pd1340

    NASA Image and Video Library

    2004-06-24

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech in Titusville, Fla., adjust a solar panel suspended from above for installation on NASA’s MESSENGER spacecraft. It is one of two large solar panels, supplemented with a nickel-hydrogen battery, that will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  19. KSC-04pd1367

    NASA Image and Video Library

    2004-06-28

    KENNEDY SPACE CENTER, FLA. - At Astrotech in Titusville, Fla., technicians with The Johns Hopkins University Applied Physics Laboratory (APL) prepare one of two solar array panels on the MESSENGER spacecraft for deployment. The panels will provide MESSENGER’s power on its journey to Mercury. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by APL in Laurel, Md.

  20. KSC-04pd1341

    NASA Image and Video Library

    2004-06-24

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech in Titusville, Fla., maneuver a solar panel into place for installation on NASA’s MESSENGER spacecraft. It is one of two large solar panels, supplemented with a nickel-hydrogen battery, that will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  1. KSC-04pd1344

    NASA Image and Video Library

    2004-06-24

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech in Titusville, Fla., help guide a solar panel toward NASA’s MESSENGER spacecraft for installation. It is one of two large solar panels, supplemented with a nickel-hydrogen battery, that will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  2. KSC-04pd1343

    NASA Image and Video Library

    2004-06-24

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech in Titusville, Fla., guide a solar panel closer to NASA’s MESSENGER spacecraft for installation. It is one of two large solar panels, supplemented with a nickel-hydrogen battery, that will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  3. KSC-04pd1338

    NASA Image and Video Library

    2004-06-24

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech in Titusville, Fla., attach a bar to a solar panel in order to lift it and move it to NASA’s MESSENGER spacecraft for installation. The two large solar panels, supplemented with a nickel-hydrogen battery, will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  4. KSC-04pd1342

    NASA Image and Video Library

    2004-06-24

    KENNEDY SPACE CENTER, FLA. - Technicians at Astrotech in Titusville, Fla., steady a solar panel suspended from above as others prepare to install it on NASA’s MESSENGER spacecraft. It is one of two large solar panels, supplemented with a nickel-hydrogen battery, that will provide MESSENGER’s power. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  5. KSC-04pd1369

    NASA Image and Video Library

    2004-06-28

    KENNEDY SPACE CENTER, FLA. - At Astrotech in Titusville, Fla., technicians with The Johns Hopkins University Applied Physics Laboratory (APL) monitor the progress of the solar array deployment on the MESSENGER spacecraft. The two panels will provide MESSENGER’s power on its journey to Mercury. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by APL in Laurel, Md.

  6. The Gravity Field of Mercury After the Messenger Low-Altitude Campaign

    NASA Technical Reports Server (NTRS)

    Mazarico, Erwan; Genova, Antonio; Goossens, Sander; Lemoine, Frank G.; Smith, David E.; Zuber, Maria T.; Neumann, Gary A.; Solomon, Sean C.

    2015-01-01

    The final year of the MESSENGER mission was designed to take advantage of the remaining propellant onboard to provide a series of lowaltitude observation campaigns and acquire novel scientific data about the innermost planet. The lower periapsis altitude greatly enhances the sensitivity to the short-wavelength gravity field, but only when the spacecraft is in view of Earth. After more than 3 years in orbit around Mercury, the MESSENGER spacecraft was tracked for the first time below 200-km altitude on 5 May 2014 by the NASA Deep Space Network (DSN). Between August and October, periapsis passages down to 25-km altitude were routinely tracked. These periods considerably improved the quality of the data coverage. Before the end of its mission, MESSENGER will fly at very low altitudes for extended periods of time. Given the orbital geometry, however the periapses will not be visible from Earth and so no new tracking data will be available for altitudes lower than 75 km. Nevertheless, the continuous tracking of MESSENGER in the northern hemisphere will help improve the uniformity of the spatial coverage at altitudes lower than 150 km, which will further improve the overall quality of the Mercury gravity field.

  7. Peaking Into the Dark

    NASA Image and Video Library

    2017-12-08

    In this dramatic scene, an unnamed crater in Mercury's northern volcanic plains is bathed in darkness as the sun sits low on the horizon. Rising from the floor of the crater is its central peak, a small mountain resulting from the crater's formation. A central peak is a type of crater morphology that lies between "simple" and "peak ring" in the range of crater morphology on Mercury. This image was acquired as a high-resolution targeted observation. Targeted observations are images of a small area on Mercury's surface at resolutions much higher than the 200-meter/pixel morphology base map. It is not possible to cover all of Mercury's surface at this high resolution, but typically several areas of high scientific interest are imaged in this mode each week. The MESSENGER spacecraft is the first ever to orbit the planet Mercury, and the spacecraft's seven scientific instruments and radio science investigation are unraveling the history and evolution of the Solar System's innermost planet. During the first two years of orbital operations, MESSENGER acquired over 150,000 images and extensive other data sets. MESSENGER is capable of continuing orbital operations until early 2015. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  8. Aquaporin 3 expression in human fetal membranes and its up-regulation by cyclic adenosine monophosphate in amnion epithelial cell culture.

    PubMed

    Wang, Shengbiao; Amidi, Fataneh; Beall, Marie; Gui, Lizhen; Ross, Michael G

    2006-04-01

    The cell membrane water channel protein aquaporins (AQPs) may be important in regulating the intramembranous (IM) pathway of amniotic fluid (AF) resorption. The objective of the present study was to determine whether aquaporin 3 (AQP3) is expressed in human fetal membranes and to further determine if AQP3 expression in primary human amnion cell culture is regulated by second-messenger cyclic adenosine monophosphate (cAMP). AQP3 expression in human fetal membranes of normal term pregnancy was studied by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). To determine the effect of cAMP on AQP3 expression, primary human amnion cell cultures were treated in either heat-inactivated medium alone (control), or heat-inactivated medium containing: (1) SP-cAMP, a membrane-permeable and phosphodiesterase resistant cAMP agonist, or (2) forskolin, an adenylate cyclase stimulator. Total RNA was isolated and multiplex real-time RT-PCR employed for relative quantitation of AQP3 expression. We detected AQP3 expression in placenta, chorion, and amnion using RT-PCR. Using IHC, we identified AQP3 protein expression in placenta syncytiotrophoblasts and cytotrophoblasts, chorion cytotrophoblasts, and amnion epithelia. In primary amnion epithelial cell culture, AQP3 mRNA significantly increased at 2 hours following forskolin or SP-cAMP, remained elevated at 10 hours following forskolin, and returned to baseline levels by 20 hours following treatment. This study provides evidence of AQP3 expression in human fetal membranes and demonstrates that AQP3 expression in primary human amnion cell culture is up-regulated by second-messenger cAMP. As AQP3 is permeable to water, urea, and glycerol, modulation of its expression in fetal membranes may contribute to AF homeostasis.

  9. Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction.

    PubMed

    Gill, Tejpal; Levine, Alan D

    2013-09-06

    T cell receptor (TCR)-initiated signal transduction is reported to increase production of intracellular reactive oxygen species, such as superoxide (O2˙(-)) and hydrogen peroxide (H2O2), as second messengers. Although H2O2 can modulate signal transduction by inactivating protein phosphatases, the mechanism and the subcellular localization of intracellular H2O2 as a second messenger of the TCR are not known. The antioxidant enzyme superoxide dismutase (SOD) catalyzes the dismutation of highly reactive O2˙(-) into H2O2 and thus acts as an intracellular generator of H2O2. As charged O2˙(-) is unable to diffuse through intracellular membranes, cells express distinct SOD isoforms in the cytosol (Cu,Zn-SOD) and mitochondria (Mn-SOD), where they locally scavenge O2˙(-) leading to production of H2O2. A 2-fold organelle-specific overexpression of either SOD in Jurkat T cell lines increases intracellular production of H2O2 but does not alter the levels of intracellular H2O2 scavenging enzymes such as catalase, membrane-bound peroxiredoxin1 (Prx1), and cytosolic Prx2. We report that overexpression of Mn-SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal transduction molecules Lck, LAT, ZAP70, PLCγ1, and SLP76 within 1 min of TCR cross-linking. This increase in mitochondrial H2O2 specifically modulates MAPK signaling through the JNK/cJun pathway, whereas overexpressing Cu,Zn-SOD had no effect on any of these TCR-mediated signaling molecules. As mitochondria translocate to the immunological synapse during TCR activation, we hypothesize this translocation provides the effective concentration of H2O2 required to selectively modulate downstream signal transduction pathways.

  10. Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine

    PubMed Central

    Chen, Mingmin; Sultan, Ayesha; Cinar, Ayhan; Yeruva, Sunil; Riederer, Brigitte; Singh, Anurag Kumar; Li, Junhua; Bonhagen, Janina; Chen, Gang; Yun, Chris; Donowitz, Mark; Hogema, Boris; deJonge, Hugo; Seidler, Ursula

    2010-01-01

    Trafficking and regulation of the epithelial brush border membrane (BBM) Na+/H+ exchanger 3 (NHE3) in the intestine involves interaction with four different members of the NHERF family in a signal-dependent and possibly segment-specific fashion. The aim of this research was to study the role of NHERF2 (E3KARP) in intestinal NHE3 BBM localization and second messenger-mediated and receptor-mediated inhibition of NHE3. Immunolocalization of NHE3 in WT mice revealed predominant microvillar localization in jejunum and colon, a mixed distribution in the proximal ileum but localization near the terminal web in the distal ileum. The terminal web localization of NHE3 in the distal ileum correlated with reduced acid-activated NHE3 activity (fluorometrically assessed). NHERF2 ablation resulted in a shift of NHE3 to the microvilli and higher basal fluid absorption rates in the ileum, but no change in overall NHE3 protein or mRNA expression. Forskolin-induced NHE3 inhibition was preserved in the absence of NHERF2, whereas Ca2+ ionophore- or carbachol-mediated inhibition was abolished. Likewise, Escherichia coli heat stable enterotoxin peptide (STp) lost its inhibitory effect on intestinal NHE3. It is concluded that in native murine intestine, the NHE3 adaptor protein NHERF2 plays important roles in tethering NHE3 to a position near the terminal web and in second messenger inhibition of NHE3 in a signal- and segment-specific fashion, and is therefore an important regulator of intestinal fluid transport. PMID:20962002

  11. Phospholipase C and D regulation of Src, calcium release and membrane fusion during Xenopus laevis development

    PubMed Central

    Stith, Bradley J.

    2015-01-01

    This review emphasizes how lipids regulate membrane fusion and the proteins involved in three developmental stages: oocyte maturation to the fertilizable egg, fertilization and during first cleavage. Decades of work show that phosphatidic acid (PA) releases intracellular calcium, and recent work shows that the lipid can activate Src tyrosine kinase or phospholipase C during Xenopus fertilization. Numerous reports are summarized to show three levels of increase in lipid second messengers inositol 1,4,5-trisphosphate and sn 1,2-diacylglycerol (DAG) during the three different developmental stages. In addition, possible roles for PA, ceramide, lysophosphatidylcholine, plasmalogens, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 4,5-bisphosphate, membrane microdomains (rafts) and phosphatidylinositol 3,4,5-trisphosphate in regulation of membrane fusion (acrosome reaction, sperm-egg fusion, cortical granule exocytosis), inositol 1,4,5-trisphosphate receptors, and calcium release are discussed. The role of six lipases involved in generating putative lipid second messengers during fertilization is also discussed: phospholipase D, autotaxin, lipin1, sphingomyelinase, phospholipase C, and phospholipase A2. More specifically, proteins involved in developmental events and their regulation through lipid binding to SH3, SH4, PH, PX, or C2 protein domains is emphasized. New models are presented for PA activation of Src (through SH3, SH4 and a unique domain), that this may be why the SH2 domain of PLCγ is not required for Xenopus fertilization, PA activation of phospholipase C, a role for PA during the calcium wave after fertilization, and that calcium/calmodulin may be responsible for the loss of Src from rafts after fertilization. Also discussed is that the large DAG increase during fertilization derives from phospholipase D production of PA and lipin dephosphorylation to DAG. PMID:25748412

  12. Calcium-Mediated Signaling during Sandalwood Somatic Embryogenesis. Role for Exogenous Calcium as Second Messenger1

    PubMed Central

    Anil, Veena S.; Rao, K. Sankara

    2000-01-01

    The possible involvement of Ca2+-mediated signaling in the induction/regulation of somatic embryogenesis from pro-embryogenic cells of sandalwood (Santalum album) has been investigated. 45Ca2+-uptake studies and fura-2 fluorescence ratio photometry were used to measure changes in [Ca2+]cyt of pro-embryogenic cells in response to culture conditions conducive for embryo development. Sandalwood pro-embryogenic cell masses (PEMs) are obtained in the callus proliferation medium that contains the auxin 2,4-dichlorophenoxyacetic acid. Subculture of PEMs into the embryo differentiation medium, which lacks 2,4-dichlorophenoxyacetic acid and has higher osmoticum, results in a 4-fold higher 45Ca2+ incorporation into the symplast. Fura-2 ratiometric analysis corroboratively shows a 10- to 16-fold increase in the [Ca2+]cyt of PEMs, increasing from a resting concentration of 30 to 50 nm to 650 to 800 nm. Chelation of exogenous Ca2+ with ethyleneglycol-bis(aminoethyl ether)-N,N′-tetraacetic acid arrests such an elevation in [Ca2+]cyt. Exogenous Ca2+ when chelated or deprived also arrests embryo development and inhibits the accumulation of a sandalwood Ca2+-dependent protein kinase. However, such culture conditions do not cause cell death as the PEMs continue to proliferate to form larger cell clumps. Culture treatment with N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide reduced embryogenic frequency by 85%, indicating that blockage of Ca2+-mediated signaling pathway(s) involving sandalwood Ca2+-dependent protein kinase and/or calmodulin causes the inhibition of embryogenesis. The observations presented are evidence to suggest a second messenger role for exogenous Ca2+ during sandalwood somatic embryogenesis. PMID:10938349

  13. Calcium-mediated signaling during sandalwood somatic embryogenesis. Role for exogenous calcium as second messenger.

    PubMed

    Anil, V S; Rao, K S

    2000-08-01

    The possible involvement of Ca(2+)-mediated signaling in the induction/regulation of somatic embryogenesis from pro-embryogenic cells of sandalwood (Santalum album) has been investigated. (45)Ca(2+)-uptake studies and fura-2 fluorescence ratio photometry were used to measure changes in [Ca(2+)](cyt) of pro-embryogenic cells in response to culture conditions conducive for embryo development. Sandalwood pro-embryogenic cell masses (PEMs) are obtained in the callus proliferation medium that contains the auxin 2,4-dichlorophenoxyacetic acid. Subculture of PEMs into the embryo differentiation medium, which lacks 2,4-dichlorophenoxyacetic acid and has higher osmoticum, results in a 4-fold higher (45)Ca(2+) incorporation into the symplast. Fura-2 ratiometric analysis corroboratively shows a 10- to 16-fold increase in the [Ca(2+)](cyt) of PEMs, increasing from a resting concentration of 30 to 50 nM to 650 to 800 nM. Chelation of exogenous Ca(2+) with ethyleneglycol-bis(aminoethyl ether)-N,N'-tetraacetic acid arrests such an elevation in [Ca(2+)](cyt). Exogenous Ca(2+) when chelated or deprived also arrests embryo development and inhibits the accumulation of a sandalwood Ca(2+)-dependent protein kinase. However, such culture conditions do not cause cell death as the PEMs continue to proliferate to form larger cell clumps. Culture treatment with N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide reduced embryogenic frequency by 85%, indicating that blockage of Ca(2+)-mediated signaling pathway(s) involving sandalwood Ca(2+)-dependent protein kinase and/or calmodulin causes the inhibition of embryogenesis. The observations presented are evidence to suggest a second messenger role for exogenous Ca(2+) during sandalwood somatic embryogenesis.

