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Sample records for conserved wobble uridine

  1. Elongator, a conserved complex required for wobble uridine modifications in Eukaryotes

    PubMed Central

    Karlsborn, Tony; Tükenmez, Hasan; Mahmud, A K M Firoj; Xu, Fu; Xu, Hao; Byström, Anders S

    2014-01-01

    Elongator is a 6 subunit protein complex highly conserved in eukaryotes. The role of this complex has been controversial as the pleiotropic phenotypes of Elongator mutants have implicated the complex in several cellular processes. However, in yeast there is convincing evidence that the primary and probably only role of this complex is in formation of the 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) side chains on uridines at wobble position in tRNA. In this review we summarize the cellular processes that have been linked to the Elongator complex and discuss its role in tRNA modification and regulation of translation. We also describe additional gene products essential for formation of ncm5 and mcm5 side chains at U34 and their influence on Elongator activity. PMID:25607684

  2. Loss of Anticodon Wobble Uridine Modifications Affects tRNALys Function and Protein Levels in Saccharomyces cerevisiae

    PubMed Central

    Klassen, Roland; Grunewald, Pia; Thüring, Kathrin L.; Eichler, Christian; Helm, Mark; Schaffrath, Raffael

    2015-01-01

    In eukaryotes, wobble uridines in the anticodons of tRNALysUUU, tRNAGluUUC and tRNAGlnUUG are modified to 5-methoxy-carbonyl-methyl-2-thio-uridine (mcm5s2U). While mutations in subunits of the Elongator complex (Elp1-Elp6), which disable mcm5 side chain formation, or removal of components of the thiolation pathway (Ncs2/Ncs6, Urm1, Uba4) are individually tolerated, the combination of both modification defects has been reported to have lethal effects on Saccharomyces cerevisiae. Contrary to such absolute requirement of mcm5s2U for viability, we demonstrate here that in the S. cerevisiae S288C-derived background, both pathways can be simultaneously inactivated, resulting in combined loss of tRNA anticodon modifications (mcm5U and s2U) without a lethal effect. However, an elp3 disruption strain displays synthetic sick interaction and synergistic temperature sensitivity when combined with either uba4 or urm1 mutations, suggesting major translational defects in the absence of mcm5s2U modifications. Consistent with this notion, we find cellular protein levels drastically decreased in an elp3uba4 double mutant and show that this effect as well as growth phenotypes can be partially rescued by excess of tRNALysUUU. These results may indicate a global translational or protein homeostasis defect in cells simultaneously lacking mcm5 and s2 wobble uridine modification that could account for growth impairment and mainly originates from tRNALysUUU hypomodification and malfunction. PMID:25747122

  3. Modification of the wobble uridine in bacterial and mitochondrial tRNAs reading NNA/NNG triplets of 2-codon boxes

    PubMed Central

    Armengod, M Eugenia; Meseguer, Salvador; Villarroya, Magda; Prado, Silvia; Moukadiri, Ismaïl; Ruiz-Partida, Rafael; Garzón, M José; Navarro-González, Carmen; Martínez-Zamora, Ana

    2014-01-01

    Posttranscriptional modification of the uridine located at the wobble position (U34) of tRNAs is crucial for optimization of translation. Defects in the U34 modification of mitochondrial-tRNAs are associated with a group of rare diseases collectively characterized by the impairment of the oxidative phosphorylation system. Retrograde signaling pathways from mitochondria to nucleus are involved in the pathophysiology of these diseases. These pathways may be triggered by not only the disturbance of the mitochondrial (mt) translation caused by hypomodification of tRNAs, but also as a result of nonconventional roles of mt-tRNAs and mt-tRNA-modifying enzymes. The evolutionary conservation of these enzymes supports their importance for cell and organismal functions. Interestingly, bacterial and eukaryotic cells respond to stress by altering the expression or activity of these tRNA-modifying enzymes, which leads to changes in the modification status of tRNAs. This review summarizes recent findings about these enzymes and sets them within the previous data context. PMID:25607529

  4. Milankovitch wobble?

    NASA Astrophysics Data System (ADS)

    Mitchell, R. N.; Thissen, C.; Kirschvink, J. L.; Schrag, D. P.; Montanari, A.; Coccioni, R.; Slotznick, S. P.; Yamazaki, T.; Penserini, B. D.; Abrahams, J. N. H.; Cruz-Heredia, M.; Evans, D. A.

    2015-12-01

    High-resolution paleomagnetism of Cretaceous-aged limestone in Italy reveals evidence for a previously unrecognized ~10˚ directional variation, or "wobble", of either the geographic or magnetic pole on a 106-year, "Milankovitch" time scale. Ten ~1 million year (Myr) wobbles of magnetic inclination can be identified and correlated across Italy from 87-74 Myr ago, potentially refining the global polarity time scale and seafloor spreading rates. Milankovitch wobble is an omnipresent geophysical process that represents, irrespective of its mechanism, a new chronometer for age calibration with paleomagnetism. If Milankovitch wobble is interpreted as a geomagnetic artifact—the long-considered but still unproven idea that astronomical variations influence the geodynamo—the geocentric-axial dipole hypothesis would only be viable when averaged over time scales 100 times greater than currently thought, making present-day geocentricity largely coincidental. If interpreted as true geographic change, Milankovitch wobble implies an unrecognized, rapid time scale (~10˚ Myr-1) of true polar wander, possibly due to ice sheet dynamics driven by the 1.2 Myr modulation of Earth's rotational obliquity. Stable isotope data co-vary with the Milankovitch wobble, possibly favoring the polar wander mechanism that predicts rapid environmental change where the geomagnetic artifact hypothesis does not.

  5. Uridine Triacetate

    MedlinePlus

    ... much of chemotherapy medications such as fluorouracil or capecitabine (Xeloda) or who develop certain severe or life-threatening toxicities within 4 days of receiving fluorouracil or capecitabine. Uridine triacetate is in a class of medications ...

  6. Transverse wobbling in ^{135}pr.

    PubMed

    Matta, J T; Garg, U; Li, W; Frauendorf, S; Ayangeakaa, A D; Patel, D; Schlax, K W; Palit, R; Saha, S; Sethi, J; Trivedi, T; Ghugre, S S; Raut, R; Sinha, A K; Janssens, R V F; Zhu, S; Carpenter, M P; Lauritsen, T; Seweryniak, D; Chiara, C J; Kondev, F G; Hartley, D J; Petrache, C M; Mukhopadhyay, S; Lakshmi, D Vijaya; Raju, M Kumar; Madhusudhana Rao, P V; Tandel, S K; Ray, S; Dönau, F

    2015-02-27

    A pair of transverse wobbling bands is observed in the nucleus ^{135}Pr. The wobbling is characterized by ΔI=1, E2 transitions between the bands, and a decrease in the wobbling energy confirms its transverse nature. Additionally, a transition from transverse wobbling to a three-quasiparticle band comprised of strong magnetic dipole transitions is observed. These observations conform well to results from calculations with the tilted axis cranking model and the quasiparticle rotor model. PMID:25768759

  7. Wobble plate engine

    SciTech Connect

    Derderian, H.; Pronovost, J.

    1980-07-01

    A description is given of a conventional Stirling cycle engine of the type characterized by an elongated cylinder having a closed end and an open end, means for applying heat to the exterior of the cylinder to heat gas in the interior of the cylinder at the closed end thereof, a displacer piston mounted for a reciprocation within the closed end of the cylinder and a power piston axially aligned with the displacer piston and mounted for coaxial reciprocation between the displacer piston and the open end of the cylinder, the reciprocation of the displacer piston leading the corresponding stroke of the power piston by a predetermined phase angle, the improved means for properly phasing the reciprocation of the two pistons and for converting the reciprocation of the power piston into rotation of an output shaft which is parallel to the axis of reciprocation comprising: a supporting frame; an output shaft mounted on said frame for rotation about a first axis which is parallel to the axis of reciprocation of the two pistons, said shaft having an inclined cylindrical bearing surface the axis of which intersects said first axis at an acute angle; gimbal means pivotally mounted on said supporting frame for oscillation about a second axis perpendicular to and intersecting first axis; a wobble plate pivotally mounted on a third axis within said gimbal means for oscillation with said gimbal means and for further oscillation about said third axis which is mutually perpendicular to and intersecting said first and second axes, said wobble plate being rotatably mounted on said inclined cylindrical bearing surface in a plane which is perpendicular to said axis of said bearing surface whereby said output shaft can rotate about said first axis as said wobble plate oscillates about said second and third axes.

  8. Prediction of the Chandler wobble

    NASA Astrophysics Data System (ADS)

    Zotov, L.; Bizouard, C.

    2015-08-01

    Chandler wobble amplitude have been decreasing in 2010s as in 1930s. We try to predict its future behaviour through prediction of its complex envelope. The excitation of the Chandler wobble (ChW) reconstructed by Panteleev's filter was also analized. The equation for the complex envelope propagation through the Euler-Liouville equation was derived. Similarities with the climate change characteristics are discussed.

  9. A conserved and essential basic region mediates tRNA binding to the Elp1 subunit of the Saccharomyces cerevisiae Elongator complex

    PubMed Central

    Di Santo, Rachael; Bandau, Susanne; Stark, Michael J R

    2014-01-01

    Elongator is a conserved, multi-protein complex discovered in Saccharomyces cerevisiae, loss of which confers a range of pleiotropic phenotypes. Elongator in higher eukaryotes is required for normal growth and development and a mutation in the largest subunit of human Elongator (Elp1) causes familial dysautonomia, a severe recessive neuropathy. Elongator promotes addition of mcm5 and ncm5 modifications to uridine in the tRNA anticodon ‘wobble’ position in both yeast and higher eukaryotes. Since these modifications are required for the tRNAs to function efficiently, a translation defect caused by hypomodified tRNAs may therefore underlie the variety of phenotypes associated with Elongator dysfunction. The Elp1 carboxy-terminal domain contains a highly conserved arginine/lysine-rich region that resembles a nuclear localization sequence (NLS). Using alanine substitution mutagenesis, we show that this region is essential for Elongator's function in tRNA wobble uridine modification. However, rather than acting to determine the nucleo-cytoplasmic distribution of Elongator, we find that the basic region plays a critical role in a novel interaction between tRNA and the Elp1 carboxy-terminal domain. Thus the conserved basic region in Elp1 may be essential for tRNA wobble uridine modification by acting as tRNA binding motif. PMID:24750273

  10. Uridine Affects Liver Protein Glycosylation, Insulin Signaling, and Heme Biosynthesis

    PubMed Central

    Urasaki, Yasuyo; Pizzorno, Giuseppe; Le, Thuc T.

    2014-01-01

    Purines and pyrimidines are complementary bases of the genetic code. The roles of purines and their derivatives in cellular signal transduction and energy metabolism are well-known. In contrast, the roles of pyrimidines and their derivatives in cellular function remain poorly understood. In this study, the roles of uridine, a pyrimidine nucleoside, in liver metabolism are examined in mice. We report that short-term uridine administration in C57BL/6J mice increases liver protein glycosylation profiles, reduces phosphorylation level of insulin signaling proteins, and activates the HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. Short-term uridine administration is also associated with reduced liver hemin level and reduced ability for insulin-stimulated blood glucose removal during an insulin tolerance test. Some of the short-term effects of exogenous uridine in C57BL/6J mice are conserved in transgenic UPase1−/− mice with long-term elevation of endogenous uridine level. UPase1−/− mice exhibit activation of the liver HRI-eIF-2α-ATF4 heme-deficiency stress response pathway. UPase1−/− mice also exhibit impaired ability for insulin-stimulated blood glucose removal. However, other short-term effects of exogenous uridine in C57BL/6J mice are not conserved in UPase1−/− mice. UPase1−/− mice exhibit normal phosphorylation level of liver insulin signaling proteins and increased liver hemin concentration compared to untreated control C57BL/6J mice. Contrasting short-term and long-term consequences of uridine on liver metabolism suggest that uridine exerts transient effects and elicits adaptive responses. Taken together, our data support potential roles of pyrimidines and their derivatives in the regulation of liver metabolism. PMID:24918436

  11. On the wobble mode of a bicycle

    NASA Astrophysics Data System (ADS)

    Plöchl, Manfred; Edelmann, Johannes; Angrosch, Bernhard; Ott, Christoph

    2012-03-01

    Wheel shimmy and wobble are well-known dynamic phenomena at automobiles, aeroplanes and motorcycles. In particular, wobble at the motorcycle is an (unstable) eigenmode with oscillations of the wheel about the steering axis, and it is no surprise that unstable bicycle wobble is perceived unpleasant or may be dangerous, if not controlled by the rider in time. Basic research on wobble at motorcycles within the last decades has revealed a better understanding of the sudden onset of wobble, and the complex relations between parameters affecting wobble have been identified. These fundamental findings have been transferred to bicycles. As mass distribution and inertial properties, rider influence and lateral compliances of tyre and frame differ at bicycle and motorcycle, models to represent wobble at motorcycles have to prove themselves, when applied to bicycles. For that purpose numerical results are compared with measurements from test runs, and parametric influences on the stability of the wobble mode at bicycles have been evolved. All numerical analysis and measurements are based on a specific test bicycle equipped with steering angle sensor, wheel-speed sensor, global positioning system (GPS) 3-axis accelerometer, and 3-axis angular velocity gyroscopic sensor.

  12. Structure and function of uridine diphosphate glucuronosyltransferases.

    PubMed

    Meech, R; Mackenzie, P I

    1997-12-01

    1. The uridine diphosphate (UDP)-glucuronosyltransferases (UGT) are a family of enzymes that catalyse the covalent addition of glucuronic acid to a wide range of lipophilic chemicals. They play a major role in the detoxification of many exogenous and endogenous compounds by generating products that are more polar and, thus, more readily excreted in bile or urine. 2. Inherited deficiencies in UGT forms are deleterious, as exemplified by the debilitating effects of hyperbilirubinaemia and neurotoxicity in subjects with mutations in the enzyme that converts bilirubin to its more polar glucuronide. 3. The UGT protein can be conceptually divided into two domains with the amino-terminal half of the protein demonstrating greater sequence divergence between isoforms. This region apparently determines aglycone specificity. The aglycone binding site is presumed to be a 'loose' fit, as many structurally diverse substrates can be bound by the same UGT isoform. The carboxyl-terminal half, which is more conserved in sequence between different isoforms, is believed to contain a binding site for the cosubstrate UDP glucuronic acid (UDPGA). 4. Uridine diphosphate glucuronosyltransferase is localized to the endoplasmic reticulum (ER) and spans the membrane with a type I topology. The putative transmembrane domain is located near the carboxyl terminus of the protein such that only a small portion of the protein resides in the cytosol. This cytosolic tail is believed to contain an ER-targeting signal. The major portion of the protein is located in the ER lumen, including the proposed substrate-binding domains and the catalytic site. 5. The microsomal membrane impedes the access of UDPGA to the active site, resulting in latency of UGT activity in intact ER-derived microsomes. Active transport of UDPGA is believed to occur in hepatocytes, but the transport system has not been fully characterized. Uridine diphosphate glucuronosyltransferase activity is also highly lipid dependent and the

  13. A nickel complex cleaves uridine in folded RNA structures: application to E. coli tmRNA and related engineered molecules.

    PubMed

    Hickerson, R P; Watkins-Sims, C D; Burrows, C J; Atkins, J F; Gesteland, R F; Felden, B

    1998-06-12

    To gain more insight about Escherichia coli tmRNA structure, NiCR, a square planar macrocyclic nickel (II) complex, was used to probe guanine N7 exposure. On the basis of this additional structural information, a refined secondary structure of the molecule is proposed. In addition to its known specificity for guanine N7, we show here that the chemical probe can also cleave at specific uridine residues. In contrast to the alkaline-labile modification of guanine, the reactivity of NiCR at these uridine residues results in direct strand scission. To better characterize the uridine cleavage sites and assess the importance of the RNA structure for the reaction to occur, smaller RNA molecules derived from one pseudoknot (PK4) of E. coli tmRNA containing two uridine cleavage sites were engineered and probed. It is shown that this pseudoknot can fold by itself in solution and that the expected uridine residues are also cleaved by the nickel complex, suggesting that only a local sequence and/or structural context is required for cleavage. In E. coli tmRNA, the five uridine cleavage sites are located in double-stranded regions. These sites contain a G-U wobble base-pair and a downstream uridine which is cleaved. Using smaller RNAs derived from one stem of PK4, systematic changes in the proposed recognition motif indicate that the G-U pair is required for cleavage. Furthermore, there is no cleavage if the G-U pair is reversed. If the recognition motif is moved within the stem, the cleavage site moves accordingly. Additionally, if the recognition motif is changed such that the G-U pair is flanked by two uridine residues, the reactivity occurs only at the 3' uridine. Radical quenching studies have indicated that sulfate radical, as in the case of guanine oxidation, is involved in uridine oxidation. Although additional studies are required to better characterize the reaction, this paper reports a novel specificity for a chemical probe which may be useful for investigating

  14. Glycal Formation in Crystals of Uridine Phosphorylase

    SciTech Connect

    Paul, Debamita; O’Leary, Sen E.; Rajashankar, Kanagalaghatta; Bu, Weiming; Toms, Angela; Settembre, Ethan C.; Sanders, Jennie M.; Begley, Tadhg P.; Ealick, Steven E.

    2010-06-22

    Uridine phosphorylase is a key enzyme in the pyrimidine salvage pathway. This enzyme catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate (or 2{prime}-deoxyuridine to 2{prime}-deoxyribose 1-phosphate). Here we report the structure of hexameric Escherichia coli uridine phosphorylase treated with 5-fluorouridine and sulfate and dimeric bovine uridine phosphorylase treated with 5-fluoro-2{prime}-deoxyuridine or uridine, plus sulfate. In each case the electron density shows three separate species corresponding to the pyrimidine base, sulfate, and a ribosyl species, which can be modeled as a glycal. In the structures of the glycal complexes, the fluorouracil O2 atom is appropriately positioned to act as the base required for glycal formation via deprotonation at C2{prime}. Crystals of bovine uridine phosphorylase treated with 2{prime}-deoxyuridine and sulfate show intact nucleoside. NMR time course studies demonstrate that uridine phosphorylase can catalyze the hydrolysis of the fluorinated nucleosides in the absence of phosphate or sulfate, without the release of intermediates or enzyme inactivation. These results add a previously unencountered mechanistic motif to the body of information on glycal formation by enzymes catalyzing the cleavage of glycosyl bonds.

  15. Chandler wobble parameters from SLR and GRACE

    NASA Astrophysics Data System (ADS)

    Nastula, J.; Gross, R.

    2015-06-01

    The period and quality factor Q of the Chandler wobble are functions of the internal structure and dissipation processes of the Earth. Better estimates of the period and Q of the Chandler wobble can therefore be used to better understand these properties of the Earth. Here the period and Q of the Chandler wobble are estimated by finding those values that minimize the power in the Chandler frequency band of the difference between observed and modeled polar motion excitation functions. The observations of the polar motion excitation functions that we used are derived from both space-geodetic polar motion observations and from satellite laser ranging (SLR) and Gravity Recovery and Climate Experiment (GRACE) observations of the degree-2 coefficients of the Earth's time-varying gravitational field. The models of the polar motion excitation functions that we used are derived from general circulation models of the atmosphere and oceans and from hydrologic models. Our preferred values for the period and Q of the Chandler wobble that we estimated using this approach are 430.9 ± 0.7 solar days and 127 (56, 255), respectively.

  16. Excitation study of the Lageos-derived Chandler wobble

    NASA Technical Reports Server (NTRS)

    Gross, R. S.; Chao, B. F.

    1985-01-01

    Euler (1765) has deduced that any nonspherical rigid body which is rotating about some axis that is not its principal moment of inertia axis will experience a wobble as it rotates. The earth's wobble predicted by Euler was actually detected by Chandler (1891). The present paper is concerned with this wobble which is now known as the Chandler wobble. The Chandler wobble has now been under observation for more than 80 years. During part of this time, the amplitude of the wobble has actually been seen to grow. It follows that there must be some mechanisms operating to maintain (or excite) the Chandler wobble preventing it from decaying. Possible excitation mechanisms considered include earthquakes and meteorological variations. In this paper, an analysis is conducted of Lageos polar motion data for the period 1977-1983 to find out what can be learned from these data about the excitation mechanisms.

  17. On the wobble GoU and related pairs.

    PubMed Central

    Masquida, B; Westhof, E

    2000-01-01

    The wobble GoU pairs have been implicated in several biological processes where RNA molecules play a key role. We review the geometrical and conformational properties of wobble GoU pairs on the basis of available crystal structures of RNAs at high resolution. The similarities with the wobble A+oC pairs and UoU pairs are illustrated, while the differences with the recently discovered bifurcated G x U pairs are contrasted. PMID:10668794

  18. Signal detection techniques applied to the Chandler wobble

    NASA Technical Reports Server (NTRS)

    Gross, R. S.

    1985-01-01

    A sudden excitation event of the Chandler wobble should induce the earth's rotation pole to undergo damped harmonic motion. This type of motion has been searched for in the observations of the Chandler wobble using techniques based upon the concept of a matched filter. Although the signal detection techniques used here were not sensitive enough to detect any such isolated sudden excitation events, the result that was obtained is consistent with a randomly excited model of the Chandler wobble.

  19. Regioselective Mitsunobu Reaction of Partially Protected Uridine.

    PubMed

    Szlenkier, Maurycy; Kamel, Karol; Boryski, Jerzy

    2016-08-01

    Mitsunobu reaction of partially acylated uridine proceeds with high regioselectivity for intramolecular SN2 anhydro linkage closuring. Under the reaction conditions, an isomeric mixture of diacyl uridine derivatives with either free 2'- or 3'-hydroxyl group was transformed into a single cyclonucleosidic product, 2,2'-anhydro-3',5'-di-O-acyluridine. This paper presents a possible mechanism of the reactions, the explanation of observed phenomenon based on semiempirical and density functional theory (DFT) calculations and possible utility of this synthetic pathway. PMID:27351239

  20. Wobbling and LSF-based maximum likelihood expectation maximization reconstruction for wobbling PET

    NASA Astrophysics Data System (ADS)

    Kim, Hang-Keun; Son, Young-Don; Kwon, Dae-Hyuk; Joo, Yohan; Cho, Zang-Hee

    2016-04-01

    Positron emission tomography (PET) is a widely used imaging modality; however, the PET spatial resolution is not yet satisfactory for precise anatomical localization of molecular activities. Detector size is the most important factor because it determines the intrinsic resolution, which is approximately half of the detector size and determines the ultimate PET resolution. Detector size, however, cannot be made too small because both the decreased detection efficiency and the increased septal penetration effect degrade the image quality. A wobbling and line spread function (LSF)-based maximum likelihood expectation maximization (WL-MLEM) algorithm, which combined the MLEM iterative reconstruction algorithm with wobbled sampling and LSF-based deconvolution using the system matrix, was proposed for improving the spatial resolution of PET without reducing the scintillator or detector size. The new algorithm was evaluated using a simulation, and its performance was compared with that of the existing algorithms, such as conventional MLEM and LSF-based MLEM. Simulations demonstrated that the WL-MLEM algorithm yielded higher spatial resolution and image quality than the existing algorithms. The WL-MLEM algorithm with wobbling PET yielded substantially improved resolution compared with conventional algorithms with stationary PET. The algorithm can be easily extended to other iterative reconstruction algorithms, such as maximum a priori (MAP) and ordered subset expectation maximization (OSEM). The WL-MLEM algorithm with wobbling PET may offer improvements in both sensitivity and resolution, the two most sought-after features in PET design.

  1. The Forced Annual Wobble in Earth's Polar Motion

    NASA Technical Reports Server (NTRS)

    Chao, Benjamin F.

    2004-01-01

    The annual wobble in Earth's polar motion is a forced motion, as opposed to an excited natural oscillation which is the Chandler wobble in the case of polar motion. It is forced by the combination of many angular momentum variations in the geophysical fluids that exchange these variations with the solid Earth, hence changing its rotation. Among all forcing sources of the annual wobble the geophysical fluid that has the dominant contribution is the atmosphere, while the oceans and the land hydrology make up the remaining budget together with tidal influences. The latter include that from the solid Earth deformation and that from the ocean tides at the annual period. The combined forcing produces both prograde and retrograde wobbles; the prograde wobble gets magnified substantially by the near-by presence of the natural Chandler wobble resonance. On the other hand, the closeness of the prograde annual forcing power to the Chandler period is an indication that some of the power leakage into the Chandler period band becomes the main excitation source for the Chandler wobble. In this paper we will review our knowledge about annual wobble and show the status in the effort of closing the budget with the annual angular momentum variations from the various geophysical fluids.

  2. The Structure of Wobbling Sound Fields

    NASA Astrophysics Data System (ADS)

    CARLEY, M.

    2001-06-01

    The acoustic field of rotating sources such as aeroplane propellers and helicopter rotors is known to develop a marked asymmetry when the incoming flow is not parallel to the axis of rotation. This effect has been modelled using a field composed of “wobbling modes”, azimuthal modes whose amplitude is a function of azimuth. A computationally efficient method is developed for the calculation of these wobbling modes and of the acoustic field at incidence. Results are presented for operating conditions representative of a range of aircraft from a high-speed propeller at low incidence to a helicopter rotor. Detailed contour plots of the acoustic pressure are presented and discussed in the context of the geometry of the acoustic field. The field structure is interpreted in terms of the tunnelling of acoustic radiation across a transition region around the sonic radius (where the source has a Mach number of unity) and the asymmetry of the field is shown to arise from variations in the thickness of this transition region as the sonic radius varies during a revolution of the rotor.

  3. Regional atmospheric influence on the Chandler wobble

    NASA Astrophysics Data System (ADS)

    Zotov, L. V.; Bizouard, C.

    2015-03-01

    From the maps of regional contribution to atmospheric angular momentum (AAM) over the period 1948-2011 (NCEP/NCAR reanalysis data) time domain excitation in Chandler frequency band was extracted by Panteleev's filtering method. This permits us to investigate the evolution of the regional atmospheric influence on Chandler wobble. It appears that the temperate latitudes bring the strongest inputs. For pressure term they are limited to continents, and highlight the role of Europe. For the wind term they mostly result from ocean area, encompassing in particular North Atlantic. A quasi-20 year cycle is found in the regional patterns of the atmospheric excitation. The integrated AAM is finally compared with the geodetic excitation reconstructed from the observed polar motion.

  4. Uridine homeostatic disorder leads to DNA damage and tumorigenesis.

    PubMed

    Cao, Zhe; Ma, Jun; Chen, Xinchun; Zhou, Boping; Cai, Chuan; Huang, Dan; Zhang, Xuewen; Cao, Deliang

    2016-03-28

    Uridine is a natural nucleoside precursor of uridine monophosphate in organisms and thus is considered to be safe and is used in a wide range of clinical settings. The far-reaching effects of pharmacological uridine have long been neglected. Here, we report that the homeostatic disorder of uridine is carcinogenic. Targeted disruption (-/-) of murine uridine phosphorylase (UPase) disrupted the homeostasis of uridine and increased spontaneous tumorigenesis by more than 3-fold. Multiple tumors (e.g., lymphoma, hepatoma and lung adenoma) occurred simultaneously in some UPase deficient mice, but not in wild-type mice raised under the same conditions. In the tissue from UPase -/- mice, the 2'-deoxyuridine,5'-triphosphate (dUTP) levels and uracil DNA were increased and p53 was activated with an increased phospho-Ser18 p53 level. Exposing cell lines (e.g., MCF-7, RKO, HCT-8 and NCI-H460) to uridine (10 or 30 µM) led to uracil DNA damage and p53 activation, which in turn triggered the DNA damage response. In these cells, phospho-ATM, phospho-CHK2, and phospho-γH2AX were increased by uridine. These data suggest that uridine homeostatic disorder leads to uracil DNA damage and that pharmacological uridine may be carcinogenic. PMID:26801745

  5. Modern Observations of the Chandler Wobble

    NASA Astrophysics Data System (ADS)

    Zuberi, M.; Smylie, D. E.

    2009-05-01

    Modern observations of polar motion with techniques such as Very Long Baseline Interferometry (VLBI) have error levels approaching three orders of magnitude below those of classical astronometric methods. In this paper we focus on the VLBI observations which are characteristically unequally spaced. We develop a very effective method of spectral analysis for unequally spaced time sequences. First, the least squares fit to the representation of the sequence by the Discrete Fourier Transform (DFT) is calculated, weighting the observations by the inverse square of the accompanying standard error. The coefficient matrix of the normal equations of this fit is nearly singular. It is subjected to a Singular Value Decomposition (SVD). In the usual application of SVD, singular values are eliminated in order to improve the stability of the numerical system but no criterion is given for how many singular values to eliminate. To overcome this shortcoming, we introduce the Parseval condition which relates the mean square in the time domain to that in the frequency domain. Singular values are eliminated until Parseval's theorem is satisfied. In the absence of excitation, the Chandler Wobble is closely a prograde motion along a circular arc. For a step excitation, the centre of the arc shifts, giving a secular motion but an equal and nearly opposite contribution to the Chandler Wobble occurs, giving only a second order discontinuity in the pole path. To detect excitation events, we fit circular arcs by least squares to the unequally spaced data, weighting by the inverse of the square of the accompanying standard errors. A break is determined if extrapolation along the circular arc leads to a forecast pole position for which the next measured position lies outside a circle of acceptance. We find that often for quite long periods of time, there seems to be relatively little continuous excitation, leading to the conclusion that much of the excitation comes from sudden events. In

  6. Post-transcriptional modification of the wobble nucleotide in anticodon-substituted yeast tRNAArgII after microinjection into Xenopus laevis oocytes.

    PubMed Central

    Fournier, M; Haumont, E; de Henau, S; Gangloff, J; Grosjean, H

    1983-01-01

    An enzymatic procedure for the replacement of the ICG anticodon of yeast tRNAArgII by NCG trinucleotide (N = A, C, G or U) is described. Partial digestion with S1-nuclease and T1-RNAase provides fragments which, when annealed together, form an "anticodon-deprived" yeast tRNAArgII. A novel anticodon, phosphorylated with (32P) label on its 5' terminal residue, is then inserted using T4-RNA ligase. Such "anticodon-substituted" yeast tRNAArgII are microinjected into the cytoplasm of Xenopus laevis oocytes and shown to be able to interact with the anticodon maturation enzymes under in vivo conditions. Our results indicate that when adenosine occurs in the wobble position (A34) in yeast tRNAArgII it is efficiently modified into inosine (I34) while uridine (U34) is transformed into two uridine derivatives, one of which is probably mcm5U. In contrast, when a cytosine (C34) or guanosine (G34) occurs, they are not modified. These results are at variance with those obtained previously under similar conditions with anticodon derivatives of yeast tRNAAsp harbouring A, C, G or U as the first anticodon nucleotide. In this case, guanosine and uridine were modified while adenosine and cytosine were not. Images PMID:6300762

  7. The Wobbling Mode in ^167Lu

    NASA Astrophysics Data System (ADS)

    Hanan, Amro; Ma, W. C.; Winger, J. A.; Li, Y.; Thompson, J.; Hagemann, G.; Herskind, B.; Sletten, G.; Wilson, J. N.; Jensen, D. R.; Fallon, P.; Ward, D.; Diamond, R. M.; Görgen, A.; Machiavelli, A.; Hübel, H.; Domscheit, J.; Wiedenhöwer, I.