  14. Characterization and distribution of a maize cDNA encoding a peptide similar to the catalytic region of second messenger dependent protein kinases

    NASA Technical Reports Server (NTRS)

    Biermann, B.; Johnson, E. M.; Feldman, L. J.

    1990-01-01

    Maize (Zea mays) roots respond to a variety of environmental stimuli which are perceived by a specialized group of cells, the root cap. We are studying the transduction of extracellular signals by roots, particularly the role of protein kinases. Protein phosphorylation by kinases is an important step in many eukaryotic signal transduction pathways. As a first phase of this research we have isolated a cDNA encoding a maize protein similar to fungal and animal protein kinases known to be involved in the transduction of extracellular signals. The deduced sequence of this cDNA encodes a polypeptide containing amino acids corresponding to 33 out of 34 invariant or nearly invariant sequence features characteristic of protein kinase catalytic domains. The maize cDNA gene product is more closely related to the branch of serine/threonine protein kinase catalytic domains composed of the cyclic-nucleotide- and calcium-phospholipid-dependent subfamilies than to other protein kinases. Sequence identity is 35% or more between the deduced maize polypeptide and all members of this branch. The high structural similarity strongly suggests that catalytic activity of the encoded maize protein kinase may be regulated by second messengers, like that of all members of this branch whose regulation has been characterized. Northern hybridization with the maize cDNA clone shows a single 2400 base transcript at roughly similar levels in maize coleoptiles, root meristems, and the zone of root elongation, but the transcript is less abundant in mature leaves. In situ hybridization confirms the presence of the transcript in all regions of primary maize root tissue.

  15. Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions.

    PubMed

    Schmidt, Martina; Dekker, Frank J; Maarsingh, Harm

    2013-04-01

    Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and gene transcription, is reflected by the award of five Nobel prizes. The discovery of Epac (exchange protein directly activated by cAMP) has ignited a new surge of cAMP-related research and has depicted novel cAMP properties independent of protein kinase A and cyclic nucleotide-gated channels. The multidomain architecture of Epac determines its activity state and allows cell-type specific protein-protein and protein-lipid interactions that control fine-tuning of pivotal biologic responses through the "old" second messenger cAMP. Compartmentalization of cAMP in space and time, maintained by A-kinase anchoring proteins, phosphodiesterases, and β-arrestins, contributes to the Epac signalosome of small GTPases, phospholipases, mitogen- and lipid-activated kinases, and transcription factors. These novel cAMP sensors seem to implement certain unexpected signaling properties of cAMP and thereby to permit delicate adaptations of biologic responses. Agonists and antagonists selective for Epac are developed and will support further studies on the biologic net outcome of the activation of Epac. This will increase our current knowledge on the pathophysiology of devastating diseases, such as diabetes, cognitive impairment, renal and heart failure, (pulmonary) hypertension, asthma, and chronic obstructive pulmonary disease. Further insights into the cAMP dynamics executed by the Epac signalosome will help to optimize the pharmacological treatment of these diseases.

  16. Pigment Translocation in Caridean Shrimp Chromatophores: Receptor Type, Signal Transduction, Second Messengers, and Cross Talk Among Multiple Signaling Cascades.

    PubMed

    Milograna, Sarah Ribeiro; Ribeiro, Márcia Regina; Bell, Fernanda Tinti; McNamara, John Campbell

    2016-11-01

    Pigment aggregation in shrimp chromatophores is triggered by red pigment concentrating hormone (RPCH), a neurosecretory peptide whose plasma membrane receptor may be a G-protein coupled receptor (GPCR). While RPCH binding activates the Ca 2+ /cGMP signaling cascades, a role for cyclic AMP (cAMP) in pigment aggregation is obscure, as are the steps governing Ca 2+ release from the smooth endoplasmic reticulum (SER). A role for the antagonistic neuropeptide, pigment dispersing homone (α-PDH) is also unclear. In red, ovarian chromatophores from the freshwater shrimp Macrobrachium olfersi, we show that a G-protein antagonist (AntPG) strongly inhibits RPCH-triggered pigment aggregation, suggesting that RPCH binds to a GPCR, activating an inhibitory G-protein. Decreasing cAMP levels may cue pigment aggregation, since cytosolic cAMP titers, when augmented by cholera toxin, forskolin or vinpocentine, completely or partially impair pigment aggregation. Triggering opposing Ca 2+ /cGMP and cAMP cascades by simultaneous perfusion with lipid-soluble cyclic nucleotide analogs induces a "tug-of-war" response, pigments aggregating in some chromatosomes with unpredictable, oscillatory movements in others. Inhibition of cAMP-dependent protein kinase accelerates aggregation and reduces dispersion velocities, suggesting a role in phosphorylation events, possibly regulating SER Ca 2+ release and pigment aggregation. The second messengers IP 3 and cADPR do not stimulate SER Ca 2+ release. α-PDH does not sustain pigment dispersion, suggesting that pigment translocation in caridean chromatophores may be regulated solely by RPCH, since PDH is not required. We propose a working hypothesis to further unravel key steps in the mechanisms of pigment translocation within crustacean chromatophores that have remained obscure for nearly a century. © 2016 Wiley Periodicals, Inc.

  17. Computational Model of the Insect Pheromone Transduction Cascade

    PubMed Central

    Gu, Yuqiao; Lucas, Philippe; Rospars, Jean-Pierre

    2009-01-01

    A biophysical model of receptor potential generation in the male moth olfactory receptor neuron is presented. It takes into account all pre-effector processes—the translocation of pheromone molecules from air to sensillum lymph, their deactivation and interaction with the receptors, and the G-protein and effector enzyme activation—and focuses on the main post-effector processes. These processes involve the production and degradation of second messengers (IP3 and DAG), the opening and closing of a series of ionic channels (IP3-gated Ca2+ channel, DAG-gated cationic channel, Ca2+-gated Cl− channel, and Ca2+- and voltage-gated K+ channel), and Ca2+ extrusion mechanisms. The whole network is regulated by modulators (protein kinase C and Ca2+-calmodulin) that exert feedback inhibition on the effector and channels. The evolution in time of these linked chemical species and currents and the resulting membrane potentials in response to single pulse stimulation of various intensities were simulated. The unknown parameter values were fitted by comparison to the amplitude and temporal characteristics (rising and falling times) of the experimentally measured receptor potential at various pheromone doses. The model obtained captures the main features of the dose–response curves: the wide dynamic range of six decades with the same amplitudes as the experimental data, the short rising time, and the long falling time. It also reproduces the second messenger kinetics. It suggests that the two main types of depolarizing ionic channels play different roles at low and high pheromone concentrations; the DAG-gated cationic channel plays the major role for depolarization at low concentrations, and the Ca2+-gated Cl− channel plays the major role for depolarization at middle and high concentrations. Several testable predictions are proposed, and future developments are discussed. PMID:19300479

  18. Coulomb interactions between cytoplasmic electric fields and phosphorylated messenger proteins optimize information flow in cells.

    PubMed

    Gatenby, Robert A; Frieden, B Roy

    2010-08-11

    Normal cell function requires timely and accurate transmission of information from receptors on the cell membrane (CM) to the nucleus. Movement of messenger proteins in the cytoplasm is thought to be dependent on random walk. However, Brownian motion will disperse messenger proteins throughout the cytosol resulting in slow and highly variable transit times. We propose that a critical component of information transfer is an intracellular electric field generated by distribution of charge on the nuclear membrane (NM). While the latter has been demonstrated experimentally for decades, the role of the consequent electric field has been assumed to be minimal due to a Debye length of about 1 nanometer that results from screening by intracellular Cl- and K+. We propose inclusion of these inorganic ions in the Debye-Huckel equation is incorrect because nuclear pores allow transit through the membrane at a rate far faster than the time to thermodynamic equilibrium. In our model, only the charged, mobile messenger proteins contribute to the Debye length. Using this revised model and published data, we estimate the NM possesses a Debye-Huckel length of a few microns and find this is consistent with recent measurement using intracellular nano-voltmeters. We demonstrate the field will accelerate isolated messenger proteins toward the nucleus through Coulomb interactions with negative charges added by phosphorylation. We calculate transit times as short as 0.01 sec. When large numbers of phosphorylated messenger proteins are generated by increasing concentrations of extracellular ligands, we demonstrate they generate a self-screening environment that regionally attenuates the cytoplasmic field, slowing movement but permitting greater cross talk among pathways. Preliminary experimental results with phosphorylated RAF are consistent with model predictions. This work demonstrates that previously unrecognized Coulomb interactions between phosphorylated messenger proteins and intracellular electric fields will optimize information transfer from the CM to the NM in cells.

  19. The Ribosome Shape Directs mRNA Translocation through Entrance and Exit Dynamics

    USDA-ARS?s Scientific Manuscript database

    The protein-synthesizing ribosome undergoes large motions to effect the translocation of tRNAs (transfer ribonucleic acids) and mRNA (messenger ribonucleic acid); here the domain motions of this system are explored with a coarse-grained elastic network model using normal mode analysis. Crystal struc...

  20. Melatonin receptors: Current status, facts, and hypothesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stankov, B.; Reiter, R.J.

    Great progress has been made in the identification of melatonin binding sites, commonly identified as melatonin receptors by many authors, in recent years. The bulk of these studies have investigated the sites using either autoradiographic and biochemical techniques with the majority of the experiments being done on the rat, Djungarian and Syrian hamster, and sheep, although human tissue has also been employed. Many of the studies have identified melatonin binding in the central nervous system with either tritium- or iodine-labelled ligands. The latter ligand seems to provide the most reproducible and consistent data. Of the central neural tissues examined, themore » suprachiasmatic nuclei are most frequently mentioned as a location for melatonin binding sites although binding seems to be widespread in the brain. The other tissue that has been prominently mentioned as a site for melatonin binding is the pars tuberalis of the anterior pituitary gland. There may be time-dependent variations in melatonin binding densities in both neural and pituitary gland tissue. Very few attempts have been made to identify melatonin binding outside of the central nervous system despite the widespread actions of melatonin. Preliminary experiments have been carried out on the intracellular second messengers which mediate the actions of melatonin.« less

  1. Neurobiological factors in aggressive behavior.

    PubMed

    Garza-Treviño, E S

    1994-07-01

    The author's aim was to review literature in the neurosciences and psychiatric clinical research reports about biological factors in aggression and the pathophysiological mechanisms that accompany aggression in neuropsychiatric syndromes. Studies were located through computer searches of relevant experimental reports and review articles mainly from the last 25 years. Several studies using neuroimaging and neurophysiological and neuropathological research techniques have identified lesions in the limbic structures, temporal lobes, and frontal lobes of the brain in abnormally aggressive individuals. Several reports have associated deficiency or dysregulation of serotonin with homicidal, suicidal, and impulsive behavior. However, few studies have focused on polypeptides or second messenger systems, although abnormalities in these systems have been reported in patients with neuropsychiatric syndromes who have shown aggressive behavior. Even fewer studies focus on the correlation of brain structures and metabolic markers. The understanding of aggressive behavior in psychiatric patients is fragmented. Some explanations are speculative and extrapolated to clinical psychiatric syndromes from experimental data on the neurophysiology of cats, rats, and other mammals. Identification of biochemical markers that can be used in predicting patients' response to pharmacological interventions may be the next step in developing more rational treatment of violent patients.

  2. KSC-04pd1566

    NASA Image and Video Library

    2004-07-27

    KENNEDY SPACE CENTER, FLA. - On Launch Pad 17-B at Cape Canaveral Air Force Station, the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft is ready for installation of the fairing, a molded structure that fits flush with the outside surface of the Delta II upper stage booster and forms an aerodynamically smooth joint, protecting the spacecraft during launch. Seen on the left is one of the solar panels on the spacecraft. On the right is part of the heat-resistant, ceramic-cloth sunshade that will protect the spacecraft’s instruments as MESSENGER orbits the Mercury where the surface reaches a high temperature near 840 degrees Fahrenheit and the solar intensity can be 11 times greater than on Earth. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket and is expected to enter Mercury orbit in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  3. Identification of messenger RNA of fetoplacental source in maternal plasma of women with normal pregnancies and pregnancies with intrauterine growth restriction

    PubMed Central

    García Robles, Reggie; Rojas, Juan Diego; Bermúdez, Martha; Bernal, Jaime

    2012-01-01

    Objective: to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies. Methods: 8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase. Results: plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p= 0.5975) nor in the messenger RNA expression of hPL gene (p= 0.5785) between cases and controls. Conclusion: messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy. PMID:24893189

  4. 750 GeV diphoton resonance, 125 GeV Higgs and muon g - 2 anomaly in deflected anomaly mediation SUSY breaking scenarios

    NASA Astrophysics Data System (ADS)

    Wang, Fei; Wu, Lei; Yang, Jin Min; Zhang, Mengchao

    2016-08-01

    We propose to interpret the 750 GeV diphoton excess in deflected anomaly mediation supersymmetry breaking scenarios, which can naturally predict couplings between a singlet field and vector-like messengers. The CP-even scalar component (S) of the singlet field can serve as the 750 GeV resonance. The messenger scale, which is of order the gravitino scale, can be as light as Fϕ ∼ O (10) TeV when the messenger species NF and the deflection parameter d are moderately large. Such messengers can induce the large loop decay process S → γγ. Our results show that such a scenario can successfully accommodate the 125 GeV Higgs boson, the 750 GeV diphoton excess and the muon g - 2 without conflicting with the LHC constraints. We also comment on the possible explanations in the gauge mediation supersymmetry breaking scenario.

  5. Identification of messenger RNA of fetoplacental source in maternal plasma of women with normal pregnancies and pregnancies with intrauterine growth restriction.

    PubMed

    Ayala Ramírez, Paola; García Robles, Reggie; Rojas, Juan Diego; Bermúdez, Martha; Bernal, Jaime

    2012-07-01

    to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies. 8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase. plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p= 0.5975) nor in the messenger RNA expression of hPL gene (p= 0.5785) between cases and controls. messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy.

  6. A Micro-Electrode Array device coupled to a laser-based system for the local stimulation of neurons by optical release of glutamate.

    PubMed

    Ghezzi, Diego; Menegon, Andrea; Pedrocchi, Alessandra; Valtorta, Flavia; Ferrigno, Giancarlo

    2008-10-30

    Optical stimulation is a promising approach to investigate the local dynamic responses of cultured neurons. In particular, flash photolysis of caged compounds offers the advantage of allowing the rapid change of concentration of either extracellular or intracellular molecules, such as neurotransmitters or second messengers, for the stimulation or modulation of neuronal activity. We describe here the use of an ultra-violet (UV) laser diode coupled to an optical fibre for the local activation of caged compounds combined with a Micro-Electrode Array (MEA) device. Local uncaging was achieved by UV irradiation through the optical fibre previously positioned by using a red laser diode. The size of the stimulation was determined using caged fluorescein, whereas its efficacy was tested by studying the effect of uncaging the neurotransmitter glutamate. Uncaged glutamate evoked neuronal responses that were recorded using either fluorescence measurements or electrophysiological recordings with MEAs, thus showing the ability of our system to induce local neuronal excitation. This method allows overcoming the limitations of the MEA system related to unfocused electrical stimulation and induction of electrical artefacts. In addition, the coupling of a UV laser diode to an optical fibre allows a precise local stimulation and a quick change of the stimulation point.

  7. Real-time dynamics of RNA Polymerase II clustering in live human cells

    NASA Astrophysics Data System (ADS)

    Cisse, Ibrahim

    2014-03-01

    Transcription is the first step in the central dogma of molecular biology, when genetic information encoded on DNA is made into messenger RNA. How this fundamental process occurs within living cells (in vivo) is poorly understood,[1] despite extensive biochemical characterizations with isolated biomolecules (in vitro). For high-order organisms, like humans, transcription is reported to be spatially compartmentalized in nuclear foci consisting of clusters of RNA Polymerase II, the enzyme responsible for synthesizing all messenger RNAs. However, little is known of when these foci assemble or their relative stability. We developed an approach based on photo-activation localization microscopy (PALM) combined with a temporal correlation analysis, which we refer to as tcPALM. The tcPALM method enables the real-time characterization of biomolecular spatiotemporal organization, with single-molecule sensitivity, directly in living cells.[2] Using tcPALM, we observed that RNA Polymerase II clusters form transiently, with an average lifetime of 5.1 (+/- 0.4) seconds. Stimuli affecting transcription regulation yielded orders of magnitude changes in the dynamics of the polymerase clusters, implying that clustering is regulated and plays a role in the cells ability to effect rapid response to external signals. Our results suggest that the transient crowding of enzymes may aid in rate-limiting steps of genome regulation.

  8. The Crust of Mercury After the MESSENGER Gravity Investigation

    NASA Astrophysics Data System (ADS)

    Mazarico, E.; Genova, A.; Goossens, S.; Neumann, G. A.; Smith, D. E.; Zuber, M. T.

    2018-05-01

    We present the results of an improved analysis of the entire MESSENGER radio tracking dataset to derive key geophysical parameters of Mercury such as its gravity field. In particular, we derive and interpret a new crustal thickness model.

  9. MESSENGER Orbital Observations of Mercury's Hydrogen Exosphere

    NASA Astrophysics Data System (ADS)

    Vervack, R. J.; Hurley, D. M.; Pryor, W.; Killen, R. M.

    2018-05-01

    We present a complete analysis of the MESSENGER H Lyman alpha altitude profiles. These data confirm the two-temperature nature of the Mariner 10 observations of H and address long-outstanding questions on the origin of Mercury's H exosphere.

  10. KSC-04PD-1575

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. On Launch Pad 17-B at Cape Canaveral Air Force Station, Boeing workers complete the installation of the fairing around the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft. The fairing is a molded structure that fits flush with the outside surface of the upper stage booster and forms an aerodynamically smooth joint, protecting the spacecraft during launch. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket and is expected to enter Mercury orbit in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  11. KSC-04pd1364

    NASA Image and Video Library

    2004-06-28

    KENNEDY SPACE CENTER, FLA. - At Astrotech in Titusville, Fla., NASA Mission Integration Manager Cheryle Mako and NASA Launch Site Integration Manager John Hueckel talk before the deployment of the solar array panels on the MESSENGER spacecraft behind them. The solar arrays will provide MESSENGER’s power on its journey to Mercury. MESSENGER is scheduled to launch Aug. 2 aboard a Boeing Delta II rocket from Pad 17-B, Cape Canaveral Air Force Station, Fla. It will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. The spacecraft uses the tug of Venus’ gravity to resize and rotate its trajectory closer to Mercury’s orbit. Three Mercury flybys, each followed about two months later by a course-correction maneuver, put MESSENGER in position to enter Mercury orbit in March 2011. During the flybys, MESSENGER will map nearly the entire planet in color, image most of the areas unseen by Mariner 10, and measure the composition of the surface, atmosphere and magnetosphere. It will be the first new data from Mercury in more than 30 years - and invaluable for planning MESSENGER’s year-long orbital mission. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  12. Inositol phosphates in the duckweed Spirodela polyrhiza L.

    PubMed Central

    Brearley, C A; Hanke, D E

    1996-01-01

    We have undertaken an analysis of the inositol phosphates of Spirodela polyrhiza at a developmental stage when massive accumulation of InsP6 indicates that a large net synthesis is occurring. We have identified Ins3P, Ins(1,4)P2, Ins(3,4)P2 and possibly Ins(4,6)P2, Ins(3,4,6)P3, Ins(3,4,5,6)P4, Ins (1,3,4,5,6)P5, D- and/or L-Ins(1,2,4,5,6)P5 and InsP6 and revealed the likely presence of a second InsP3 with chromatographic properties similar to Ins(1,4,5)P3. The higher inositol phosphates identified show no obvious direct link to pathways of metabolism of second messengers purported to operate in higher plants, nor do they resemble the immediate products of plant phytase action on InsP6. PMID:8660286

  13. GPR30: A G protein-coupled receptor for estrogen.

    PubMed

    Prossnitz, Eric R; Arterburn, Jeffrey B; Sklar, Larry A

    2007-02-01

    Estrogen is a critical steroid in human physiology exerting its effect both at the transcriptional level as well as at the level of rapid intracellular signaling through second messengers. Many of estrogen's transcriptional effects have long been known to be mediated through classical nuclear steroid receptors but recent studies also demonstrate the existence of a 7-transmembrane G protein-coupled receptor, GPR30 that responds to estrogen with rapid cellular signaling. There is currently controversy over the ability of classical estrogen receptors to recapitulate GPR30-mediated signaling mechanisms and vice versa. This article will summarize recent literature and address the relationship between GPR30 and conventional estrogen receptor signaling.

  14. Proceedings of the International Conference on Cyclic Nucleotides, Calcium and Protein Phosphorylation (6th) Held in Bethesda, Maryland on September 2-7, 1986. Advances in Second Messenger and Phosphorprotein Research. Volume 21A. Abstracts Volume

    DTIC Science & Technology

    1988-11-16

    oxoireamorine. Oxotremorine inhibited Ach release for a shorter duration. The ACh release-inhibition induced by 50 PH Aech-M was only acutely blocked...and the partial agonist oxotresorine in the presence of 59K of Lit. Carbacbol showed a 10-fold lover ECS0-value (3.7liM) and oxotremorine a 3-fold...however, only a decrease in the maximal response was seen. In both tissues, the maximal, response of the partial agonist oxotremorine was suppressed

  15. NVP melt/magma viscosity: insight on Mercury lava flows

    NASA Astrophysics Data System (ADS)

    Rossi, Stefano; Morgavi, Daniele; Namur, Olivier; Vetere, Francesco; Perugini, Diego; Mancinelli, Paolo; Pauselli, Cristina

    2016-04-01

    After more than four years of orbiting Mercury, NASA's MESSENGER spacecraft came to an end in late April 2015. MESSENGER has provided many new and surprising results. This session will again highlight the latest results on Mercury based on MESSENGER observations or updated modelling. The session will further address instrument calibration and science performance both retrospective on MESSENGER and on the ESA/JAXA BepiColombo mission. Papers covering additional themes related to Mercury are also welcomed. Please be aware that this session will be held as a PICO session. This will allow an intensive exchange of expertise and experience between the individual instruments and mission. NVP melt/magma viscosity: insight on Mercury lava flows S. Rossi1, D. Morgavi1, O. Namur2, D. Perugini1, F.Vetere1, P. Mancinelli1 and C. Pauselli1 1 Dipartimento di Fisica e Geologia, Università di Perugia, piazza Università 1, 06123 Perugia, Italy 2 Uni Hannover Institut für Mineralogie, Leibniz Universität Hannover, Callinstraβe 3, 30167 Hannover, Germany In this contribution we report new measurements of viscosity of synthetic komatitic melts, used the behaviour of silicate melts erupted at the surface of Mercury. Composition of Mercurian surface magmas was calculated using the most recent maps produced from MESSENGER XRS data (Weider et al., 2015). We focused on the northern hemisphere (Northern Volcanic Province, NVP, the largest lava flow on Mercury and possibly in the Solar System) for which the spatial resolution of MESSENGER measurements is high and individual maps of Mg/Si, Ca/Si, Al/Si and S/Si were combined. The experimental starting material contains high Na2O content (≈7 wt.%) that strongly influences viscosity. High temperature viscosity measurements were carried out at 1 atm using a concentric cylinder apparatus equipped with an Anton Paar RheolabQC viscometer head at the Department of Physics and Geology (PVRG_lab) at the University of Perugia (Perugia, Italy). The change of melt viscosity induced by crystallization of a NVP composition was measured in the temperature ranges from 1463 to 1229 °C. Results showed an increase in effective viscosity from 4.3 Pa s to 1090 Pa s as the crystal content increased from 0 vol% to ca. 25 vol.%. The crystallization processes in the nominally dry NVP began at 1308 °C. Interestingly, melts viscosity changes from 4 to 16 Pa s as temperature varies from 1463 to 1327 °C. The extreme Mercurian lava fluidity experimentally measured has revealed the potentiality of NVP lavas to cover huge areas as shown by satellite data. Keywords: Viscosity, Concentric cylinders, NVP, Mercury.

  16. Prostanoid-induced expression of matrix metalloproteinase-1 messenger ribonucleic acid in rat osteosarcoma cells

    NASA Technical Reports Server (NTRS)

    Clohisy, J. C.; Connolly, T. J.; Bergman, K. D.; Quinn, C. O.; Partridge, N. C.

    1994-01-01

    Individual prostanoids have distinct potencies in activating intracellular signaling pathways and regulating gene expression in osteoblastic cells. The E-series prostaglandins (PGs) are known to stimulate matrix metalloproteinase-1 (MMP-1) synthesis and secretion in certain rodent and human osteoblastic cells, yet the intracellular events involved remain unclear. To further characterize this response and its signal transduction pathway(s), we examined prostanoid-induced expression of the MMP-1 gene in the rat osteoblastic osteosarcoma cell line UMR 106-01. Northern blot analysis demonstrated that prostaglandin E2 (PGE2) and PGE1 were very potent stimulators (40-fold) of MMP-1 transcript abundance, PGF2 alpha and prostacyclin were weak stimulators (4-fold), and thromboxane-B2 had no effect. The marked increase in MMP-1 transcript abundance after PGE2 treatment was first detected at 2 h, became maximal at 4 h, and persisted beyond 24 h. This response was dose dependent and elicited maximal and half-maximal effects with concentrations of 10(-6) and 0.6 x 10(-7) M, respectively. Cycloheximide, a protein synthesis inhibitor, completely blocked this effect of PGE2, suggesting that the expression of other genes is required. Nuclear run-on experiments demonstrated that PGE2 rapidly activates MMP-1 gene transcription, with a maximal increase at 2-4 h. The second messenger analog, 8-bromo-cAMP, mimicked the effects of PGE2 by stimulating a dose-dependent increase in MMP-1 messenger RNA (mRNA) levels, with a maximal effect quantitatively similar to that observed with PGE2. Thus, in UMR 106-01 cells, different prostanoids have distinct potencies in stimulating MMP-1 mRNA abundance. Our data suggest that PGE2 stimulation of MMP-1 synthesis is due to activation of MMP-1 gene transcription and a subsequent marked increase in MMP-1 mRNA abundance. This effect is dependent on de novo protein synthesis and is mimicked by protein kinase-A activation.

  17. TCCTA Messenger, 1999-2000.

    ERIC Educational Resources Information Center

    TCCTA Messenger, 2000

    2000-01-01

    The Texas Community College Teachers Association (TCCTA), formerly known as the Texas Junior College Teachers Association (TJCTA), publishes the TCCTA Messenger newsletter four times a year to cover events, legislation and TCCTA activities affecting Texas community colleges and their faculty. This document contains four newsletter issues…

  18. Optimizing Conferencing Freeware

    ERIC Educational Resources Information Center

    Baggaley, Jon; Klaas, Jim; Wark, Norine; Depow, Jim

    2005-01-01

    The increasing range of options provided by two popular conferencing freeware products, "Yahoo Messenger" and "MSN Messenger," are discussed. Each tool contains features designed primarily for entertainment purposes, which can be customized for use in online education. This report provides suggestions for optimizing the educational potential of…

  19. Systemic delivery of factor IX messenger RNA for protein replacement therapy

    PubMed Central

    Ramaswamy, Suvasini; Tonnu, Nina; Tachikawa, Kiyoshi; Limphong, Pattraranee; Vega, Jerel B.; Karmali, Priya P.; Chivukula, Pad; Verma, Inder M.