    2002-10-01

    Here we report on the experimental evidence for the wobbling mode in ^167Lu. High spin states in ^167Lu were populated through the ^123Sb(^48Ca,4n) reaction at 203 MeV from the 88 inch Cyclotron at LBNL. Five TSD bands were found in ^167Lu. The two strongest populated, TSD1 and TSD3, bands have been firmly linked to normal deformed (ND) structures. Several transitions connecting TSD2 to TSD1 were identified. From angular distribution and angular correlation analysis, spins and parities for TSD1, TSD2, and TSD3 have been determined. In addition, the mixing and branching ratios for the linking transiti on where experimentally determined to extract the B(E2)_out/B(E2)_in were obtained. These values are much larger than those expected from the signature partner. Furthermore, no three-quasiparticle excitation of the correct spin and parity is expected with similar excitation energies for TSD2 from cranking calculations. This work is supported by US DOE grants DE-FG02-95ER40939 (MSU) and DE-FG02-91ER-40609 (Yale) , the Danish Science Foundation and the German BMBF (contract No. 06 BN 907).

  8. Gravitational wave damping of neutron star wobble

    NASA Astrophysics Data System (ADS)

    Cutler, Curt; Jones, David Ian

    2001-01-01

    We calculate the effect of gravitational wave (GW) back reaction on realistic neutron stars (NS's) undergoing torque-free precession. By ``realistic'' we mean that the NS is treated as a mostly fluid body with an elastic crust, as opposed to a rigid body. We find that GW's damp NS wobble on a time scale τθ~2×105 yr [10- 7/(ΔId/I0)]2(kHz/ νs)4, where νs is the spin frequency and ΔId is the piece of the NS's inertia tensor that ``follows'' the crust's principal axis (as opposed to its spin axis). We give two different derivations of this result: one based solely on energy and angular momentum balance, and another obtained by adding the Burke-Thorne radiation reaction force to the Newtonian equations of motion. This problem was treated long ago by Bertotti and Anile, but their claimed result is wrong. When we convert from their notation to ours, we find that their τθ is too short by a factor of ~105 for the typical cases of interest and even has the wrong sign for ΔId negative. We show where their calculation went astray.

  9. Balancing wobbles in the body sodium.

    PubMed

    Titze, Jens; Rakova, Natalia; Kopp, Christoph; Dahlmann, Anke; Jantsch, Jonathan; Luft, Friedrich C

    2016-07-01

    Sodium balance is achieved within a matter of days and everything that enters should come out; sodium stores are of questionable relevance and sodium accumulation is accompanied by weight gain. Careful balance studies oftentimes conflicted with this view, and long-term studies suggested that total body sodium (TBNa) fluctuates independent of intake or body weight. We recently performed the opposite experiment in that we fixed sodium intake for weeks at three levels of sodium intake and collected all urine made. We found weekly (circaseptan) patterns in sodium excretion that were inversely related to aldosterone and directly related to cortisol. TBNa was not dependent on sodium intake, but instead exhibited far longer (greater than or equal to monthly) infradian rhythms independent of extracellular water, body weight or blood pressure. To discern the mechanisms further, we delved into sodium magnetic resonance imaging (Na-MRI) to identify sodium storage clinically. We found that sodium stores are greater in men than in women, increase with age and are higher in hypertensive than normotensive persons. We have suggestive evidence that these sodium stores can be mobilized, also in dialysis patients. The observations are in accordance with our findings that immune cells regulate a hypertonic interface in the skin interstitium that could serve as a protective barrier. Returning to our balance studies, we found that due to biological variability in 24-h sodium excretion, collecting urine for a day could not separate 12, 9 or 6 g/day sodium intakes with the precision of tossing a coin. Every other daily urine sampling correctly classified a 3-g difference in salt intake less than half the time, making the gold standard 24-h urine collection of little value in predicting salt intake. We suggest that wobbles in expected outcomes can lead to novel clinical insights even with respect to banal salt questions. PMID:26410883

  10. The Chandler wobble of the poles and its amplitude modulation

    NASA Astrophysics Data System (ADS)

    Sidorenkov, N.

    2015-08-01

    It is shown that the period of the Chandler wobble of the poles (CWP) is a combined oscillation caused by three periodic processes experienced by the Earth: (a) lunisolar tides, (b) the precession of the orbit of the Earth's monthly revolution around the barycenter of the Earth-Moon system, and (c) the motion of the perigee of this orbit. The addition of the 1.20 - year Chandler wobble to sidereal, anomalistic, and synodic lunar yearly forcing gives rise slow periodic variations in the CWP amplitude with periods of 32 to 51 years.

  11. A passive pendulum wobble damper for a low spin rate Jupiter flyby spacecraft

    NASA Technical Reports Server (NTRS)

    Fowler, R. C.

    1972-01-01

    When the spacecraft has a low spin rate and precise pointing requirements, the wobble angle must be damped in a time period equivalent to a very few wobble cycles. The design, analysis, and test of a passive pendulum wobble damper are described.

  12. Out of the Toolbox: Toddlers Differentiate Wobbly and Wooden Handrails

    ERIC Educational Resources Information Center

    Berger, Sarah E.; Adolph, Karen E.; Lobo, Sharon A.

    2005-01-01

    This study examined whether 16-month-old walking infants take the material composition of a handrail into account when assessing its effectiveness as a tool to augment balance. Infants were encouraged to cross from one platform to another via bridges of various widths (10, 20, 40cm) with either a wobbly (foam or latex) or a wooden handrail…

  13. The wobbling-to-swimming transition of rotated helices

    NASA Astrophysics Data System (ADS)

    Man, Yi; Lauga, Eric

    2013-07-01

    A growing body of work aims at designing and testing micron-scale synthetic swimmers. One method, inspired by the locomotion of flagellated bacteria, consists of applying a rotating magnetic field to a rigid, helically shaped, propeller attached to a magnetic head. When the resulting device, termed an artificial bacteria flagellum, is aligned perpendicularly to the applied field, the helix rotates and the swimmer moves forward. Experimental investigation of artificial bacteria flagella shows that at low frequency of the applied field, the axis of the helix does not align perpendicularly to the field but wobbles around the helix, with an angle decreasing as the inverse of the field frequency. Using numerical computations and asymptotic analysis, we provide a theoretical explanation for this wobbling behavior. We numerically demonstrate the wobbling-to-swimming transition as a function of the helix geometry and the dimensionless Mason number which quantifies the ratio of viscous to magnetic torques. We then employ an asymptotic expansion for near-straight helices to derive an analytical estimate for the wobbling angle allowing to rationalize our computations and past experimental results. These results can help guide future design of artificial helical swimmers.

  14. 2' and 3' Carboranyl uridines and their diethyl ether adducts

    DOEpatents

    Soloway, Albert H.; Barth, Rolf F.; Anisuzzaman, Abul K.; Alam, Fazlul; Tjarks, Werner

    1992-01-01

    There is disclosed a process for preparing carboranyl uridine nucleoside compounds and their diethyl ether adducts, which exhibit a tenfold increase in boron content over prior art boron containing nucleoside compounds. Said carboranyl uridine nucleoside compounds exhibit enhanced lipophilicity and hydrophilic properties adequate to enable solvation in aqueous media for subsequent incorporation of said compounds in methods for boron neutron capture therapy in mammalian tumor cells.

  15. Chandler wobble and free core nutation of single pulsar

    NASA Astrophysics Data System (ADS)

    Gusev, A.

    2011-10-01

    PSR B1828-11 has long-term, highly periodic and correlated variations pulse shape and of the rate of slow-down with period variations approximately 1000, 500 and 250 days (Stairs et al., 2000). There are three potential explanations of pulses time-of-arrival from pulsar concerned with the interior of the neutron star, planetary bodies, free precession and nutation. We use the Hamiltonian canonical method of Getino et al. (1999) for the dynamically symmetrical pulsar consisting of the rigid crust, elliptical liquid outer core and solid inner core of PSR B1828-11. Correctly extending theory of differential rotation of a pulsar, we investigated dependence on Chandler wobble period, Inner Chandler Wobble, retrograde Free Core Nutation and prograde Free Inner Core Nutation from ellipticity of inner crystal core, outer liquid core and total pulsar.

  16. Atmospheric excitation of the earth's annual wobble - 1980-1988

    NASA Technical Reports Server (NTRS)

    Chao, B. Fong; Au, Andrew Y.

    1991-01-01

    Global meteorological analyses from the European Center for Medium Range Weather Forecasts are employed to compute the atmospheric excitation psi of the polar motion for the 9-year period of 1980-1988. Both the matter component psi(matter) and the motion component psi (motion) are computed, the former with and without the oceanic inverted barometer (IB) effect. It is found that psi(motion) contributes significantly to the total excitation psi overall and nonnegligibly to the annual signal in psi, or the annual wobble excitation in particular. The results for the annual wobble excitation, in terms of the prograde component psi(t) and the retrogade component phsi(-) for January 1, are within the (rather large) range of previous estimates. The IB effect has a small impact on psi(+), whereas its impact on psi(-) is considerable.

  17. Measuring Motor-Shaft Clearance And Wobble During Operation

    NASA Technical Reports Server (NTRS)

    Chern, Engmin James

    1996-01-01

    Noncontact proximity sensor, preferably eddy-current liftoff probe, provides realtime measurement of distance and small variations of distance between two mechanical components designed to be maintained at precise, fixed distance. In particular, system intended for use in measuring lateral clearance and variations in lateral clearance (wobble) of motor shaft relative to motor housing while shaft turning. Provides early indication of wear in motor bearings. Rate of rotation also measured.

  18. Uridine and cytidine in the brain: their transport and utilization.

    PubMed

    Cansev, Mehmet

    2006-09-01

    The pyrimidines cytidine (as CTP) and uridine (which is converted to UTP and then CTP) contribute to brain phosphatidylcholine and phosphatidylethanolamine synthesis via the Kennedy pathway. Their uptake into brain from the circulation is initiated by nucleoside transporters located at the blood-brain barrier (BBB), and the rate at which uptake occurs is a major factor determining phosphatide synthesis. Two such transporters have been described: a low-affinity equilibrative system and a high-affinity concentrative system. It is unlikely that the low-affinity transporter contributes to brain uridine or cytidine uptake except when plasma concentrations of these compounds are increased several-fold experimentally. CNT2 proteins, the high-affinity transporters for purines like adenosine as well as for uridine, have been found in cells comprising the BBB of rats. However, to date, no comparable high-affinity carrier protein for cytidine, such as CNT1, has been detected at this location. Thus, uridine may be more available to brain than cytidine and may be the major precursor in brain for both the salvage pathway of pyrimidine nucleotides and the Kennedy pathway of phosphatide synthesis. This recognition may bear on the effects of cytidine or uridine sources in neurodegenerative diseases. PMID:16769123

  19. Estimating the Period and Q of the Chandler Wobble from Observations and Models of its Excitation

    NASA Astrophysics Data System (ADS)

    Gross, R. S.; Nastula, J.

    2014-12-01

    Any irregularly shaped solid body rotating about some axis that is not aligned with its figure axis will freely wobble as it rotates. For the Earth, this free wobble is known as the Chandler wobble in honor of S. C. Chandler, Jr. who first observed it in 1891. Unlike the forced wobbles of the Earth, such as the annual wobble, whose periods are the same as the periods of the forcing mechanisms, the period of the free Chandler wobble is a function of the internal structure and rheology of the Earth, and its decay time constant, or quality factor Q, is a function of the dissipation mechanism(s), like mantle anelasticity, that are acting to dampen it. Improved estimates of the period and Q of the Chandler wobble can therefore be used to improve our understanding of these properties of the Earth. Here, estimates of the period and Q of the Chandler wobble are obtained by finding those values that minimize the power within the Chandler band of the difference between observed and modeled polar motion excitation spanning 1962-2010. Atmosphere, ocean, and hydrology models are used to model the excitation caused by both mass and motion variations within these global geophysical fluids. Direct observations of the excitation caused by mass variations as determined from GRACE time varying gravitational field measurements are also used. The resulting estimates of the period and Q of the Chandler wobble will be presented along with a discussion of the robustness of the estimates.

  20. Radioimmunoassays of plasma thymidine, uridine, deoxyuridine, and cytidine/deoxycytidine

    SciTech Connect

    Dudman, N.P.B.; Deveski, W.B.; Tattersall, M.H.N.

    1981-08-01

    Radioimmunoassay techniques have been developed for the assay of thymidine, uridine, deoxyuridine, and deoxycytidine. Plasma levels of the first three nucleosides have been measured, and an upper limit has been determined for the plasma concentration of deoxycytidine. The assays involve displacement of a (3H)pyrimidine nucleoside from the appropriate labeled rabbit immunoglobulin. By assaying a mixture of uridine and deoxyuridine in the presence and absence of borax, the concentrations of both nucleosides have been measured. In seven healthy adults, plasma levels of uridine were 21.1 +/- 8.4 ..mu..M (mean +/- SD) and of deoxyuridine were 0.62 +/- 0.39 ..mu..M. In cancer patients, thymidine levels were 7.5 +/- 2.7 x 10/sup -7/M. The upper limit for plasma deoxycytidine levels in six healthy adults was 0.71 +/- 0.1 ..mu..M.

  1. Structural and evolutionary classification of G/U wobble basepairs in the ribosome

    PubMed Central

    Mokdad, Ali; Krasovska, Maryna V.; Sponer, Jiri; Leontis, Neocles B.

    2006-01-01

    We present a comprehensive structural, evolutionary and molecular dynamics (MD) study of the G/U wobble basepairs in the ribosome based on high-resolution crystal structures, including the recent Escherichia coli structure. These basepairs are classified according to their tertiary interactions, and sequence conservation at their positions is determined. G/U basepairs participating in tertiary interactions are more conserved than those lacking any interactions. Specific interactions occurring in the G/U shallow groove pocket—like packing interactions (P-interactions) and some phosphate backbone interactions (phosphate-in-pocket interactions)—lead to higher G/U conservation than others. Two salient cases of unique phylogenetic compensation are discovered. First, a P-interaction is conserved through a series of compensatory mutations involving all four participating nucleotides to preserve or restore the G/U in the optimal orientation. Second, a G/U basepair forming a P-interaction and another one forming a phosphate-in-pocket interaction are replaced by GNRA loops that maintain similar tertiary contacts. MD simulations were carried out on eight P-interactions. The specific GU/CG signature of this interaction observed in structure and sequence analysis was rationalized, and can now be used for improving sequence alignments. PMID:16522645

  2. Estimating the Q of the Chandler Wobble from Its Free Decay

    NASA Astrophysics Data System (ADS)

    Gross, Richard

    2015-04-01

    The Earth wobbles as it rotates because it is not rotating about its figure axis. In addition to the forced wobbles of the Earth that are caused by changes in the motion and distribution of the mass of its various components like its atmosphere and oceans, the Earth also naturally wobbles. In the absence of excitation, and because of dissipation processes within the Earth, the amplitude of this natural, or Chandler, wobble would exponentially decay with a time constant proportional to its Q, the quality factor of the wobble. Examining observations of the Chandler wobble since 1900 reveals that it apparently freely decayed during the early 1960s. The Q associated with this apparent free decay is 32.5, somewhat lower than estimates of the Chandler wobble's Q that have been obtained recently by modeling its excitation by surface geophysical fluids. This may indicate that the Chandler wobble was, in fact, not in free decay during the early 1960s or, alternatively, that recent estimates of its Q based on modeling its excitation are biased high.

  3. Polymerase Interactions with Wobble Mismatches in Synthetic Genetic Systems and Their Evolutionary Implications.

    PubMed

    Winiger, Christian B; Kim, Myong-Jung; Hoshika, Shuichi; Shaw, Ryan W; Moses, Jennifer D; Matsuura, Mariko F; Gerloff, Dietlind L; Benner, Steven A

    2016-07-19

    In addition to completing the Watson-Crick nucleobase matching "concept" (big pairs with small, hydrogen bond donors pair with hydrogen bond acceptors), artificially expanded genetic information systems (AEGIS) also challenge DNA polymerases with a complete set of mismatches, including wobble mismatches. Here, we explore wobble mismatches with AEGIS with DNA polymerase 1 from Escherichia coli. Remarkably, we find that the polymerase tolerates an AEGIS:standard wobble that has the same geometry as the G:T wobble that polymerases have evolved to exclude but excludes a wobble geometry that polymerases have never encountered in natural history. These results suggest certain limits to "structural analogy" and "evolutionary guidance" as tools to help synthetic biologists expand DNA alphabets. PMID:27347689

  4. Functional and structural consequences of uridine substitutions on H/ACA ribonucleoprotein particle pseudouridine synthase

    PubMed Central

    Zhou, Jing; Liang, Bo; Li, Hong

    2010-01-01

    Box H/ACA ribonucleoprotein protein particles catalyze the majority of pseudouridylation in functional RNA. Different from stand alone pseudouridine synthases, the RNP pseoduridine synthase comprises multiple protein and an RNA subunits. Previous studies showed that each subunit, regardless its location, is sensitive to the step of subunit placement at the catalytic center and potentially to the reaction status of the substrate. Here we describe the impact of chemical substitutions of target uridine on enzyme activity and structure. We found that 3-methyluridine in place of uridine inhibited its isomerization while 2’-deoxyuridine or 4-thiouridine did not. Significantly, crystal structures of an archaeal box H/ACA RNP bound with the nonreactive and the two post-reactive substrate analogs showed only subtle structural changes throughout the assembly except for a conserved tyrosine and a substrate anchoring loop of Cbf5. Our results suggest a potential role of these elements and the subunit that contacts them in substrate binding and product release. PMID:20575532

  5. Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice

    PubMed Central

    Urasaki, Yasuyo; Pizzorno, Giuseppe; Le, Thuc T.

    2016-01-01

    Uridine is a pyrimidine nucleoside that exerts restorative functions in tissues under stress. Short-term co-administration of uridine with multiple unrelated drugs prevents drug-induced liver lipid accumulation. Uridine has the ability to modulate liver metabolism; however, the precise mechanism has not been delineated. In this study, long-term effects of uridine on liver metabolism were examined in both HepG2 cell cultures and C57BL/6J mice. We report that uridine administration was associated with O-GlcNAc modification of FOXO1, increased gluconeogenesis, reduced insulin signaling activity, and reduced expression of a liver-specific fatty acid binding protein FABP1. Long-term uridine feeding induced systemic glucose intolerance and severe liver lipid accumulation in mice. Our findings suggest that the therapeutic potentials of uridine should be designed for short-term acute administration. PMID:26789264

  6. Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice.

    PubMed

    Urasaki, Yasuyo; Pizzorno, Giuseppe; Le, Thuc T

    2016-01-01

    Uridine is a pyrimidine nucleoside that exerts restorative functions in tissues under stress. Short-term co-administration of uridine with multiple unrelated drugs prevents drug-induced liver lipid accumulation. Uridine has the ability to modulate liver metabolism; however, the precise mechanism has not been delineated. In this study, long-term effects of uridine on liver metabolism were examined in both HepG2 cell cultures and C57BL/6J mice. We report that uridine administration was associated with O-GlcNAc modification of FOXO1, increased gluconeogenesis, reduced insulin signaling activity, and reduced expression of a liver-specific fatty acid binding protein FABP1. Long-term uridine feeding induced systemic glucose intolerance and severe liver lipid accumulation in mice. Our findings suggest that the therapeutic potentials of uridine should be designed for short-term acute administration. PMID:26789264

  7. Conservation.

    ERIC Educational Resources Information Center

    National Audubon Society, New York, NY.

    This set of teaching aids consists of seven Audubon Nature Bulletins, providing the teacher and student with informational reading on various topics in conservation. The bulletins have these titles: Plants as Makers of Soil, Water Pollution Control, The Ground Water Table, Conservation--To Keep This Earth Habitable, Our Threatened Air Supply,…

  8. Code OK3 - An upgraded version of OK2 with beam wobbling function

    NASA Astrophysics Data System (ADS)

    Ogoyski, A. I.; Kawata, S.; Popov, P. H.

    2010-07-01

    structure, including beam wobbling function. Reasons for new version: The code OK3 is based on OK2 [3] and uses the same algorithm with some improvements, the most important one is the beam wobbling function. Summary of revisions:In the code OK3, beams are subdivided on many bunches. The displacement of each bunch center from the initial beam direction is calculated. Code OK3 allows the beamlet number to vary from bunch to bunch. That reduces the calculation error especially in case of very complicated mesh structure with big internal holes. The target temperature rises during the time of energy deposition. Some procedures are improved to perform faster. The energy conservation is checked up on each step of calculation process and corrected if necessary. New procedures included in OK3 Procedure BeamCenterRot( ) rotates the beam axis around the impinging direction of each beam. Procedure BeamletRot( ) rotates the beamlet axes that belong to each beam. Procedure Rotation( ) sets the coordinates of rotated beams and beamlets in chamber and pellet systems. Procedure BeamletOut( ) calculates the lost energy of ions that have not impinged on the target. Procedure TargetT( ) sets the temperature of the target layer of energy deposition during the irradiation process. Procedure ECL( ) checks up the energy conservation law at each step of the energy deposition process. Procedure ECLt( ) performs the final check up of the energy conservation law at the end of deposition process. Modified procedures in OK3 Procedure InitBeam( ): This procedure initializes the beam radius and coefficients A1, A2, A3, A4 and A5 for Gauss distributed beams [2]. It is enlarged in OK3 and can set beams with radii from 1 to 20 mm. Procedure kBunch( ) is modified to allow beamlet number variation from bunch to bunch during the deposition. Procedure ijkSp( ) and procedure Hole( ) are modified to perform faster. Procedure Espl( ) and procedure ChechE( ) are modified to increase the calculation accuracy

  9. Wobble of a racing bicycle with a rider hands on and hands off the handlebar

    NASA Astrophysics Data System (ADS)

    Klinger, Florian; Nusime, Julia; Edelmann, Johannes; Plöchl, Manfred

    2014-05-01

    So far fundamental papers on the understanding of the wobble mode at motorcycles have been published, but in contrast, little research has been published on the wobble mode at bicycles. Wobble denotes a characteristic unstable oscillatory mode dominated by oscillations of the front wheel about the steering axis. The wobble mode of a trekking bicycle at low speeds has already been analysed, where no influence of the rider's hands on the steering system is taken into account. The wobble mode of a racing bicycle at higher speeds has not been addressed in more detail so far. The paper points out the difference between a trekking bicycle and a racing bicycle in particular with respect to the wobble mode. Different geometry, mass and stiffness properties of both types of bicycles and different characteristic positions of the rider are considered. As the wobble at racing bicycles often occurs at high speeds, when riding down a grade with hands on a dropped handlebar, a passive rider model, that takes into account the movement of the rider's arms, is presented.

  10. Rotational structures and the wobbling mode in {sup 167}Ta

    SciTech Connect

    Hartley, D. J.; Ludington, A.; Pifer, R.; Seyfried, E. P.; Vanhoy, J. R.; Janssens, R. V. F.; Carpenter, M. P.; Lauritsen, T.; McCutchan, E. A.; Zhu, S.; Riedinger, L. L.; Darby, I. G.; Riley, M. A.; Wang, X.; Aguilar, A.; Chiara, C. J.; Chowdhury, P.; Lakshmi, S.; Shirwadkar, U.; Tandel, S. K.

    2011-06-15

    Excited states in the neutron-deficient nucleus {sup 167}Ta were studied through the {sup 120}Sn({sup 51}V,4n) reaction. Twelve rotational bands have been observed and the relative excitation energy of each sequence is now known owing to the multiple interband connections. Several quasineutron alignments were observed that aided in the quasiparticle assignments of these bands. The resulting interpretation is in line with observations in neighboring nuclei. Trends in the wobbling phonon energy seen in {sup 161,163,165,167}Lu and {sup 167}Ta are also discussed and particle-rotor model calculations (assuming constant moments of inertia) are found to be inconsistent with the experimental data.

  11. The period and Q of the Chandler wobble

    NASA Technical Reports Server (NTRS)

    Smith, M. L.; Dahlen, F. A.

    1981-01-01

    The calculation of the theoretical period of the Chandler wobble is extended to account for the non-hydrostatic portion of the earth's equatorial bulge and the effect of the fluid core upon the lengthening of the period due to the pole tide. The theoretical period of a realistic perfectly elastic earth with an equilibrium pole tide is found to be 426.7 sidereal days, which is 8.5 days shorter than the observed period of 435.2 days. Using Rayleigh's principle for a rotating earth, this discrepancy is exploited together with the observed Chandler Q to place constraints on the frequency dependence of mantle anelasticity. In all cases these limits arise from exceeding the 68 percent confidence limits of + or - 2.6 days in the observed period. Since slight departures from an equilibrium pole tide affect the Q much more strongly than the period, these limits are believed to be robust.

  12. A secondary wobbling mechanism for a balloon-borne infrared telescope

    NASA Astrophysics Data System (ADS)

    Matsuhara, Hideo; Hiromoto, Norihisa; Shibai, Hiroshi; Nakagawa, Takao; Okuda, Haruyuki; Maihara, Toshinori

    1991-11-01

    A wobbling mechanism for a secondary mirror has been developed for a balloon-borne infrared telescope. Friction of the wobbling mechanism is negligibly small, and hence the wobbling mechanism is very reliable for the use in a severe environment at balloon altitudes. Motion is controlled by servo electronics, whose transfer function includes the second-order differential term of the error signal in order to improve the waveform. Good performance of the drive mechanism has been confirmed in two balloon flights in 1988 at an altitude of 31 km.

  13. The influence of earthquakes on the Chandler wobble during 1977-1983

    NASA Technical Reports Server (NTRS)

    Gross, R. S.

    1986-01-01

    Variations in the Chandler wobble's excitation function are examined in order to study the effect of 1287 earthquakes on the Chandler wobble. The computation of the moment tensor data using the centroid-moment tensor solution technique is described. An excitation function is calculated from the moment tensor data and compared to an observed excitation function derived from the polar motion observations of Gross and Chao (1985). It is observed, based on the power spectrum of the earthquake excitation function, that the earthquakes' static deformation fields have little influence on the Chandler wobble during 1977-1983.

  14. High-syn conformation of uridine and asymmetry of the hexameric molecule revealed in the high-resolution structures of Shewanella oneidensis MR-1 uridine phosphorylase in the free form and in complex with uridine.

    PubMed

    Safonova, Tatyana N; Mikhailov, Sergey N; Veiko, Vladimir P; Mordkovich, Nadezhda N; Manuvera, Valentin A; Alekseev, Cyril S; Kovalchuk, Mikhail V; Popov, Vladimir O; Polyakov, Konstantin M

    2014-12-01

    Uridine phosphorylase (UP; EC 2.4.2.3), a key enzyme in the pyrimidine-salvage pathway, catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate. Expression of UP from Shewanella oneidensis MR-1 (SoUP) was performed in Escherichia coli. The high-resolution X-ray structure of SoUP was solved in the free form and in complex with uridine. A crystal of SoUP in the free form was grown under microgravity and diffracted to ultrahigh resolution. Both forms of SoUP contained sulfate instead of phosphate in the active site owing to the presence of ammonium sulfate in the crystallization solution. The latter can be considered as a good mimic of phosphate. In the complex, uridine adopts a high-syn conformation with a nearly planar ribose ring and is present only in one subunit of the hexamer. A comparison of the structures of SoUP in the free form and in complex with the natural substrate uridine showed that the subunits of the hexamer are not identical, with the active sites having either an open or a closed conformation. In the monomers with the closed conformation, the active sites in which uridine is absent contain a glycerol molecule mimicking the ribose moiety of uridine. PMID:25478848

  15. Data-to-Wobble Cross Talk Cancellation in Optical Disc Systems

    NASA Astrophysics Data System (ADS)

    Yin, Bin; Padiy, Alexander; Schep, Kees

    2004-07-01

    In this paper, a signal processing method for removing the data-to-wobble cross talk is presented. First, various causes of the leakage from the data signal to the wobble channel are analyzed. Then a general method for using a finite impulse response (FIR) filter to cancel this leakage is proposed, which is realized electronically and adaptively, and thus is cheap and robust. Instead of a full-fledged filter, a simple structure with only one adaptable gain is suggested, specifically aimed at tackling the cross talk caused by the light path astigmatism, which is considered to be the main cause of the data leakage to the push-pull channel. This simplification results in a very cost-effective solution. Finally, the experimental results show that the cross talk cancellation significantly improves the carrier-to-noise ratio (CNR) of the wobble signal, thereby leading to more reliable wobble detection.

  16. Evaluation of a Wobbling Method Applied to Correcting Defective Pixels of CZT Detectors in SPECT Imaging

    PubMed Central

    Xie, Zhaoheng; Li, Suying; Yang, Kun; Xu, Baixuan; Ren, Qiushi

    2016-01-01

    In this paper, we propose a wobbling method to correct bad pixels in cadmium zinc telluride (CZT) detectors, using information of related images. We build up an automated device that realizes the wobbling correction for small animal Single Photon Emission Computed Tomography (SPECT) imaging. The wobbling correction method is applied to various constellations of defective pixels. The corrected images are compared with the results of conventional interpolation method, and the correction effectiveness is evaluated quantitatively using the factor of peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). In summary, the proposed wobbling method, equipped with the automatic mechanical system, provides a better image quality for correcting defective pixels, which could be used for all pixelated detectors for molecular imaging. PMID:27240368

  17. Evaluation of a Wobbling Method Applied to Correcting Defective Pixels of CZT Detectors in SPECT Imaging.

    PubMed

    Xie, Zhaoheng; Li, Suying; Yang, Kun; Xu, Baixuan; Ren, Qiushi

    2016-01-01

    In this paper, we propose a wobbling method to correct bad pixels in cadmium zinc telluride (CZT) detectors, using information of related images. We build up an automated device that realizes the wobbling correction for small animal Single Photon Emission Computed Tomography (SPECT) imaging. The wobbling correction method is applied to various constellations of defective pixels. The corrected images are compared with the results of conventional interpolation method, and the correction effectiveness is evaluated quantitatively using the factor of peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). In summary, the proposed wobbling method, equipped with the automatic mechanical system, provides a better image quality for correcting defective pixels, which could be used for all pixelated detectors for molecular imaging. PMID:27240368

  18. Illumination non-uniformity of spirally wobbling beam in heavy ion fusion

    NASA Astrophysics Data System (ADS)

    Suzuki, T.; Noguchi, K.; Kurosaki, T.; Barada, D.; Kawata, S.; Ma, Y. Y.; Ogoyski, A. I.

    2016-03-01

    In inertial confinement fusion, the driver beam illumination non-uniformity leads a degradation of fusion energy output. The illumination non-uniformity allowed is less than a few percent in inertial fusion target implosion. Heavy ion beam (HIB) accelerator provides a capability to oscillate a beam axis with a high frequency. The wobbling beams may provide a new method to reduce or smooth the beam illumination non-uniformity. In this paper the HIBs wobbling illumination scheme was optimized.

  19. Quasiparticle-random-phase approximation treatment of the transverse wobbling mode reconsidered

    NASA Astrophysics Data System (ADS)

    Frauendorf, S.; Dönau, F.

    2015-12-01

    The quasiparticle-random-phase approximation is used to study the properties of the wobbling bands in 163Lu. Assuming that the wobbling mode represents pure isoscalar orientation oscillations results in too low wobbling frequencies and transition probabilities between the one- and zero-phonon wobbling bands that are strongly collective but yet too weak for B (E2 ) out and too strong for B (M1 ) out . The inclusion of an LL interaction, which couples the wobbling mode to the scissors mode, generates the right upshift of the wobbling frequencies and the right suppression of the B (M1 ) out values toward the experimental values, but does not change the B (E2 ) out values. In analogy to the quenching of low-energy E 1 transition by coupling to the isovector giant dipole resonance, a general reduction of the M 1 transitions between quasiparticle configurations caused by coupling to the scissors mode is suggested. The small B (E2 ) out values are related to small triaxiality of the density distribution, which is found by all mean field calculations for the triaxial strongly deformed nuclei in the mass 160 region.

  20. Wobbling and Precessing Jets from Warped Disks in Binary Systems

    NASA Astrophysics Data System (ADS)

    Sheikhnezami, Somayeh; Fendt, Christian

    2015-12-01

    We present results of the first ever three-dimensional (3D) magnetohydrodynamic (MHD) simulations of the accretion-ejection structure. We investigate the 3D evolution of jets launched symmetrically from single stars but also jets from warped disks in binary systems. We have applied various model setups and tested them by simulating a stable and bipolar symmetric 3D structure from a single star-disk-jet system. Our reference simulation maintains a good axial symmetry and also a bipolar symmetry for more than 500 rotations of the inner disk, confirming the quality of our model setup. We have then implemented a 3D gravitational potential (Roche potential) due by a companion star and run a variety of simulations with different binary separations and mass ratios. These simulations show typical 3D deviations from axial symmetry, such as jet bending outside the Roche lobe or spiral arms forming in the accretion disk. In order to find indications of precession effects, we have also run an exemplary parameter setup, essentially governed by a small binary separation of only ≃200 inner disk radii. This simulation shows a strong indication that we observe the onset of a jet precession caused by the wobbling of the jet-launching disk. We estimate the opening angle of the precession cone defined by the lateral motion of the jet axis to be about 4° after about 5000 dynamical time steps.

  1. Estimating the period and Q of the Chandler Wobble from observations and models of its excitation (Abstract)

    NASA Astrophysics Data System (ADS)

    Gross, R.; Nastula, J.

    2015-08-01

    Any irregularly shaped solid body rotating about some axis that is not aligned with its figure axis will freely wobble as it rotates. For the Earth, this free wobble is known as the Chandler wobble in honor of S.C. Chandler, Jr. who first observed it in 1891. Unlike the forced wobbles of the Earth, such as the annual wobble, whose periods are the same as the periods of the forcing mechanisms, the period of the free Chandler wobble is a function of the internal structure and rheology of the Earth, and its decay time constant, or quality factor Q, is a function of the dissipation mechanism(s), like mantle anelasticity, that are acting to dampen it. Improved estimates of the period and Q of the Chandler wobble can therefore be used to improve our understanding of these properties of the Earth. Here, estimates of the period and Q of the Chandler wobble are obtained by finding those values that minimize the power within the Chandler band of the difference between observed and modeled polar motion excitation spanning 1962- 2010. Atmosphere, ocean, and hydrology models are used to model the excitation caused by both mass and motion variations within these global geophysical fluids. Direct observations of the excitation caused by mass variations as determined from GRACE time varying gravitational field measurements are also used. The resulting estimates of the period and Q of the Chandler wobble will be presented along with a discussion of the robustness of the estimates.

  2. Excitation of the Earth's Chandler wobble by southern oscillation/El Nino, 1900-1979

    NASA Technical Reports Server (NTRS)

    Chao, B. F.

    1985-01-01

    The southern oscillation/El Nino (ENSO) is the single most prominent interannual signal in global atmospheric/oceanic fluctuations. The following question is addressed: how important is the angular momentum carried by ENSO in exciting the Earth's Chandler wobble? The question is attacked through a statistical analysis of the coherence spectra (correlation as a function of frequency) between two data sets spanning 1900 to 1979-the southern oscillation index (SOI) time series and the excitation function psi (with x-component psi sub x and y-component psi sub y) of the Chandler wobble derived from the homogeneous ILS (International Latitude Service) polar motion data. The coherence power and phase in the Chandler frequency band (approx. 0.79 to 0.89 cpy) are studied. It is found that, during 1900 to 1979 the coherence between SOI and psi sub x is significant well over the 95% confidence threshold whereas that between SOI and psi sub y is practically nil. Quantitatively, the coherence study shows that ENSO provides some 20% of the observed Chandler wobble excitation power. Since earlier investigations have shown that the total atmospheric/oceanic variation can account for the Chandler wobble excitation at about 20% level, the implication is that ENSO maybe an important (interannual) part of the atmospheric/oceanic variation that is responsible for the Chandler wobble excitation during 1900 to 1979.

  3. A geometric model of a V-slit Sun sensor correcting for spacecraft wobble

    NASA Technical Reports Server (NTRS)

    Mcmartin, W. P.; Gambhir, S. S.

    1994-01-01

    A V-Slit sun sensor is body-mounted on a spin-stabilized spacecraft. During injection from a parking or transfer orbit to some final orbit, the spacecraft may not be dynamically balanced. This may result in wobble about the spacecraft spin axis as the spin axis may not be aligned with the spacecraft's axis of symmetry. While the widely used models in Spacecraft Attitude Determination and Control, edited by Wertz, correct for separation, elevation, and azimuthal mounting biases, spacecraft wobble is not taken into consideration. A geometric approach is used to develop a method for measurement of the sun angle which corrects for the magnitude and phase of spacecraft wobble. The algorithm was implemented using a set of standard mathematical routines for spherical geometry on a unit sphere.

  4. On the horizontal wobbling of an object levitated by near-field acoustic levitation.

    PubMed

    Kim, Cheol-Ho; Ih, Jeong-Guon

    2007-11-01

    A circular planar object can be levitated with several hundreds of microns by ultrasonic near-field acoustic levitation (NFAL). However, when both the sound source and the levitated object are circularly shaped and the center of the levitated object does not coincide with the source center, instability problem often occurs. When this happens, it becomes difficult to pick up or transport the object for the next process. In this study, when the center of the levitated object was offset from the source center, the moving direction of the levitated object was predicted by using the time averaged potential around the levitated object. The wobbling frequency of the levitated object was calculated by analyzing the nonlinear wobbling motion of the object. It was shown that the predicted wobbling frequencies agreed with measured ones well. Finally, a safe zone was suggested to avoid the unstable movement of an object. PMID:17590402

  5. Functional and structural impact of target uridine substitutions on the H/ACA ribonucleoprotein particle pseudouridine synthase.

    PubMed

    Zhou, Jing; Liang, Bo; Li, Hong

    2010-07-27

    Box H/ACA ribonucleoprotein protein particles catalyze the majority of pseudouridylation in functional RNA. Different from stand alone pseudouridine synthases, the RNP pseudouridine synthase comprises multiple protein subunits and an RNA subunit. Previous studies showed that each subunit, regardless its location, is sensitive to the step of subunit placement at the catalytic center and potentially to the reaction status of the substrate. Here we describe the impact of chemical substitutions of target uridine on enzyme activity and structure. We found that 3-methyluridine in place of uridine inhibited its isomerization while 2'-deoxyuridine or 4-thiouridine did not. Significantly, crystal structures of an archaeal box H/ACA RNP bound with the nonreactive and the two postreactive substrate analogues showed only subtle structural changes throughout the assembly except for a conserved tyrosine and a substrate anchoring loop of Cbf5. Our results suggest a potential role of these elements and the subunit that contacts them in substrate binding and product release. PMID:20575532

  6. Wobble Pairs of the HDV Ribozyme Play Specific Roles in Stabilization of Active Site Dynamics

    PubMed Central

    Sripathi, Kamali N.; Banáš, Pavel; Reblova, Kamila; Šponer, Jiři; Otyepka, Michal

    2015-01-01

    The hepatitis delta virus (HDV) is the only known human pathogen whose genome contains a catalytic RNA motif (ribozyme). The overall architecture of the HDV ribozyme is that of a double-nested pseudoknot, with two GU pairs flanking the active site. Although extensive studies have shown that mutation of either wobble results in decreased catalytic activity, little work has focused on linking these mutations to specific structural effects on catalytic fitness. Here we use molecular dynamics simulations based on an activated structure to probe the active site dynamics as a result of wobble pair mutations. In both wild-type and mutant ribozymes, the in-line fitness of the active site (as a measure of catalytic proficiency) strongly depends on the presence of a C75(N3H3+)N1(O5′) hydrogen bond, which positions C75 as the general acid for the reaction. Our mutational analyses show that each GU wobble supports catalytically fit conformations in distinct ways; the reverse G25U20 wobble promotes high in-line fitness, high occupancy of the C75(N3H3+)G1(O5′) general-acid hydrogen bond and stabilization of the G1U37 wobble, while the G1U37 wobble acts more locally by stabilizing high in-line fitness and the C75(N3H3+)G1(O5′) hydrogen bond. We also find that stable type I A-minor and P1.1 hydrogen bonding above and below the active site, respectively, prevent local structural disorder from spreading and disrupting global conformation. Taken together, our results define specific, often redundant architectural roles for several structural motifs of the HDV ribozyme active site, expanding the known roles of these motifs within all HDV-like ribozymes and other structured RNAs. PMID:25631765

  7. Pharmacokinetics of Uridine Following Ocular, Oral and Intravenous Administration in Rabbits

    PubMed Central

    Kim, Eunyoung; Kang, Wonku

    2013-01-01

    The pyrimidine nucleoside uridine has recently been reported to have a protective effect on cultured human corneal epithelial cells, in an animal model of dry eye and in patients. In this study, we investigate the pharmacokinetic profile of uridine in rabbits, following topical ocular (8 mg/eye), oral (450 mg/kg) and intravenous (100 mg/kg) administration. Blood and urine samples were serially taken, and uridine was measured by high-performance liquid chromatography-tandem mass spectrometry. No symptoms were noted in the animals after uridine treatment. Uridine was not detected in either plasma or urine after topical ocular administration, indicating no systemic exposure to uridine with this treatment route. Following a single intravenous dose, the plasma concentration of uridine showed a bi-exponential decay, with a rapid decline over 10 min, followed by a slow decay with a terminal half-life of 0.36 ± 0.05 h. Clearance and volume of distribution were 1.8 ± 0.6 L/h/kg and 0.58 ± 0.32 L/kg, respectively. The area under the plasma concentration-time curves (AUC) was 59.7 ± 18.2 μg·hr/ml, and urinary excretion up to 12 hr was ~7.7% of the dose. Plasma uridine reached a peak of 25.8 ± 4.1 μg/ml at 2.3 ± 0.8 hr after oral administration. The AUC was 79.0 ± 13.9 μg·hr/ml, representing ~29.4% of absolute bioavailability. About 1% of the oral dose was excreted in the urine. These results should prove useful in the design of future clinical and nonclinical studies conducted with uridine. PMID:24009876

  8. Wobbling The Galactic Disk with Bombardment of Satellite Galaxies

    NASA Astrophysics Data System (ADS)

    D'Onghia, Elena

    We propose to assess the effect of impacts of large visible satellite galaxies on a disk, as well as the relevance of the continuing bombardment of the Galactic disk by dark matter clumps as predicted by the current cosmological framework that can wobble the disk, heating it and eventually exciting ragged spiral structures. In particular, we make detailed predictions for observable features such as spiral arms, rings and their associated stars in galactic disks and relate them to the physical processes that drive their formation and evolution in our Milky Way galaxy and nearby spirals. To do this, we will combine analytic methods and numerical simulations that allow us to calculate observables, which we will compare to present and forthcoming observations. Our methodology utilizes a combination of state of the art hydrodynamic simulations of galaxy evolution and multi- wavelength radiative transfer simulations. Our primary goals are: (1) To identify the physical processes that are responsible for spiral structure formation observed in our Milky Way and nearby disk galaxies, from the flocculent to grand- designed spiral galaxies and to provide observable signatures to be compared with data on nearby galaxies combining maps of 24 micron emission (Spitzer) and cold gas, CO (Heracles) and HI (THINGS). (2) To explore different morphologies of spiral galaxies: from the multi-armed galaxies to the Milky Way sized galaxies with few arms. (3) For a Milky Way disk we will assess the effect of impacts of substructures passing through the disk to origin the asymmetry in the number density of stars recently discovered from SDSS and SEGUE data and confirmed from RAVE data. We will also investigate the disk heating in the vertical plane due to the formation of vertical oscillations that are produced by the impact and migration of stars in the disk as consequence of the heating as compared to the classical stellar migration mechanism. (4) We will measure the spiral pattern speed

  9. Improvement of the spatial resolution of the MicroPET R4 scanner by wobbling the bed.

    PubMed

    Suk, Joon Young; Thompson, Christopher J; Labuda, Aleks; Goertzen, Andrew L

    2008-04-01

    The MicroPET R4 scanner was designed for imaging small rodents such as mice and rats. In many cases the spatial resolution of this system is not sufficient for resolving structures of interest. In order to improve the spatial resolution of the MicroPET R4 through improved spatial sampling, the authors have implemented a variable radius eccentric motion, commonly referred to as wobbling, which is applied to the animal bed during scanning. The wobble motion is incorporated into the sinograms using modified histogramming software, capable of reading the bed wobble position from the list-mode data. The histogramming software corrects the data for the dwell time, apparent crystal location, and crystal-pair efficiency and applies a resolution matching filter. The data acquisition, reconstruction, and image display programs provided from the manufacturer required no modifications. For all studies a wobble period of 8 s was used. The optimal wobble radius was found to be 1.50 mm. The wobbled bed acquisition technique was tested by scanning a resolution phantom and a rat. Images from both studies acquired when using the wobble motion showed an improved spatial resolution when compared with comparable images acquired without the wobble motion. The bed wobbling mechanism can be added to any MicroPET system without major changes and without compromising any imaging modes. Implementing the wobble mechanism may represent a cost-effective method to upgrade the spatial resolution of a MicroPET when compared to the purchase of a newer generation system. PMID:18491514

  10. Photophysical properties of zinc phthalocyanine-uridine single walled carbon nanotube - conjugates

    NASA Astrophysics Data System (ADS)

    Ogbodu, Racheal O.; Amuhaya, Edith K.; Mashazi, Philani; Nyokong, Tebello

    2015-10-01

    The photophysical properties of the conjugate of uridine and zinc mono carboxy phenoxy phthalocyanine (ZnMCPPc-uridine, 4) are reported in this work. The conjugate was also adsorbed onto single walled carbon nanotubes (ZnMCPPc-uridine-SWCNT, 5). The X-ray photoelectron spectroscopy of 4 showed three N 1s peaks while that of 5 showed four N 1s peak, a new peak at 399.4 eV of 5 was assigned to pyrrolidonic nitrogen, due to the interaction of the pyrrolic nitrogen of 4 with the oxygen moiety of SWCNT-COOH in 5. The triplet lifetime, triplet and singlet oxygen quantum yields of the zinc mono carboxy phenoxy phthalocyanine increased by over 40% in the presence of uridine. SWCNTs resulted in only a small quenching of the triplet state parameters of 4.

  11. Gas-phase study on uridine: Conformation and X-ray photofragmentation.

    PubMed

    Itälä, Eero; Kooser, Kuno; Rachlew, Elisabeth; Levola, Helena; Ha, Dang Trinh; Kukk, Edwin

    2015-05-21

    Fragmentation of RNA nucleoside uridine, induced by carbon 1s core ionization, has been studied. The measurements by combined electron and ion spectroscopy have been performed in gas phase utilizing synchrotron radiation. As uridine is a combination of d-ribose and uracil, which have been studied earlier with the same method, this study also considers the effect of chemical environment and the relevant functional groups. Furthermore, since in core ionization the initial core hole is always highly localized, charge migration prior to fragmentation has been studied here. This study also demonstrates the destructive nature of core ionization as in most cases the C 1s ionization of uridine leads to concerted explosions producing only small fragments with masses ≤43 amu. In addition to fragmentation patterns, we found out that upon evaporation the sugar part of the uridine molecule attains hexagonal form. PMID:26001457

  12. Gas-phase study on uridine: Conformation and X-ray photofragmentation

    NASA Astrophysics Data System (ADS)

    Itälä, Eero; Kooser, Kuno; Rachlew, Elisabeth; Levola, Helena; Ha, Dang Trinh; Kukk, Edwin

    2015-05-01

    Fragmentation of RNA nucleoside uridine, induced by carbon 1s core ionization, has been studied. The measurements by combined electron and ion spectroscopy have been performed in gas phase utilizing synchrotron radiation. As uridine is a combination of d-ribose and uracil, which have been studied earlier with the same method, this study also considers the effect of chemical environment and the relevant functional groups. Furthermore, since in core ionization the initial core hole is always highly localized, charge migration prior to fragmentation has been studied here. This study also demonstrates the destructive nature of core ionization as in most cases the C 1s ionization of uridine leads to concerted explosions producing only small fragments with masses ≤43 amu. In addition to fragmentation patterns, we found out that upon evaporation the sugar part of the uridine molecule attains hexagonal form.

  13. Gas-phase study on uridine: Conformation and X-ray photofragmentation

    SciTech Connect

    Itälä, Eero Kooser, Kuno; Levola, Helena; Rachlew, Elisabeth; Ha, Dang Trinh; Kukk, Edwin

    2015-05-21

    Fragmentation of RNA nucleoside uridine, induced by carbon 1s core ionization, has been studied. The measurements by combined electron and ion spectroscopy have been performed in gas phase utilizing synchrotron radiation. As uridine is a combination of d-ribose and uracil, which have been studied earlier with the same method, this study also considers the effect of chemical environment and the relevant functional groups. Furthermore, since in core ionization the initial core hole is always highly localized, charge migration prior to fragmentation has been studied here. This study also demonstrates the destructive nature of core ionization as in most cases the C 1s ionization of uridine leads to concerted explosions producing only small fragments with masses ≤43 amu. In addition to fragmentation patterns, we found out that upon evaporation the sugar part of the uridine molecule attains hexagonal form.

  14. Modern observations of the effect of earthquakes on the Chandler wobble

    NASA Astrophysics Data System (ADS)

    Smylie, D. E.; Henderson, Gary A.; Zuberi, Midhat

    2015-01-01

    Earthquakes have long been postulated as the source of excitation of the Chandler wobble (Mansinha and Smylie, 1967). More recently, the classical astronometric observations of the polar motion have been replaced by very long baseline interferometric (VLBI) observations with an improvement in accuracy by a factor of several thousand. We analyze the record of nearly 29 years of VLBI polar motion observations from the Goddard Space Flight Center. In addition to the Chandler wobble, the polar motion has annual components making the analysis more difficult. The present study extends the polar motion sequence in both directions by the maximum entropy method (MEM). This allows the annual components, both the prograde motion and a weaker retrograde motion, to be identified and removed, leaving a pure Chandler wobble and secular polar shift. In the absence of excitation, the free Chandler wobble is closely a prograde circular motion. Circular arcs are fitted to the pole path, free of the annual components, to determine breaks corresponding to sudden excitations. The event times of earthquakes of magnitude greater than or equal to 7.5 are shown on the plotted pole paths. Often, the effects on the pole path precede the earthquake by many days, confirming the establishment of the far-field displacements in advance of the earthquake. The precursory rise in P-wave attenuation before the 2004 Parkfield earthquake, as discovered by Chun et al. (2010), may indicate a similar effect from local deformations.

  15. 2[prime] and 3[prime] Carboranyl uridines and their diethyl ether adducts

    DOEpatents

    Soloway, A.H.; Barth, R.F.; Anisuzzaman, A.K.; Alam, F.; Tjarks, W.

    1992-12-15

    A process is described for preparing carboranyl uridine nucleoside compounds and their diethyl ether adducts, which exhibit a tenfold increase in boron content over prior art boron containing nucleoside compounds. The carboranyl uridine nucleoside compounds exhibit enhanced lipophilicity and hydrophilic properties adequate to enable solvation in aqueous media for subsequent incorporation of the compounds in methods for boron neutron capture therapy in mammalian tumor cells. No Drawings

  16. Vitamin A deprivation selectively lowers uridine nucleotide pools in cultured sertoli cells.

    PubMed

    Carson, D D; Lennarz, W J

    1983-02-10

    The effects of retinoid addition of vitamin A-depleted (UV-irradiated) culture medium on uridine metabolism in cultured Sertoli cells have been studied. After vitamin A depletion, a consistent 2- to 4-fold enhancement of [3H]uridine incorporation into RNA was observed. Several lines of evidence indicate that this enhancement is the result of an increase in the specific activity of the uridine-labeled precursors of RNA. Although vitamin A depletion did not affect either uridine uptake or alter cellular RNA content, a 5-fold increase in the specific activity of UMP was found in vitamin A-depleted cells. This increase results because the cellular content of uracil nucleosides plus nucleotides is selectively lowered in vitamin A-depleted cells. The decreased content of uridine derivatives could be accounted for by a 45-57% decrease in the activity of glutamine-dependent carbamylphosphate synthetase in vitamin A-depleted cells. The effects of vitamin A deprivation on uridine incorporation, as well as carbamylphosphate synthetase activity, could be completely restored to or above control values by supplementing vitamin A-depleted cell culture medium with either retinol or retinoic acid. This effect of vitamin A depletion appears to be highly specific. Under the same conditions, no gross alteration in either the pattern or extent of synthesis of cellular or secreted proteins, glycoproteins, glycosaminoglycans, and lipids was observed. In addition, vitamin A depletion/repletion had no effect on the growth rate or morphology of the cells. PMID:6822526

  17. Bioconjugation of zirconium uridine monophosphate: application to myoglobin direct electrochemistry.

    PubMed

    Qiao, Yuanbiao; Jian, Fangfang; Bai, Qian

    2008-03-14

    Porous nano-granule of zirconium uridine monophosphate, Zr(UMP)2.H2O is, for the first time, synthesized under mild experimental conditions and applied to the bioconjugation of myoglobin (Mb) to realize its direct electron transfer. UV-vis and resonance Raman spectroscopies prove that Mb in the Zr(UMP)2.H2O film maintains its secondary structure similar to the native state. The conjugation film of the Mb-Zr(UMP)2.H2O on the glassy carbon (GC) electrode gives a well-defined and quasi-reversible cyclic voltammogram, which reflects the direct electron transfer of the heme Fe III/Fe II couple of Mb. On the basis of the satisfying bioelectrocatalysis of the nano-conjugation of Mb and genetic substrate, a kind of mediator-free biosensor for H2O2 is developed. The linear range for H2O2 detection is estimated to be 3.92-180.14 microM. The apparent Michaelis-Menten constant (Km) and the detection limit based on the signal-to-noise ratio of 3 are found to be 196.1 microM and 1.52 microM, respectively. Both the apparent Michaelis-Menten constant and the detection limit herein are much lower than currently reported values from other Mb films. This kind of sensor possesses excellent stability, long-term life (more than 20 days) and good reproducibility. PMID:18180152

  18. Statin Lactonization by Uridine 5'-Diphospho-glucuronosyltransferases (UGTs).

    PubMed

    Schirris, Tom J J; Ritschel, Tina; Bilos, Albert; Smeitink, Jan A M; Russel, Frans G M

    2015-11-01

    Statins are cholesterol-lowering drugs that have proven to be effective in lowering the risk of major cardiovascular events. Although well tolerated, statin-induced myopathies are the most common side effects. Compared to their pharmacologically active acid form, statin lactones are more potent inducers of toxicity. They can be formed by glucuronidation mediated by uridine 5'-diphospho-glucuronosyltransferases (UGTs), but a systematic characterization of subtype specificity and kinetics of lactonization is lacking. Here, we demonstrate for six clinically relevant statins that only UGT1A1, 1A3, and 2B7 contribute significantly to their lactonization. UGT1A3 appeared to have the highest lactonization capacity with marked differences in statin conversion rates: pitavastatin ≫ atorvastatin > cerivastatin > lovastatin > rosuvastatin (simvastatin not converted). Using in silico modeling we could identify a probable statin interaction region in the UGT binding pocket. Polymorphisms in these regions of UGT1A1, 1A3, and 2B7 may be a contributing factor in statin-induced myopathies, which could be used in personalization of statin therapy with improved safety. PMID:26412035

  19. Measuring the wobble of radiation field centers during gantry rotation and collimator movement on a linear accelerator

    SciTech Connect

    Du, Weiliang; Gao, Song

    2011-08-15

    Purpose: The isocenter accuracy of a linear accelerator is often assessed with star-shot films. This approach is limited in its ability to quantify three dimensional wobble of radiation field centers (RFCs). The authors report a Winston-Lutz based method to measure the 3D wobble of RFCs during gantry rotation, collimator rotation, and collimator field size change. Methods: A stationary ball-bearing phantom was imaged using multileaf collimator-shaped radiation fields at various gantry angles, collimator angles, and field sizes. The center of the ball-bearing served as a reference point, to which all RFCs were localized using a computer algorithm with subpixel accuracy. Then, the gantry rotation isocenter and the collimator rotation axis were derived from the coordinates of these RFCs. Finally, the deviation or wobble of the individual RFC from the derived isocenter or rotation axis was quantified. Results: The results showed that the RFCs were stable as the field size of the multileaf collimator was varied. The wobble of RFCs depended on the gantry angle and the collimator angle and was reproducible, indicating that the mechanical imperfections of the linac were mostly systematic and quantifiable. It was found that the 3D wobble of RFCs during gantry rotation was reduced after compensating for a constant misalignment of the multileaf collimator. Conclusions: The 3D wobble of RFCs can be measured with submillimeter precision using the proposed method. This method provides a useful tool for checking and adjusting the radiation isocenter tightness of a linac.

  20. Transport mechanisms for adenosine and uridine in primary-cultured rat cortical neurons and astrocytes.

    PubMed

    Nagai, Katsuhito; Nagasawa, Kazuki; Fujimoto, Sadaki

    2005-09-01

    Endogenous adenosine and uridine are important modulators of neural survival and activity. In the present study, we examined transport mechanisms of adenosine and uridine in primary-cultured rat cortical neurons, and compared the results for neurons with those for astrocytes. Reverse transcription-polymerase chain reaction identified the mRNAs for ENT1, ENT2, and CNT2, but not CNT1 and CNT3, in neurons and astrocytes. [3H]Adenosine and [3H]uridine were time-, temperature-, and concentration-dependently taken up into neurons and astrocytes. In kinetic analyses, the uptake of both substrates by neurons and astrocytes consisted of two and one, respectively, saturable transport components. The uptake clearance for both substrates by neurons was greater than that by astrocytes. The relative contribution of the high-affinity major component of both substrates to total uptake was estimated to be approximately 80% in neurons. The uptake of [3H]adenosine and [3H]uridine by both neurons and astrocytes was almost entirely Na+-independent, and sensitive to micro, but not nano, molar concentrations of nitrobenzylmercaptopurine riboside, which are transport characteristics of ENT2. Therefore, it was indicated that adenosine and uridine are more efficiently taken up into neurons than into astrocytes, and ENT2 may predominantly contribute to the transport of the nucleosides as a high-affinity transport system in neurons, as in the case of astrocytes. PMID:16043124

  1. Quantum mechanics/molecular mechanics investigation of the mechanism of phosphate transfer in human uridine-cytidine kinase 2

    PubMed Central

    Smith, Adam J. T.; Li, Ying; Houk, K. N.

    2011-01-01

    The mechanisms of enzyme-catalyzed phosphate transfer and hydrolysis reactions are of great interest due to their importance and abundance in biochemistry. The reaction may proceed in a stepwise fashion, with either a pentavalent phosphorane or a metaphosphate anion intermediate, or by a concerted SN2 mechanism. Despite much theoretical work focused on a few key enzymes, a consensus for the mechanism has not been reached, and examples of all three possibilities have been demonstrated. We have investigated the mechanism of human uridine-cytidine kinase 2 (UCK2, EC 2.7.1.48), which catalyzes the transfer of a phosphate group from ATP to the ribose 5′-hydroxyl of cytidine and uridine. UCK2 is normally expressed in human placenta, but is overexpressed in certain cancer cells, where it is responsible for activating a class of antitumor prodrugs. The UCK2 mechanism was investigated by generating a 2D potential energy surface as a function of the P–O bonds forming and breaking, with energies calculated using a quantum mechanics/molecular mechanics potential (B3LYP/6–31G(d):AMBER). The mechanism of phosphate transfer is shown to be concerted, and is accompanied by concerted proton transfer from the 5′-hydroxyl to a conserved active site aspartic acid that serves as a catalytic base. The calculated barrier for this reaction is 15.1 kcal/mol, in relatively good agreement with the experimental barrier of 17.5 kcal/mol. The interactions of the enzyme active site with the reactant, transition state, and product are examined for their implications on the design of anticancer prodrugs or positron emission tomography (PET) reporter probes for this enzyme. PMID:19532987

  2. Microscopic nuclear structure models and methods: chiral symmetry, wobbling motion and γ–bands

    NASA Astrophysics Data System (ADS)

    Sheikh, Javid A.; Bhat, Gowhar H.; Dar, Waheed A.; Jehangir, Sheikh; Ganai, Prince A.

    2016-06-01

    A systematic investigation of the nuclear observables related to the triaxial degree of freedom is presented using the multi-quasiparticle triaxial projected shell model (TPSM) approach. These properties correspond to the observation of γ-bands, chiral doublet bands and the wobbling mode. In the TPSM approach, γ-bands are built on each quasiparticle configuration and it is demonstrated that some observations in high-spin spectroscopy that have remained unresolved for quite some time could be explained by considering γ-bands based on two-quasiparticle configurations. It is shown in some Ce-, Nd- and Ge-isotopes that the two observed aligned or s-bands originate from the same intrinsic configuration with one of them as the γ-band based on a two-quasiparticle configuration. In the present work, we have also performed a detailed study of γ-bands observed up to the highest spin in dysposium, hafnium, mercury and uranium isotopes. Furthermore, several measurements related to chiral symmetry breaking and wobbling motion have been reported recently. These phenomena, which are possible only for triaxial nuclei, have been investigated using the TPSM approach. It is shown that doublet bands observed in lighter odd–odd Cs-isotopes can be considered as candidates for chiral symmetry breaking. Transverse wobbling motion recently observed in 135Pr has also been investigated and it is shown that TPSM approach provides a reasonable description of the measured properties.

  3. Apparent Stellar Wobble by a Planet in a Circumstellar Disk: Limitations on Planet Detection by Astrometry

    NASA Technical Reports Server (NTRS)

    Takeuchi, Taku; Velusamy, T.; Lin, D. N. C.

    2005-01-01

    Astrometric detection of a stellar wobble on the plane of the sky will provide us the next breakthrough in searching for extrasolar planets. The Space Interferometry Mission (SIM) is expected to achieve high-precision astrometry as accurate as 1 (mu)as, which is precise enough to discover a newborn Jupiter mass planet around a pre-main-sequence (PMS) star in the Taurus-Auriga star-forming region. PMS stars, however, have circumstellar disks that may be obstacles to the precise measurement of the stellar position.We present results on disk influences on the stellar wobble. The density waves excited by a planet move both the disk's mass center and the photocenter. The motion of the disk mass center induces an additional wobble of the stellar position, and the motion of the disk photocenter causes a contamination in the measurement of the stellar position. We show that the additional stellar motion dynamically caused by the disk's gravity is always negligible but that the contamination by the disk light can interfere with the precise measurement of the stellar position if the planet's mass is smaller than approximately 10MJ. The motion of the disk photocenter is sensitive to a slight change in the wave pattern and the disk properties. Measurements by interferometers are generally insensitive to extended sources such as disks. Because of this property, SIM will not suffer significant contamination by the disk light, even if the planet's mass is as small as 1M(sub J).