    2017-01-01

    Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. In this report, we demonstrate systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles (LNPs) to treat a Factor IX (FIX)-deficient mouse model of hemophilia B. Delivery of human FIX (hFIX) mRNA encapsulated in our LUNAR LNPs results in a rapid pulse of FIX protein (within 4–6 h) that remains stable for up to 4–6 d and is therapeutically effective, like the recombinant human factor IX protein (rhFIX) that is the current standard of care. Extensive cytokine and liver enzyme profiling showed that repeated administration of the mRNA–LUNAR complex does not cause any adverse innate or adaptive immune responses in immune-competent, hemophilic mice. The levels of hFIX protein that were produced also remained consistent during repeated administrations. These results suggest that delivery of long mRNAs is a viable therapeutic alternative for many clotting disorders and for other hepatic diseases where recombinant proteins may be unaffordable or unsuitable. PMID:28202722

  20. Intense energetic electron flux enhancements in Mercury's magnetosphere: An integrated view with high‐resolution observations from MESSENGER

    PubMed Central

    Dewey, Ryan M.; Lawrence, David J.; Goldsten, John O.; Peplowski, Patrick N.; Korth, Haje; Slavin, James A.; Krimigis, Stamatios M.; Anderson, Brian J.; Ho, George C.; McNutt, Ralph L.; Raines, Jim M.; Schriver, David; Solomon, Sean C.

    2016-01-01

    Abstract The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) mission to Mercury has provided a wealth of new data about energetic particle phenomena. With observations from MESSENGER's Energetic Particle Spectrometer, as well as data arising from energetic electrons recorded by the X‐Ray Spectrometer and Gamma‐Ray and Neutron Spectrometer (GRNS) instruments, recent work greatly extends our record of the acceleration, transport, and loss of energetic electrons at Mercury. The combined data sets include measurements from a few keV up to several hundred keV in electron kinetic energy and have permitted relatively good spatial and temporal resolution for many events. We focus here on the detailed nature of energetic electron bursts measured by the GRNS system, and we place these events in the context of solar wind and magnetospheric forcing at Mercury. Our examination of data at high temporal resolution (10 ms) during the period March 2013 through October 2014 supports strongly the view that energetic electrons are accelerated in the near‐tail region of Mercury's magnetosphere and are subsequently “injected” onto closed magnetic field lines on the planetary nightside. The electrons populate the plasma sheet and drift rapidly eastward toward the dawn and prenoon sectors, at times executing multiple complete drifts around the planet to form “quasi‐trapped” populations. PMID:27830111

  1. Nitric oxide: a physiologic messenger.

    PubMed

    Lowenstein, C J; Dinerman, J L; Snyder, S H

    1994-02-01

    To review the physiologic role of nitric oxide, an unusual messenger molecule that mediates blood vessel relaxation, neurotransmission, and pathogen suppression. A MEDLINE search of articles published from 1987 to 1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide synthase. Animal and human studies were selected from 3044 articles to analyze the clinical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxide acts as a biological messenger molecule. Biochemical and physiologic studies were analyzed if the same results were found by three or more independent observers. Two major classes of nitric oxide synthase enzymes produce nitric oxide. The constitutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, whereas the inducible isoform found in macrophages releases large amounts of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iron, nitric oxide plays many important physiologic roles. It regulates blood pressure, transmits signals between neurons, and suppresses pathogens. Excess amounts, however, can damage host cells, causing neurotoxicity during strokes and causing the hypotension associated with sepsis. Nitric oxide is a simple molecule with many physiologic roles in the cardiovascular, neurologic, and immune systems. Although the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disease.

  2. NASA Captures First Color Image of Mercury from Orbit

    NASA Image and Video Library

    2011-03-30

    NASA image acquired: March 29, 2011 The first image acquired by MESSENGER from orbit around Mercury was actually part of an eight-image sequence, for which images were acquired through eight of the WAC’s eleven filters. Here we see a color version of that first imaged terrain; in this view the images obtained through the filters with central wavelengths of 1000 nm, 750 nm, and 430 nm are displayed in red, green, and blue, respectively. One of MESSENGER’s measurement objectives is to create an eight-color global base map at a resolution of 1 km/pixel (0.6 miles/pixel) to help understand the variations of composition across Mercury’s surface. On March 17, 2011 (March 18, 2011, UTC), MESSENGER became the first spacecraft ever to orbit the planet Mercury. The mission is currently in its commissioning phase, during which spacecraft and instrument performance are verified through a series of specially designed checkout activities. In the course of the one-year primary mission, the spacecraft's seven scientific instruments and radio science investigation will unravel the history and evolution of the Solar System's innermost planet. Visit the Why Mercury? section of this website to learn more about the science questions that the MESSENGER mission has set out to answer. Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Carnegie Institution of Washington NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Join us on Facebook

  3. New Understanding of Mercury's Magnetosphere from MESSENGER'S First Flyby

    NASA Technical Reports Server (NTRS)

    Slavin, James A.; Acuna, Mario H.; Anderson, Brian J.; Baker, Daniel N.; Benna, Mehdi; Gloeckler, George; Gold, Robert E.; Ho, George C.; Killen, M.; Korth, Haje; hide

    2008-01-01

    Observations by the MESSENGER spacecraft on 14 January 2008 have revealed new features of the solar system's smallest planetary magnetosphere. The interplanetary magnetic field orientation was unfavorable for large inputs of energy from the solar wind and no evidence of magnetic substorms, internal magnetic reconnection, or energetic particle acceleration was detected. Large-scale rotations of the magnetic field were measured along the dusk flank of the magnetosphere and ultra-tow frequency waves were frequently observed beginning near closest approach. Outbound the spacecraft encountered two current-sheet boundaries across which the magnetic field intensity decreased in a step-like manner. The outer current sheet is the magnetopause boundary. The inner current sheet is similar in structure, but weaker and -1000 km closer to the planet. Between these two current sheets the magnetic field intensity is depressed by the diamagnetic effect of planetary ions created by the photo-ionization of Mercury's exosphere.

  4. Chemical Approaches to Control Gene Expression

    PubMed Central

    Gottesfeld, Joel M.; Turner, James M.; Dervan, Peter B.

    2000-01-01

    A current goal in molecular medicine is the development of new strategies to interfere with gene expression in living cells in the hope that novel therapies for human disease will result from these efforts. This review focuses on small-molecule or chemical approaches to manipulate gene expression by modulating either transcription of messenger RNA-coding genes or protein translation. The molecules under study include natural products, designed ligands, and compounds identified through functional screens of combinatorial libraries. The cellular targets for these molecules include DNA, messenger RNA, and the protein components of the transcription, RNA processing, and translational machinery. Studies with model systems have shown promise in the inhibition of both cellular and viral gene transcription and mRNA utilization. Moreover, strategies for both repression and activation of gene transcription have been described. These studies offer promise for treatment of diseases of pathogenic (viral, bacterial, etc.) and cellular origin (cancer, genetic diseases, etc.). PMID:11097426

  5. KSC-04pd1567

    NASA Image and Video Library

    2004-07-27

    KENNEDY SPACE CENTER, FLA. - On Launch Pad 17-B at Cape Canaveral Air Force Station, the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft is seen atop the Delta II upper stage booster (middle) and the Delta II launch vehicle below. The spacecraft is ready for installation of the fairing, a molded structure that fits flush with the outside surface of the upper stage booster and forms an aerodynamically smooth joint, protecting the spacecraft during launch. Seen on the right is one of the solar panels on the spacecraft. On the left is the heat-resistant, ceramic-cloth sunshade that will protect the spacecraft’s instruments as MESSENGER orbits the Mercury where the surface reaches a high temperature near 840 degrees Fahrenheit and the solar intensity can be 11 times greater than on Earth. MESSENGER is scheduled to launch Aug. 2 and is expected to enter Mercury orbit in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  6. A cervical cancer community-based participatory research project in a Native American community.

    PubMed

    Christopher, Suzanne; Gidley, Allison L; Letiecq, Bethany; Smith, Adina; McCormick, Alma Knows His Gun

    2008-12-01

    The Messengers for Health on the Apsáalooke Reservation project uses a community-based participatory research (CBPR) approach and lay health advisors (LHAs) to generate knowledge and awareness about cervical cancer prevention among community members in a culturally competent manner. Northern Plains Native Americans, of whom Apsáalooke women are a part, continue to be disproportionately affected by cervical cancer. This article examines quantitative and qualitative changes that occurred in the community since the inception of the Messengers for Health program. Paired sample t tests are used to evaluate the one-group pretest and posttest interviews of 83 Apsáalooke women in knowledge, comfort, and cancer awareness levels. Results reveal cervical cancer knowledge gains, gains in participants' comfort discussing cancer issues, and gains in awareness of cervical cancer and the Messengers program. Field notes, meeting minutes, and community perceptions are used to qualitatively evaluate the effectiveness of the Messengers program. Practice implications are discussed.

  7. Mercury MESSENGER Stamp Unveiling

    NASA Image and Video Library

    2011-05-03

    From left, NASA Deputy Director, Planetary Science Division, Science Mission Directorate, Jim Adams, NASA Kennedy Space Center Director of Education and External Relations Cheryl Hurst, United States Postal Service Vice President of Finance Steve Masse, NASA Mercury Astronaut Scott Carpenter, NASA Administrator Charles Boldin, Daughters of NASA astronaut Alan Shepard, Alice Wackermann, Laura Shepard Churchley, and Julie Jenkins, and NASA Kennedy Space Center Director Robert Cabana pose for a photograph during an unveiling ceremony of two USPS stamps that commemorate and celebrate 50 years of US Spaceflight and the MESSENGER program during an event, Wednesday, May 4, 2011 at the NASA Kennedy Space Center in Cape Canaveral, Fla. One stamp commemorates NASA’s Project Mercury, America’s first manned spaceflight program, and NASA astronaut Alan Shepard’s historic flight on May 5, 1961, aboard spacecraft Freedom 7. The other stamp draws attention to NASA’s unmanned MESSENGER mission, a scientific investigation of the planet Mercury. On March 17, 2011, MESSENGER became the first spacecraft to enter into orbit around Mercury. Photo Credit: (NASA/Bill Ingalls)

  8. BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation.

    PubMed

    Moreira, Ricardo N; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M

    2017-09-19

    The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes. Here, we establish the importance of the balance between these two factors for accurate regulation of the transition between the planktonic and sessile lifestyles. This balance is achieved by negative-feedback regulation of BolA and c-di-GMP. BolA not only contributes directly to the motility of bacteria but also regulates the expression of diguanylate cyclases and phosphodiesterases. This expression modulation influences the synthesis and degradation of c-di-GMP, while this signaling metabolite has a negative influence in bolA mRNA transcription. Finally, we present evidence of the dominant role of BolA in biofilm, showing that, even in the presence of elevated c-di-GMP levels, biofilm formation is reduced in the absence of BolA. C-di-GMP is one of the most important bacterial second messengers involved in several cellular processes, including virulence, cell cycle regulation, biofilm formation, and flagellar synthesis. In this study, we unravelled a direct connection between the bolA morphogene and the c-di-GMP signaling molecule. We show the important cross-talk that occurs between these two molecular regulators during the transition between the motile/planktonic and adhesive/sessile lifestyles in Escherichia coli This work provides important clues that can be helpful in the development of new strategies, and the results can be applied to other organisms with relevance for human health. IMPORTANCE Bacterial cells have evolved several mechanisms to cope with environmental stresses. BolA-like proteins are widely conserved from prokaryotes to eukaryotes, and in Escherichia coli , in addition to its pleiotropic effects, this protein plays a determinant role in bacterial motility and biofilm formation regulation. Similarly, the bacterial second messenger c-di-GMP is a molecule with high importance in coordinating the switch between planktonic and sessile life in bacteria. Here we have unravelled the importance of accurate regulation of cross-talk between BolA and c-di-GMP for a proper response in the regulation of these bacterial lifestyles. This finding underlines the complexity of bacterial cell regulation, revealing the existence of one additional tool for fine-tuning such important cellular molecular mechanisms. The relationship between BolA and c-di-GMP gives new perspectives regarding biofilm formation and opens the possibility to extend our studies to other organisms with relevance for human health. Copyright © 2017 Moreira et al.

  9. Expression of messenger RNAs encoding ionotropic glutamate receptors in rat brain: regulation by haloperidol.

    PubMed

    Brené, S; Messer, C; Nestler, E J

    1998-06-01

    In situ hybridization was used to study the regional distribution of messenger RNAs encoding ionotropic glutamate receptor subtypes in the rat brain's dopaminergic cell body regions and their forebrain projection areas. Short oligonucleotide probes specific for the messenger RNAs encoding the flip or flop splice forms of the GluR1 and GluR2 AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptor subunits, or for the messenger RNAs encoding the N-methyl-D-aspartate R1 subunit, were used. Significant differences were seen in the relative messenger RNA levels, and the distribution of the flip and flop splice forms, of GluR1 and GluR2. In the dopaminergic cell groups of the substantia nigra pars compacta and the ventral tegmental area, the flip form of both GluR1 and GluR2 dominated over the flop form. Similarly, in the core division of the nucleus accumbens, GluR1 and GluR2 flip forms dominated over the flop forms. In contrast, in the accumbens shell, the GluR1 and GluR2 flop forms dominated over the flip forms. As a comparison to the AMPA receptor subunits, N-methyl-D-aspartate R1 messenger RNA was relatively evenly distributed in all the regions analysed. The results demonstrate a heterogeneous distribution of the flip and flop splice forms of GluR1 and GluR2 in the brain's dopaminergic pathways, which could contribute to physiological differences in regulation of the pathways by glutamatergic neurotransmission. We also studied regulation of glutamate receptor subunit expression in these regions by antipsychotic drugs, based on previous reports of altered levels of subunit immunoreactivity after drug treatment. Chronic administration of the typical antipsychotic drug, haloperidol, caused a small but significant induction of GluR2 flip messenger RNA in the dorsolateral caudate putamen. This effect was not seen after chronic administration of the atypical antipsychotic drug, clozapine. Significant drug regulation of the other glutamate receptor subunits studied was not observed.

  10. Effect of the Intelligent Health Messenger Box on health care professionals' knowledge, attitudes, and practice related to hand hygiene and hand bacteria counts.