  4. Mechanisms of the tRNA wobble cytidine modification essential for AUA codon decoding in prokaryotes.

    PubMed

    Numata, Tomoyuki

    2015-01-01

    Bacteria and archaea have 2-lysylcytidine (L or lysidine) and 2-agmatinylcytidine (agm(2)C or agmatidine), respectively, at the first (wobble) position of the anticodon of the AUA codon-specific tRNA(Ile). These lysine- or agmatine-conjugated cytidine derivatives are crucial for the precise decoding of the genetic code. L is synthesized by tRNA(Ile)-lysidine synthetase (TilS), which uses l-lysine and ATP as substrates. Agm(2)C formation is catalyzed by tRNA(Ile)-agm(2)C synthetase (TiaS), which uses agmatine and ATP for the reaction. Despite the fact that TilS and TiaS synthesize structurally similar cytidine derivatives, these enzymes belong to non-related protein families. Therefore, these enzymes modify the wobble cytidine by distinct catalytic mechanisms, in which TilS activates the C2 carbon of the wobble cytidine by adenylation, while TiaS activates it by phosphorylation. In contrast, TilS and TiaS share similar tRNA recognition mechanisms, in which the enzymes recognize the tRNA acceptor stem to discriminate tRNA(Ile) and tRNA(Met). PMID:25348586

  5. Preliminary Effects of Oral Uridine on the Ocular Surface in Dry Eye Patients

    PubMed Central

    Chang, Ki Cheol; Oh, Joo Youn; In, Youn Seok; Shin, Ki Cheul; Wee, Won Ryang; Lee, Jin Hak; Park, Myung Gyu

    2009-01-01

    We designed a randomized, double blinded, 3-months controlled prospective clinical study to investigate effects of oral uridine on the ocular surface in dry eye patients. Twenty-seven patients who diagnosed as dry eye with lower than 5 mm of wetting in the Schirmer strip, with corneal epithelial erosion and who completely followed-up till 3 months were enrolled. Corneal-conjunctival fluorescein staining, non-anesthetic Schirmer test, impression cytology, and Ocular Surface Disease Index (OSDI) were evaluated in the experimental and placebo groups at the baseline, 1 and 3 months after start of medication in a double blinded manner. Fluorescein stain score of the cornea was markedly decreased in oral uridine group compared to the placebo group at 3 months after medication (P=0.032, Mann-Whitney U test). The Schirmer wetting score for the oral uridine group was significantly increased (P=0.001, Wilcoxon signed rank test) at 3 months and its difference between two groups was statistically significant (P=0.030, Mann-Whitney U test). OSDI scores were significantly decreased at 1 and 3 months in treatment group. Oral uridine is effective in treatment of dry eyes. PMID:19654956

  6. Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism

    PubMed Central

    Phan, Chia-Wei; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

    2015-01-01

    Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1±0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80±0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine. PMID:26565787

  7. Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism.

    PubMed

    Phan, Chia-Wei; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

    2015-01-01

    Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80 ± 0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine. PMID:26565787

  8. WOBBLE: A Proposed Mission to Characterize Past and Present Water on Mars

    NASA Technical Reports Server (NTRS)

    Udrea, Bogdan; Delory, Greg; Landis, Geoffrey; Duvet, Ludovic; Choudhuri, Ahsan; Prina, Mauro; Moreels, Pierre; Bedard, Donald; Furano, Gianluca

    2002-01-01

    WOBBLE ("Water Observations from a Balloon Borne Light Explorer") is a mission concept study for a small robotic probe to explore Mars and to accomplish a scientific mission compatible with the goals of the NASA Code S enterprise. The detection of past or present water is a crucial goal for Mars exploration, representing a cross-cutting science theme relevant to past or extant life, climate history, sample return missions and eventual human exploration. The WOBBLE mission concept was developed to study evidence of water using in-situ detection methods. The features on Mars most suited to this investigation are the gullies identified by Malin and Edgett as evidence for recent, near-surface runoff of liquid water. These features are typically located on the inside face of crater rims, where the local slope angle is at or near the angle of repose. This makes the terrain difficult or impossible to access with conventional wheeled rover technology. Combined with the small size of the gullies in relation to a standard landing error ellipse, scientific investigation of these features requires a new approach to surface mobility. WOBBLE uses a low-altitude balloon-borne platform to traverse the surface from the landing site, to the investigation site, and then rise up the slope to investigate the regions of interest at close range. Of the mobility technologies available for near-term Mars exploration, only a balloon platform is capable of a well targeted, detailed sampling of the gully regions over periods of days or more. The science approach embodied in WOBBLE is two-pronged, designed to investigate both the historical evidence of liquid water utilizing high-resolution geomorphology and the characterization of mineral deposits, and present subsurface liquid water using radar sounding techniques. The WOBBLE balloon is a high-pressure hydrogen gas design, 24 meters in diameter and lifting a total payload of 130 kg, including a high-resolution camera/IR imager, Raman

  9. Antimalarial activity of a combination of 5-fluoroorotate and uridine in mice.

    PubMed Central

    Gómez, Z M; Rathod, P K

    1990-01-01

    Malarial parasites, in contrast to mammalian cells, utilize orotic acid more efficiently than uracil or uridine. Recently, chloroquine-susceptible and chloroquine-resistant clones of Plasmodium falciparum were shown to be inhibited by 5-fluoroorotate, with a 50% inhibitory concentration of 6 nM in vitro. Mammalian cells were far less sensitive to 5-fluoroorotate, particularly in the presence of uridine. In this report, the antimalarial activity of 5-fluoroorotate was tested in vivo. Initially, levels of 5-fluoroorotate in plasma were determined in Swiss mice injected intraperitoneally with radioactive 5-fluoroorotate. On the basis of the pharmacokinetics profile, mice infected with Plasmodium yoelii were treated with 5-fluoroorotate at a dose of 0.2 or 5 mg/kg (body weight) every 4 h for 3 days. At the nontoxic dose of 0.2 mg/kg, the reduction in parasitemia was followed by a temporary resurgence of parasitemia. This second wave of parasitemia cleared without additional 5-fluoroorotate treatment. To radically eliminate P. yoelii from mice and avoid the second wave of parasitemia, a higher dose of 5 mg of 5-fluoroorotate per kg had to be used. In the absence of uridine, repeated doses of 5 mg/kg were toxic to mice, as judged by weight loss, diarrhea, decreased numbers of leukocytes, and increased mortality. However, in the presence of uridine, repeated doses of 5 mg/kg could be used for antimalarial chemotherapy without obvious toxicity. Mice cured with 5-fluoroorotate and uridine were immune to subsequent challenge with a potentially lethal inoculum of P. yoelii. PMID:2386369

  10. G-induced vestibular dysfunction ('the wobblies') among aerobatic pilots: a case report and review

    NASA Technical Reports Server (NTRS)

    Muller, Thomas Upson

    2002-01-01

    G-induced vestibular dysfunction (GIVD) is a condition well known to aircraft pilots who experience high positive and negative G loads during unlimited-aerobatic competitions and air-show demonstrations. After landing and walking from their aircraft, pilots with GIVD manifest an extremely unstable gait, which they call the wobblies. This article includes a report of one such case of GIVD, which to the author's knowledge is the first published case report of this condition in the medical literature. The author also discusses what is known and theorized about the pathogenesis of GIVD, and he reviews its diagnosis, treatment, and prevention.

  11. Astrocytoma in an African hedgehog (Atelerix albiventris) suspected wobbly hedgehog syndrome.

    PubMed

    Nakata, Makoto; Miwa, Yasutsugu; Itou, Takuya; Uchida, Kazuyuki; Nakayama, Hiroyuki; Sakai, Takeo

    2011-10-01

    A 28-month-old African hedgehog was referred to our hospital with progressive tetraparesis. On the first presentation, the hedgehog was suspected as having wobbly hedgehog syndrome (WHS) and the animal was treated with medication and rehabilitation. The animal died 22 days after onset. Pathological examination revealed that the animal was involved in astrocytoma between the medulla oblongata and the spinal cord (C1). This report indicates that a primary central nervous system tumor should be considered as one of the differential diagnoses for hedgehogs presenting with progressive paresis, together with WHS. PMID:21628867

  12. Spin rotation, Chandler wobble and free core nutation of isolated multi-layer pulsars

    NASA Astrophysics Data System (ADS)

    Gusev, Alexander; Kitiashvili, Irina

    2013-03-01

    At present time there are investigations of precession and nutation for very different celestial multi-layer bodies: the Earth (Getino 1995), Moon (Gusev 2010), planets of Solar system (Gusev 2010) and pulsars (Link et al. 2007). The long-periodic precession phenomenon was detected for few pulsars: PSR B1828-11, PSR B1557-50, PSR 2217+47, PSR 0531+21, PSR B0833-45, and PSR B1642-03. Stairs, Lyne & Shemar (2000) have found that the arrival-time residuals from PSR B1828-11 vary periodically with a different periods. According to our model, the neutron star has the rigid crust (RC), the fluid outer core (FOC) and the solid inner core (SIC). The model explains generation of four modes in the rotation of the pulsar: two modes of Chandler wobble (CW, ICW) and two modes connecting with free core nutation (FCN, FICN) (Gusev & Kitiashvili 2008). We are propose the explanation for all harmonics of Time of Arrival (TOA) pulses variations as precession of a neutron star owing to differential rotation of RC, FOC and crystal SIC of the pulsar PSR B1828-11: 250, 500, 1000 days. We used canonical method for interpretation TOA variations by Chandler Wobble (CW) and Free Core Nutation (FCN) of pulsar.

  13. Inner core wobble and free core nutation of pulsar PSR B1828-11

    NASA Astrophysics Data System (ADS)

    Kitiashvili, I.; Gusev, A.

    2008-10-01

    PSR B1828-11 has long-term, highly periodic and correlated variations in pulse shape and a slow-down rate with period variations of approximately 1000, 500 and 250 days [Stairs, I.H., Lyne, A.G., Shemar, S.L. Evidence for free precession in a pulsar. Nature 406, 484-486, 2000]. There are three potential explanations of pulses time-of-arrival from a pulsar. These are related to the interior of the neutron star, planetary bodies, free precession and nutation. We use the Hamiltonian canonical method of Getino (1995) for analyzing the dynamically symmetric pulsar PSR B1828-11, consisting of a rigid crust, elliptical liquid outer core and solid inner core. Using the theory of differential rotation of a pulsar, we investigate the dependence on Chandler wobble period, inner core wobble, retrograde free core nutation and prograde free inner core nutation from ellipticity of the inner crystal core, outer liquid core and total pulsar.

  14. The triaxial particle plus rotor model and wobbling mode: A semiclassical view

    SciTech Connect

    Gupta, Rajiv; Malik, S. S.; Jain, A. K.; Jain, S. R.

    2010-11-24

    A systematic analysis of the triaxial particle rotor model with single-j shell configuration is carried out to explain the prominent features of observed wobbling excitations in odd A nuclei. The equations of motion for the angular momentum vectors I-vector and j-vector generate two types of equilibrium (i.e., (i) the axes aligned and (ii) the planar) states. The planar equilibrium states involve mainly the orientation degree of freedom {gamma} and their Jacobian matrix J gives purely imaginary eigenvalues in conjugate pairs. Also, our dynamical results show a substantial projection of angular momentum vectors on all the three principal axes, which implies that the resultant angular momentum lies outside the planes of three axes. Both these signatures confirm the spontaneous breakdown of time reversal (T) plus rotation by 180 deg. (R{sub {pi}}) i.e., R{sub {pi}T} symmetry and as a result nearly two identical bands consisting of even and odd spins emerge. We have tested our dynamical formalism for the wobbling mode observed in {sup 163}Lu.

  15. Quantitative determination of uridine in rabbit plasma and urine by liquid chromatography coupled to a tandem mass spectrometry.

    PubMed

    Kang, Wonku

    2012-04-01

    Recently a pyrimidine nucleoside, uridine, has been show to have a protective effect on cultured human corneal epithelial cells, and on dry eye animal model and patients. In this study, we introduce a sensitive liquid chromatography/tandem mass spectrometry method for the determination of uridine in rabbit plasma and urine. After protein precipitation with methanol including methaqualone (internal standard), the analyte was chromatographed on a reversed-phase column with a mobile phase of 0.1% formic acid aqueous solution and methanol (1:4, v/v). The accuracy and precision of the assay were in accordance with Food and Drug Administration regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of uridine in plasma and urine after a single oral administration of 450 mg/kg uridine in rabbits. PMID:22392515

  16. Single nucleotide modulation of uridine to pseudouridine rearrangement in transfer RNA catalyzed by pseudouridine synthase I.

    PubMed

    Chihade, J W; Horne, D A

    1996-01-01

    E. coli pseudouridine synthase I (PSUI) catalyzes the rearrangement of uridine residues in positions 38, 39 and 40 of tRNA transcripts to pseudouridine. These positions are located in the anticodon stem-loop of the tRNA molecule. Fourteen different E. coli tRNAs are substrates for the enzyme, whereas four other tRNAs which contain uridine in position 38 are not. Investigations were focused on the basis of enzyme differentiation between substrate and non-substrate tRNAs. Comparison of modification reactions with mutant and wild-type tRNA transcripts demonstrates that the presence of a G36 residue modulates modification by PSUI at position 38. In addition to local sequence effects, steady-state kinetic analyses suggest the existence of other recognition elements distinct from the immediate vicinity of modification. PMID:9174935

  17. Nonenzymatic template-directed synthesis on hairpin oligonucleotides. III - Incorporation of adenosine and uridine residues

    NASA Technical Reports Server (NTRS)

    Wu, Taifeng; Orgel, Leslie E.

    1992-01-01

    Nonenzymatic template-directed incorporation of adenosine and uridine residues into template sequences was obtained using nucleoside-5-prime phosphoro (2-methyl)imidazolides as substrates and hairpin oligonucleotides as templates. The reactions are regiospecific, producing mainly 3-prime-5-prime phosphodiester bonds. Limited synthesis of CA and AC sequences was observed along with some synthesis of the AA sequences on templates containing TG and GT sequences, along wilth some synthesis of the AA sequences on templates containing TT sequences.

  18. Synthesis and Solution Conformation Studies of 3-Substituted Uridine and Pseudouridine Derivatives

    PubMed Central

    Chang, Yu-Cheng; Herath, Jayatilake; Wang, Tony H.-H.; Chow, Christine S.

    2008-01-01

    A series of 3-substituted uridine and pseudouridine derivatives, based on the naturally occurring 3-(3-amino-3-carboxypropyl) modification, were synthesized. Their aqueous solution conformations were determined by using circular dichroism and NMR spectroscopy. Functional group composition and chain length were shown to have only a subtle influence on the distribution of syn/anti conformations of the modified nucleosides. The dominating factor appears to be the glycosidic linkage (C– vs. N–glycoside) in determining the nucleoside conformation. PMID:18078759

  19. a Nucleoside Under Observation in the Gas Phase: a Rotational Study of Uridine

    NASA Astrophysics Data System (ADS)

    Peña, Isabel; Alonso, José L.

    2014-06-01

    The nucleoside of uridine has been placed in the gas phase by laser ablation and the most stable C2{'}-anti conformation characterized by broadband chirped pulse (CP-FTMW) and narrowband molecular beam Fourier transform microwave (LA-MB-FTMW) spectroscopies. The quadrupole hyperfine structure, originated by two 14N nuclei, has been completely resolved. Intramolecular hydrogen bonds involving uracil and ribose moieties have been found to play an important role in the stabilization of the nucleoside.

  20. Thiolated uridine substrates and templates improve the rate and fidelity of ribozyme-catalyzed RNA copying.

    PubMed

    Prywes, Noam; Michaels, Yale S; Pal, Ayan; Oh, Seung Soo; Szostak, Jack W

    2016-05-01

    Ribozyme-catalyzed RNA polymerization is inefficient and error prone. Here we demonstrate that two alternative bases, 2-thio-uridine (s(2)U) and 2-thio-ribo-thymidine (s(2)T), improve the rate and fidelity of ribozyme catalyzed nucleotide addition as NTP substrates and as template bases. We also demonstrate the functionality of s(2)U and s(2)T-containing ribozymes. PMID:27109314

  1. Isolation, crystallization and preliminary crystallographic analysis of Salmonella typhimurium uridine phosphorylase crystallized with 2,2′-anhydrouridine

    SciTech Connect

    Timofeev, Vladimir I.; Lashkov, Alexander A.; Gabdoulkhakov, Azat G.; Pavlyuk, Bogdan Ph.; Kachalova, Galina S.; Betzel, Christian

    2007-10-01

    S. typhimurium uridine phosphorylase has been isolated and crystallized in the presence of ligand. Uridine phosphorylase (UPh; EC 2.4.2.3) is a member of the pyrimidine nucleoside phosphorylase family of enzymes which catalyzes the phosphorolytic cleavage of the C—N glycoside bond of uridine, with the formation of ribose 1-phosphate and uracil. This enzyme has been shown to be important in the activation and catabolism of fluoropyrimidines. Modulation of its enzymatic activity may affect the therapeutic efficacy of chemotherapeutic agents. The structural investigation of the bacterial uridine phosphorylases, both unliganded and complexed with substrate/product analogues and inhibitors, may help in understanding the catalytic mechanism of the phosphorolytic cleavage of uridine. Salmonella typhimurium uridine phosphorylase has been crystallized with 2,2′-anhydrouridine. X-ray diffraction data were collected to 2.15 Å. Preliminary analysis of the diffraction data indicates that the crystal belongs to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 88.52, b = 123.98, c = 133.52 Å. The solvent content is 45.51%, assuming the presence of one hexamer molecule per asymmetric unit.

  2. Structural investigation of the thymidine phosphorylase from Salmonella typhimurium in the unliganded state and its complexes with thymidine and uridine.

    PubMed

    Balaev, Vladislav V; Lashkov, Alexander A; Gabdulkhakov, Azat G; Dontsova, Maria V; Seregina, Tatiana A; Mironov, Alexander S; Betzel, Christian; Mikhailov, Al'bert M

    2016-03-01

    Highly specific thymidine phosphorylases catalyze the phosphorolytic cleavage of thymidine, with the help of a phosphate ion, resulting in thymine and 2-deoxy-α-D-ribose 1-phosphate. Thymidine phosphorylases do not catalyze the phosphorolysis of uridine, in contrast to nonspecific pyrimidine nucleoside phosphorylases and uridine phosphorylases. Understanding the mechanism of substrate specificity on the basis of the nucleoside is essential to support rational drug-discovery investigations of new antitumour and anti-infective drugs which are metabolized by thymidine phosphorylases. For this reason, X-ray structures of the thymidine phosphorylase from Salmonella typhimurium were solved and refined: the unliganded structure at 2.05 Å resolution (PDB entry 4xr5), the structure of the complex with thymidine at 2.55 Å resolution (PDB entry 4yek) and that of the complex with uridine at 2.43 Å resolution (PDB entry 4yyy). The various structural features of the enzyme which might be responsible for the specificity for thymidine and not for uridine were identified. The presence of the 2'-hydroxyl group in uridine results in a different position of the uridine furanose moiety compared with that of thymidine. This feature may be the key element of the substrate specificity. The specificity might also be associated with the opening/closure mechanism of the two-domain subunit structure of the enzyme. PMID:26919527

  3. Detection of RNA nucleoside modifications with the uridine-specific ribonuclease MC1 from Momordica charantia.

    PubMed

    Addepalli, Balasubrahmanym; Lesner, Nicholas P; Limbach, Patrick A

    2015-10-01

    A codon-optimized recombinant ribonuclease, MC1 is characterized for its uridine-specific cleavage ability to map nucleoside modifications in RNA. The published MC1 amino acid sequence, as noted in a previous study, was used as a template to construct a synthetic gene with a natural codon bias favoring expression in Escherichia coli. Following optimization of various expression conditions, the active recombinant ribonuclease was successfully purified as a C-terminal His-tag fusion protein from E. coli [Rosetta 2(DE3)] cells. The isolated protein was tested for its ribonuclease activity against oligoribonucleotides and commercially available E. coli tRNA(Tyr I). Analysis of MC1 digestion products by ion-pairing reverse phase liquid-chromatography coupled with mass spectrometry (IP-RP-LC-MS) revealed enzymatic cleavage of RNA at the 5'-termini of uridine and pseudouridine, but cleavage was absent if the uridine was chemically modified or preceded by a nucleoside with a bulky modification. Furthermore, the utility of this enzyme to generate complementary digestion products to other common endonucleases, such as RNase T1, which enables the unambiguous mapping of modified residues in RNA is demonstrated. PMID:26221047

  4. Microsystem to evaluate the incorporation of 3H-uridine in macrophage RNA

    SciTech Connect

    Varesio, L.; Naglich, J.; Brunda, M.J.; Taramelli, D.; Eva, A.

    1981-01-01

    A method is described for the evaluation of the total 3H-uridine incorporated by macrophages in vitro into trichloroacetic acid (TCA)-precipitable material. The technique is based upon solubilization of the macrophage monolayers by guanidine-HC1, followed by TCA precipitation. The recovery of RNA into the precipitate and the reproducibility of the results were strictly dependent on the use of filtered reagents and on incubation of the TCA precipitate for 2 or more hours at 4 degree C before harvesting. Treatment with quanidine-HC1 did not affect the recovery of labeled RNA. Moreover, we observed that radioactive precipitate had the characteristics of RNA, since its recovery was sensitive to the addition of unlabeled uridine in the culture medium and to the treatment of the macrophages with inhibitors of RNA synthesis, but not of protein synthesis. Tritiated uridine incorporation in microcultures of macrophages can be assessed with this technique, by processing the cells directly in the wells. The main advantages of this procedure are: 1) the radioactivity can be measured by semiautomatic cell harvesters, 2) a small number of macrophages are required, and 3) many samples can be processed simultaneously. Overall, the technique is simple, rapid, and could be successfully adapted to study other metabolic pathways.

  5. Plastid uridine salvage activity is required for photoassimilate allocation and partitioning in Arabidopsis.

    PubMed

    Chen, Mingjie; Thelen, Jay J

    2011-08-01

    Nucleotides are synthesized from de novo and salvage pathways. To characterize the uridine salvage pathway, two genes, UKL1 and UKL2, that tentatively encode uridine kinase (UK) and uracil phosphoribosyltransferase (UPRT) bifunctional enzymes were studied in Arabidopsis thaliana. T-DNA insertions in UKL1 and UKL2 reduced transcript expression and increased plant tolerance to toxic analogs 5-fluorouridine and 5-fluorouracil. Enzyme activity assays using purified recombinant proteins indicated that UKL1 and UKL2 have UK but not UPRT activity. Subcellular localization using a C-terminal enhanced yellow fluorescent protein fusion indicated that UKL1 and UKL2 localize to plastids. The ukl2 mutant shows reduced transient leaf starch during the day. External application of orotate rescued this phenotype in ukl2, indicating pyrimidine pools are limiting for starch synthesis in ukl2. Intermediates for lignin synthesis were upregulated, and there was increased lignin and reduced cellulose content in the ukl2 mutant. Levels of ATP, ADP, ADP-glucose, UTP, UDP, and UDP-glucose were altered in a light-dependent manner. Seed composition of the ukl1 and ukl2 mutants included lower oil and higher protein compared with the wild type. Unlike single gene mutants, the ukl1 ukl2 double mutant has severe developmental defects and reduced biomass accumulation, indicating these enzymes catalyze redundant reactions. These findings point to crucial roles played by uridine salvage for photoassimilate allocation and partitioning. PMID:21828290

  6. The aetiology of wobbly possum disease: Reproduction of the disease with purified nidovirus.

    PubMed

    Giles, Julia; Perrott, Matthew; Roe, Wendi; Dunowska, Magdalena

    2016-04-01

    The objective of this study was to investigate a role of a recently discovered marsupial nidovirus in the development of a neurological disease, termed wobbly possum disease (WPD), in the Australian brushtail possum (Trichosurus vulpecula). Four possums received 1 mL of a standard inoculum that had been prepared from tissues of WPD-affected possums, 4 possums received 1.8 mL (1 × 10(6) TCID50) of a cell lysate from inoculated cultures, and 4 possums received 1 mL (× 10(7) TCID50) of a purified WPD isolate. All but one possum that received infectious inocula developed neurological disease and histopathological lesions characteristic for WPD. High levels of viral RNA were detected in livers from all possums that received infectious inocula, but not from control possums. Altogether, our data provide strong experimental evidence for the causative involvement of WPD virus in development of a neurological disease in infected animals. PMID:26874014

  7. Suppression of E. coli tumbling and wobbling in dilute polymeric fluids

    NASA Astrophysics Data System (ADS)

    Patteson, Alison; Gopinath, Arvind; Arratia, Paulo

    2015-03-01

    Bacteria commonly utilize a run-and-tumble swimming behavior to navigate through complex environments, such as mucus in the lungs or digestive system. This swimming behavior has been extensively studied in water-like fluids; yet, studies on the role of particles/polymers on the run-and-tumble technique are limited. Here, we experimentally investigate the role of polymer concentration on the swimming dynamics of E. coli. We find that small amounts of polymer drastically change the run-and-tumble behavior of E. coli cells, significantly enhancing the translational diffusion. The average cell velocity increases with polymer concentration (and viscosity) and the mean run times are enhanced. By varying polymer molecular weight, we show that enhanced translation is a result of two mechanisms: (1) suppression of cell wobbling due to elasticity and (2) enhancement of run times due to viscosity. Our results show that the transport of chemotactic cells can be independently modified by viscosity and elasticity.

  8. Estimation of the Chandler wobble parameters by the use of the Kalman deconvolution filter

    NASA Astrophysics Data System (ADS)

    Brzezinski, A.; Rajner, M.

    2014-12-01

    We estimate the Chandler wobble (CW) parameters, the period T and the quality factor Q, based on the stochastic models of polar motion and geophysical excitation data. We apply the Kalman deconvolution filter developed by Brzezinski (1992). This filter can be used to analyze either the polar motion data alone, or simultaneously the polar motion and the excitation data, in order to estimate the unknown residual excitation. By imposing the minimum variance constraint upon the estimated unknown excitation we can find the best value of the resonant parameters T and Q. The CW parameters estimated from different sets of polar motion and geophysical excitation data are compared to each other as well as to the earlier results derived by the alternative algorithms.

  9. The Chandler wobble as a trigger of the El Niño excitation

    NASA Astrophysics Data System (ADS)

    Serykh, Ilya; Sonechkin, Dmitry

    2014-05-01

    Using data of the Met Office Hadley Centre, time series of the near surface temperature and sea-surface pressure for the period 1875-2012 are processed to compute the Oceanic Niño Index (ONI) and the Equatorial Southern Oscillation Index (ESOI). Detailed spectra of the ONI and ESOI show peaks that exist throughout the year, but the most powerful in the boreal winter months. Peak periods are consist of 29, 43 and 58 months, which is roughly equivalent to 2, 3 and 4 periods of the well-known 14-month Chandler wobble of the Earth's pole motion. A plausible physical mechanism of the Chandler wobble influence on the El Niño excitation is presented. A computation of the global fields of the spectral energy at each of the periods afore-indicated admits to identify some distinctive features of the spatial structure of the most powerful disturbances during El Niño. Detailed spectra of the El Niño Modoki Index (EMI) computed for each month separately show differences between main oscillations of El Niño Modoki and classic El Niño. Besides, computations are made of cross-correlations and lead/lag interrelations between El Niño and some other processes in the global climate system for all afore-indicated periods. Some regions are identified for which the cross-correlations are essential, but the processes being considered either lead or lag El Niño. This finding admits to suppose that there exists an external force common for both, El Niño and other macroscale climatic processes.

  10. A new description of Earth's wobble modes using Clairaut coordinates: 1. Theory

    NASA Astrophysics Data System (ADS)

    Rochester, M. G.; Crossley, D. J.; Zhang, Y. L.

    2014-09-01

    This paper presents a novel mathematical reformulation of the theory of the free wobble/nutation of an axisymmetric reference earth model in hydrostatic equilibrium, using the linear momentum description. The new features of this work consist in the use of (i) Clairaut coordinates (rather than spherical polars), (ii) standard spherical harmonics (rather than generalized spherical surface harmonics), (iii) linear operators (rather than J-square symbols) to represent the effects of rotational and ellipticity coupling between dependent variables of different harmonic degree and (iv) a set of dependent variables all of which are continuous across material boundaries. The resulting infinite system of coupled ordinary differential equations is given explicitly, for an elastic solid mantle and inner core, an inviscid outer core and no magnetic field. The formulation is done to second order in the Earth's ellipticity. To this order it is shown that for wobble modes (in which the lowest harmonic in the displacement field is degree 1 toroidal, with azimuthal order m = ±1), it is sufficient to truncate the chain of coupled displacement fields at the toroidal harmonic of degree 5 in the solid parts of the earth model. In the liquid core, however, the harmonic expansion of displacement can in principle continue to indefinitely high degree at this order of accuracy. The full equations are shown to yield correct results in three simple cases amenable to analytic solution: a general earth model in rigid rotation, the tiltover mode in a homogeneous solid earth model and the tiltover and Chandler periods for an incompressible homogeneous solid earth model. Numerical results, from programmes based on this formulation, are presented in part II of this paper.

  11. A new description of Earth's wobble modes using Clairaut coordinates 2: results and inferences on the core mode spectrum

    NASA Astrophysics Data System (ADS)

    Crossley, D. J.; Rochester, M. G.

    2014-09-01

    Numerical solutions are presented for the formulation of the linear momentum description of Earth's dynamics using Clairaut coordinates. We have developed a number of methods to integrate the equations of motion, including starting at the Earth's centre of mass, starting at finite radius and separating the displacement associated with the primary rigid rotation. We include rotation and ellipticity to second order up to spherical harmonic T_5^m, starting with the primary displacement T_1^m with m = ±1. We are able to confirm many of the previous results for models PREM (with no surface ocean) and 1066A, both in their original form and with neutrally stratified liquid cores. Our period search ranges from the near-seismic band [0.1 sidereal days (sd)] to 3500 sd, within which we have identified the four well-known wobble-nutation modes: the Free Core Nutation (retrograde) at -456 sd, the Free Inner Core Nutation (FICN, prograde) at 468 sd, the Chandler Wobble (prograde) at 402 sd, and the Inner Core Wobble (ICW, prograde) at about 2842 sd (7.8 yr) for neutral PREM. The latter value varies significantly with earth model and integration method. In addition we have verified to high accuracy the tilt-over mode at 1 sd within a factor 10-6. In an exhaustive search we found no additional near-diurnal wobble modes that could be identified as nutations. We show that the eigenfunctions for the as-yet-unidentified ICW are extremely sensitive to the details of the earth model, especially the core stability profile and there is no well-defined sense of its wobble relative to the mantle. Calculations are also done for a range of models derived from PREM with homogeneous layers, as well as with incompressible cores. For this kind of model the ICW ceases to have just a simple IC rigid motion when the fluid compressibility is either unchanged or multiplied by a factor 10; in this case the outer core exhibits oscillations that arise from an unstable fluid density stratification. For

  12. The crystal structure and activity of a putative trypanosomal nucleoside phosphorylase reveal it to be a homodimeric uridine phosphorylase

    PubMed Central

    Larson, Eric T.; Mudeppa, Devaraja G.; Gillespie, J. Robert; Mueller, Natascha; Napuli, Alberto J.; Arif, Jennifer A.; Ross, Jenni; Arakaki, Tracy L.; Lauricella, Angela; DeTitta, George; Luft, Joseph; Zucker, Frank; Verlinde, Christophe L. M. J.; Fan, Erkang; Van Voorhis, Wesley C.; Buckner, Frederick S.; Rathod, Pradipsinh K.; Hol, Wim G. J.; Merritt, Ethan A.

    2010-01-01

    Purine nucleoside phosphorylases and uridine phosphorylases are closely related enzymes involved in purine and pyrimidine salvage, respectively, which catalyze the removal of the ribosyl moiety from nucleosides so that the nucleotide base may be recycled. Parasitic protozoa generally are incapable of de novo purine biosynthesis so the purine salvage pathway is of potential therapeutic interest. Information about pyrimidine biosynthesis in these organisms is much more limited. Though all seem to carry at least a subset of enzymes from each pathway, the dependency on de novo pyrimidine synthesis versus salvage varies from organism to organism and even from one growth stage to another. We have structurally and biochemically characterized a putative nucleoside phosphorylase from the pathogenic protozoan Trypanosoma brucei and find that it is a homodimeric uridine phosphorylase. This is the first characterization of a uridine phosphorylase from a trypanosomal source despite this activity being observed decades ago. Although this gene was broadly annotated as a putative nucleoside phosphorylase, it was widely inferred to be a purine nucleoside phosphorylase. Our characterization of this trypanosomal enzyme shows that it is possible to distinguish between purine and uridine phosphorylase activity at the sequence level based on the absence or presence of a characteristic uridine phosphorylase-specificity insert. We suggest that this recognizable feature may aid in proper annotation of the substrate specificity of enzymes in the nucleoside phosphorylase family. PMID:20070944

  13. The Crystal Structure of Streptococcus pyogenes Uridine Phosphorylase Reveals a Distinct Subfamily of Nucleoside Phosphorylases

    SciTech Connect

    Tran, Timothy H.; Christoffersen, S.; Allan, Paula W.; Parker, William B.; Piskur, Jure; Serra, I.; Terreni, M.; Ealick, Steven E.

    2011-09-20

    Uridine phosphorylase (UP), a key enzyme in the pyrimidine salvage pathway, catalyzes the reversible phosphorolysis of uridine or 2'-deoxyuridine to uracil and ribose 1-phosphate or 2'-deoxyribose 1-phosphate. This enzyme belongs to the nucleoside phosphorylase I superfamily whose members show diverse specificity for nucleoside substrates. Phylogenetic analysis shows Streptococcus pyogenes uridine phosphorylase (SpUP) is found in a distinct branch of the pyrimidine subfamily of nucleoside phosphorylases. To further characterize SpUP, we determined the crystal structure in complex with the products, ribose 1-phosphate and uracil, at 1.8 {angstrom} resolution. Like Escherichia coli UP (EcUP), the biological unit of SpUP is a hexamer with an ?/? monomeric fold. A novel feature of the active site is the presence of His169, which structurally aligns with Arg168 of the EcUP structure. A second active site residue, Lys162, is not present in previously determined UP structures and interacts with O2 of uracil. Biochemical studies of wild-type SpUP showed that its substrate specificity is similar to that of EcUP, while EcUP is {approx}7-fold more efficient than SpUP. Biochemical studies of SpUP mutants showed that mutations of His169 reduced activity, while mutation of Lys162 abolished all activity, suggesting that the negative charge in the transition state resides mostly on uracil O2. This is in contrast to EcUP for which transition state stabilization occurs mostly at O4.

  14. Reaction of uridine diphosphate galactose 4-epimerase with a suicide inactivator

    SciTech Connect

    Flentke, G.R.; Frey, P.A. )

    1990-03-06

    UDPgalactose 4-epimerase from Escherichia coli is rapidly inactivated by the compounds uridine 5{prime}-diphosphate chloroacetol (UDC) and uridine 5{prime}-diphosphate bromoacetol (UCB). Both UDC and UDB inactivate the enzyme in neutral solution concomitant with the appearance of chromophores absorbing maximally at 325 and 328 nm, respectively. The reaction of UDC with the enzyme follows saturation kinetics characterized by a K{sub D} of 0.110 mM and k{sub inact} of 0.84 min{sup {minus}1} at pH 8.5 and ionic strength 0.2 M. The inactivation by UDC is competitively inhibited by competitive inhibitors of UDPgalactose 4-epimerase, and it is accompanied by the tight but noncovalent binding of UDC to the enzyme in a stoichiometry of 1 mol of UDC/mol of enzyme dimer, corresponding to 1 mol of UDC/mol of enzyme-bound NAD{sup +}. The inactivation of epimerase by uridine 5{prime}-diphosphate ({sup 2}H{sub 2})chloroacetol proceeds with a primary kinetic isotope effect (k{sub H}/k{sub D}) of 1.4. The inactivation mechanism is proposed to involve a minimum of three steps: (a) reversible binding of UDC to the active site of UDPgalactose 4-epimerase; (b) enolization of the chloroacetol moiety of enzyme-bound UDC, catalyzed by an enzymic general base at the active site; (c) alkylation of the nicotinamide ring of NAD{sup +} at the active site by the chloroacetol enolate. The resulting adduct between UDC and NAD{sup +} is proposed to be the chromophore with {lambda}{sub max} at 325 nm. The enzymic general base required to facilitate proton transfer in redox catalysis by this enzyme may be the general base that facilitates enolization of the chloroacetol moiety of UDC in the inactivation reaction.

  15. Spectral analysis of the Chandler wobble: comparison of the discrete Fourier analysis and the maximum entropy method

    NASA Astrophysics Data System (ADS)

    Brzezinski, A.

    2014-12-01

    The methods of spectral analysis are applied to solve the following two problems concerning the free Chandler wobble (CW): 1) to estimate the CW resonance parameters, the period T and the quality factor Q, and 2) to perform the excitation balance of the observed free wobble. It appears, however, that the results depend on the algorithm of spectral analysis applied. Here we compare the following two algorithms which are frequently applied for analysis of the polar motion data, the classical discrete Fourier analysis and the maximum entropy method corresponding to the autoregressive modeling of the input time series. We start from general description of both methods and of their application to the analysis of the Earth orientation observations. Then we compare results of the analysis of the polar motion and the related excitation data.

  16. Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code

    NASA Astrophysics Data System (ADS)

    Rozov, Alexey; Demeshkina, Natalia; Khusainov, Iskander; Westhof, Eric; Yusupov, Marat; Yusupova, Gulnara

    2016-01-01

    Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNALysUUU with hypermodified 5-methylaminomethyl-2-thiouridine (mnm5s2U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine-pyrimidine mismatches. We show that mnm5s2U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism.

  17. Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code.

    PubMed

    Rozov, Alexey; Demeshkina, Natalia; Khusainov, Iskander; Westhof, Eric; Yusupov, Marat; Yusupova, Gulnara

    2016-01-01

    Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNA(Lys)(UUU) with hypermodified 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine-pyrimidine mismatches. We show that mnm(5)s(2)U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism. PMID:26791911

  18. Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code

    PubMed Central

    Rozov, Alexey; Demeshkina, Natalia; Khusainov, Iskander; Westhof, Eric; Yusupov, Marat; Yusupova, Gulnara

    2016-01-01

    Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNALysUUU with hypermodified 5-methylaminomethyl-2-thiouridine (mnm5s2U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine–pyrimidine mismatches. We show that mnm5s2U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism. PMID:26791911

  19. Uridine Triacetate.

    PubMed

    Cada, Dennis J; Mbogu, Uzoma; Bindler, Ross J; Baker, Danial E

    2016-06-01

    Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. The June 2016 monograph topics are elbasvir/grazoprevir, ixekizumab, brivaracetam, reslizumab, and sofosbuvir/velpatasvir. The Safety MUE is on reslizumab. PMID:27354750

  20. Thermodynamics of binding of divalent magnesium and manganese to uridine phosphates: implications for diabetes-related hypomagnesaemia and carbohydrate biocatalysis

    PubMed Central

    Zea, Corbin J; Camci-Unal, Gulden; Pohl, Nicola L

    2008-01-01

    Background Although the necessity of divalent magnesium and manganese for full activity of sugar nucleotidyltransferases and glycosyltransferases is well known, the role of these metal cations in binding the substrates (uridine 5'-triphosphate, glucose-1-phosphate, N-acetylglucosamine-1-phosphate, and uridine 5'-diphosphate glucose), products (uridine 5'-diphosphate glucose, uridine 5'-diphosphate N-acetylglucosamine, pyrophosphate, and uridine 5'-diphosphate), and/or enzyme is not clearly understood. Results Using isothermal titration calorimetry we have studied the binding relationship between the divalent metals, magnesium and manganese, and uridine 5'-phosphates to determine the role these metals play in carbohydrate biosynthesis. It was determined from the isothermal titration calorimetry (ITC) data that Mg+2 and Mn+2 are most tightly bound to PPi, Kb = 41,000 ± 2000 M-1 and 28,000 ± 50,000 M-1 respectively, and UTP, Kb = 14,300 ± 700 M-1 and 13,000 ± 2,000 M-1 respectively. Conclusion Our results indicate that the formal charge state of the phosphate containing substrates determine the binding strength. Divalent metal cations magnesium and manganese showed similar trends in binding to the sugar substrates. Enthalpy of binding values were all determined to be endothermic except for the PPi case. In addition, entropy of binding values were all found to be positive. From this data, we discuss the role of magnesium and manganese in both sugar nucleotidyltransferase and glycosyltransferase reactions, the differences in metal-bound substrates expected under normal physiological metal concentrations and those of hypomagnesaemia, and the implications for drug design. PMID:18627619

  1. Structural basis for the mechanism of inhibition of uridine phosphorylase from Salmonella typhimurium

    SciTech Connect

    Lashkov, A. A.; Zhukhlistova, N. E.; Sotnichenko, S. E.; Gabdulkhakov, A. G.; Mikhailov, A. M.

    2010-01-15

    The three-dimensional structures of three complexes of Salmonella typhimurium uridine phosphorylase with the inhibitor 2,2'-anhydrouridine, the substrate PO{sub 4}, and with both the inhibitor 2,2'-anhydrouridine and the substrate PO{sub 4} (a binary complex) were studied in detail by X-ray diffraction. The structures of the complexes were refined at 2.38, 1.5, and 1.75 A resolution, respectively. Changes in the three-dimensional structure of the subunits in different crystal structures are considered depending on the presence or absence of the inhibitor molecule and (or) the phosphate ion in the active site of the enzyme. The presence of the phosphate ion in the phosphate-binding site was found to substantially change the orientations of the side chains of the amino-acid residues Arg30, Arg91, and Arg48 coordinated to this ion. A comparison showed that the highly flexible loop L9 is unstable. The atomic coordinates of the refined structures of the complexes and the corresponding structure factors were deposited in the Protein Data Bank (their PDB ID codes are 3DD0 and 3C74). The experimental data on the spatial reorganization of the active site caused by changes in its functional state from the unligated to the completely inhibited state suggest the structural basis for the mechanism of inhibition of Salmonella typhimurium uridine phosphorylase.

  2. Inhibitor design for ribonuclease A: the binding of two 5′-phosphate uridine analogues

    PubMed Central

    Tsirkone, Vicky G.; Dossi, Kyriaki; Drakou, Christina; Zographos, Spyros E.; Kontou, Maria; Leonidas, Demetres D.

    2009-01-01

    In the quest for the rational design of selective and potent inhibitors for members of the pancreatic ribonuclease A (RNase A) family of biomedical interest, the binding of uridine 5′-phosphate (U5P) and uridine 5′-diphosphate (UDP) to RNase A have been investigated using kinetic studies and X-ray crystallography. Both nucleotides are competitive inhibitors of the enzyme, with K i values of 4.0 and 0.65 mM, respectively. They bind to the active site of the enzyme by anchoring two molecules connected to each other by hydrogen bonds and van der Waals interactions. While the first of the inhibitor molecules binds with its nucleobase in the pyrimidinyl-binding subsite, the second is bound at the purine-preferring subsite. The unexpected binding of a pyrimidine at the purine-binding subsite has added new important elements to the rational design approach for the discovery of new potent inhibitors of the RNase A superfamily. PMID:19574636

  3. Inhibitor design for ribonuclease A: the binding of two 5'-phosphate uridine analogues.

    PubMed

    Tsirkone, Vicky G; Dossi, Kyriaki; Drakou, Christina; Zographos, Spyros E; Kontou, Maria; Leonidas, Demetres D

    2009-07-01

    In the quest for the rational design of selective and potent inhibitors for members of the pancreatic ribonuclease A (RNase A) family of biomedical interest, the binding of uridine 5'-phosphate (U5P) and uridine 5'-diphosphate (UDP) to RNase A have been investigated using kinetic studies and X-ray crystallography. Both nucleotides are competitive inhibitors of the enzyme, with K(i) values of 4.0 and 0.65 mM, respectively. They bind to the active site of the enzyme by anchoring two molecules connected to each other by hydrogen bonds and van der Waals interactions. While the first of the inhibitor molecules binds with its nucleobase in the pyrimidinyl-binding subsite, the second is bound at the purine-preferring subsite. The unexpected binding of a pyrimidine at the purine-binding subsite has added new important elements to the rational design approach for the discovery of new potent inhibitors of the RNase A superfamily. PMID:19574636

  4. Effects of thymidine and uridine on the phosphorylation of 3'-azido-3'-deoxythymidine (zidovudine) in human mononuclear cells

    SciTech Connect

    Szebeni, J.; Patel, S.S.; Hung, K.; Wahl, L.M.; Weinstein, J.N. )

    1991-01-01

    The effects of thymidine and uridine on the phosphorylation of 3'-azido-3'-deoxythymidine (AZT) were studied in various human mononuclear cell preparations. Thymidine suppressed ({sup 3}H)AZT phosphorylation in the same concentration range (20 to 100 microM) in which it antagonizes the anti-human immunodeficiency virus activity of AZT. Uridine, in turn, had no influence on AZT phosphorylation, just as it has no effect on the anti-human immunodeficiency virus activity of AZT. These findings are consistent with a close relationship between the inhibition of AZT phosphorylation and the influence of physiological nucleosides on the antiviral activity of AZT.

  5. Triaxial Earth's rotation: Chandler wobble, free core nutation and diurnal polar motion (Abstract)

    NASA Astrophysics Data System (ADS)

    Sun, R.; Shen, W.-B.

    2015-08-01

    In this study, we formulate two-layered triaxial Earth rotation theory, focusing on the influence of the triaxiality on the Chandler wobble (CW), free core nutation (FCN) and diurnal polar motion. We estimate the frequencies of the normal modes CW and FCN, and results show that though the influence of two-layer triaxiality on the CW and FCN frequencies are very small, there appear some new natures. The response of the Earth's polar motion to the excitation consists of two parts. One is in response to the same frequency excitation and the other is in response to the opposite frequency excitation. For an Earth model with triaxial mantle and core, both of these two parts have four resonant frequencies rather than two that are suggested by rotational symmetric Earth model. However, due to the small strength of these new resonances, the effects of these resonances are only significant when the excitation frequencies are very near to these resonance frequencies. In addition, compared to the biaxial case, the influences of the triaxiality on the prograde and retrograde diurnal polar motions excited by ocean tide component K1 are estimated as - 1.4 μas and - 0.9 μas respectively, which should be taken into account in theory. This study is supported by National 973 Project China (grant No. 2013CB733305), NSFC (grant Nos. 41174011, 41210006, 41128003, 41021061).

  6. Probabilistic approach to describing the Chandler wobble: the role of the ocean

    NASA Astrophysics Data System (ADS)

    Tsurkis, I.; Kuchay, M.; Spiridonov, E.; Sinyukhina, S.

    2015-08-01

    The atmospheric component of polar motion can be treated as the anisotropic Markov process with discrete time, and the torque exerted by the atmosphere on the solid Earth, as the white noise. The efficiency of the atmospheric mechanism in the excitation of the Chandler wobble (CW) is estimated in the context of the probabilistic model. It was shown, that one can interprets the oceanic perturbation as a stationary anisotropic random process characterized by the correlation time less than 100 days. The probabilistic approach to the description of the CW is expanded to the case of anisotropic random load. The polar motion is treated as a two-dimensional Markov process, i.e. the solution of the Liouville equation with discrete time. With a sufficiently large time step, the polar motion can be considered as an isotropic process irrespective of the particular ratio between the eigenvalues of the diffusion matrix. Thus, it is demonstrated that the observed variations in amplitude can be explained in the context of the probabilistic approach without hypothesizing the isotropy of the random load.

  7. Primary possum macrophage cultures support the growth of a nidovirus associated with wobbly possum disease.

    PubMed

    Giles, Julia C; Perrott, Matthew R; Dunowska, Magdalena

    2015-09-15

    The objective of the study was to establish a system for isolation of a recently described, thus far uncultured, marsupial nidovirus associated with a neurological disease of possums, termed wobbly possum disease (WPD). Primary cultures of possum macrophages were established from livers of adult Australian brushtail possums (Trichosurus vulpecula). High viral copy numbers (up to 6.9×10(8)/mL of cell lysate) were detected in infected cell culture lysates from up to the 5th passage of the virus, indicating that the putative WPD virus (WPDV) was replicating in cultured cells. A purified virus stock with a density of 1.09 g/mL was prepared using iodixanol density gradient ultracentrifugation. Virus-like particles approximately 60 nm in diameter were observed using electron microscopy in negatively stained preparations of the purified virus. The one-step growth curve of WPDV in macrophage cultures showed the highest increase in intracellular viral RNA between 6 and 12h post-infection. Maximum levels of cell-associated viral RNA were detected at 24h post-infection, followed by a decline. Levels of extracellular RNA increased starting at 9h post-infection, with maximum levels detected at 48 h post-infection. The establishment of the in vitro system to culture WPDV will facilitate further characterisation of this novel nidovirus. PMID:26028426

  8. tRNA structure and ribosomal function. I. tRNA nucleotide 27-43 mutations enhance first position wobble.

    PubMed

    Schultz, D W; Yarus, M

    1994-02-01

    Transfer RNA su7 G36 is a derivative of tRNA(Trp) with a 3'GUC anticodon complementary to the glutamine codon CAG. This tRNA requires a normally forbidden G-U wobble at the first codon position to suppress a UAG (amber) termination codon. Measurement of amber suppression by mutated su7 G36 tRNAs and correction for tRNA levels and aminoacylation allowed calculation of KUAG, a linearized index of in vivo ribosomal function. Following saturating mutagenesis of the anticodon arm of su7 G36, screening for UAG suppression using a lacZ reporter yielded tRNAs with up to 40-fold increased first position G-U wobble, judged from KUAG. The parental anticodon helix has minimized this type of miscoding, and virtually all changes in the top base-pair of the anticodon helix, nucleotides (nt) 27-43, increased the error. Thus, misincorporation of amino acids due to aberrant first position wobble is apparently prevented by normal tRNA structure, which is specifically altered by substitution at nt 27-43, the top base-pair of the anticodon helix. All 16 permutations of nt 27-43, the hotspot for increased wobble, were subsequently constructed and compared. Comparison of values for tRNA coding function, tRNA level, and aminoacylation for the 16 suggest that a tRNA conformational change, specifically involving both nt 27-43, differentially affects all these tRNA functions. This conformational alteration, which presumably occurs normally on the ribosome, appears more complex than simple breakage of the normal 27-43 base-pair. We suggest that the change is in the angle and/or flexibility of the tRNA L-shape. Among these 16 tRNAs, efficient wobble is strongly and inversely correlated with good aminoacylation and high tRNA levels; this quality may have been selected. Constraints on the sequences of natural tRNAs suggest that nt 27-43 have effects on function in many tRNAs. PMID:8107080

  9. Characterization of thymus- and bone marrow-derived lymphocytes in rats by means of 3H-uridine incorporation.

    PubMed

    Klobusická, M; Babusíková, O; Koníková, E; Novotná, L

    1975-01-01

    Lymphocytes from various lymphoid organs and of the thoracic duct of normal and thymectomized rats, irradiated and reconstituted with syngeneic bone marrow were tested in vitro in a minimal non-enriched cultivation medium with 3H-uridine, and the percentage of uridine-labeled lymphocytes was determined. The highest number of heavily labeled small lymphocytes was found in the thymus and the thoracic duct, less in peripheral blood, the lymph nodes and the spleen, and the smallest numbers in the bone marrow. A reduced ability of uridine uptake was noted in the thymectomized animals. The method of immune rosette formation was used to determine the presence of B lymphocytes in the lymphoid rat population. The highest quantity of B lymphocytes was noted in bone marrow and the least in the thymus and the thoracic duct. Thymectomized animals had a significantly higher percentage of EAC rosettes than normal and sham-operated animals. The methods employed and existing literary data enabled us to identify the heavily uridine-labeled lymphocytes as T cells, while unlabeled lymphocytes are considered to be B cells. The difference in uriding uptake by rat lymphocytes may serve as one of the T lymphocyte markers in a heterologous lymphoid population. PMID:1082556

  10. The pivotal role of uridine-cytidine kinases in pyrimidine metabolism and activation of cytotoxic nucleoside analogues in neuroblastoma.

    PubMed

    van Kuilenburg, André B P; Meinsma, Rutger

    2016-09-01

    Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine and cytidine as well as the pharmacological activation of several cytotoxic pyrimidine ribonucleoside analogues. In this study, we investigated the functional role of two isoforms of UCK in neuroblastoma cell lines. Analysis of mRNA coding for UCK1 and UCK2 showed that UCK2 is the most abundantly expressed UCK in a panel of neuroblastoma cell lines. Transient and stable overexpression of UCK2 in neuroblastoma cells increased the metabolism of uridine and cytidine as well as the cytotoxicity of 3-deazauridine. Knockdown of endogenous UCK2 as well as overexpression of UCK1 resulted in decreased metabolism of uridine and cytidine and protected the neuroblastoma cells from 3-deazauridine-induced toxicity. Subcellular localization studies showed that UCK1-GFP and UCK2-GFP were localized in the cell nucleus and cytosol, respectively. However, co-expression of UCK1 with UCK2 resulted in a nuclear localization of UCK2 instead of its normal cytosolic localization, thereby impairing its normal function. The physical association of UCK1 and UCK2 was further demonstrated through pull-down analysis using his-tagged UCK. The discovery that UCK2 is highly expressed in neuroblastoma opens the possibility for selectively targeting neuroblastoma cells using UCK2-dependent pyrimidine analogues, while sparing normal tissues. PMID:27239701

  11. The binding of 3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine to ribonuclease A in the crystal.

    PubMed

    Leonidas, Demetres D; Maiti, Tushar Kanti; Samanta, Anirban; Dasgupta, Swagata; Pathak, Tanmaya; Zographos, Spyros E; Oikonomakos, Nikos G

    2006-09-01

    The binding of a moderate inhibitor, 3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine, to ribonuclease A has been studied by X-ray crystallography at 1.7A resolution. Two inhibitor molecules are bound in the central RNA binding cavity of RNase A exploiting interactions with residues from peripheral binding sites rather than from the active site of the enzyme. The uracyl moiety of the first inhibitor molecule occupies the purine-preferring site of RNase A, while the rest of the molecule projects to the solvent. The second inhibitor molecule binds with the carboxyl group at the pyrimidine recognition site and the uridine moiety exploits interactions with RNase A residues Lys66, His119 and Asp121. Comparative structural analysis of the 3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine complex with other RNase A-ligand complexes provides a structural explanation of its potency. The crystal structure of the RNase A-3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine complex provides evidence of a novel ligand-binding pattern in RNase A for 3'-N-aminonucleosides that was not anticipated by modelling studies, while it also suggests ways to improve the efficiency and selectivity of such compounds to develop pharmaceuticals against pathologies associated with RNase A homologues. PMID:16730994

  12. G.T wobble base-pairing in Z-DNA at 1.0 A atomic resolution: the crystal structure of d(CGCGTG).

    PubMed Central

    Ho, P S; Frederick, C A; Quigley, G J; van der Marel, G A; van Boom, J H; Wang, A H; Rich, A

    1985-01-01

    The DNA oligomer d(CGCGTG) crystallizes as a Z-DNA double helix containing two guanine-thymine base pair mismatches of the wobble type. The crystal diffracts to 1 A resolution and the structure has been solved and refined. At this resolution, a large amount of information is revealed about the organization of the water molecules in the lattice generally and more specifically around the wobble base pairs. By comparing this structure with the analogous high resolution structure of d(CGCGCG) we can visualize the structural changes as well as the reorganization of the solvent molecules associated with wobble base pairing. There is only a small distortion of the Z-DNA backbone resulting from introduction of the GT mismatched base pairs. The water molecules cluster around the wobble base pair taking up all of the hydrogen bonding capabilities of the bases due to wobble pairing. These bridging water molecules serve to stabilize the base-base interaction and, thus, may be generally important for base mispairing either in DNA or in RNA molecules. PMID:4092690

  13. Influence of C-5 halogenation of uridines on hairpin versus duplex RNA folding.

    PubMed

    Ennifar, Eric; Bernacchi, Serena; Wolff, Philippe; Dumas, Philippe

    2007-09-01

    Halogenation of bases is a widespread method used for solving crystal structures of nucleic acids. However, this modification may have important consequences on RNA folding and thus on the success of crystallization. We have used a combination of UV thermal melting, steady-state fluorescence, X-ray crystallography, and gel electrophoresis techniques to study the influence of uridine halogenation (bromination or iodination) on the RNA folding. The HIV-1 Dimerization Initiation Site is an RNA hairpin that can adopt an alternative duplex conformation and was used as a model. We have shown that, unexpectedly, the RNA hairpin/duplex ratio is strongly dependent not only on the presence but also on the position of halogenation. PMID:17630326

  14. Influence of C-5 halogenation of uridines on hairpin versus duplex RNA folding

    PubMed Central

    Ennifar, Eric; Bernacchi, Serena; Wolff, Philippe; Dumas, Philippe

    2007-01-01

    Halogenation of bases is a widespread method used for solving crystal structures of nucleic acids. However, this modification may have important consequences on RNA folding and thus on the success of crystallization. We have used a combination of UV thermal melting, steady-state fluorescence, X-ray crystallography, and gel electrophoresis techniques to study the influence of uridine halogenation (bromination or iodination) on the RNA folding. The HIV-1 Dimerization Initiation Site is an RNA hairpin that can adopt an alternative duplex conformation and was used as a model. We have shown that, unexpectedly, the RNA hairpin/duplex ratio is strongly dependent not only on the presence but also on the position of halogenation. PMID:17630326

  15. Re-editing the paradigm of Cytidine (C) to Uridine (U) RNA editing

    PubMed Central

    Fossat, Nicolas; Tam, Patrick P L

    2014-01-01

    Cytidine (C) to Uridine (U) RNA editing is a post-trancriptional modification that until recently was known to only affect Apolipoprotein b (Apob) RNA and minimally require 2 components of the C to U editosome, the deaminase APOBEC1 and the RNA-binding protein A1CF. Our latest work has identified a novel RNA-binding protein, RBM47, as a core component of the editosome, which can substitute A1CF for the editing of ApoB mRNA. In addition, new RNA species that are subjected to C to U editing have been identified. Here, we highlight these recent discoveries and discuss how they change our view of the composition of the C to U editing machinery and expand our knowledge of the functional attributes of C to U RNA editing. PMID:25585043

  16. Addition of uridines to edited RNAs in trypanosome mitochondria occurs independently of transcription

    SciTech Connect

    Harris, M.E.; Moore, D.R.; Hajduk, S.L. )

    1990-07-05

    RNA editing is a novel RNA processing event of unknown mechanism that results in the introduction of nucleotides not encoded in the DNA into specific RNA molecules. We have examined the post-transcriptional addition of nucleotides into the mitochondrial RNA of Trypanosoma brucei. Utilizing an isolated organelle system we have determined that addition of uridines to edited RNAs does not require ongoing transcription. Trypanosome mitochondria incorporate CTP, ATP, and UTP into RNA in the absence of transcription. GTP is incorporated into RNA only as a result of the transcription process. Post-transcriptional CTP and ATP incorporation can be ascribed to known enzymatic activities. CTP is incorporated into tRNAs as a result of synthesis or turnover of their 3{prime} CCA sequences. ATP is incorporated into the 3{prime} CCA of tRNAs and into mitochondrial messenger RNAs due to polyadenylation. In the absence of transcription, UTP is incorporated into transcripts known to undergo editing, and the degree of UTP incorporation is consistent with the degree of editing occurring in these transcripts. Cytochrome b mRNAs, which contain a single editing site near their 5{prime} ends, are initially transcribed unedited at that site. Post-transcriptional labeling of cytochrome b mRNAs in the organelle with (alpha-32P)UTP results in the addition of uridines near the 5{prime} end of the RNA but not in a 3{prime} region which lacks an editing site. These results indicate that RNA editing is a post-transcriptional process in the mitochondria of trypanosomes.

  17. Detection of a pneumonia virus of mice (PVM) in an African hedgehog (Atelerix arbiventris) with suspected wobbly hedgehog syndrome (WHS).

    PubMed

    Madarame, Hiroo; Ogihara, Kikumi; Kimura, Moe; Nagai, Makoto; Omatsu, Tsutomu; Ochiai, Hideharu; Mizutani, Tetsyuya

    2014-09-17

    A pneumonia virus of mice (PVM) from an African hedgehog (Atelerix arbiventris) with suspected wobbly hedgehog syndrome (WHS) was detected and genetically characterized. The affected hedgehog had a nonsuppurative encephalitis with vacuolization of the white matter, and the brain samples yielded RNA reads highly homogeneous to PVM strain 15 (96.5% of full genomic sequence homology by analysis of next generation sequencing). PVM antigen was also detected in the brain and the lungs immunohistochemically. A PVM was strongly suggested as a causative agent of encephalitis of a hedgehog with suspected WHS. This is a first report of PVM infection in hedgehogs. PMID:25129384

  18. Io's wobbling flux tube and nonuniform surface conductivity - Longitude control of decametric emission and other magnetospheric interactions

    NASA Technical Reports Server (NTRS)

    Nash, D. B.

    1979-01-01

    Study of systematic relations between Io's flux tube orientation, decametric emission control, and areal surface properties suggest a model that can account for longitude control of principal Io-associated decametric emissions and other observed Io/magnetosphere interactions. The model is based on the fact that Jupiter's magnetic field structure is dominated by a tilted dipole rotating at a different angular velocity than Io's orbital motion. This caused Io's flux tube near Io to wobble (precess) with respect to Io's rotational axis. Discrete contact junctions are invoked between the active current-sheet regions in the flux tube and Io's surface.

  19. Nonenzymatic template-directed synthesis on hairpin oligonucleotides. 3. Incorporation of adenosine and uridine residues

    NASA Technical Reports Server (NTRS)

    Wu, T.; Orgel, L. E.

    1992-01-01

    We have used [32P]-labeled hairpin oligonucleotides to study template-directed synthesis on templates containing one or more A or T residues within a run of C residues. When nucleoside-5'-phosphoro(2-methyl)imidazolides are used as substrates, isolated A and T residues function efficiently in facilitating the incorporation of U and A, respectively. The reactions are regiospecific, producing mainly 3'-5'-phosphodiester bonds. Pairs of consecutive non-C residues are copied much less efficiently. Limited synthesis of CA and AC sequences on templates containing TG and GT sequences was observed along with some synthesis of the AA sequences on templates containing TT sequences. The other dimer sequences investigated, AA, AG, GA, TA, and AT, could not be copied. If A is absent from the reaction mixture, misincorporation of G residues is a significant reaction on templates containing an isolated T residue or two consecutive T residues. However, if both A and G are present, A is incorporated to a much greater extent than G. We believe that wobble-pairing between T and G is responsible for misincorporation when only G is present.

  20. Structural and Kinetic Characterization of Escherichia coli TadA, the Wobble-Specific tRNA Deaminase

    SciTech Connect

    Kim,J.; Malashkevich, V.; Roday, S.; Lisbin, M.; Schramm, V.; Almo, S.