    PubMed

    Saffari, Mohsen; Ghanizadeh, Ghader; Fattahipour, Rasoul; Khalaji, Kazem; Pakpour, Amir H; Koenig, Harold G

    2016-12-01

    We assessed the effectiveness of the Intelligent Health Messenger Box in promoting hand hygiene using a quasiexperimental design. Knowledge, attitudes, and self-reported practices related to hand hygiene as well as hand bacteria counts and amount of liquid soap used were measured. The intervention involved broadcasting preventive audio messages. All outcomes showed significant change after the intervention compared with before. The Intelligent Health Messenger Box can serve as a practical way to improve hand hygiene. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  11. Updated science issues and observation plans of BepiColombo Mercury Magnetosphere Orbiter (MMO)

    NASA Astrophysics Data System (ADS)

    Murakami, G.; Fujimoto, M.; Hayakawa, H.

    2017-12-01

    After the successful observation by the first Mercury orbiter MESSENGER ended in 2015, Mercury becomes one of the most curious planets to investigate. MESSENGER raised new science issues, such as the northward offset of planetary dipole magnetic filed, the highly dynamic magnetosphere, and the year-to-year constant exosphere. These outstanding discoveries still remain as open issues due to some limitations of instruments onboard MESSENGER and its extended elliptical orbit with apherm in southern hemisphere. The next Mercury exploration project BepiColombo will address these open issues. BepiColombo is an ESA-JAXA joint mission to Mercury with the aim to understand the process of planetary formation and evolution as well as to understand Mercury's extreme environment in the solar system. Two spacecraft, i.e. the Mercury Planetary Orbiter (MPO) and the Mercury Magnetospheric Orbiter (MMO), will be launched in October 2018 by an Ariane-5 launch vehicle and arrive at Mercury in December 2025. The mechanical test in a complete stack configuration has been performed in the ESA test center and successfully finished. MMO is mainly designed for plasma observations and is expected to extract essential elements of space plasma physics that become visible in the Hermean environment. MMO has large constraints on science operations, such as thermal issue and limited telemetry rate. Due to the thermal issue each science instrument cannot always be turned on. In addition, due to the low telemetry rate in average, only a part ( 20-30%) of science mission data with high resolution can be downlinked. Therefore, in order to maximize the scientific results and outcomes to be achieved by MMO, we are now working to optimize the science observation and downlink plans in detail. Here we present the updated science goals for MMO based on the latest MESSENGER results and the current observation plans how to approach these science issues.

  12. Comparison of methods of extracting messenger Ribonucleic Acid from ejaculated Porcine (Sus Scrofa) Spermatozoa

    USDA-ARS?s Scientific Manuscript database

    H. D. Guthrie, G.R. Welch, and L. A. Blomberg. Comparison of Methods of Extracting Messenger Ribonucleic Acid from Ejaculated Porcine (Sus Scrofa) Spermatozoa. Biotechnology and Germplasm Laboratory, Agricultural Research Service U. S. Department of Agriculture, Beltsville, MD 20705 The purpos...

  13. 78 FR 66962 - Advisory Committee on Construction Safety and Health (ACCSH)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... Assistant Secretary of Labor request for nominations for membership on ACCSH. DATES: ACCSH meeting: ACCSH... Office at (202) 693- 1648. Regular mail, express mail, hand delivery, or messenger (courier) service...). OSHA's Docket Office accepts deliveries (hand deliveries, express mail, and messenger service) during...

  14. MESSENGER Observation of Mercury's Magnetopause: Structure and Dynamics

    NASA Technical Reports Server (NTRS)

    Slavin, J. A.; Acuna, M. H.; Anderson, B. J.; Baker, D. N.; Benna, M.; Boardsen, S. A.; Gloeckler, G.; Gold, R. E.; Ho, G. C.; Korth, H.; hide

    2008-01-01

    MESSENGER'S 14 January 2008 encounter with Mercury has provided new observations of the magnetopause of this small magnetosphere, particularly concerning the effect of the direction of the interplanetary magnetic field (IMF) on the structure and dynamics of this boundary. The IMF was northward immediately prior to and following the passage of the MESSENGER spacecraft through Mercury's magnetosphere. However, several-minute episodes of southward IMF were observed in the magnetosheath during the inbound portion of the encounter. Evidence for reconnection at the dayside magnetopause in the form of well-developed flux transfer events (FTEs) was observed in the magnetosheath following some of these southward-B, intervals. The inbound magnetopause crossing seen in the magnetic field measurements is consistent with a transition from the magnetosheath into the plasma sheet. Immediately following MESSENGER'S entry into the magnetosphere, rotational perturbations in the magnetic field similar to those seen at the Earth in association with large-scale plasma sheet vortices driven by Kelvin-Helmholtz waves along the magnetotail boundary at the Earth were observed. The outbound magnetopause occurred during northward IMF B(sub z) and had the characteristics of a tangential discontinuity. These new observations by MESSENGER may be combined and compared with the magnetopause measurements collected by Mariner 10 to derive new understanding of the response of Mercury's magnetopause to IMF direction and its effect on the rate of solar wind energy and mass input to this small magnetosphere.

  15. Expression of endothelin-1 and constitutional nitric oxide synthase messenger RNA in saphenous vein endothelial cells exposed to arterial flow shear stress.

    PubMed

    Zhu, Z G; Li, H H; Zhang, B R

    1997-11-01

    It has long been speculated that increased blood flow shear stress might be one of the major factors affecting the patency of grafted saphenous vein in coronary artery bypass operations. The underlying cellular and molecular mechanisms for so-called "shear stress damage" have not yet been well elucidated. Endothelial cells harvested from human saphenous vein were cultured in vitro and then exposed to a high arterial level flow shear stress in the parallel flow chamber. The expression levels of endothelin-1 and constitutional nitric oxide synthase by the endothelial cells were evaluated semiquantitatively at the gene transcription (messenger RNA) level using reverse transcription polymerase chain reaction. After 7 hours of exposure to arterial level shear stress, the expression of constitutional nitric oxide synthase messenger RNA by saphenous vein endothelial cells was significantly reduced, whereas the expression of endothelin-1 messenger RNA was substantially increased. These changes were more predominant at 24 hours. Arterial level flow shear stress could cause important changes in the gene transcription level in saphenous vein endothelial cells within a short period of time. The functional alterations of saphenous vein endothelial cells, as manifested by the increased expression of endothelin-1 and decreased expression of nitric oxide synthase messenger RNA, might play a crucial role in the vein graft remodeling process.

  16. Realising effective theories of tribrid inflation: are there effects from messenger fields?

    NASA Astrophysics Data System (ADS)

    Antusch, Stefan; Nolde, David

    2015-09-01

    Tribrid inflation is a variant of supersymmetric hybrid inflation in which the inflaton is a matter field (which can be charged under gauge symmetries) and inflation ends by a GUT-scale phase transition of a waterfall field. These features make tribrid inflation a promising framework for realising inflation with particularly close connections to particle physics. Superpotentials of tribrid inflation involve effective operators suppressed by some cutoff scale, which is often taken as the Planck scale. However, these operators may also be generated by integrating out messenger superfields with masses below the Planck scale, which is in fact quite common in GUT and/or flavour models. The values of the inflaton field during inflation can then lie above this mass scale, which means that for reliably calculating the model predictions one has to go beyond the effective theory description. We therefore discuss realisations of effective theories of tribrid inflation and specify in which cases effects from the messenger fields are expected, and under which conditions they can safely be neglected. In particular, we point out how to construct realisations where, despite the fact that the inflaton field values are above the messenger mass scale, the predictions for the observables are (to a good approximation) identical to the ones calculated in the effective theory treatment where the messenger mass scale is identified with the (apparent) cutoff scale.

  17. Realising effective theories of tribrid inflation: are there effects from messenger fields?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Antusch, Stefan; Max-Planck-Institut für Physik; Nolde, David

    2015-09-22

    Tribrid inflation is a variant of supersymmetric hybrid inflation in which the inflaton is a matter field (which can be charged under gauge symmetries) and inflation ends by a GUT-scale phase transition of a waterfall field. These features make tribrid inflation a promising framework for realising inflation with particularly close connections to particle physics. Superpotentials of tribrid inflation involve effective operators suppressed by some cutoff scale, which is often taken as the Planck scale. However, these operators may also be generated by integrating out messenger superfields with masses below the Planck scale, which is in fact quite common in GUTmore » and/or flavour models. The values of the inflaton field during inflation can then lie above this mass scale, which means that for reliably calculating the model predictions one has to go beyond the effective theory description. We therefore discuss realisations of effective theories of tribrid inflation and specify in which cases effects from the messenger fields are expected, and under which conditions they can safely be neglected. In particular, we point out how to construct realisations where, despite the fact that the inflaton field values are above the messenger mass scale, the predictions for the observables are (to a good approximation) identical to the ones calculated in the effective theory treatment where the messenger mass scale is identified with the (apparent) cutoff scale.« less

  18. Realising effective theories of tribrid inflation: are there effects from messenger fields?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Antusch, Stefan; Nolde, David, E-mail: stefan.antusch@unibas.ch, E-mail: david.nolde@unibas.ch

    2015-09-01

    Tribrid inflation is a variant of supersymmetric hybrid inflation in which the inflaton is a matter field (which can be charged under gauge symmetries) and inflation ends by a GUT-scale phase transition of a waterfall field. These features make tribrid inflation a promising framework for realising inflation with particularly close connections to particle physics. Superpotentials of tribrid inflation involve effective operators suppressed by some cutoff scale, which is often taken as the Planck scale. However, these operators may also be generated by integrating out messenger superfields with masses below the Planck scale, which is in fact quite common in GUTmore » and/or flavour models. The values of the inflaton field during inflation can then lie above this mass scale, which means that for reliably calculating the model predictions one has to go beyond the effective theory description. We therefore discuss realisations of effective theories of tribrid inflation and specify in which cases effects from the messenger fields are expected, and under which conditions they can safely be neglected. In particular, we point out how to construct realisations where, despite the fact that the inflaton field values are above the messenger mass scale, the predictions for the observables are (to a good approximation) identical to the ones calculated in the effective theory treatment where the messenger mass scale is identified with the (apparent) cutoff scale.« less

  19. Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

    PubMed Central

    Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; Nguyen, Desiree; Yong, Taiming; Yang, Paul G; Poretsky, Elly; Belknap, Thomas F; Waadt, Rainer; Alemán, Fernando; Schroeder, Julian I

    2015-01-01

    A central question is how specificity in cellular responses to the eukaryotic second messenger Ca2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruple mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca2+-dependent and Ca2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca2+-signaling on a cellular, genetic, and biochemical level. DOI: http://dx.doi.org/10.7554/eLife.03599.001 PMID:26192964

  20. Correction: Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

    DOE PAGES

    Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; ...

    2015-07-20

    One central question is how specificity in cellular responses to the eukaryotic second messenger Ca 2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca 2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca 2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca 2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruplemore » mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca 2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca 2+-dependent and Ca 2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca 2+-signaling on a cellular, genetic, and biochemical level.« less

  1. Modeling of the Modulation by Buffers of Ca2+ Release through Clusters of IP3 Receptors

    PubMed Central

    Zeller, S.; Rüdiger, S.; Engel, H.; Sneyd, J.; Warnecke, G.; Parker, I.; Falcke, M.

    2009-01-01

    Abstract Intracellular Ca2+ release is a versatile second messenger system. It is modeled here by reaction-diffusion equations for the free Ca2+ and Ca2+ buffers, with spatially discrete clusters of stochastic IP3 receptor channels (IP3Rs) controlling the release of Ca2+ from the endoplasmic reticulum. IP3Rs are activated by a small rise of the cytosolic Ca2+ concentration and inhibited by large concentrations. Buffering of cytosolic Ca2+ shapes global Ca2+ transients. Here we use a model to investigate the effect of buffers with slow and fast reaction rates on single release spikes. We find that, depending on their diffusion coefficient, fast buffers can either decouple clusters or delay inhibition. Slow buffers have little effect on Ca2+ release, but affect the time course of the signals from the fluorescent Ca2+ indicator mainly by competing for Ca2+. At low [IP3], fast buffers suppress fluorescence signals, slow buffers increase the contrast between bulk signals and signals at open clusters, and large concentrations of buffers, either fast or slow, decouple clusters. PMID:19686646

  2. Nonreproductive role of gonadotropin-releasing hormone in the control of ascidian metamorphosis.

    PubMed

    Kamiya, Chisato; Ohta, Naoyuki; Ogura, Yosuke; Yoshida, Keita; Horie, Takeo; Kusakabe, Takehiro G; Satake, Honoo; Sasakura, Yasunori

    2014-12-01

    Gonadotropin-releasing hormones (GnRHs) are neuropeptides that play central roles in the reproduction of vertebrates. In the ascidian Ciona intestinalis, GnRHs and their receptors are expressed in the nervous systems at the larval stage, when animals are not yet capable of reproduction, suggesting that the hormones have non-reproductive roles. We showed that GnRHs in Ciona are involved in the animal's metamorphosis by regulating tail absorption and adult organ growth. Absorption of the larval tail and growth of the adult organs are two major events in the metamorphosis of ascidians. When larvae were treated with GnRHs, they completed tail absorption more frequently than control larvae. cAMP was suggested to be a second messenger for the induction of tail absorption by GnRHs. tGnRH-3 and tGnRH-5 (the "t" indicates "tunicate") inhibited the growth of adult organs by arresting cell cycle progression in parallel with the promotion of tail absorption. This study provides new insights into the molecular mechanisms of ascidian metamorphosis conducted by non-reproductive GnRHs. © 2014 Wiley Periodicals, Inc.

  3. Calcium as a signal integrator in developing epithelial tissues.

    PubMed

    Brodskiy, Pavel A; Zartman, Jeremiah J

    2018-05-16

    Decoding how tissue properties emerge across multiple spatial and temporal scales from the integration of local signals is a grand challenge in quantitative biology. For example, the collective behavior of epithelial cells is critical for shaping developing embryos. Understanding how epithelial cells interpret a diverse range of local signals to coordinate tissue-level processes requires a systems-level understanding of development. Integration of multiple signaling pathways that specify cell signaling information requires second messengers such as calcium ions. Increasingly, specific roles have been uncovered for calcium signaling throughout development. Calcium signaling regulates many processes including division, migration, death, and differentiation. However, the pleiotropic and ubiquitous nature of calcium signaling implies that many additional functions remain to be discovered. Here we review a selection of recent studies to highlight important insights into how multiple signals are transduced by calcium transients in developing epithelial tissues. Quantitative imaging and computational modeling have provided important insights into how calcium signaling integration occurs. Reverse-engineering the conserved features of signal integration mediated by calcium signaling will enable novel approaches in regenerative medicine and synthetic control of morphogenesis.

  4. Correction: Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

    DOE PAGES

    Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; ...