    2006-01-01

    The essential tRNA-specific adenosine deaminase catalyzes the deamination of adenosine to inosine at the wobble position of tRNAs. This modification allows for a single tRNA species to recognize multiple synonymous codons containing A, C, or U in the last (3'-most) position and ensures that all sense codons are appropriately decoded. We report the first combined structural and kinetic characterization of a wobble-specific deaminase. The structure of the Escherichia coli enzyme clearly defines the dimer interface and the coordination of the catalytically essential zinc ion. The structure also identifies the nucleophilic water and highlights residues near the catalytic zinc likely to be involved in recognition and catalysis of polymeric RNA substrates. A minimal 19 nucleotide RNA stem substrate has permitted the first steady-state kinetic characterization of this enzyme (k{sub cat} = 13 {+-} 1 min{sup -1} and K{sub M} = 0.83 {+-} 0.22 {micro}M). A continuous coupled assay was developed to follow the reaction at high concentrations of polynucleotide substrates (>10 {micro}M). This work begins to define the chemical and structural determinants responsible for catalysis and substrate recognition and lays the foundation for detailed mechanistic analysis of this essential enzyme.

  1. Synthesis and biological evaluation of 5'-glycyl derivatives of uridine as inhibitors of 1,4-β-galactosyltransferase.

    PubMed

    Paszkowska, Jadwiga; Kral, Katarzyna; Bieg, Tadeusz; Żaba, Karolina; Węgrzyk, Katarzyna; Jaśkowiak, Natalia; Molinaro, Antonio; Silipo, Alba; Wandzik, Ilona

    2015-02-01

    New 5'-glycyl derivatives of uridine containing fragments of varying lipophilicity were synthesized as analogues of natural peptidyl antibiotics. One of the studied compounds, 5'-O-(N-succinylglycyl)-2',3'-O-isopropylideneuridine (A4), showed moderate inhibition against 1,4-β-galactosyltransferase. However, additional studies showed that the observed inhibitory effect was due to binding to bovine serum albumin, which was used in assays as a stabilizer. PMID:25462623

  2. Treatment of acute, non-traumatic pain using a combination of diclofenac-cholestyramine, uridine triphosphate, cytidine monophosphate, and hydroxycobalamin.

    PubMed

    Mibielli, Marco Antonio; Nunes, Carlos Pereira; Cohen, José Carlos; Scussel, Ari Boulanger; Higashi, Rafael; Bendavit, Gabriel Gherman; Oliveira, Lisa; Geller, Mauro

    2010-01-01

    This randomized, controlled, double-blind clinical study in parallel groups evaluated the safety and efficacy of an oral combination diclofenac-cholestyramine, nucleotides (uridine and cytidine) and vitamin B12 versus the oral combination of nucleotides and vitamin B12 in the treatment of acute, non-traumatic pain. Subjects received twice-daily, 10-day oral administration of diclofenac-cholestyramine + uridine + cytidine + vitamin B12 (Group DN, n=40) or uridine + cytidine + vitamin B12 (Group NB, n=41). The primary study endpoint was the number of subjects with VAS reduction of >30mm after 10 days of treatment. Secondary endpoints included the number of patients with improvement >5 points in the Patient Functionality Questionnaire after 10 days of treatment, and the number of subjects presenting adverse events. Treatment with the combination of diclofenac-cholestyramine, nucleotides and Vitamin B12 resulted in a higher number of subjects with VAS score reductions >30mm after 10 days of treatment (87.5% subjects) than in the control group administered nucleotides and Vitamin B12 (51.23% of subjects), (p>0.0006). A significantly higher number of subjects in the DN group (80%) had a score reduction of >5 points in the Patient Functionality Questionnaire at after 10 days of treatment compared to Group NB (29.3%), (p<0.001). The number of subjects presenting AEs did not vary significantly between treatment groups (p=0.587). The combination of diclofenac-cholestyramine with uridine, cytidine and vitamin B12 was well-tolerated over a 10-day treatment period. The combination reduced pain and improved functionality among subjects presenting acute, non-traumatic pain in the lower back, hips, and neck. PMID:22128442

  3. Crystallization and preliminary X-ray study of Vibrio cholerae uridine phosphorylase in complex with 6-methyluracil

    PubMed Central

    Prokofev, Igor I.; Lashkov, Alexander A.; Gabdulkhakov, Azat G.; Dontsova, Mariya V.; Seregina, Tatyana A.; Mironov, Alexander S.; Betzel, Christian; Mikhailov, Al’bert M.

    2014-01-01

    Uridine phosphorylase catalyzes the phosphorolysis of ribonucleosides, with the nitrogenous base and ribose 1-phosphate as products. Additionally, it catalyzes the reverse reaction of the synthesis of ribonucleosides from ribose 1-phosphate and a nitrogenous base. However, the enzyme does not catalyze the synthesis of nucleosides when the substrate is a nitrogenous base substituted at the 6-­position, such as 6-methyluracil (6-MU). In order to explain this fact, it is essential to investigate the three-dimensional structure of the complex of 6-MU with uridine phosphorylase. 6-MU is a pharmaceutical agent that improves tissue nutrition and enhances cell regeneration by normalization of nucleotide exchange in humans. 6-MU is used for the treatment of diseases of the gastrointestinal tract, including infectious diseases. Here, procedures to obtain the uridine phosphorylase from the pathogenic bacterium Vibrio cholerae (VchUPh), purification of this enzyme, crystallization of the complex of VchUPh with 6-MU, and X-ray data collection and preliminary X-ray analysis of the VchUPh–6-MU complex at atomic resolution are reported. PMID:24419619

  4. Using Constraints from Satellite Gravimetry to Study Meteorological Excitations of the Chandler Wobble for an Earth Model with Frequency-dependent Responses

    NASA Astrophysics Data System (ADS)

    Chen, W.; Li, J.; Ray, J.; Cheng, M.; Chen, J.; Wilson, C. R.

    2015-12-01

    What maintain(s) the damping Chandler wobble (CW) is still under debate though meteorological excitations are now more preferred. However, controversial results have been obtained: Gross [2000] and Gross et al. [2003] suggested oceanic processes are more efficient to excite the CW than atmospheric ones during 1980 - 2000. Brzezinski and Nastula [2002] concluded that their contributions are almost the same, and they can only provide ~80% of the power needed to maintain the CW observed during 1985 - 1996. Polar motion excitations involve not only the perturbations within the Earth system (namely, mass redistributions and motions of relative to the mantle), but also the Earth's responses to those perturbations (namely, the rheology of the Earth). Chen et al. [2013a] developed an improved theory for polar motion excitation taking into account the Earth's frequency-dependent responses, of which the polar motion transfer functions are ~10% higher than those of previous theories around the CW band. Chen et al. [2013b] compared the geophysical excitations derived from various global atmospheric, oceanic and hydrological models (NCEP, ECCO, ERA40, ERAinterim and ECMWF operational products), and found significant and broad-band discrepancies for models released by different institutes. In addition, the atmosphere, ocean and hydrology models are usually developed in a somewhat independent manner and thus the global (atmospheric, oceanic and hydrological) mass is not conserved [e.g., Yan and Chao, 2012]. Therefore, the matter-term excitations estimated from those models are problematic. In one word, it is unlikely to obtain reliable conclusions on meteorological excitations of CW on the basis of the original meteorological models. Satellite gravimetry can measure mass transportations caused by atmospheric, oceanic and hydrological processes much more accurately than those provided by the original meteorological models, and can force the global (atmospheric, oceanic and

  5. Coordinating properties of uridine 5'-monophosphate with selected Ln(3+) ions in ionic micellar media.

    PubMed

    Sudhiranjan Singh, M; Homendra, Naorem; Lonibala, R K

    2012-12-01

    Coordinating properties of uridine 5'-monophosphate (UMP) towards trivalent La, Pr, Nd, Sm, Eu and Gd ions in presence of cationic and anionic micelles have been investigated by potentiometric pH-titration and spectroscopic methods. Stability constants of the 2:1 complexes have been determined and the change in free energy, enthalpy and entropy associated with the complexation are also calculated. Nd(III) complexes isolated from aqueous and aqueous-micellar media do not show any significant structural difference. Formation of Ln(III) complexes in all cases completes below pH 7.5 showing that UMP best interacts with Ln(3+) ions at the physiological pH range 7.3-7.5. The nucleobase is not involved in the complexation and the metal ion coordination of UMP is through the phosphate moiety only. Coordinating tendency of UMP with lanthanides, Nd(III) ion in particular, at different pH is also discussed. Luminescent properties of Eu(III) complex and its decay lifetime are also presented. This information may prove helpful regarding the use of lanthanides as biological probes for calcium/magnesium ions. PMID:23001701

  6. The Cytidine Analog Fluorocyclopentenylcytosine (RX-3117) Is Activated by Uridine-Cytidine Kinase 2.

    PubMed

    Sarkisjan, Dzjemma; Julsing, Joris R; Smid, Kees; de Klerk, Daniël; van Kuilenburg, André B P; Meinsma, Rutger; Lee, Young B; Kim, Deog J; Peters, Godefridus J

    2016-01-01

    Fluorocyclopentenylcytosine (RX-3117) is an orally available cytidine analog, currently in Phase I clinical trial. RX-3117 has promising antitumor activity in various human tumor xenografts including gemcitabine resistant tumors. RX-3117 is activated by uridine-cytidine kinase (UCK). Since UCK exists in two forms, UCK1 and UCK2, we investigated which form is responsible for RX-3117 phosphorylation. For that purpose we transfected A549 and SW1573 cell lines with UCK-siRNAs. Transfection of UCK1-siRNA efficiently downregulated UCK1-mRNA, but not UCK2-mRNA expression, and did not affect sensitivity to RX-3117. However, transfection of UCK2-siRNA completely downregulated UCK2-mRNA and protein and protected both A549 and SW1573 against RX-3117. UCK enzyme activity in two panels of tumor cell lines and xenograft cells correlated only with UCK2-mRNA expression (r = 0.803 and 0.915, respectively), but not with UCK1-mRNA. Moreover, accumulation of RX-3117 nucleotides correlated with UCK2 expression. In conclusion, RX-3117 is activated by UCK2 which may be used to select patients potentially sensitive to RX-3117. PMID:27612203

  7. Stacking-unstacking of the dinucleoside monophosphate guanylyl-3',5'-uridine studied with molecular dynamics.

    PubMed

    Norberg, J; Nilsson, L

    1994-08-01

    Molecular dynamics simulations were carried out on two conformations of the dinucleoside monophosphate guanylyl-3',5'-uridine (GpU) in aqueous solution with one sodium counterion. One stacked conformation and one with the C3'-O3'-P-O5' backbone torsion angle twisted 180 degrees to create an unstacked conformation. We observed a relatively stable behavior of the stacked conformation, which remained stacked throughout the simulation, whereas the unstacked conformation showed major changes in the backbone torsion and glycosidic angles. During the simulation the unstacked conformation transformed into a more stacked form and then back again to an unstacked one. The calculated correlation times for rotational diffusion from the molecular dynamics simulations are in agreement with fluorescence anisotropy and nuclear magnetic resonance data. As expected, the correlation times for rotational diffusion of the unstacked conformation were observed to be longer than for the stacked conformation. The 2'OH group may contribute in stabilizing the stacked conformation, where the O2'-H...O4' hydrogen bond occurred in 82.7% of the simulation. PMID:7948694

  8. Synthesis of 5-Hydroxymethylcytidine- and 5-Hydroxymethyl-uridine-Modified RNA

    PubMed Central

    Riml, Christian; Micura, Ronald

    2016-01-01

    We report on the syntheses of 5-hydroxymethyl-uridine [5hm(rU)] and -cytidine [5hm(rC)] phosphoramidites and their incorporation into RNA by solid-phase synthesis. Deprotection of the oligonucleotides is accomplished in a straightforward manner using standard conditions, confirming the appropriateness of the acetyl protection used for the pseudobenzylic alcohol moieties. The approach provides robust access to 5hm(rC/U)-modified RNAs that await applications in pull-down experiments to identify potential modification enzymes. They will also serve as synthetic probes for the development of high-throughput-sequencing methods in native RNAs. 1Introduction2Protection Strategies Reported for the Synthesis of 5hm(dC)-Modified DNA3Synthesis of 5-Hydroxymethylpyrimidine-Modified RNA3.1Synthesis of 5hm(rC) Phosphoramidite3.2Synthesis of 5hm(rU) Phosphoramidite3.3Synthesis of 5hm(rC)- and 5hm(rU)-Modified RNA4Conclusions PMID:27413246

  9. Effect of electrical convulsions on uridine labeling and activity pattern in nerve cells in mice

    SciTech Connect

    Pakkenberg, H.; Pakkenberg, B.; Fog, R.

    1985-07-01

    Male white mice were exposed to electroshock and then injected intravenously with 5-(3H)uridine immediately after the shock. After 5, 30, or 60 min or 6, 12, or 24 h, the mice were killed, microautoradiographs were prepared, and grains were counted in the cortex, hippocampus, and basal ganglia. The results of the grain counts were compared with grain counts in the cortex, hippocampus, and basal ganglia of mice exposed to anoxia for 25 s and then treated in the same manner as the first groups. After electroshock the grain count decreased to 25% of that in control animals in the hippocampus and to 50% in the cortex but was normal in the basal ganglia. The counts returned to normal values within 6 h in the hippocampus, and within 1 h in the cortex. After anoxia, the grain counts were normal in the cortex and hippocampus but increased in the basal ganglia. The distribution of cells with a high or low grain count in vertical and horizontal columns of the cortex in control and convulsion animals was analyzed. There were random variations from column to column in both control and convulsion animals. In some anatomic layers there were significantly different grain counts, indicating differences in functional activity.

  10. Conjugation of Uridine with Oleanolic Acid Derivatives as Potential Antitumor Agents.

    PubMed

    Cheng, Ke-Guang; Su, Chun-Hua; Huang, Jia-Yan; Liu, Jun; Zheng, Yuan-Ting; Chen, Zhen-Feng

    2016-09-01

    According to fused two bioactive moieties together by bonds covalently and available as a new single hybrid entity known as pharmacophore hybridization, a total of 10 targeted uridine-oleanolic acid hybrids were synthesized. Most of these hybrids showed excellent proliferation inhibition against tested Hep-G2, A549, BGC-823, MCF-7, and PC-3 tumor cell lines (IC50 < 8 μm), even with some IC50 values under 0.1 μm. The detection of cytotoxicity selectivity revealed that hybrids 5 and 18 exhibited low cytotoxicity toward normal human liver cell HL-7702. Further studies revealed that selected hybrid 5 could induce apoptosis in Hep-G2 cells through the investigation of acridine orange/ethidium bromide, Hoechst 33258 fluorescence stainings, and annexin V/propidium iodide assay. It was also found that hybrid 5 could induce mitochondrial membrane potential disruption, arrest Hep-G2 cell line at G1 phase, and activate effector caspase-3/9 to trigger cell apoptosis. PMID:26990000

  11. Structural and mechanistic basis for enhanced translational efficiency by 2-thiouridine at the tRNA anticodon wobble position

    PubMed Central

    Rodriguez-Hernandez, Annia; Spears, Jessica L.; Gaston, Kirk W.; Limbach, Patrick A.; Gamper, Howard; Hou, Ya-Ming; Kaiser, Rob; Agris, Paul F.; Perona, John J.

    2013-01-01

    The 2-thiouridine (s2U) at the wobble position of certain bacterial and eukaryotic tRNAs enhances aminoacylation kinetics, assists proper codon-anticodon base pairing at the ribosome A-site, and prevents frameshifting during translation. By mass spectrometry of affinity-purified native E. coli tRNA1GlnUUG, we show that the complete modification at the wobble position 34 is 5-carboxyaminomethyl-2-thiouridine (cmnm5s2U). The crystal structure of E. coli GlnRS bound to native tRNA1Gln and ATP demonstrates that cmnm5s2U34 improves the order of a previously unobserved 11 amino acid surface loop in the distal β-barrel domain of the enzyme, and imparts other local rearrangements of nearby amino acids that create a binding pocket for the 2-thio moiety. Together with previously solved structures, these observations explain the degenerate recognition of C34 and modified U34 by GlnRS. Comparative pre-steady state aminoacylation kinetics of native tRNA1Gln, synthetic tRNA1Gln containing s2U34 as sole modification, and unmodified wild-type and mutant tRNA1Gln and tRNA2Gln transcripts demonstrates that the exocyclic sulfur moiety improves tRNA binding affinity to GlnRS 10-fold compared with the unmodified transcript, and that an additional four-fold improvement arises from the presence of the cmnm5 moiety. Measurements of Gln-tRNAGln interactions at the ribosome A-site show that the s2U modification enhances binding affinity to the glutamine codons CAA and CAG, and increases the rate of GTP hydrolysis by E. coli EF-Tu by five-fold. PMID:23727144

  12. Oligomerization of uridine phosphorimidazolides on montmorillonite: a model for the prebiotic synthesis of RNA on minerals

    NASA Technical Reports Server (NTRS)

    Ding, P. Z.; Kawamura, K.; Ferris, J. P.

    1996-01-01

    The 5'-phosphorimidazolide of uridine reacts on Na(+)-montmorillonite 22A in aqueous solution to give oligomers as long as 7 mers. The maximum chain length increases to 9 mers and the overall oligomer yield increases when 9:1 ImpU, A5' ppA mixtures react under the same conditions. The oligomer yield and maximum chain length decreases with the structure of the added pyrophosphate in the order A5' ppA > A5' ppU > U5' ppU. Structure analysis of individual oligomer fractions was performed by selective enzymatic hydrolyses followed by HPLC analysis of the products. The regioselectivity for 3',5'-bond formation is 80-90% in the 9:1 ImpU, A5' ppA reaction, a percentage comparable to that observed in the 9:1 ImpA, A5' ppA reaction. Oligomerization of ImpU is inhibited by addition of dA5' ppdA, and MeppA. No oligomers containing A5' ppU were products of the 9:1 ImpU,A5' ppA reaction, a finding consistent with the simple addition of the ImpU to the A5' ppA and not the rearrangement of an ImpU-A5' ppA adduct. Concentrations of lysine or arginine which were close to that of the ImpU did not inhibit oligomer formation. Treatment of Na(+)-montmorillonite with 1 M arginine yielded arginine-montmorillonite, an amino acid-mineral adduct which did not catalyze ImpU oligomerization. Neither the 4-9 mers formed in the 9:1 ImpU, A5' ppA reaction nor the 4-9 mers formed by the base hydrolysis of poly(U) served as templates for the formation of oligo(A)s.

  13. Uridine insertion/deletion editing in trypanosomes: a playground for RNA-guided information transfer.

    PubMed

    Aphasizhev, Ruslan; Aphasizheva, Inna

    2011-01-01

    RNA editing is a collective term referring to enzymatic processes that change RNA sequence apart from splicing, 5' capping or 3' extension. In this article, we focus on uridine insertion/deletion mRNA editing found exclusively in mitochondria of kinetoplastid protists. This type of editing corrects frameshifts, introduces start and stops codons, and often adds much of the coding sequence to create an open reading frame. The mitochondrial genome of trypanosomatids, the most extensively studied clade within the order Kinetoplastida, is composed of ∼50 maxicircles with limited coding capacity and thousands of minicircles. To produce functional mRNAs, a multitude of nuclear-encoded factors mediate interactions of maxicircle-encoded pre-mRNAs with a vast repertoire of minicircle-encoded guide RNAs. Editing reactions of mRNA cleavage, U-insertions or U-deletions, and ligation are catalyzed by the RNA editing core complex (RECC, the 20S editosome) while each step of this enzymatic cascade is directed by guide RNAs. These 50-60 nucleotide (nt) molecules are 3' uridylated by RET1 TUTase and stabilized via association with the gRNA binding complex (GRBC). Remarkably, the information transfer between maxicircle and minicircle transcriptomes does not rely on template-dependent polymerization of nucleic acids. Instead, intrinsic substrate specificities of key enzymes are largely responsible for the fidelity of editing. Conversely, the efficiency of editing is enhanced by assembling enzymes and RNA binding proteins into stable multiprotein complexes. WIREs RNA 2011 2 669-685 DOI: 10.1002/wrna.82 For further resources related to this article, please visit the WIREs website. PMID:21823228

  14. Uridine Diphosphate-Glucuronosyltransferase (UGT) Xenobiotic Metabolizing Activity and Genetic Evolution in Pinniped Species.

    PubMed

    Kakehi, Mayu; Ikenaka, Yoshinori; Nakayama, Shouta M M; Kawai, Yusuke K; Watanabe, Kensuke P; Mizukawa, Hazuki; Nomiyama, Kei; Tanabe, Shinsuke; Ishizuka, Mayumi

    2015-10-01

    There are various interspecies differences in xenobiotic-metabolizing enzymes. It is known that cats show slow glucuronidation of drugs such as acetaminophen and strong side effects due to the UGT1A6 pseudogene. Recently, the UGT1A6 pseudogene was found in the Northern elephant seal and Otariidae was suggested to be UGT1A6-deficient. From the results of measurements of uridine diphosphate-glucuronosyltransferase (UGT) activity using liver microsomes, the Steller sea lion, Northern fur seal, and Caspian seal showed UGT activity toward 1-hydroxypyrene and acetaminophen as low as in cats, which was significantly lower than in rat and dog. Furthermore, UGT1A6 pseudogenes were found in Steller sea lion and Northern fur seal, and all Otariidae species were suggested to have the UGT1A6 pseudogene. The UGT1 family genes appear to have undergone birth-and-death evolution based on a phylogenetic and synteny analysis of the UGT1 family in mammals including Carnivora. UGT1A2-1A5 and UGT1A7-1A10 are paralogous genes to UGT1A1 and UGTA6, respectively, and their numbers were lower in cat, ferret and Pacific walrus than in human, rat, and dog. Felidae and Pinnipedia, which are less exposed to natural xenobiotics such as plant-derived toxins due to their carnivorous diet, have experienced fewer gene duplications of xenobiotic-metabolizing UGT genes, and even possess UGT1A6 pseudogenes. Artificial environmental pollutants and drugs conjugated by UGT are increasing dramatically, and their elimination to the environment can be of great consequence to cat and Pinnipedia species, whose low xenobiotic glucuronidation capacity makes them highly sensitive to these compounds. PMID:26179383

  15. [The effect of uridine on the endurance of animals with different resistance to physical stress: the role of mitochondrial ATP-dependent potassium channel].

    PubMed

    Man'kovskaia, I N; Nosar', V I; Gorbacheva, O S; Gonchar, O A; Gavenauskas, B L; Bratus', L V; Mironova, G D

    2014-01-01

    The effect of a metabolic precursor of natural activator of mitochondrial ATP-dependent potassium channel (mitochondrial K+(ATP))--uridine on animal's endurance to physical stress was studied. The endurance was determined by recording the time period during which the rat loaded with a plummet of 20% of body weight can swim until physical exhaustion at 32 degrees C. It was found that highly resistant animals swam until exhaustion for 7.40 ± 0.35 min, whereas low resistant rats hold out 2.07 ± 0.10 min only. The injection of uridine influenced the swimming time of the animals, increasing it twofold in low-resistant rats. The effect of uridine was decreased by injection of inhibitors of mitochondrial K+(ATP) channel. It was found that the injection of uridine into low resistant rats increased the rate of potassium transport in mitochondria isolated from liver of these rats, and inhibitors of the channel prevent the channel activating effect of uridine. The role of mitochondrial K+(ATP) cannel in the formation of animal's resistance to physical stress and protection of tissues from hypoxia is discussed. PMID:25730977

  16. Non-enzymatic synthesis of the coenzymes, uridine diphosphate glucose and cytidine diphosphate choline, and other phosphorylated metabolic intermediates

    NASA Technical Reports Server (NTRS)

    Mar, A.; Dworkin, J.; Oro, J.

    1987-01-01

    Using urea and cyanamide, the two condensing agents considered to have been present on the primitive earth, uridine diphosphate glucose (UDPG), cytidine diphosphate choline (CDP-choline), glucose-1-phosphate (G1P), and glucose-6-phosphate (G6P) were synthesized under simulated prebiotic conditions. The reaction products were separated and identified using paper chromatography, thin layer chromatography, enzymatic analyses, and ion-pair reverse-phase high performance liquid chromatography. The possibility of nonenzymatic synthesis of metabolic intermediates on the primitive earth from simple precursors was thus demonstrated.

  17. Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

    PubMed Central

    Wirth, Marius; Niro, Giuliana; Leyerer, Kristin

    2016-01-01

    Summary Muraymycins are a promising class of antimicrobial natural products. These uridine-derived nucleoside-peptide antibiotics inhibit the bacterial membrane protein translocase I (MraY), a key enzyme in the intracellular part of peptidoglycan biosynthesis. This review describes the structures of naturally occurring muraymycins, their mode of action, synthetic access to muraymycins and their analogues, some structure–activity relationship (SAR) studies and first insights into muraymycin biosynthesis. It therefore provides an overview on the current state of research, as well as an outlook on possible future developments in this field. PMID:27340469

  18. Cerebrospinal fluid concentrations of hypoxanthine, xanthine, uridine and inosine: high concentrations of the ATP metabolite, hypoxanthine, after hypoxia.

    PubMed Central

    Harkness, R A; Lund, R J

    1983-01-01

    CSF obtained for clinical purposes from newborn, children and adults has been analysed by high pressure liquid chromatography for hypoxanthine, xanthine, inosine, uridine and urate. Large rises in hypoxanthine and to a lesser extent xanthine occur for about 24 h after hypoxia. High concentrations were associated with later evidence of brain damage or subsequent death. Changes in CSF could be independent of those in plasma. Small or negligible rises were associated with localised and generalised infections including bacterial meningitis, fits, or both. Marked and rapid rises were found after death. These estimations may "predict" the extent of brain damage or brain death. PMID:6681617

  19. Feature extraction of micro-motion frequency and the maximum wobble angle in a small range of missile warhead based on micro-Doppler effect

    NASA Astrophysics Data System (ADS)

    Li, M.; Jiang, Y. S.

    2014-11-01

    Micro-Doppler effect is induced by the micro-motion dynamics of the radar target itself or any structure on the target. In this paper, a simplified cone-shaped model for ballistic missile warhead with micro-nutation is established, followed by the theoretical formula of micro-nutation is derived. It is confirmed that the theoretical results are identical to simulation results by using short-time Fourier transform. Then we propose a new method for nutation period extraction via signature maximum energy fitting based on empirical mode decomposition and short-time Fourier transform. The maximum wobble angle is also extracted by distance approximate approach in a small range of wobble angle, which is combined with the maximum likelihood estimation. By the simulation studies, it is shown that these two feature extraction methods are both valid even with low signal-to-noise ratio.

  20. The occurrence of uridine diphosphate N-acetylgalactosamine 6-sulfate in quail egg white and characteristic distribution of sulfated sugar nucleotides in different avian eggs.

    PubMed

    Nakanishi, Y; Okuda, S; Tsuji, M; Suzuki, S

    1979-08-29

    A sulfated sugar nucleotide has been isolated from quail egg white, and accounts for nearly 80% of the total sugar nucleotides found in the egg white. Evidence is presented that this nucleotide is uridine diphosphate N-acetylgalactosamine 6-sulfate, an isomer of the 4-sulfated derivative of uridine diphosphate N-acetylgalactosamine previously found in chicken egg white. Further studies on the distribution of sulfated sugar nucleotides in egg white of various birds (chicken, quail, pheasant, peafowl, turkey, goose, and duck) demonstrate that each species has a characteristic composition, differing from one another regarding the relative amounts of 4-sulfated, 6-sulfated, and 4,6-bissulfated derivatives of uridine diphosphate N-acetylgalactosamine. PMID:534643

  1. In vivo protective effect of Uridine, a pyrimidine nucleoside, on genotoxicity induced by Levodopa/Carbidopa in mice.

    PubMed

    Orenlili Yaylagul, Esra; Cansev, Mehmet; Celikler Kasimogullari, Serap

    2015-08-01

    Parkinson's disease (PD) is a common neurodegenerative disorder that affects millions of people all over the world. Motor symptoms of PD are most commonly controlled by L-3,4-dihydroxyphenylalanine (Levodopa, L-DOPA), a precursor of dopamine, plus a peripherally-acting aromatic-L-amino-acid decarboxylase (dopa decarboxylase) inhibitor, such as carbidopa. However, chronic treatment with a combination of Levodopa plus carbidopa has been demonstrated to cause a major complication, namely abnormal involuntary movements. On the other hand, the effect of this treatment on bone marrow cells is unknown. Therefore, in this study, we aimed to investigate possible genotoxic effects of Levodopa and Carbidopa using male Balb/C mice. Our results showed that Levodopa alone or in combination with carbidopa caused genotoxicity in in vivo micronucleus test (mouse bone marrow) and Comet assay (blood cells). Furthermore, we showed that simultaneous administration of uridine, a pyrimidine nucleoside, reversed the genotoxic effect of Levodopa and Carbidopa in both assays. Our data show for the first time that Levodopa plus carbidopa combination causes genotoxicity which is reversed by uridine treatment. These findings might enhance our understanding for the complications of a common Parkinson's treatment and confer benefit in terms of reducing a possible genotoxic effect of this treatment. PMID:25976300

  2. The ribosome prohibits the G•U wobble geometry at the first position of the codon-anticodon helix.

    PubMed

    Rozov, Alexey; Westhof, Eric; Yusupov, Marat; Yusupova, Gulnara

    2016-07-27

    Precise conversion of genetic information into proteins is essential to cellular health. However, a margin of error exists and is at its highest on the stage of translation of mRNA by the ribosome. Here we present three crystal structures of 70S ribosome complexes with messenger RNA and transfer RNAs and show that when a G•U base pair is at the first position of the codon-anticodon helix a conventional wobble pair cannot form because of inescapable steric clash between the guanosine of the A codon and the key nucleotide of decoding center adenosine 1493 of 16S rRNA. In our structure the rigid ribosomal decoding center, which is identically shaped for cognate or near-cognate tRNAs, forces this pair to adopt a geometry close to that of a canonical G•C pair. We further strengthen our hypothesis that spatial mimicry due either to base tautomerism or ionization dominates the translation infidelity mechanism. PMID:27174928

  3. 5-Iodo-2'-deoxy-L-uridine and (E)-5-(2-bromovinyl)-2'-deoxy-L-uridine: selective phosphorylation by herpes simplex virus type 1 thymidine kinase, antiherpetic activity, and cytotoxicity studies.

    PubMed

    Spadari, S; Ciarrocchi, G; Focher, F; Verri, A; Maga, G; Arcamone, F; Iafrate, E; Manzini, S; Garbesi, A; Tondelli, L

    1995-06-01

    5-Iodo-2'-deoxy-L-uridine (L-IdU) and (E)-5-(2-bromovinyl)-2'-deoxy-L-uridine (L-BVdU) have been prepared and found to inhibit herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with activities comparable to those of their analogs with the natural D-sugar configuration. The mechanism of inhibition is purely competitive for L-IdU (Ki = 0.24 microM) and mixed-type for L-BVdU (Ki = 0.13 microM). High performance liquid chromatographic analysis of the reaction products demonstrated that the viral enzyme phosphorylates both L-enantiomers to their corresponding monophosphates with efficiency comparable to that for D-enantiomers. Neither L-enantiomer inhibits the human cytosolic TK. In contrast to their D-enantiomers, L-IdU and L-BVdU have no effect on human thymidylate synthase, either in HeLa cells or in TK-deficient HeLa cells transformed with the HSV-1 TK gene. Both L-enantiomers (i) have no effect on HeLa cell growth, (ii) are 1000-fold less cytotoxic toward TK-deficient HeLa cells transformed with the HSV-1 TK gene than are their D-enantiomers, (iii) in contrast to their D-enantiomers, are fully resistant to hydrolysis by nucleoside phosphorylase, and, (iv) in spite of their much lower cytotoxicity, most probably due to the very low affinity of L-BVdU monophosphate and L-IdU monophosphate for thymidylate synthase, are only 1 or 2 orders of magnitude less potent than their D-enantiomers in inhibiting viral growth, with potency comparable to that of acyclovir. PMID:7603465

  4. Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

    NASA Astrophysics Data System (ADS)

    Balaev, V. V.; Lashkov, A. A.; Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M.