    2015-07-29

    A central question is how specificity in cellular responses to the eukaryotic second messenger Ca 2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca 2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca 2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca 2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruplemore » mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca 2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca 2+-dependent and Ca 2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca 2+-signaling on a cellular, genetic, and biochemical level.« less

  5. A Perspective on Studying G-Protein-Coupled Receptor Signaling with Resonance Energy Transfer Biosensors in Living Organisms.

    PubMed

    van Unen, Jakobus; Woolard, Jeanette; Rinken, Ago; Hoffmann, Carsten; Hill, Stephen J; Goedhart, Joachim; Bruchas, Michael R; Bouvier, Michel; Adjobo-Hermans, Merel J W

    2015-09-01

    The last frontier for a complete understanding of G-protein-coupled receptor (GPCR) biology is to be able to assess GPCR activity, interactions, and signaling in vivo, in real time within biologically intact systems. This includes the ability to detect GPCR activity, trafficking, dimerization, protein-protein interactions, second messenger production, and downstream signaling events with high spatial resolution and fast kinetic readouts. Resonance energy transfer (RET)-based biosensors allow for all of these possibilities in vitro and in cell-based assays, but moving RET into intact animals has proven difficult. Here, we provide perspectives on the optimization of biosensor design, of signal detection in living organisms, and the multidisciplinary development of in vitro and cell-based assays that more appropriately reflect the physiologic situation. In short, further development of RET-based probes, optical microscopy techniques, and mouse genome editing hold great potential over the next decade to bring real-time in vivo GPCR imaging to the forefront of pharmacology. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue.

    PubMed

    Gray, Jesse M; Karow, David S; Lu, Hang; Chang, Andy J; Chang, Jennifer S; Ellis, Ronald E; Marletta, Michael A; Bargmann, Cornelia I

    2004-07-15

    Specialized oxygen-sensing cells in the nervous system generate rapid behavioural responses to oxygen. We show here that the nematode Caenorhabditis elegans exhibits a strong behavioural preference for 5-12% oxygen, avoiding higher and lower oxygen levels. 3',5'-cyclic guanosine monophosphate (cGMP) is a common second messenger in sensory transduction and is implicated in oxygen sensation. Avoidance of high oxygen levels by C. elegans requires the sensory cGMP-gated channel tax-2/tax-4 and a specific soluble guanylate cyclase homologue, gcy-35. The GCY-35 haem domain binds molecular oxygen, unlike the haem domains of classical nitric-oxide-regulated guanylate cyclases. GCY-35 and TAX-4 mediate oxygen sensation in four sensory neurons that control a naturally polymorphic social feeding behaviour in C. elegans. Social feeding and related behaviours occur only when oxygen exceeds C. elegans' preferred level, and require gcy-35 activity. Our results suggest that GCY-35 is regulated by molecular oxygen, and that social feeding can be a behavioural strategy for responding to hyperoxic environments.

  7. GPER (GPR30): A Nongenomic Receptor (GPCR) for Steroid Hormones with Implications for Cardiovascular Disease and Cancer.

    PubMed

    Feldman, Ross D; Limbird, Lee E

    2017-01-06

    Although the rapid effects of steroids, such as estrogen and aldosterone, were postulated originally to be nongenomic, it is now appreciated that activation of such signaling pathways via a steroid-acting G protein-coupled receptor, the G protein estrogen receptor (GPER), has important transcription-dependent outcomes in the regulation of cell growth and programmed cell death secondary to GPER-regulated second-messenger pathways. GPER is expressed ubiquitously and has diverse biological effects, including regulation of endocrine, immune, neuronal, and cardiovascular functions. Perhaps the most biologically important consequences of GPER activation are the regulation of cell growth, migration, and apoptotic cell death. These cell growth regulatory effects, important in cancer biology, are also relevant in the regulation of cardiac and vascular hypertrophy and in the response to ischemia. This review provides a summary of relevant findings of the impact of GPER regulation by either estradiol or aldosterone in in vitro model systems and extends those findings to in vivo studies of direct clinical relevance for development of GPER-directed agents for treatment of cancer and cardiovascular diseases associated with cellular proliferation.

  8. Principles in redox signaling: from chemistry to functional significance.

    PubMed

    Bindoli, Alberto; Rigobello, Maria Pia

    2013-05-01

    Reactive oxygen and nitrogen species are currently considered not only harmful byproducts of aerobic respiration but also critical mediators of redox signaling. The molecules and the chemical principles sustaining the network of cellular redox regulated processes are described. Special emphasis is placed on hydrogen peroxide (H(2)O(2)), now considered as acting as a second messenger, and on sulfhydryl groups, which are the direct targets of the oxidant signal. Cysteine residues of some proteins, therefore, act as sensors of redox conditions and are oxidized in a reversible reaction. In particular, the formation of sulfenic acid and disulfide, the initial steps of thiol oxidation, are described in detail. The many cell pathways involved in reactive oxygen species formation are reported. Central to redox signaling processes are the glutathione and thioredoxin systems controlling H(2)O(2) levels and, hence, the thiol/disulfide balance. Lastly, some of the most important redox-regulated processes involving specific enzymes and organelles are described. The redox signaling area of research is rapidly expanding, and future work will examine new pathways and clarify their importance in cellular pathophysiology.

  9. Systemic Induction of NO-, Redox-, and cGMP Signaling in the Pumpkin Extrafascicular Phloem upon Local Leaf Wounding

    PubMed Central

    Gaupels, Frank; Furch, Alexandra C. U.; Zimmermann, Matthias R.; Chen, Faxing; Kaever, Volkhard; Buhtz, Anja; Kehr, Julia; Sarioglu, Hakan; Kogel, Karl-Heinz; Durner, Jörg

    2016-01-01

    Cucurbits developed the unique extrafascicular phloem (EFP) as a defensive structure against herbivorous animals. Mechanical leaf injury was previously shown to induce a systemic wound response in the EFP of pumpkin (Cucurbita maxima). Here, we demonstrate that the phloem antioxidant system and protein modifications by NO are strongly regulated during this process. Activities of the central antioxidant enzymes dehydroascorbate reductase, glutathione reductase and ascorbate reductase were rapidly down-regulated at 30 min with a second minimum at 24 h after wounding. As a consequence levels of total ascorbate and glutathione also decreased with similar bi-phasic kinetics. These results hint toward a wound-induced shift in the redox status of the EFP. Nitric oxide (NO) is another important player in stress-induced redox signaling in plants. Therefore, we analyzed NO-dependent protein modifications in the EFP. Six to forty eight hours after leaf damage total S-nitrosothiol content and protein S-nitrosylation were clearly reduced, which was contrasted by a pronounced increase in protein tyrosine nitration. Collectively, these findings suggest that NO-dependent S-nitrosylation turned into peroxynitrite-mediated protein nitration upon a stress-induced redox shift probably involving the accumulation of reactive oxygen species within the EFP. Using the biotin switch assay and anti-nitrotyrosine antibodies we identified 9 candidate S-nitrosylated and 6 candidate tyrosine-nitrated phloem proteins. The wound-responsive Phloem Protein 16-1 (PP16-1) and Cyclophilin 18 (CYP18) as well as the 26.5 kD isoform of Phloem Protein 2 (PP2) were amenable to both NO modifications and could represent important redox-sensors within the cucurbit EFP. We also found that leaf injury triggered the systemic accumulation of cyclic guanosine monophosphate (cGMP) in the EFP and discuss the possible function of this second messenger in systemic NO and redox signaling within the EFP. PMID:26904092

  10. 12 CFR 303.41 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Virgin Islands, and the Northern Mariana Islands at which deposits are received or checks paid or money... relating to transactions in which deposits are received or checks paid or money lent. A messenger service... with the FDIC to determine if the messenger service constitutes a branch. (2) A mobile branch, other...

  11. 12 CFR 303.41 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Virgin Islands, and the Northern Mariana Islands at which deposits are received or checks paid or money... relating to transactions in which deposits are received or checks paid or money lent. A messenger service... with the FDIC to determine if the messenger service constitutes a branch. (2) A mobile branch, other...

  12. 12 CFR 303.41 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Virgin Islands, and the Northern Mariana Islands at which deposits are received or checks paid or money... relating to transactions in which deposits are received or checks paid or money lent. A messenger service... with the FDIC to determine if the messenger service constitutes a branch. (2) A mobile branch, other...

  13. 12 CFR 303.41 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Virgin Islands, and the Northern Mariana Islands at which deposits are received or checks paid or money... relating to transactions in which deposits are received or checks paid or money lent. A messenger service... with the FDIC to determine if the messenger service constitutes a branch. (2) A mobile branch, other...

  14. 12 CFR 303.41 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Virgin Islands, and the Northern Mariana Islands at which deposits are received or checks paid or money... relating to transactions in which deposits are received or checks paid or money lent. A messenger service... with the FDIC to determine if the messenger service constitutes a branch. (2) A mobile branch, other...

  15. 12 CFR 7.1012 - Messenger service.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... service” means any service, such as a courier service or armored car service, used by a national bank and... service do not advertise, or otherwise represent, that the bank itself is providing the service, although the bank may advertise that its customers may use one or more third party messenger services to...

  16. Messenger RNA transcripts

    Treesearch

    Dan Cullen

    2004-01-01

    In contrast to DNA, messenger RNA (mRNA) in complex substrata is rarely analyzed, in large part because labile RNA molecules are difficult to purify. Nucleic acid extractions from fungi that colonize soil are particularly difficult and plagued by humic substances that interfere with Taq polymerase (Tebbe and Vahjen 1993 and references therein). Magnetic capture...

  17. FATHEAD MINNOW VITELLOGENIN: COMPLEMENTARY DNA SEQUENCE AND MESSENGER RNA AND PROTEIN EXPRESSION AFTER 17B-ESTRADIOL TREATMENT

    EPA Science Inventory

    Induction of vitellogenin (VTG) in oviparous animals has been proposed as a sensitive indicator of invironmental contaminants that activate the estrogen receptor. In the present study, a sensitive ribonuclease protection assay (RPA) for VTG messenger RNA (mRNA) was developed for ...

  18. Social and Virtual Networks: Evaluating Synchronous Online Interviewing Using Instant Messenger

    ERIC Educational Resources Information Center

    Hinchcliffe, Vanessa; Gavin, Helen

    2009-01-01

    This paper describes an evaluation of the quality and utility of synchronous online interviewing for data collection in social network research. Synchronous online interviews facilitated by Instant Messenger as the communication medium, were undertaken with ten final year university students. Quantitative and qualitative content analysis of…

  19. Biochemical reactions of ozone in plants

    Treesearch

    J. Brian Mudd

    1998-01-01

    Plants react biochemically to ozone in three phases: with constitutive chemicals in the apoplastic fluid and cell membranes; by forming messenger molecules by the affected constitutive materials (ethylene); and by responding to the messenger molecules with pathogenic RNAs and proteins. For instance, plant reactions with ozone result in constitutive molecules such as...

  20. Synthesis of Messenger RNA and Chromosome Structure in the Cellular Slime Mold*

    PubMed Central

    Lodish, Harvey F.; Jacobson, Allan; Firtel, Richard; Alton, Tom; Tuchman, Jessica

    1974-01-01

    This paper summarizes our knowledge of the structure and biosynthesis of messenger RNA in the slime mold Dictyostelium discoideum, the arrangement of DNA sequences in the Dictyostelium chromosome, and the changes in the pattern of predominant polypeptides synthesized during Dictyostelium development. Images PMID:4531041

  1. Intercultural Learning via Instant Messenger Interaction

    ERIC Educational Resources Information Center

    Jin, Li; Erben, Tony

    2007-01-01

    This paper reports on a qualitative study investigating the viability of instant messenger (IM) interaction to facilitate intercultural learning in a foreign language class. Eight students in a Chinese as a foreign language (CFL) class participated in the study. Each student was paired with a native speaker (NS) of Chinese, and each pair…

  2. Mercury's Messenger

    ERIC Educational Resources Information Center

    Chapman, Clark R.

    2004-01-01

    Forty years after Mariner 2, planetary exploration has still only just begun, and many more missions are on drawing boards, nearing the launch pad, or even en route across interplanetary space to their targets. One of the most challenging missions that will be conducted this decade is sending the MESSENGER spacecraft to orbit the planet Mercury.…

  3. KSC-04pd1630

    NASA Image and Video Library

    2004-08-03

    KENNEDY SPACE CENTER, FLA. - Wrapped in clouds of smoke, the Boeing Delta II rocket with its MESSENGER spacecraft on top climbs free as it lifts off on time at 2:15:56 a.m. EDT from Launch Pad 17-B, Cape Canaveral Air Force Station. MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) is on a seven-year, 4.9-billion-mile journey to the planet Mercury. The spacecraft will fly by Earth, Venus and Mercury several times, as well as circling the sun 15 times, to burn off energy before making its final approach to the inner planet on March 18, 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md.

  4. Attitude Sensor and Gyro Calibration for Messenger

    NASA Technical Reports Server (NTRS)

    O'Shaughnessy, Daniel; Pittelkau, Mark E.

    2007-01-01

    The Redundant Inertial Measurement Unit Attitude Determination/Calibration (RADICAL(TM)) filter was used to estimate star tracker and gyro calibration parameters using MESSENGER telemetry data from three calibration events. We present an overview of the MESSENGER attitude sensors and their configuration is given, the calibration maneuvers are described, the results are compared with previous calibrations, and variations and trends in the estimated calibration parameters are examined. The warm restart and covariance bump features of the RADICAL(TM) filter were used to estimate calibration parameters from two disjoint telemetry streams. Results show that the calibration parameters converge faster with much less transient variation during convergence than when the filter is cold-started at the start of each telemetry stream.

  5. KSC-04PD-1535

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. In the mobile service tower at Launch Complex 17-B, Cape Canaveral Air Force Station, workers move a panel into place above the MESSENGER (Mercury Surface, Space Environment, Geochemistry and Ranging) spacecraft. The overhead panel will suspend an environmental curtain around the spacecraft while in the tower before encapsulation. Scheduled to launch Aug. 2, MESSENGER will return to Earth for a gravity boost in July 2005, then fly past Venus twice, in October 2006 and June 2007. It is expected to enter Mercury orbit in March 2011. MESSENGER was built for NASA by the Johns Hopkins University Applied Physics Laboratory in Laurel, Md. Processing is being done at Astrotech Space Operations in Titusville, Fla

  6. Sphingosine 1-Phosphate Receptor Modulators and Drug Discovery

    PubMed Central

    Park, Soo-Jin; Im, Dong-Soon

    2017-01-01

    Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, S1P1–5. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn’s disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications. PMID:28035084

  7. Ca2+ waves across gaps in non-excitable cells induced by femtosecond laser exposure

    NASA Astrophysics Data System (ADS)

    He, Hao; Wang, Shaoyang; Li, Xun; Li, Shiyang; Hu, Minglie; Cao, Youjia; Wang, Ching-Yue

    2012-04-01

    Calcium is a second messenger in all cells for various cellular processes. It was found in astrocytes and neurons that femtosecond laser stimulation could induce Ca2+ wave propagation. In this work, a femtosecond laser with a power above a certain threshold was focused on single HeLa/HEK293T cells for Ca2+ mobilization. Several types of Ca2+ oscillation patterns were found in neighboring cells. The Ca2+ wave propagated very fast across 40-μm gaps in the Ca2+-free medium mediated by the adenosine-triphosphate released from cells. This approach could provide a clean methodology to investigate the Ca2+ dynamics in non-excitable cells.

  8. Congo Red Stain Identifies Matrix Overproduction and Is an Indirect Measurement for c-di-GMP in Many Species of Bacteria.

    PubMed

    Jones, Christopher J; Wozniak, Daniel J

    2017-01-01

    Congo red is a diazo textile dye that has been used to visualize the production of amyloid fibers for nearly a century. Microbiological applications were later developed, especially in identifying strains that produce amyloid appendages called curli and overexpressing polysaccharides in the biofilm matrix. The second messenger cyclic diguanylate (c-di-GMP) regulates the production of biofilm matrix polysaccharides, and therefore Congo red staining of samples can be utilized as an indirect measurement of elevated c-di-GMP production in bacteria. Congo red allows the identification of strains producing high c-di-GMP in an inexpensive, quantitative, and high-throughput manner.

  9. Fructose use in clinical nutrition: metabolic effects and potential consequences.

    PubMed

    Moulin, Sandra; Seematter, Gérald; Seyssel, Kevin

    2017-07-01

    The current article presents recent findings on the metabolic effects of fructose. Fructose has always been considered as a simple 'caloric' hexose only metabolized by splanchnic tissues. Nevertheless, there is growing evidence that fructose acts as a second messenger and induces effects throughout the human body. Recent discoveries made possible with the evolution of technology have highlighted that fructose induces pleiotropic effects on different tissues. The fact that all these tissues express the specific fructose carrier GLUT5 let us reconsider that fructose is not only a caloric hexose, but could also be a potential actor of some behaviors and metabolic pathways. The physiological relevance of fructose as a metabolic driver is pertinent regarding recent scientific literature.

  10. Calcium signaling in immune cells

    PubMed Central

    Vig, Monika; Kinet, Jean-Pierre

    2010-01-01

    Calcium acts as a second messenger in many cell types, including lymphocytes. Resting lymphocytes maintain a low concentration of Ca2+. However, engagement of antigen receptors induces calcium influx from the extracellular space by several routes. A chief mechanism of Ca2+ entry in lymphocytes is through store-operated calcium (SOC) channels. The identification of two important molecular components of SOC channels, CRACM1 (the pore-forming subunit) and STIM1 (the sensor of stored calcium), has allowed genetic and molecular manipulation of the SOC entry pathway. In this review, we highlight advances in the understanding of Ca2+ signaling in lymphocytes with special emphasis on SOC entry. We also discuss outstanding questions and probable future directions of the field. PMID:19088738

  11. Differential Gene Expression of Longan Under Simulated Acid Rain Stress.

    PubMed

    Zheng, Shan; Pan, Tengfei; Ma, Cuilan; Qiu, Dongliang

    2017-05-01

    Differential gene expression profile was studied in Dimocarpus longan Lour. in response to treatments of simulated acid rain with pH 2.5, 3.5, and a control (pH 5.6) using differential display reverse transcription polymerase chain reaction (DDRT-PCR). Results showed that mRNA differential display conditions were optimized to find an expressed sequence tag (EST) related with acid rain stress. The potential encoding products had 80% similarity with a transcription initiation factor IIF of Gossypium raimondii and 81% similarity with a protein product of Theobroma cacao. This fragment is the transcription factor activated by second messenger substances in longan leaves after signal perception of acid rain.

  12. KSC-2011-3296

    NASA Image and Video Library

    2011-05-04

    CAPE CANAVERAL, Fla. -- In the Rocket Garden at NASA's Kennedy Space Center Visitor Complex in Florida, Laura Churchley (left), Alice Wackerman and Julie Jenkins, daughters of Mercury Astronaut Alan Shepard, applaud during an event unveiling two new stamps to commemorate the 50th anniversary of human spaceflight from the United States Postal Service. One stamp commemorates NASA's Project Mercury and Alan Shepard's historic launch on May 5, 1961, aboard the spacecraft Freedom 7. The second stamp honors NASA's MESSENGER, which reached Mercury in March to become the first spacecraft to orbit the planet. The two missions frame a remarkable 50-year period in which America advanced space exploration through more than 1,500 crewed and uncrewed flights. Photo credit: NASA/Kim Shiflett

  13. 29 CFR 516.30 - Learners, apprentices, messengers, students, or handicapped workers employed under special...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Learners, apprentices, messengers, students, or handicapped... handicapped workers employed under special certificates as provided in section 14 of the Act. (a) With respect... education, or handicapped workers employed at special minimum hourly rates under Special Certificates...

  14. 29 CFR 516.30 - Learners, apprentices, messengers, students, or handicapped workers employed under special...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Learners, apprentices, messengers, students, or handicapped... handicapped workers employed under special certificates as provided in section 14 of the Act. (a) With respect... education, or handicapped workers employed at special minimum hourly rates under Special Certificates...

  15. 29 CFR 516.30 - Learners, apprentices, messengers, students, or handicapped workers employed under special...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Learners, apprentices, messengers, students, or handicapped... handicapped workers employed under special certificates as provided in section 14 of the Act. (a) With respect... education, or handicapped workers employed at special minimum hourly rates under Special Certificates...

  16. 29 CFR 516.30 - Learners, apprentices, messengers, students, or handicapped workers employed under special...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Learners, apprentices, messengers, students, or handicapped... handicapped workers employed under special certificates as provided in section 14 of the Act. (a) With respect... education, or handicapped workers employed at special minimum hourly rates under Special Certificates...

  17. 29 CFR 516.30 - Learners, apprentices, messengers, students, or handicapped workers employed under special...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Learners, apprentices, messengers, students, or handicapped... handicapped workers employed under special certificates as provided in section 14 of the Act. (a) With respect... education, or handicapped workers employed at special minimum hourly rates under Special Certificates...

  18. Navajo Code Talker Joe Morris, Sr. shared insights from his time as a secret World War Two messenger

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Navajo Code Talker Joe Morris, Sr. shared insights from his time as a secret World War Two messenger with his audience at NASA's Dryden Flight Research Center on Nov. 26, 2002. NASA Dryden is located on Edwards Air Force Base in California's Mojave Desert.

  19. How to Tell Bad News

    ERIC Educational Resources Information Center

    Long, Nicholas J.

    2012-01-01

    Therapists, physicians, police officers, and emergency staff often are the messengers of bad news. They have to tell a patient, a parent, or a loved one about a death, an accident, a school shooting, a life-threatening diagnosis, a terrorist attack, or a suicide. Usually the messenger bears a heavy responsibility but has little training and seeks…

  20. Unveiling MERCURY's Mysteries with Bepicolombo

    NASA Astrophysics Data System (ADS)

    Benkhoff, J.; Fujimoto, M.; Murakami, G.; Zender, J.

    2017-09-01

    NASA's MESSENGER mission has fundamentally changed our view of the innermost planet. Mercury is in many ways a very different planet from what we were expecting. Now BepiColombo has to follow up on answering the fundamental questions that MESSENGER raised and go beyond. The authors are the JAXA and ESA Project Scientists of this wonderful mission.

  1. Messenger in the Barn: Networking in a Learning Environment

    ERIC Educational Resources Information Center

    Rutter, Malcolm

    2009-01-01

    This case study describes the use of a synchronous communication application (MSN Messenger) in a large academic computing environment. It draws on data from interviews, questionnaires and student marks to examine the link between use of the application and success measured through module marks. The relationship is not simple. Total abstainers and…

  2. Corrective Feedback via Instant Messenger Learning Activities in NS-NNS and NNS-NNS Dyads

    ERIC Educational Resources Information Center

    Sotillo, Susana

    2005-01-01

    This exploratory study examines corrective feedback in native speaker-nonnative speaker (NS-NNS) and NNS-NNS dyads while participants were engaged in communicative and problem-solving activities via "Yahoo! Instant Messenger" (YIM). As "negotiation of meaning" studies of the 1990s have shown, linguistic items which learners negotiate in…

  3. Comparing Six Video Chat Tools: A Critical Evaluation by Language Teachers

    ERIC Educational Resources Information Center

    Eroz-Tuga, Betil; Sadler, Randall

    2009-01-01

    This article presents a critical comparison of the usefulness and practicality of six CMC video chat tools (CUworld, ICQ, MSN Messenger, Paltalk, Skype, and Yahoo Messenger) from the perspective of language teaching professionals. This comparison is based on the results of a semester-long project between graduate students at an American university…

  4. Audience and Witnessing: Research into Dramatherapy using Vignettes and aMSN Messenger

    ERIC Educational Resources Information Center

    Jones, Phil

    2008-01-01

    This article describes the process of research undertaken to examine therapists' responses to the concept of the core processes of change in dramatherapy. The research uses a combination of vignette description and analysis using aMSN messenger. The article describes the theoretical underpinning and rationale to the approach, and the…

  5. A Contemporary, Laboratory-Intensive Course on Messenger RNA Transcription and Processing

    ERIC Educational Resources Information Center

    Carson, Sue; Miller, Heather

    2012-01-01

    Messenger ribonucleic acid (mRNA) plays a pivotal role in the central dogma of molecular biology. Importantly, molecular events occurring during and after mRNA synthesis have the potential to create multiple proteins from one gene, leading to some of the remarkable protein diversity that genomes hold. The North Carolina State University…

  6. Tomographic Reconstruction of Mercury's Exosphere from MESSENGER Flyby Data

    NASA Technical Reports Server (NTRS)

    Killen, Rosemary M.; McClintock, William E.; Slavin, James A.; Solomon, Sean C.; Vervack, Ronald J., Jr.

    2011-01-01

    The exosphere of Mercury is among the best-studied examples of a common type of atmosphere, a surface-bounded exosphere. Mercury's exosphere was probed in 2008-2009 with Ultraviolet and Visible Spectrometer (UVVS) measurements obtained during three planetary flybys by the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft [1-3]. The measurements detailed the distribution of two previously known metallic constituents of Mercury's exosphere, Na and Ca, and indicated the presence in the gas phase of yet another metallic species, Mg. Such measurements can answer fundamental scientific questions regarding the relative importance of possible source and loss processes for exospheric species ejected from a surface boundary [4]. The trajectory of MESSENGER during the last of its three flybys provided the best spatial coverage prior to orbit insertion. The measurements by MESSENGER of Na, Ca, and Mg during the third flyby have been analyzed with a novel tomographic method. This approach maximizes the amount of information that can be extracted from line-of-sight measurements because it yields three-dimensional distributions of neutrals consistent with the data.

  7. Optimal and fast E/B separation with a dual messenger field

    NASA Astrophysics Data System (ADS)

    Kodi Ramanah, Doogesh; Lavaux, Guilhem; Wandelt, Benjamin D.

    2018-05-01

    We adapt our recently proposed dual messenger algorithm for spin field reconstruction and showcase its efficiency and effectiveness in Wiener filtering polarized cosmic microwave background (CMB) maps. Unlike conventional preconditioned conjugate gradient (PCG) solvers, our preconditioner-free technique can deal with high-resolution joint temperature and polarization maps with inhomogeneous noise distributions and arbitrary mask geometries with relative ease. Various convergence diagnostics illustrate the high quality of the dual messenger reconstruction. In contrast, the PCG implementation fails to converge to a reasonable solution for the specific problem considered. The implementation of the dual messenger method is straightforward and guarantees numerical stability and convergence. We show how the algorithm can be modified to generate fluctuation maps, which, combined with the Wiener filter solution, yield unbiased constrained signal realizations, consistent with observed data. This algorithm presents a pathway to exact global analyses of high-resolution and high-sensitivity CMB data for a statistically optimal separation of E and B modes. It is therefore relevant for current and next-generation CMB experiments, in the quest for the elusive primordial B-mode signal.

  8. Role of WhatsApp Messenger in the Laboratory Management System: A Boon to Communication.

    PubMed

    Dorwal, Pranav; Sachdev, Ritesh; Gautam, Dheeraj; Jain, Dharmendra; Sharma, Pooja; Tiwari, Assem Kumar; Raina, Vimarsh

    2016-01-01

    The revolution of internet and specifically mobile internet has occurred at a blinding pace over the last decade. With the advent of smart phones, the hand held device has become much more than a medium of voice calling. Healthcare has been catching up with the digital revolution in the form of Hospital Information System and Laboratory Information System. However, the advent of instant messaging services, which are abundantly used by the youth, can be used to improve communication and coordination among the various stake holders in the healthcare sector. We have tried to look at the impact of using the WhatsApp messenger service in the laboratory management system, by forming multiple groups of the various subsections of the laboratory. A total of 35 members used this service for a period of 3 months and their response was taken on a scale of 1 to 10. There was significant improvement in the communication in the form of sharing photographic evidence, information about accidents, critical alerts, duty rosters, academic activities and getting directives from seniors. There was also some increase in the load of adding information to the application and disturbance in the routine activities; but the benefits far outweighed the minor hassles. We thereby suggest and foresee another communication revolution which will change the way information is shared in a healthcare sector, with hospital specific dedicated apps.

  9. GABAB receptor attenuation of GABAA currents in neurons of the mammalian central nervous system.

    PubMed

    Shen, Wen; Nan, Changlong; Nelson, Peter T; Ripps, Harris; Slaughter, Malcolm M

    2017-03-01

    Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABA B receptor can suppress the ionotropic GABA A receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions. Expression of amygdala membrane microdomains in Xenopus oocytes by microtransplantation produced functional ionotropic and metabotropic GABA receptors. Most GABA A receptors had properties of α -subunit containing receptors, with ~5% having ρ -subunit properties. Only GABA A receptors with α -subunit-like properties were regulated by GABA B receptors. In mouse retinal ganglion cells, where only α -subunit-containing GABA A receptors are expressed, GABA B receptors suppressed GABA A receptor currents. This suppression was blocked by GABA B receptor antagonists, G-protein inhibitors, and GABA B receptor antibodies. Based on the kinetic differences between metabotropic and ionotropic receptors, their interaction would suppress repeated, rapid GABAergic inhibition. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  10. Light and Dark of Reactive Oxygen Species for Vascular Function: 2014 ASVB (Asian Society of Vascular Biology).