    2015-03-01

    Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis ( YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability ( R work = 16.2, R free = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh.

  5. Structure of a complex of uridine phosphorylase from Yersinia pseudotuberculosis with the modified bacteriostatic antibacterial drug determined by X-ray crystallography and computer analysis

    SciTech Connect

    Balaev, V. V.; Lashkov, A. A. Gabdoulkhakov, A. G.; Seregina, T. A.; Dontsova, M. V.; Mikhailov, A. M.

    2015-03-15

    Pseudotuberculosis and bubonic plague are acute infectious diseases caused by the bacteria Yersinia pseudotuberculosis and Yersinia pestis. These diseases are treated, in particular, with trimethoprim and its modified analogues. However, uridine phosphorylases (pyrimidine nucleoside phosphorylases) that are present in bacterial cells neutralize the action of trimethoprim and its modified analogues on the cells. In order to reveal the character of the interaction of the drug with bacterial uridine phosphorylase, the atomic structure of the unligated molecule of uridine-specific pyrimidine nucleoside phosphorylase from Yersinia pseudotuberculosis (YptUPh) was determined by X-ray diffraction at 1.7 Å resolution with high reliability (R{sub work} = 16.2, R{sub free} = 19.4%; r.m.s.d. of bond lengths and bond angles are 0.006 Å and 1.005°, respectively; DPI = 0.107 Å). The atoms of the amino acid residues of the functionally important secondary-structure elements—the loop L9 and the helix H8—of the enzyme YptUPh were located. The three-dimensional structure of the complex of YptUPh with modified trimethoprim—referred to as 53I—was determined by the computer simulation. It was shown that 53I is a pseudosubstrate of uridine phosphorylases, and its pyrimidine-2,4-diamine group is located in the phosphate-binding site of the enzyme YptUPh.

  6. Is capillary electrophoresis on microchip devices able to genotype uridine diphosphate glucuronosyltransferase 1A1 TATA-box polymorphisms?

    PubMed

    Minucci, Angelo; Canu, Giulia; De Bonis, Maria; Delibato, Elisabetta; Capoluongo, Ettore

    2014-06-01

    In this commentary, we focused our attention on capillary electrophoresis. It achieves the efficient separation of molecular species by the application of high voltages to samples in solution. Actually, capillary electrophoresis can be performed on microchip devices, based on an automated and miniaturized electrophoresis system, based on lab-on-a-chip technology. By this technology it is possible to separate nucleic acid fragments (DNA or RNA) with respect to sizing accuracy and sizing resolution. Currently, two automated capillary electrophoresis on microchips devices are available: the Agilent 2100 Bioanalyzer and the Experion™ Automated Electrophoresis System. In this study, we evaluated if the CE is able to distinguish the three uridine diphosphate glucuronosyltransferase 1A1 TATA-box genotypes. PMID:24687976

  7. Stimulating effects of inosine, uridine and glutamine on the tissue distribution of radioactive D-leucine in tumor bearing mice.

    PubMed

    Goto, R; Takeda, A; Tamemasa, O; Chaney, J E; Digenis, G A

    1984-02-01

    This experiment was carried out in search for stimulators of the in vivo uptake of D- and L-leucine by tumor and pancreas for the possible application to gamma-emitter labeled amino acids in nuclear medical diagnosis. Inosine, uridine, and glutamine which are stimulators of the in vitro incorporation of radioactive L-amino acids into some tumor cells significantly enhanced the uptake of D-leucine into the pancreas, while in Ehrlich solid tumor only a little if any increase was observed. Of the compounds tested inosine showed the highest stimulation of pancreas uptake in the range of doses used, resulting in the best pancreas-to-liver concentration ratio, a factor of significant consideration for pancreas imaging. The uptake of L-leucine by the tumor and pancreas was little affected by these compounds. PMID:6739860

  8. Identification of two uridine binding domain peptides of the UDP-glucose-binding site of rabbit muscle glycogenin.

    PubMed

    Carrizo, M E; Curtino, J A

    1998-12-30

    Glycogenin, the autoglucosyltransferase that initiates the de novo biosynthesis of glycogen, photoaffinity labeled with [beta32P]5-azido-UDP-glucose. The photoinsertion of the azidouridine derivative showed activating ultraviolet light dependency, saturation effects, and inhibition by UDP-glucose, thus demonstrating the specificity of the interaction. In the absence of Mn2+, the requirement for the catalytic activity of glycogenin, the photolabeling decreased by 70%. Competitive binding experiments indicated that the pyrophosphate or a phosphate was the moiety of UDP-glucose implicated in the strongest interaction at the binding site. Proteolytic digestion of photolabeled glycogenin resulted in the identification of two labeled fragments, 89-143 and 168-233, that carried the uridine binding sites. This is the first report of the region of glycogenin that harbors the UDP-glucose-binding domain. PMID:9918805

  9. PCR screening for carriers of bovine leukocyte adhesion deficiency (BLAD) and uridine monophosphate synthase (DUMPS) in Argentine Holstein cattle.

    PubMed

    Poli, M A; Dewey, R; Semorile, L; Lozano, M E; Albariño, C G; Romanowski, V; Grau, O

    1996-05-01

    BLAD (Bovine Leukocyte Adhesion Deficiency) and DUMPS (Deficiency of Uridine Monophosphate Synthase) are monogenic autosomal, recessive inherited diseases of Holstein cattle. Single nucleotide changes (point mutations) responsible for the genetic disorders were detected by polymerase chain reaction coupled with restriction fragment length polymorphism assays (PCR-RFLP). Using oligonucleotide primers, DNA fragments of predicted sizes were amplified, and the products' specificity was assessed by nucleotide sequencing. Mutations were detected in DNA samples from bovine blood and semen by the presence or absence of restriction sites within the PCR amplification products (Taq I, Hae III for BLAD, Ava I for DUMPS). The test included 104 bulls and 950 cows of Argentinean Holstein breed. Defective alleles frequencies were as follows: 2.88% BLAD in bulls used in artificial insemination, 1.79% in cows; 0.96% DUMPS in bulls and 0.11% in cows. PMID:8693839

  10. In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica.

    PubMed

    Malami, Ibrahim; Abdul, Ahmad Bustamam; Abdullah, Rasedee; Bt Kassim, Nur Kartinee; Waziri, Peter; Christopher Etti, Imaobong

    2016-01-01

    Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective UCK2 inhibitors of natural origin using bioinformatics tools. An in vitro kinase assay was established by measuring the amount of ADP production in the presence of ATP and 5-fluorouridine as a substrate. Molecular docking studies revealed an interesting ligand interaction with the UCK2 protein for both flavokawain B and alpinetin. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity in vitro. In conclusion, we have identified flavokawain B and alpinetin as potential natural UCK2 inhibitors as determined by their interactions with UCK2 protein using in silico molecular docking studies. This can provide information to identify lead candidates for further drug design and development. PMID:27070566

  11. Analysis of two Schistosoma mansoni uridine phosphorylases isoforms suggests the emergence of a protein with a non-canonical function.

    PubMed

    da Silva Neto, Antônio Marinho; Torini de Souza, Juliana Roberta; Romanello, Larissa; Cassago, Alexandre; Serrão, Vitor Hugo Balasco; DeMarco, Ricardo; Brandão-Neto, José; Garratt, Richard Charles; Pereira, Humberto D'Muniz

    2016-06-01

    Reports of Schistosoma mansoni strains resistant to praziquantel, the only therapeutic strategy available for the treatment of schistosomiasis, have motivated the scientific community towards the search for new possible therapies. Biochemical characterization of the parasite's metabolism is an essential component for the rational development of new therapeutic alternatives. One of the so far uncharacterized enzymes is uridine phosphorylase (UP) (EC 2.4.2.3), for which the parasite genome presents two isoforms (SmUPa and SmUPb) that share 92% sequence identity. In this paper, we present crystal structures for SmUPa and SmUPb in their free states as well as bound to different ligands. This we have complemented by enzyme kinetic characterization and phylogenetic analyses. Both enzymes present an overall fold and active site structure similar to other known UPs. The kinetic analyses showed conclusively that SmUPa is a regular uridine phosphorylase but by contrast SmUPb presented no detectable activity. This is particularly noteworthy given the high level of sequence identity between the two isoforms and is probably the result of the significant differences observed for SmUPb in the vicinity of the active site itself, suggesting that it is not a UP at all. On the other hand, it was not possible to identify an alternative function for SmUPb, although our phylogenetic analyses and expression data suggest that SmUPb is still functional and plays a role in parasite metabolism. The unusual UPb isoform may open up new opportunities for understanding unique features of S. mansoni metabolism. PMID:26898674

  12. LKB1 promotes cell survival by modulating TIF-IA-mediated pre-ribosomal RNA synthesis under uridine downregulated conditions

    PubMed Central

    Liu, Xiuju; Huang, Henry; Wilkinson, Scott C.; Zhong, Diansheng; Khuri, Fadlo R.; Fu, Haian; Marcus, Adam; He, Yulong; Zhou, Wei

    2016-01-01

    We analyzed the mechanism underlying 5-aminoimidazole-4-carboxamide riboside (AICAR) mediated apoptosis in LKB1-null non-small cell lung cancer (NSCLC) cells. Metabolic profile analysis revealed depletion of the intracellular pyrimidine pool after AICAR treatment, but uridine was the only nucleotide precursor capable of rescuing this apoptosis, suggesting the involvement of RNA metabolism. Because half of RNA transcription in cancer is for pre-ribosomal RNA (rRNA) synthesis, which is suppressed by over 90% after AICAR treatment, we evaluated the role of TIF-IA-mediated rRNA synthesis. While the depletion of TIF-IA by RNAi alone promoted apoptosis in LKB1-null cells, the overexpression of a wild-type or a S636A TIF-IA mutant, but not a S636D mutant, attenuated AICAR-induced apoptosis. In LKB1-null H157 cells, pre-rRNA synthesis was not suppressed by AICAR when wild-type LKB1 was present, and cellular fractionation analysis indicated that TIF-IA quickly accumulated in the nucleus in the presence of a wild-type LKB1 but not a kinase-dead mutant. Furthermore, ectopic expression of LKB1 was capable of attenuating AICAR-induced death in AMPK-null cells. Because LKB1 promotes cell survival by modulating TIF-IA-mediated pre-rRNA synthesis, this discovery suggested that targeted depletion of uridine related metabolites may be exploited in the clinic to eliminate LKB1-null cancer cells. PMID:26506235

  13. ERRATIC JET WOBBLING IN THE BL LACERTAE OBJECT OJ287 REVEALED BY SIXTEEN YEARS OF 7 mm VLBA OBSERVATIONS

    SciTech Connect

    Agudo, Ivan; Gomez, Jose L.; Marscher, Alan P.; Jorstad, Svetlana G.; Perucho, Manel; Piner, B. Glenn; Rioja, Maria; Dodson, Richard

    2012-03-01

    We present the results from an ultra-high-resolution 7 mm Very Long Baseline Array study of the relativistic jet in the BL Lacertae object OJ287 from 1995 to 2011 containing 136 total intensity images. Analysis of the image sequence reveals a sharp jet-position-angle swing by >100 Degree-Sign during [2004,2006], as viewed in the plane of the sky, which we interpret as the crossing of the jet from one side of the line of sight to the other during a softer- and longer-term swing of the inner jet. Modulating such long-term swing, our images also show for the first time a prominent erratic wobbling behavior of the innermost {approx}0.4 mas of the jet with fluctuations in position angle of up to {approx}40 Degree-Sign over timescales {approx}2 yr. This is accompanied by highly superluminal motions along non-radial trajectories, which reflect the remarkable non-ballistic nature of the jet plasma on these scales. The erratic nature and short timescales of the observed behavior rule out scenarios such as binary black hole systems, accretion disk precession, and interaction with the ambient medium as possible origins of the phenomenon on the scales probed by our observations, although such processes may cause longer-term modulation of the jet direction. We propose that variable asymmetric injection of the jet flow, perhaps related to turbulence in the accretion disk, coupled with hydrodynamic instabilities leads to the non-ballistic dynamics that causes the observed non-periodic changes in the direction of the inner jet.

  14. Codon-biased translation can be regulated by wobble-base tRNA modification systems during cellular stress responses

    PubMed Central

    Endres, Lauren; Dedon, Peter C; Begley, Thomas J

    2015-01-01

    tRNA (tRNA) is a key molecule used for protein synthesis, with multiple points of stress-induced regulation that can include transcription, transcript processing, localization and ribonucleoside base modification. Enzyme-catalyzed modification of tRNA occurs at a number of base and sugar positions and has the potential to influence specific anticodon-codon interactions and regulate translation. Notably, altered tRNA modification has been linked to mitochondrial diseases and cancer progression. In this review, specific to Eukaryotic systems, we discuss how recent systems-level analyses using a bioanalytical platform have revealed that there is extensive reprogramming of tRNA modifications in response to cellular stress and during cell cycle progression. Combined with genome-wide codon bias analytics and gene expression studies, a model emerges in which stress-induced reprogramming of tRNA drives the translational regulation of critical response proteins whose transcripts display a distinct codon bias. Termed Modification Tunable Transcripts (MoTTs),1 we define them as (1) transcripts that use specific degenerate codons and codon biases to encode critical stress response proteins, and (2) transcripts whose translation is influenced by changes in wobble base tRNA modification. In this review we note that the MoTTs translational model is also applicable to the process of stop-codon recoding for selenocysteine incorporation, as stop-codon recoding involves a selective codon bias and modified tRNA to decode selenocysteine during the translation of a key subset of oxidative stress response proteins. Further, we discuss how in addition to RNA modification analytics, the comprehensive characterization of translational regulation of specific transcripts requires a variety of tools, including high coverage codon-reporters, ribosome profiling and linked genomic and proteomic approaches. Together these tools will yield important new insights into the role of translational

  15. SU-E-T-594: Out-Of-Field Neutron and Gamma Dose Estimated Using TLD-600/700 Pairs in the Wobbling Proton Therapy System

    SciTech Connect

    Chen, Y; Lin, Y; Tsai, H

    2015-06-15

    Purpose: Secondary fast neutrons and gamma rays are mainly produced due to the interaction of the primary proton beam with the beam delivery nozzle. These secondary radiation dose to patients and radiation workers are unwanted. The purpose of this study is to estimate the neutron and gamma dose equivalent out of the treatment volume during the wobbling proton therapy system. Methods: Two types of thermoluminescent (TL) dosimeters, TLD-600 ({sup 6}LiF: Mg, Ti) and TLD-700 ({sup 7}LiF: Mg, Ti) were used in this study. They were calibrated in the standard neutron and gamma sources at National Standards Laboratory. Annealing procedure is 400°C for 1 hour, 100°C for 2 hours and spontaneously cooling down to the room temperature in a programmable oven. Two-peak method (a kind of glow curve analysis technique) was used to evaluate the TL response corresponding to the neutron and gamma dose. The TLD pairs were placed outside the treatment field at the neutron-gamma mixed field with 190-MeV proton beam produced by the wobbling system through the polyethylene plate phantom. The results of TLD measurement were compared to the Monte Carlo simulation. Results: The initial experiment results of calculated dose equivalents are 0.63, 0.38, 0.21 and 0.13 mSv per Gy outside the field at the distance of 50, 100, 150 and 200 cm. Conclusion: The TLD-600 and TLD-700 pairs are convenient to estimate neutron and gamma dosimetry during proton therapy. However, an accurate and suitable glow curve analysis technique is necessary. During the wobbling system proton therapy, our results showed that the neutron and gamma doses outside the treatment field are noticeable. This study was supported by the grants from the Chang Gung Memorial Hospital (CMRPD1C0682)

  16. Collections Conservation.

    ERIC Educational Resources Information Center

    DeCandido, Robert

    Collections conservation is an approach to the preservation treatment of books and book-like materials that is conceptualized and organized in terms of large groups of materials. This guide is intended to enable a library to evaluate its current collections conservation activities. The introduction describes collections conservation and gives…

  17. Queuine, a tRNA anticodon wobble base, maintains the proliferative and pluripotent potential of HL-60 cells in the presence of the differentiating agent 6-thioguanine.

    PubMed Central

    French, B T; Patrick, D E; Grever, M R; Trewyn, R W

    1991-01-01

    6-Thioguanine (6-TG)-induced differentiation of hypoxanthine phosphoribosyltransferase (IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8)-deficient HL-60 cells is characterized by 2 days of growth, after which morphological differentiation proceeds. Addition of the tRNA wobble base queuine, in the presence of 6-TG, maintains the proliferative capability of the cells. The ability of 6-TG to induce differentiation correlates with c-myc mRNA down-regulation, but queuine has no effect on this parameter. Treatment with 6-TG for 2-3 days commits HL-60 cells to granulocytic differentiation, and, once committed, these cells do not respond to the monocytic inducer phorbol 12-myristate 13-acetate. Nonetheless, when cells are treated with queuine and 6-TG, they maintain the promyelocytic morphology and are capable of being induced down the monocytic pathway by phorbol 12-myristate 13-acetate as indicated by stabilization of c-fms mRNA and cell adherence. In the absence of queuine, phorbol 12-myristate 13-acetate is incapable of inducing monocytic markers in the 6-TG-treated cells. The data presented indicate that 6-TG-induced differentiation of HL-60 cells is a tRNA-facilitated event and that the tRNA wobble base queuine is capable of maintaining both the proliferative and pluripotent potential of the cells. Images PMID:1988936

  18. Microenvironmental Effect of 2'-O-(1-Pyrenylmethyl)uridine Modified Fluorescent Oligonucleotide Probes on Sensitive and Selective Detection of Target RNA.

    PubMed

    Imincan, Gülnur; Pei, Fen; Yu, Lijia; Jin, Hongwei; Zhang, Liangren; Yang, Xiaoda; Zhang, Lihe; Tang, XinJing

    2016-04-19

    2'-O-(1-Pyrenylmethyl)uridine modified oligoribonucleotides provide highly sensitive pyrene fluorescent probes for detecting specific nucleotide mutation of RNA targets. To develop more stable and cost-effective oligonucleotide probes, we investigated the local microenvironmental effects of nearby nucleobases on pyrene fluorescence in duplexes of RNAs and 2'-O-(1-pyrenylmethyl)uridine modified oligonucleotides. By incorporation of deoxyribonucleotides, ribonucleotides, 2'-MeO-nucleotides and 2'-F-nucleotides at both sides of 2'-O-(1-pyrenylmethyl)uridine (Up) in oligodeoxynucleotide probes, we synthesized a series of pyrene modified oligonucleotide probes. Their pyrene fluorescence emission spectra indicated that only two proximal nucleotides have a substantial effect on the pyrene fluorescence properties of these oligonucleotide probes hybridized with target RNA with an order of fluorescence sensitivity of 2'-F-nucleotides > 2'-MeO-nucleotides > ribonucleotides ≫ deoxyribonucleotides. While based on circular dichroism spectra, overall helix conformations (either A- or B-form) of the duplexes have marginal effects on the sensitivity of the probes. Instead, the local substitution reflected the propensity of the nucleotide sugar ring to adopt North type conformation and, accordingly, shifted their helix geometry toward a more A-type like conformation in local microenvironments. Thus, higher enhancement of pyrene fluorescence emission favored local A-type helix structures and more polar and hydrophobic environments (F > MeO > OH at 2' substitution) of duplex minor grooves of probes with the target RNA. Further dynamic simulation revealed that local microenvironmental effect of 2'-F-nucleotides or ribonucleotides was enough for pyrene moiety to move out of nucleobases to the minor groove of duplexes; in addition, 2'-F-nucleotide had less effect on π-stack of pyrene-modified uridine with upstream and downstream nucleobases. The present oligonucleotide probes

  19. Synthesis and properties of triplex-forming oligonucleotides containing 2'-O-(2-methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine.

    PubMed

    Lou, Chenguang; Xiao, Qiang; Brennan, Lavinia; Light, Mark E; Vergara-Irigaray, Nuria; Atkinson, Elizabeth M; Holden-Dye, Lindy M; Fox, Keith R; Brown, Tom

    2010-09-01

    2'-O-(2-Methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine phosphoramidite (MEPU) has been synthesized from d-ribose and 5-iodouracil and incorporated into triplex-forming oligonucleotides (TFOs) by automated solid-phase oligonucleotide synthesis. The TFOs gave very high triplex stability with their target duplexes as measured by ultraviolet/fluorescence melting and DNase I footprinting. The incorporation of MEPU into TFOs renders them resistant to degradation by serum nucleases. PMID:20674370

  20. Dimerization of human uridine diphosphate glucuronosyltransferase allozymes 1A1 and 1A9 alters their quercetin glucuronidation activities

    PubMed Central

    Liu, Yan-Qing; Yuan, Ling-Min; Gao, Zhang-Zhao; Xiao, Yong-Sheng; Sun, Hong-Ying; Yu, Lu-Shan; Zeng, Su

    2016-01-01

    Uridine diphosphate glucuronosyltransferase 1A (UGT1A) is a major phase II drug-metabolism enzyme superfamily involved in the glucuronidation of endobiotics and xenobiotics in humans. Many polymorphisms in UGT1A genes are reported to inhibit or decrease UGT1A activity. In this study, two UGT1A1 allozymes, UGT1A1 wild-type and a splice mutant, as well as UGT1A9 wild-type and its three UGT1A9 allozymes, UGT1A9*2(C3Y), UGT1A9*3(M33T), and UGT1A9*5(D256N) were single- or double-expressed in a Bac-to-Bac expression system. Dimerization of UGT1A1 or UGT1A9 allozymes was observed via fluorescence resonance energy transfer (FRET) and co-immunoprecipitation analysis. SNPs of UGT1A altered the ability of protein-protein interaction, resulting in differential FRET efficiencies and donor-acceptor r distances. Dimerization changed the chemical regioselectivity, substrate-binding affinity, and enzymatic activity of UGT1A1 and UGT1A9 in glucuronidation of quercetin. These findings provide molecular insights into the consequences of homozygous and heterozygous UGT1A1 and UGT1A9 allozymes expression on quercetin glucuronidation. PMID:27025983

  1. Dimerization of human uridine diphosphate glucuronosyltransferase allozymes 1A1 and 1A9 alters their quercetin glucuronidation activities.

    PubMed

    Liu, Yan-Qing; Yuan, Ling-Min; Gao, Zhang-Zhao; Xiao, Yong-Sheng; Sun, Hong-Ying; Yu, Lu-Shan; Zeng, Su

    2016-01-01

    Uridine diphosphate glucuronosyltransferase 1A (UGT1A) is a major phase II drug-metabolism enzyme superfamily involved in the glucuronidation of endobiotics and xenobiotics in humans. Many polymorphisms in UGT1A genes are reported to inhibit or decrease UGT1A activity. In this study, two UGT1A1 allozymes, UGT1A1 wild-type and a splice mutant, as well as UGT1A9 wild-type and its three UGT1A9 allozymes, UGT1A9*2(C3Y), UGT1A9*3(M33T), and UGT1A9*5(D256N) were single- or double-expressed in a Bac-to-Bac expression system. Dimerization of UGT1A1 or UGT1A9 allozymes was observed via fluorescence resonance energy transfer (FRET) and co-immunoprecipitation analysis. SNPs of UGT1A altered the ability of protein-protein interaction, resulting in differential FRET efficiencies and donor-acceptor r distances. Dimerization changed the chemical regioselectivity, substrate-binding affinity, and enzymatic activity of UGT1A1 and UGT1A9 in glucuronidation of quercetin. These findings provide molecular insights into the consequences of homozygous and heterozygous UGT1A1 and UGT1A9 allozymes expression on quercetin glucuronidation. PMID:27025983

  2. Antennal uridine diphosphate (UDP)-glycosyltransferases in a pest insect: diversity and putative function in odorant and xenobiotics clearance.

    PubMed

    Bozzolan, F; Siaussat, D; Maria, A; Durand, N; Pottier, M-A; Chertemps, T; Maïbèche-Coisne, M

    2014-10-01

    Uridine diphosphate UDP-glycosyltransferases (UGTs) are detoxification enzymes widely distributed within living organisms. They are involved in the biotransformation of various lipophilic endogenous compounds and xenobiotics, including odorants. Several UGTs have been reported in the olfactory organs of mammals and involved in olfactory processing and detoxification within the olfactory mucosa but, in insects, this enzyme family is still poorly studied. Despite recent transcriptomic analyses, the diversity of antennal UGTs in insects has not been investigated. To date, only three UGT cDNAs have been shown to be expressed in insect olfactory organs. In the present study, we report the identification of eleven putative UGTs expressed in the antennae of the model pest insect Spodoptera littoralis. Phylogenetic analysis revealed that these UGTs belong to five different families, highlighting their structural diversity. In addition, two genes, UGT40R3 and UGT46A6, were either specifically expressed or overexpressed in the antennae, suggesting specific roles in this sensory organ. Exposure of male moths to the sex pheromone and to a plant odorant differentially downregulated the transcription levels of these two genes, revealing for the first time the regulation of insect UGTs by odorant exposure. Moreover, the specific antennal gene UGT46A6 was upregulated by insecticide topical application on antennae, suggesting its role in the protection of the olfactory organ towards xenobiotics. This work highlights the structural and functional diversity of UGTs within this highly specialized tissue. PMID:24698447

  3. Commitment of apolipoprotein B RNA to the splicing pathway regulates cytidine-to-uridine editing-site utilization.

    PubMed Central

    Sowden, M P; Smith, H C

    2001-01-01

    A tripartite motif located in the centre of the 7.5 kb exon 26 of apolipoprotein B (apoB) mRNA directs editosome assembly and site-specific cytidine-to-uridine editing at nucleotide 6666. apoB mRNA editing is a post-transcriptional event, occurring primarily at the time exon 26 is spliced or at a time after splicing, but before nuclear export. We show, through reporter RNA constructs, that RNA splice sites suppress editing of precursor RNAs when placed proximal or distal to the editing site. Processed RNAs were edited more efficiently than precursor RNAs. Mutation of both the splice donor and acceptor sites was necessary for RNAs to be edited efficiently. The results suggested that commitment of pre-mRNA to the splicing and/or nuclear-export pathways may play a role in regulating editing-site utilization. The HIV-1 Rev-Rev response element ('RRE') interaction was utilized to uncouple the commitment of precursor RNAs to the spliceosome assembly pathway and associated nuclear-export pathway. Under these conditions, unspliced reporter RNAs were edited efficiently. We propose that pre-mRNA passage through the temporal or spatial restriction point where they become committed to spliceosome assembly contributes regulatory information for subsequent editosome activity. PMID:11672445

  4. Abscisic Acid Uridine Diphosphate Glucosyltransferases Play a Crucial Role in Abscisic Acid Homeostasis in Arabidopsis1[C][W

    PubMed Central

    Dong, Ting; Xu, Zheng-Yi; Park, Youngmin; Kim, Dae Heon; Lee, Yongjik; Hwang, Inhwan

    2014-01-01

    The phytohormone abscisic acid (ABA) is crucial for plant growth and adaptive responses to various stress conditions. Plants continuously adjust the ABA level to meet physiological needs, but how ABA homeostasis occurs is not fully understood. This study provides evidence that UGT71B6, an ABA uridine diphosphate glucosyltransferase (UGT), and its two closely related homologs, UGT71B7 and UGT71B8, play crucial roles in ABA homeostasis and in adaptation to dehydration, osmotic stress, and high-salinity stresses in Arabidopsis (Arabidopsis thaliana). UGT RNA interference plants that had low levels of these three UGT transcripts displayed hypersensitivity to exogenous ABA and high-salt conditions during germination and exhibited a defect in plant growth. However, the ectopic expression of UGT71B6 in the atbg1 (for β-glucosidase) mutant background aggravated the ABA-deficient phenotype of atbg1 mutant plants. In addition, modulation of the expression of the three UGTs affects the expression of CYP707A1 to CYP707A4, which encode ABA 8′-hydroxylases; four CYP707As were expressed at higher levels in the UGT RNA interference plants but at lower levels in the UGT71B6:GFP-overexpressing plants. Based on these data, this study proposes that UGT71B6 and its two homologs play a critical role in ABA homeostasis by converting active ABA to an inactive form (abscisic acid-glucose ester) depending on intrinsic cellular and environmental conditions in plants. PMID:24676855

  5. Orotate phosphoribosyl transferase MoPyr5 is involved in uridine 5'-phosphate synthesis and pathogenesis of Magnaporthe oryzae.

    PubMed

    Qi, Zhongqiang; Liu, Muxing; Dong, Yanhan; Yang, Jie; Zhang, Haifeng; Zheng, Xiaobo; Zhang, Zhengguang

    2016-04-01

    Orotate phosphoribosyl transferase (OPRTase) plays an important role in de novo and salvage pathways of nucleotide synthesis and is widely used as a screening marker in genetic transformation. However, the function of OPRTase in plant pathogens remains unclear. In this study, we characterized an ortholog of Saccharomyces cerevisiae Ura5, the OPRTase MoPyr5, from the rice blast fungus Magnaporthe oryzae. Targeted gene disruption revealed that MoPyr5 is required for mycelial growth, appressorial turgor pressure and penetration into plant tissues, invasive hyphal growth, and pathogenicity. Interestingly, the ∆Mopyr5 mutant is also involved in mycelial surface hydrophobicity. Exogenous uridine 5'-phosphate (UMP) restored vegetative growth and rescued the defect in pathogenicity on detached barley and rice leaf sheath. Collectively, our results show that MoPyr5 is an OPRTase for UMP biosynthesis in M. oryzae and indicate that UTP biosynthesis is closely linked with vegetative growth, cell wall integrity, and pathogenicity of fungus. Our results also suggest that UMP biosynthesis would be a good target for the development of novel fungicides against M. oryzae. PMID:26810198

  6. Non-adenosine nucleoside inosine, guanosine and uridine as promising antiepileptic drugs: a summary of current literature.

    PubMed

    Kovacs, Zsolt; Kekesi, Katalin A; Juhasz, Gabor; Barna, Janos; Heja, Laszlo; Lakatos, Renata; Dobolyi, Arpad

    2015-01-01

    Adenosine (Ado) and some non-adenosine (non-Ado) nucleosides including inosine (Ino), guanosine (Guo) and uridine (Urd) are modulatory molecules in the central nervous system (CNS), regulating different physiological and pathophysiological processes in the brain such as sleep and epilepsy. Indeed, different drugs effective on adenosinergic system (e.g., Ado metabolism inhibitors, agonists and antagonists of Ado receptors) are being used in drug development for the treatment of epileptic disorders. Although (i) endogenous Ino, Guo and Urd showed anticonvulsant/antiepileptic effects (e.g., in quinolinic acid - induced seizures and in different epilepsy models such as hippocampal kindling models), and (ii) there is a need to generate new and more effective antiepileptic drugs for the treatment of drug-resistant epilepsies, our knowledge about antiepileptic influence of non-Ado nucleosides is far from complete. Thus, in this review article, we give a short summary of anticonvulsant/antiepileptic effects and mechanisms evoked by Ino, Guo, and Urd. Finally, we discuss some non-Ado nucleoside derivatives and their structures, which may be candidates as potential antiepileptic agents. PMID:25382017

  7. Wobbly Corner: Magnetism

    ERIC Educational Resources Information Center

    Corbett, Lisa; Maklad, Rania; Dunne, Mick; Grace, Pierre

    2014-01-01

    During a final seminar with BA year 4 science specialist trainee teachers, the authors posed a question about the difficulties associated with understanding magnetism. The ensuing discussion focused on a number of concerns commonly identified by students, which may also be of interest to classroom teachers teaching magnetism. Issues raised…

  8. Our wobbly galaxy

    NASA Astrophysics Data System (ADS)

    Moskvitch, Katia

    2014-04-01

    It is well known that the Milky Way rotates around a supermassive black hole, but researchers have found that our galaxy undulates up and down as well like a giant galactic merry-go-round. Katia Moskvitch reports on this surprising finding.