    PubMed

    Shimokawa, Hiroaki; Satoh, Kimio

    2015-05-01

    Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species, leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine.

  11. Plant natriuretic peptides: systemic regulators of plant homeostasis and defense that can affect cardiomyoblasts.

    PubMed

    Gehring, Chris; Irving, Helen

    2013-06-01

    Immunologic evidence has suggested the presence of biologically active natriuretic peptide (NPs) hormones in plants because antiatrial NP antibodies affinity purify biologically active plant NPs (PNP). In the model plant, an Arabidopsis thaliana PNP (AtPNP-A) has been identified and characterized. AtPNP-A belongs to a novel class of molecules that share some similarity with the cell wall loosening expansins but do not contain the carbohydrate-binding wall anchor thus suggesting that PNPs and atrial natriuretic peptides are heterologs. AtPNP-A acts systemically, and this is consistent with its localization in the apoplastic extracellular space and the conductive tissue. Furthermore, AtPNP-A signals via the second messenger cyclic guanosine 3',5'-monophosphate and modulates ion and water transport and homeostasis. It also plays a critical role in host defense against pathogens. AtPNP-A can be classified as novel paracrine plant hormone because it is secreted into the apoplastic space in response to stress and can enhance its own expression. Interestingly, purified recombinant PNP induces apoptosis in a dose-dependent manner and was most effective on cardiac myoblast cell lines. Because PNP is mimicking the effect of ANP in some instances, PNP may prove to provide useful leads for development of novel therapeutic NPs.

  12. Interaction of the Lyme disease spirochete with its tick vector.

    PubMed

    Caimano, Melissa J; Drecktrah, Dan; Kung, Faith; Samuels, D Scott

    2016-07-01

    Borrelia burgdorferi, the causative agent of Lyme disease (along with closely related genospecies), is in the deeply branching spirochete phylum. The bacterium is maintained in nature in an enzootic cycle that involves transmission from a tick vector to a vertebrate host and acquisition from a vertebrate host to a tick vector. During its arthropod sojourn, B. burgdorferi faces a variety of stresses, including nutrient deprivation. Here, we review some of the spirochetal factors that promote persistence, maintenance and dissemination of B. burgdorferi in the tick, and then focus on the utilization of available carbohydrates as well as the exquisite regulatory systems invoked to adapt to the austere environment between blood meals and to signal species transitions as the bacteria traverse their enzootic cycle. The spirochetes shift their source of carbon and energy from glucose in the vertebrate to glycerol in the tick. Regulation of survival under limiting nutrients requires the classic stringent response in which RelBbu controls the levels of the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively termed (p)ppGpp), while regulation at the tick-vertebrate interface as well as regulation of protective responses to the blood meal require the two-component system Hk1/Rrp1 to activate production of the second messenger cyclic-dimeric-GMP (c-di-GMP). © 2016 John Wiley & Sons Ltd.

  13. The amphiphilic action of vasopressin and analogues on the plasma membrane of Amoeba proteus.

    PubMed

    Mayers, P; Couillard, P

    1990-10-01

    Arginine (AVP) and lysine vasopressin induce a weak but statistically significant increase in the water permeability of Amoeba proteus plasmalemma. Vasotocin and deaminovasopressin, which share the hydroosmotic properties of AVP on classical vertebrate systems, are without effects on Amoeba while SKF 101926, a synthetic AVP antagonist, is even more effective than the parent compound. Theophyllin and dibutyryl-cAMP do not affect AVP action on Amoeba. Lithium, oxytocin, and carbachol are also without effect. Thus, it is unlikely that either V2 (cAMP) or V1 (phosphatidylinositol choline) receptors are involved. A clear correlation has been found between the amphiphilic character of tested peptides and their effect on Amoeba water permeability. Classical amphiphilic peptides, melittin, mastoparan, and fragment 1-8 of alpha-neoendorphin, also increased water permeability in Amoeba. It is known that vasopressin can interact with artificial lipid membranes, increasing their permeability to water. We propose that amphiphilic members of the AVP family interact directly with the lipid phase of the Amoeba membrane. Their incorporation within the lipid bilayer may cause local disruptions or may create micellar water channels as shown for other amphiphilic proteins. Our observations provide a model for the early evolution of peptide hormone systems, preceding the appearance of specific membrane receptors and associated second messenger amplifying mechanisms.

  14. Cytosolic sensing of immuno-stimulatory DNA, the enemy within.

    PubMed

    Dhanwani, Rekha; Takahashi, Mariko; Sharma, Sonia

    2018-02-01

    In the cytoplasm, DNA is sensed as a universal danger signal by the innate immune system. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor/enzyme that catalyzes formation of 2'-5'-cGAMP, an atypical cyclic di-nucleotide second messenger that binds and activates the Stimulator of Interferon Genes (STING), resulting in recruitment of Tank Binding Kinase 1 (TBK1), activation of the transcription factor Interferon Regulatory Factor 3 (IRF3), and trans-activation of innate immune response genes, including type I Interferon cytokines (IFN-I). Activation of the pro-inflammatory cGAS-STING-IRF3 response is triggered by direct recognition of the DNA genomes of bacteria and viruses, but also during RNA virus infection, neoplastic transformation, tumor immunotherapy and systemic auto-inflammatory diseases. In these circumstances, the source of immuno-stimulatory DNA has often represented a fundamental yet poorly understood aspect of the response. This review focuses on recent findings related to cGAS activation by an array of self-derived DNA substrates, including endogenous retroviral elements, mitochondrial DNA (mtDNA) and micronuclei generated as a result of genotoxic stress and DNA damage. These findings emphasize the role of the cGAS axis as a cell-intrinsic innate immune response to a wide variety of genomic insults. Copyright © 2017. Published by Elsevier Ltd.

  15. Presence of gonadotropin-releasing hormone and its messenger ribonucleic acid in human ovarian epithelial carcinoma.

    PubMed

    Ohno, T; Imai, A; Furui, T; Takahashi, K; Tamaya, T

    1993-09-01

    The purpose of this study was to investigate the expression of gonadotropin-releasing hormone messenger ribonucleic acid and the presence of gonadotropin-releasing hormone in human ovarian carcinoma known to have gonadotropin-releasing hormone binding sites and to be affected by gonadotropin-releasing hormone analog. Human ovarian carcinomas surgically removed and human ovarian carcinoma cell lines were examined. Gonadotropin-releasing hormone was determined by a radioimmunoassay and a bioassay. Gonadotropin-releasing hormone messenger ribonucleic acid was determined by reverse transcription polymerase chain reaction using oligonucleotide primers synthesized according to the published human gonadotropin-releasing hormone sequence. Gonadotropin-releasing hormone was shown to be present in extracts of ovarian mucinous cystadenocarcinoma sample (0.8 +/- 0.12 pg/mg of protein) and ovarian adenocarcinoma cell line SK-OV3 (0.92 +/- 0.17 pg/mg of protein) but not in the normal ovary and placenta. Two of two extract samples from individual cases evoked dose-dependent phosphoinositide breakdown in rat granulosa cells similar to that caused by authentic gonadotropin-releasing hormone. Gonadotropin-releasing hormone messenger ribonucleic acid was detected in two of two mucinous cystadenocarcinoma specimens, one of one serous cystadenocarcinoma, and SK-OV3 cells but not in the dysgerminoma, mucinous cystadenoma, and normal ovary and placenta. The demonstration of gonadotropin-releasing hormone and its messenger ribonucleic acid raises the possibility that gonadotropin-releasing hormone may play an autocrine regulatory role in the growth of ovarian carcinoma.

  16. Modeling the Solar Probe Plus Dust Environment: Comparison with MESSENGER Observations

    NASA Astrophysics Data System (ADS)

    Strong, S. B.; Strikwerda, T.

    2009-12-01

    NASA’s Solar Probe Plus mission will be the first to approach the Sun as close as 9 solar radii from the surface. This mission will provide the only in-situ observations of the Sun’s corona. In the absence of observational data (e.g. Helios, Pioneer), specifically at distances less than 0.4 AU, the precise ambient dust distributions at these distances remain unknown and limited to extrapolative models for distances < 1 AU (e.g. Mann et al. 2004). For the Solar Probe Plus mission, it has become critical to characterize the inner solar system dust environment in order to examine potential impacts on spacecraft health and attitude. We have implemented the Mann et al. (2004) and Grün et al. (1985) dust distribution theory along with Mie scattering effects to determine the magnitude of solar irradiance scattered towards an optical sensor such as a star tracker as a function of ecliptic latitude and longitude for distances 0.05 to 1 AU. Background irradiance data from NASA’s MESSENGER mission (down to 0.3 AU) reveal trends consistent with our model predictions, potentially validating Mann et al. (2004) and Grün et al. (1985) theory, but perhaps suggesting an enhancement of dust density short ward of 0.3 AU. This paper will present the scattering model and analysis of MESSENGER data gathered to date, during the phasing orbits, and includes star tracker background irradiance, irradiance distribution over the sky, and effects on star magnitude sensitivity and position accuracy.

  17. Mercury Conditions for the MESSENGER Mission Simulated in High- Solar-Radiation Vacuum Tests

    NASA Technical Reports Server (NTRS)

    Wong, Wayne A.

    2003-01-01

    The MESSENGER (Mercury Surface, Space Environment, Geochemistry, and Ranging) spacecraft, planned for launch in March 2004, will perform two flybys of Mercury before entering a year-long orbit of the planet in September 2009. The mission will provide opportunities for detailed characterization of the surface, interior, atmosphere, and magnetosphere of the closest planet to the Sun. The NASA Glenn Research Center and the MESSENGER spacecraft integrator, the Johns Hopkins University Applied Physics Laboratory, have partnered under a Space Act Agreement to characterize a variety of critical components and materials under simulated conditions expected near Mercury. Glenn's Vacuum Facility 6, which is equipped with a solar simulator, can simulate the vacuum and high solar radiation anticipated in Mercury orbit. The MESSENGER test hardware includes a variety of materials and components that are being characterized during the Tank 6 vacuum tests, where the hardware will be exposed to up to 11 suns insolation, simulating conditions expected in Mercury orbit. In 2002, ten solar vacuum tests were conducted, including beginning of life, end of life, backside exposure, and solar panel thermal shock cycling tests. Components tested include candidate solar array panels, sensors, thermal shielding materials, and communication devices. As an example, for the solar panel thermal shock cycling test, two candidate solar array panels were suspended on a lift mechanism that lowered the panels into a liquid-nitrogen-cooled box. After reaching -140 C, the panels were then lifted out of the box and exposed to the equivalent of 6 suns (8.1 kilowatts per square meters). After five cold soak/heating cycles were completed successfully, there was no apparent degradation in panel performance. An anticipated 100-hr thermal shield life test is planned for autumn, followed by solar panel flight qualification tests in winter. Glenn's ongoing support to the MESSENGER program has been instrumental in identifying design solutions and validating thermal performance models under a very aggressive development schedule. The test data have assisted Johns Hopkins engineers in selecting a flight solar array vendor and a thermal shield design. MESSENGER is one in a series of missions in NASA's Discovery Program. Infrared thermography provides data on the thermal gradients in the MESSENGER components during high solar insolation vacuum testing.

  18. New Horizons Educator Fellowship Program: Taking You to Pluto

    NASA Astrophysics Data System (ADS)

    Weir, H. M.; Beisser, K.; Hallau, K. G.

    2011-12-01

    The New Horizons Educator Fellowship Program (NHEFP), originally based on the MESSENGER Fellows Program, is a public outreach initiative for motivated volunteers across the nation. These volunteers are master teachers who communicate the excitement of NASA's New Horizons mission to Pluto and information about recent discoveries to teachers, students, and people in their local communities. Many of the Fellows utilize their experiences and knowledge as members of other programs such as MESSENGER Fellows, Heliophysics Educator Ambassadors, Solar System Educators and Ambassadors to promote the mission thorough professional development workshops incorporating themes, activities, and recent discoveries with other NASA programs to present a well-rounded view of our Solar System. Unlike teacher-volunteer programs tied to missions that take place closer to Earth, the time between New Horizons' launch and its closest approach to Pluto is 9.5 years, with the spacecraft in hibernation for most of its voyager. NHEFP has maintained a core group of Fellows who, through periodic face-to-face or remote training, have taken advantage of opportunities for networking, sharing of ideas in best practices, activities, and presenting and keeping audiences interested in the mission during its long journey to Pluto. This involvement has been key to the program's success.

  19. Solar system expansion and strong equivalence principle as seen by the NASA MESSENGER mission

    NASA Astrophysics Data System (ADS)

    Genova, Antonio; Mazarico, Erwan; Goossens, Sander; Lemoine, Frank G.; Neumann, Gregory A.; Smith, David E.; Zuber, Maria T.

    2018-01-01

    The NASA MESSENGER mission explored the innermost planet of the solar system and obtained a rich data set of range measurements for the determination of Mercury's ephemeris. Here we use these precise data collected over 7 years to estimate parameters related to general relativity and the evolution of the Sun. These results confirm the validity of the strong equivalence principle with a significantly refined uncertainty of the Nordtvedt parameter η = (-6.6 ± 7.2) × 10-5. By assuming a metric theory of gravitation, we retrieved the post-Newtonian parameter β = 1 + (-1.6 ± 1.8) × 10-5 and the Sun's gravitational oblateness, J2⊙J2⊙ = (2.246 ± 0.022) × 10-7. Finally, we obtain an estimate of the time variation of the Sun gravitational parameter, GM⊙°/GM⊙GM⊙°/GM⊙ = (-6.13 ± 1.47) × 10-14, which is consistent with the expected solar mass loss due to the solar wind and interior processes. This measurement allows us to constrain ∣∣G°∣∣/GG°/G to be <4 × 10-14 per year.

  20. Eight Wonders of the solar system.

    PubMed

    Bell, Edward

    2010-04-01

    Artist Ron Miller takes us on a journey to eight of the most breathtaking views that await intrepid explorers of our solar system. The scale of these natural wonders dwarfs anything Earth has to offer. What might we see and feel if we could travel to these distant domains? The artist's eye-interpreting data from probes such as NASA's Cassini, which is now exploring the Saturnian system, and MESSENGER, which has flown by Mercury three times and goes into permanent orbit next March-allows us an early visit to these unforgettable locales.

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