  9. Inhibitory Effects of Aschantin on Cytochrome P450 and Uridine 5'-diphospho-glucuronosyltransferase Enzyme Activities in Human Liver Microsomes.

    PubMed

    Kwon, Soon-Sang; Kim, Ju-Hyun; Jeong, Hyeon-Uk; Cho, Yong Yeon; Oh, Sei-Ryang; Lee, Hye Suk

    2016-01-01

    Aschantin is a bioactive neolignan found in Magnolia flos with antiplasmodial, Ca(2+)-antagonistic, platelet activating factor-antagonistic, and chemopreventive activities. We investigated its inhibitory effects on the activities of eight major human cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes of human liver microsomes to determine if mechanistic aschantin-enzyme interactions were evident. Aschantin potently inhibited CYP2C8-mediated amodiaquine N-de-ethylation, CYP2C9-mediated diclofenac 4'-hydroxylation, CYP2C19-mediated [S]-mephenytoin 4'-hydroxylation, and CYP3A4-mediated midazolam 1'-hydroxylation, with Ki values of 10.2, 3.7, 5.8, and 12.6 µM, respectively. Aschantin at 100 µM negligibly inhibited CYP1A2-mediated phenacetin O-de-ethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated bupropion hydroxylation, and CYP2D6-mediated bufuralol 1'-hydroxylation. At 200 µM, it weakly inhibited UGT1A1-catalyzed SN-38 glucuronidation, UGT1A6-catalyzed N-acetylserotonin glucuronidation, and UGT1A9-catalyzed mycophenolic acid glucuronidation, with IC50 values of 131.7, 144.1, and 71.0 µM, respectively, but did not show inhibition against UGT1A3, UGT1A4, or UGT2B7 up to 200 µM. These in vitro results indicate that aschantin should be examined in terms of potential interactions with pharmacokinetic drugs in vivo. It exhibited potent mechanism-based inhibition of CYP2C8, CYP2C9, CYP2C19, and CYP3A4. PMID:27128896

  10. Isolation and characterization of the orotidine 5'-monophosphate decarboxylase domain of the multifunctional protein uridine 5'-monophosphate synthase.

    PubMed

    Floyd, E E; Jones, M E

    1985-08-01

    The multifunctional protein uridine 5'-monophosphate (UMP) synthase catalyzes the final two reactions of the de novo biosynthesis of UMP in mammalian cells by the sequential action of orotate phosphoribosyltransferase (EC 2.4.2.10) and orotidine 5'-monophosphate (OMP) decarboxylase (EC 4.1.1.23). This protein is composed of one or two identical subunits; the monomer weighs of 51,500 daltons. UMP synthase from mouse Ehrlich ascites cells can exist as three distinct species as determined by sucrose density gradient centrifugation: a 3.6 S monomer, a 5.1 S dimer, and a 5.6 S conformationally altered dimer. Limited digestion of each of these three species with trypsin produced a 28,500-dalton peptide that was relatively resistant to further proteolysis. The peptide appears to be one of the two enzyme domains of UMP synthase for it retained only OMP decarboxylase activity. Similar results were obtained when UMP synthase was digested with elastase. OMP decarboxylase activity was less stable for the domain than for UMP synthase; the domain can rapidly lose activity upon storage or upon dilution. The size of the mammalian OMP decarboxylase domain is similar to that of yeast OMP decarboxylase. If the polypeptides which are cleaved from UMP synthase by trypsin are derived exclusively from either the amino or the carboxyl end of UMP synthase, then the size of a fragment possessing the orotate phosphoribosyltransferase domain could be as large as 23,000 daltons which is similar in size to the orotate phosphoribosyltransferase of yeast and of Escherichia coli. PMID:3839509

  11. Tautomerization lowers the activation barriers for N-glycosidic bond cleavage of protonated uridine and 2'-deoxyuridine.

    PubMed

    Wu, R R; Rodgers, M T

    2016-09-21

    The gas-phase conformations of protonated uridine, [Urd+H](+), and its 2'-deoxy form, protonated 2'-deoxyuridine, [dUrd+H](+), have been examined in detail previously by infrared multiple photon dissociation action spectroscopy techniques. Both 2,4-dihydroxy tautomers and O4 protonated conformers of [Urd+H](+) and [dUrd+H](+) were found to coexist in the experiments with the 2,4-dihydroxy tautomers dominating the population. In the present study, the kinetic energy dependence of the collision-induced dissociation behavior of [Urd+H](+) and [dUrd+H](+) are examined using a guided ion beam tandem mass spectrometer to probe the mechanisms and energetics for activated dissociation of these protonated nucleosides. The primary dissociation pathways observed involve N-glycosidic bond cleavage leading to competitive elimination of protonated or neutral uracil. The potential energy surfaces (PESs) for these N-glycosidic bond cleavage pathways are mapped out via electronic structure calculations for the mixture of 2,4-dihydroxy tautomers and O4 protonated conformers of [Urd+H](+) and [dUrd+H](+) populated in the experiments. The calculated activation energies (AEs) and heats of reaction (ΔHrxns) for N-glycosidic bond cleavage at both the B3LYP and MP2(full) levels of theory are compared to the measured values. The agreement between experiment and theory indicates that B3LYP provides better estimates of the energetics of the species along the PESs for N-glycosidic bond cleavage than MP2, and that the 2,4-dihydroxy tautomers, which are stabilized by strong hydrogen-bonding interactions, predominantly influence the observed threshold dissociation behavior of [Urd+H](+) and [dUrd+H](+). PMID:27536972

  12. Up-regulated uridine kinase gene identified by RLCS in the ventral horn after crush injury to rat sciatic nerves.

    PubMed

    Yuh, I; Yaoi, T; Watanabe, S; Okajima, S; Hirasawa, Y; Fushiki, S

    1999-12-01

    Rat sciatic nerve crush injury is one of the models commonly employed for studying the mechanisms of nerve regeneration. In this study, we analyzed the temporal change of gene expression after injury in this model, to elucidate the molecular mechanisms involved in nerve regeneration. First, a cDNA analysis method, Restriction Landmark cDNA Scanning (RLCS), was applied to cells in the ventral horn of the spinal cord during a 7-day period after the crush injury. A total of 1991 cDNA species were detected as spots on gels, and 37 of these were shown to change after the injury. Temporally changed patterns were classified into three categories: the continuously up-regulated type (10 species), the transiently up-regulated type (22 species), and the down-regulated type (5 species). These complex patterns of gene expression demonstrated after the injury suggest that precise regulation in molecular pathways is required for accomplishing nerve regeneration. Secondly, the rat homologue of uridine kinase gene was identified as one of the up-regulated genes. Northern blot analysis on rat ventral horn tissue and brain revealed that the UK gene had three transcripts with different sizes (4.3, 1. 4, and 1.35 kb, respectively). All of the transcripts, especially the 4.3 kb one, were up-regulated mainly in a bimodal fashion during the 28-day period after the injury. The RLCS method that we employed in the present study shows promise as a means to fully analyze molecular changes in nerve regeneration in detail. PMID:10581173

  13. Absence epileptic activity changing effects of non-adenosine nucleoside inosine, guanosine and uridine in Wistar Albino Glaxo Rijswijk rats.

    PubMed

    Kovács, Z; Kékesi, K A; Dobolyi, Á; Lakatos, R; Juhász, G

    2015-08-01

    Adenosine (Ado) and non-adenosine (non-Ado) nucleosides such as inosine (Ino), guanosine (Guo) and uridine (Urd) may have regionally different roles in the regulation of physiological and pathophysiological processes in the central nervous system (CNS) such as epilepsy. It was demonstrated previously that Ino and Guo decreased quinolinic acid (QA)-induced seizures and Urd reduced penicillin-, bicuculline- and pentylenetetrazole (PTZ)-induced seizures. It has also been demonstrated that Ino and Urd may exert their effects through GABAergic system by altering the function of GABA(A) type of gamma-aminobutyric acid receptors (GABAA receptors) whereas Guo decreases glutamate-induced excitability through glutamatergic system, which systems (GABAergic and glutamatergic) are involved in pathomechanisms of absence epilepsy. Thus, we hypothesized that Ino and Guo, similarly to the previously described effect of Urd, might also decrease absence epileptic activity. We investigated in the present study whether intraperitoneal (i.p.) application of Ino (500 and 1000mg/kg), Guo (20 and 50mg/kg), Urd (500 and 1000mg/kg), GABA(A) receptor agonist muscimol (1 and 3mg/kg), GABA(A) receptor antagonist bicuculline (2 and 4mg/kg), non-selective Ado receptor antagonist theophylline (5 and 10mg/kg) and non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine maleate (MK-801, 0.0625 and 0.1250mg/kg) alone and in combination have modulatory effects on absence epileptic activity in Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. We found that Guo decreased the number of spike-wave discharges (SWDs) whereas Ino increased it dose-dependently. We strengthened that Urd can decrease absence epileptic activity. Our results suggest that Guo, Urd and their analogs could be potentially effective drugs for treatment of human absence epilepsy. PMID:26037802

  14. Conservation Presentation.

    ERIC Educational Resources Information Center

    Friday, Gerald

    2001-01-01

    Introduces a project in which students teach about the importance of recycling and conservation by presenting demonstrations. Includes demonstrations on water, plastic, and other recycling products such as steel. (YDS)

  15. Improving the quality of infant sleep through the inclusion at supper of cereals enriched with tryptophan, adenosine-5'-phosphate, and uridine-5'-phosphate.

    PubMed

    Cubero, Javier; Chanclón, Belen; Sánchez, Soledad; Rivero, Montserrat; Rodríguez, Ana Beatriz; Barriga, Carmen

    2009-12-01

    The present study evaluated whether the administration of cereals enriched with nutrients that are facilitators of sleep could help improve the sleep of infants who had sleep disorders at night time. Thirty infants aged 8-16 months with sleep disorders involving at least three nocturnal waking episodes took part in the study. They were given a night-time 'sleep facilitating cereal' product containing 225 mg tryptophan, 5.3 mg adenosine-5'-P, and 6.3 mg uridine-5'-P per 100 g of product. These cereals were given in a double-blind procedure lasting 5 weeks, with ingestion of the cereal between 18:00 and 06:00. In the control week, the children received a standard cereal (75 mg tryptophan/100 g product without nucleotides) dissolved in a standard formula milk (231.5 mg tryptophan, 2.6 mg adenosine-5'-P, 5 mg uridine-5'-P, per 100 g product). In one experimental week, the children received the night-time sleep facilitating cereal together with the standard formula milk. In another week, they received the sleep facilitating cereal together with a night milk specially formulated to attain the sleep rhythm (480 mg tryptophan, 8.8 mg uridine-5'-P, and 7.6 mg adenosine-5'-P per 100 g product). The three experimental weeks were separated by two wash-out weeks in which the milk and cereal administered was identical in composition to that of the control week. All the infants received a programmed writer actimeter which they wore continually, attached to their ankles, to record their motor activity. The recorded activity was used to calculate information about the time in bed, assumed sleep, actual sleep, sleep efficiency, sleep latency, immobility, and total activity. The infants receiving the enriched cereal during the time of darkness showed improvements in their sleep parameters, regardless of whether the milk they took at night was standard or enriched with tryptophan, adenosine-5'-P, and uridine-5'-P. In summary, the administration of enriched cereals led to an

  16. Study of Uridine 5'-Diphosphate (UDP)-Galactopyranose Mutase Using UDP-5-Fluorogalactopyranose as a Probe: Incubation Results and Mechanistic Implications.

    PubMed

    Lin, Geng-Min; Sun, He G; Liu, Hung-Wen

    2016-07-15

    Uridine 5'-diphosphate-5-fluorogalactopyranose (UDP-5F-Galp, 7) was synthesized, and its effect on UDP-Galp mutase (UGM) was investigated. UGM facilitated the hydrolysis of 7 to yield UDP and 5-oxogalactose (24), but no 11 was detected. (19)F NMR and trapping experiments demonstrated that the reaction involves the initial formation of a substrate-cofactor adduct followed by decomposition of the resulting C5 gem-fluorohydrin to generate a 5-oxo intermediate (10). The results support the current mechanistic proposal for UGM and suggest new directions for designing mechanism-based inhibitors. PMID:27384425

  17. Transient conductivity OF 1,3-dimethyluracil, uridine and 3-methyluridine in aqueous solution following 20-ns laser excitation at 248 nm

    NASA Astrophysics Data System (ADS)

    Görner, Helmut; Currell, Leslie J.

    1996-09-01

    Uridine, 3-methyluridine and 1,3-dimethyluracil in aqueous solution were studied by timeresolved conductimetry after excitation at 248 nm by 20-ns laser pulses. The conductivity signal increases to the maximum value at the pulse end (Δκ m) and decreases then with time, depending on the saturating gas (Ar, N 2O, O 2 or McCI) and pH. The Δκ m signal is suggested to originate from hydrated electrons (e aq-) and protons, the latter resulting from radical cations after rapid reaction with water. Biphotonic photoionization occurs in the whole pH range 3-11 with a quantum yield of 0.016 or smaller for laser intensities of ⩽ 8 MW/cm 2. The reaction of eaq with uncharged bases in Ar-saturated solution at pH 5-8 generates radical anions which are subsequently protonated. The neutralization reaction kinetics of the uracil derivatives depend essentially on the transient proton concentration and lead to the disappearance of most of the conductivity (>90%) within a few microseconds or less in neutral or acidic solution, respectively. For 3-methyluridine and uridine after neutralization, the presence of a long-lived species with acidic properties was observed (in small yield) upon biphotonic (but not monophotonic) excitation. The time-resolved conductivity pattern in the alkaline pH range is different for each of the three pyrimidines, depending essentially on the generation or consumption of OH - in the radical termination reactions.

  18. Three-dimensional structures of unligated uridine phosphorylase from Yersinia pseudotuberculosis at 1.4 Å resolution and its complex with an antibacterial drug

    NASA Astrophysics Data System (ADS)

    Balaev, V. V.; Lashkov, A. A.; Gabdulkhakov, A. G.; Dontsova, M. V.; Mironov, A. S.; Betzel, C.; Mikhailov, A. M.

    2015-07-01

    Uridine phosphorylases play an essential role in the cellular metabolism of some antibacterial agents. Acute infectious diseases (bubonic plague, yersiniosis, pseudotuberculosis, etc., caused by bacteria of the genus Yersinia) are treated using both sulfanilamide medicines and antibiotics, including trimethoprim. The action of an antibiotic on a bacterial cell is determined primarily by the character of its interactions with cellular components, including those which are not targets (for example, with pyrimidine phosphorylases). This type of interaction should be taken into account in designing drugs. The three-dimensional structure of uridine phosphorylase from the bacterium Yersinia pseudotuberculosis ( YptUPh) with the free active site was determined for the first time by X-ray crystallography and refined at 1.40 Å resolution (DPI = 0.062 Å; ID PDB: 4OF4). The structure of the complex of YptUPh with the bacteriostatic drug trimethoprim was studied by molecular docking and molecular dynamics methods. The trimethoprim molecule was shown to be buffered by the enzyme YptUPh, resulting in a decrease in the efficiency of the treatment of infectious diseases caused by bacteria of the genus Yersinia with trimethoprim.

  19. Marketing Conservation.

    ERIC Educational Resources Information Center

    Ellis, William B.

    1987-01-01

    In 1986, Northeast Utilities began helping shool administrators combat school building energy wastage through a program called Energy Alliance. The typical school can reduce its energy bill by 30 percent by adopting a wide range of conservation measures, including cogeneration, relamping, and energy audits. (MLH)

  20. [Conservation Units.

    ERIC Educational Resources Information Center

    Texas Education Agency, Austin.

    Instructional units deal with each aspect of conservation: forests, wildlife, rangelands, water, minerals, and soil. The area of the secondary school curriculum with which each is correlated is indicated. Lists of general and specific objectives are followed by suggested teaching procedures, including ideas for introducing the topic, questions to…

  1. [Conservation Units.

    ERIC Educational Resources Information Center

    Texas Education Agency, Austin.

    Each of the six instructional units deals with one aspect of conservation: forests, water, rangeland, minerals (petroleum), and soil. The area of the elementary school curriculum with which each correlates is indicated. Lists of general and specific objectives are followed by suggested teaching procedures, including ideas for introducing the…

  2. Colorful Conservation

    ERIC Educational Resources Information Center

    Skophammer, Karen

    2011-01-01

    Some people only think about conservation on Earth Day. Being in the "art business" however, this author is always conscious of the many products she thinks get wasted when they could be reused, recycled, and restored--especially in a school building and art room. In this article, she describes an art lesson that allows students to paint…

  3. Conservation physiology

    PubMed Central

    Kronfeld-Schor, Noga

    2014-01-01

    Global change presents a huge and exciting challenge to the study of thermal physiology. The implication of thermoregulatory strategies and abilities for the survival of individuals and species, are of high importance for predicting species response to global change challenges and ways to mitigate them, and for conservation acts. A good example of such a study is the paper by Cooper and Withers in this issue.1

  4. Heron conservation

    USGS Publications Warehouse

    2000-01-01

    Herons are large, popular and, in many cases, spectacular birds found in wetlands world-wide, both tropical and temperate, natural and man-made. Some populations are very small and localized, some have decreased, some have expanded their ranges, and a few are pests of human activities. In the fifteen years since the publication of the latest monographic treatment of the family, The Herons Handbook, there has been a tremendous increase in our knowledge of heron status and conservation requirements, set against a backdrop of increasing concern about the future of the world?s wetland habitats. This book provides a comprehensive update following two distinct threads. The status and conservation needs of herons are first presented on a regional basis, in a series of chapters set at a continental or subcontinental scale. Over 200 biologists and heron conservationists have contributed to the data summarized here, and the very latest census and survey results provide the most up-to-date and detailed picture of heron populations currently available. Chapters discussing several critical issues in heron conservation follow, tending to focus on the international nature of the problems.

  5. Incidence of bovine leukocyte adhesion deficiency, complex vertebral malformation, and deficiency of uridine-5-monophosphate synthase carriers in Brazilian Girolando cattle.

    PubMed

    Paiva, D S; Fonseca, I; Pinto, I S B; Ianella, P; Campos, T A; Caetano, A R; Paiva, S R; Silva, M V G B; Martins, M F

    2013-01-01

    Among the various hereditary diseases that have been widely studied in dairy cattle, bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine-5-monophosphate synthase (DUMPS), and complex vertebral malformation (CVM) are noteworthy because of their high impact on overall herd productivity as a consequence of increased calf mortality. The aim of this study was to verify the frequency of carriers of BLAD, CVM, and DUMPS mutant alleles in cows and bulls from the National Girolando Progeny Test carried out in Brazil by using polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR assays. A total of 777 animals were genotyped for BLAD, 783 for CVM, and 122 for DUMPS. The frequencies of carriers for BLAD and CVM were 0.77 and 1.53%, respectively, whereas no carriers of DUMPS were observed. PMID:24065661

  6. In silico analysis of the three-dimensional structures of the homodimer of uridine phosphorylase from Yersinia Pseudotuberculosis in the ligand-free state and in a complex with 5-fluorouracil

    NASA Astrophysics Data System (ADS)

    Lashkov, A. A.; Sotnichenko, S. E.; Mikhailov, A. M.

    2013-03-01

    Pseudotuberculosis is an acute infectious disease characterized by a lesion of the gastrointestinal tract. A positive therapeutic effect can be achieved by selectively suppressing the activity of uridine phosphorylase from the causative agent of the disease Yersinia pseudotuberculosis. The synergistic effect of a combination of the chemotherapeutic agent 5-fluorouracil and antimicrobial drugs, which block the synthesis of pyrimidine bases, on the cells of pathogenic protozoa and bacteria is described in the literature. The three-dimensional structures of uridine phosphorylase from Yersinia pseudotuberculosis ( YptUPh) both in the ligand-free state and in complexes with pharmacological agents are unknown, which hinders the search for and design of selective inhibitors of YptUPh. The three-dimensional structure of the ligand-free homodimer of YptUPh was determined by homology-based molecular modeling. The three-dimensional structure of the subunit of the YptUPh molecule belongs to α/β proteins, and its topology is a three-layer α/β/α sandwich. The subunit monomer of the YptUPh molecule consists of 38% helices and 24% β strands. A model of the homodimer structure of YptUPh in a complex with 5-FU was obtained by the molecular docking. The position of 5-FU in the active site of the molecule is very consistent with the known data on the X-ray diffraction structures of other bacterial uridine phosphorylases (the complex of uridine phosphorylase from Salmonella typhimurium ( StUPh) with 5-FU, ID PDB: 4E1V and the complex of uridine phosphorylase from Escherichia coli ( EcUPh) with 5-FU and ribose 1-phosphate, ID PDB: 1RXC).

  7. In silico analysis of the three-dimensional structures of the homodimer of uridine phosphorylase from Yersinia Pseudotuberculosis in the ligand-free state and in a complex with 5-fluorouracil

    SciTech Connect

    Lashkov, A. A. Sotnichenko, S. E.; Mikhailov, A. M.

    2013-03-15

    Pseudotuberculosis is an acute infectious disease characterized by a lesion of the gastrointestinal tract. A positive therapeutic effect can be achieved by selectively suppressing the activity of uridine phosphorylase from the causative agent of the disease Yersinia pseudotuberculosis. The synergistic effect of a combination of the chemotherapeutic agent 5-fluorouracil and antimicrobial drugs, which block the synthesis of pyrimidine bases, on the cells of pathogenic protozoa and bacteria is described in the literature. The three-dimensional structures of uridine phosphorylase from Yersinia pseudotuberculosis (YptUPh) both in the ligand-free state and in complexes with pharmacological agents are unknown, which hinders the search for and design of selective inhibitors of YptUPh. The three-dimensional structure of the ligand-free homodimer of YptUPh was determined by homology-based molecular modeling. The three-dimensional structure of the subunit of the YptUPh molecule belongs to {alpha}/{beta} proteins, and its topology is a three-layer {alpha}/{beta}/{alpha} sandwich. The subunit monomer of the YptUPh molecule consists of 38% helices and 24% {beta} strands. A model of the homodimer structure of YptUPh in a complex with 5-FU was obtained by the molecular docking. The position of 5-FU in the active site of the molecule is very consistent with the known data on the X-ray diffraction structures of other bacterial uridine phosphorylases (the complex of uridine phosphorylase from Salmonella typhimurium (StUPh) with 5-FU, ID PDB: 4E1V and the complex of uridine phosphorylase from Escherichia coli (EcUPh) with 5-FU and ribose 1-phosphate, ID PDB: 1RXC).

  8. Conservative Remapper

    Energy Science and Technology Software Center (ESTSC)

    2006-03-31

    Conservative Remapper (CORE) is a C++ language software library for remapping cell masses and cell-averaged densities on unstructured two dimensional grids, maintaining conservation of total mass in the process. CORE contains implementation of two remapping algorithms: a new, efficient "swept region" algorithm, and a more traditional algorithm basedon the computation of cell intersections. Grids may be Cartesian or cylindrical, and cells may have three or more vertices, with no upper limit. CORE can run inmore » serial and in parallel, but in order to achieve wide applicability, CORE used no particular parallel communication library. Instead it achieves parallel communication through strategically placed, user defined callbacks. Users can also provide callbacks to redefine different parts or subcomponents of the remapping process. CORE allows the use of different data types, e.g. single-, double-, and quadruple- precision floating-point numbers, through the use of C++ templates. Using CORE is simple, and requires no configuration scripts or makefiles.« less

  9. Chemical synthesis of the 5-taurinomethyl(-2-thio)uridine modified anticodon arm of the human mitochondrial tRNA(Leu(UUR)) and tRNA(Lys).

    PubMed

    Leszczynska, Grazyna; Leonczak, Piotr; Wozniak, Karolina; Malkiewicz, Andrzej

    2014-06-01

    5-Taurinomethyluridine (τm(5)U) and 5-taurinomethyl-2-thiouridine (τm(5)s(2)U) are located at the wobble position of human mitochondrial (hmt) tRNA(Leu(UUR)) and tRNA(Lys), respectively. Both hypermodified units restrict decoding of the third codon letter to A and G. Pathogenic mutations in the genes encoding hmt-tRNA(Leu(UUR)) and hmt-tRNA(Lys) are responsible for the loss of the discussed modifications and, as a consequence, for the occurrence of severe mitochondrial dysfunctions (MELAS, MERRF). Synthetic oligoribonucleotides bearing modified nucleosides are a versatile tool for studying mechanisms of genetic message translation and accompanying pathologies at nucleoside resolution. In this paper, we present site-specific chemical incorporation of τm(5)U and τm(5)s(2)U into 17-mers related to the sequence of the anticodon arms hmt-tRNA(Leu(UUR)) and hmt-tRNA(Lys), respectively employing phosphoramidite chemistry on CPG support. Selected protecting groups for the sulfonic acid (4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutyl) and the exoamine function (-C(O)CF3) are compatible with the blockage of the canonical monomeric units. The synthesis of τm(5)s(2)U-modified RNA fragment was performed under conditions eliminating the formation of side products of 2-thiocarbonyl group oxidation and/or oxidative desulphurization. The structure of the final oligomers was confirmed by mass spectroscopy and enzymatic cleavage data. PMID:24757169

  10. Variable Frequency of Plastid RNA Editing among Ferns and Repeated Loss of Uridine-to-Cytidine Editing from Vascular Plants

    PubMed Central

    Guo, Wenhu; Grewe, Felix; Mower, Jeffrey P.

    2015-01-01

    The distinct distribution and abundance of C-to-U and U-to-C RNA editing among land plants suggest that these two processes originated and evolve independently, but the paucity of information from several key lineages limits our understanding of their evolution. To examine the evolutionary diversity of RNA editing among ferns, we sequenced the plastid transcriptomes from two early diverging species, Ophioglossum californicum and Psilotum nudum. Using a relaxed automated approach to minimize false negatives combined with manual inspection to eliminate false positives, we identified 297 C-to-U and three U-to-C edit sites in the O. californicum plastid transcriptome but only 27 C-to-U and no U-to-C edit sites in the P. nudum plastid transcriptome. A broader comparison of editing content with the leptosporangiate fern Adiantum capillus-veneris and the hornwort Anthoceros formosae uncovered large variance in the abundance of plastid editing, indicating that the frequency and type of RNA editing is highly labile in ferns. Edit sites that increase protein conservation among species are more abundant and more efficiently edited than silent and non-conservative sites, suggesting that selection maintains functionally important editing. The absence of U-to-C editing from P. nudum plastid transcripts and other vascular plants demonstrates that U-to-C editing loss is a recurrent phenomenon in vascular plant evolution. PMID:25568947

  11. 2'-O-methyl-5-formylcytidine (f5Cm), a new modified nucleotide at the 'wobble' of two cytoplasmic tRNAs Leu (NAA) from bovine liver.

    PubMed Central

    Païs de Barros, J P; Keith, G; El Adlouni, C; Glasser, A L; Mack, G; Dirheimer, G; Desgrès, J

    1996-01-01

    The nucleotide analysis of a cytoplasmic tRNA(Leu) isolated from bovine liver revealed the presence of an unknown modified nucleotide N. The corresponding N nucleoside was isolated by different enzymatic and chromatographic protocols from a partially purified preparation of this tRNA(Leu). Its chemical characterization was determined from its chromatographic properties, UV-absorption spectroscopy and mass spectrometric measurements, as well as from those of the borohydride reduced N nucleoside and its etheno-trimethylsilyl derivative. The structure of N was established as 2'-O-methyl-5-formylcytidine (f5CM), and its reduced derivative as 2'-O-methyl-5-hydroxy-methylcytidine (om5Cm). By sequencing the bovine liver tRNA(Leu), the structure of the anticodon was determined as f5CmAA. In addition, the nucleotide sequence showed two primary structures differing only by the nucleotide 47c which is either uridine or adenosine. The two slightly differing bovine liver tRNAs-Leu(f5CmAA) are the only tRNAs so far sequenced which contain f5Cm. The role of such a modified cytidine at the first position of the anticodon is discussed in terms of decoding properties for the UUG and UUA leucine codons. Recently, precise evidence was obtained for the presence of f5Cm at the same position in tRNAs(Leu)(NAA) isolated from rabbit and lamb liver. Therefore, the 2'-O-methyl-5-formyl modification of cytidine at position 34 could be a general feature of cytoplasmic tRNAs(Leu)(NAA) in mammals. PMID:8628682

  12. Radioautographic visualization of differences in the pattern of (/sup 3/H)uridine and (/sup 3/H)orotic acid incorporation into the RNA of migrating columnar cells in the rat small intestine

    SciTech Connect

    Uddin, M.; Altmann, G.G.; Leblond, C.P.

    1984-05-01

    The epithelium of rat small intestine was radioautographed to examine whether RNA is synthesized by the salvage pathway as shown after (/sup 3/H)uridine injection or by the de novo pathway as shown after (/sup 3/H)orotic acid injection. The two modes of RNA synthesis were thus investigated during the migration of columnar cells from crypt base to villus top, and the rate of synthesis was assessed by counting silver grains over the nucleolus and nucleoplasm at six levels along the duodenal epithelium - that is, in the base, mid, and top regions of the crypts and in the base, mid, and top regions of the villi. Concomitant biochemical analyses established that, after injection of either (5-/sup 3/H)uridine or (5-/sup 3/H)orotic acid: (a) buffered glutaraldehyde fixative was as effective as perchloric acid or trichloroacetic acid in insolubilizing the nucleic acids of rat small intestine; (b) a major fraction of the nucleic acid label was in RNA, that is, 91% after (/sup 3/H)uridine and 72% after (/sup 3/H)orotic acid, with the rest in DNA; and (c) a substantial fraction of the RNA label was in poly A/sup +/ RNA (presumed to be messenger RNA). In radioautographs of duodenum prepared after (/sup 3/H)uridine injection, the count of silver grains was high over nucleolus and nucleoplasm in crypt base cells and gradually decreased at the upper levels up to the villus base. In the rest of the villus, the grain count over the nucleolus was negligible, while over the nucleoplasm it was low but significant.

  13. B Cell Lymphoma (Bcl)-2 Protein Is the Major Determinant in bcl-2 Adenine-Uridine-rich Element Turnover Overcoming HuR Activity*

    PubMed Central

    Ghisolfi, Laura; Calastretti, Angela; Franzi, Sara; Canti, Gianfranco; Donnini, Martino; Capaccioli, Sergio; Nicolin, Angelo; Bevilacqua, Annamaria

    2009-01-01

    In the 3′-untranslated region, the destabilizing adenine-uridine (AU)-rich elements (AREs) control the expression of several transcripts through interactions with ARE-binding proteins (AUBPs) and RNA degradation machinery. Although the fundamental role for AUBPs and associated factors in eliciting ARE-dependent degradation of cognate mRNAs has been recently highlighted, the molecular mechanisms underlying the specific regulation of individual mRNA turnover have not yet been fully elucidated. Here we focused on the post-transcriptional regulation of bcl-2 mRNA in human cell lines under different conditions and genetic backgrounds. In the context of an AUBPs silencing approach, HuR knockdown reduced the expression of endogenous bcl-2, whereas unexpectedly, a bcl-2 ARE-reporter transcript increased significantly, suggesting that HuR expression has opposite effects on endogenous and ectopic bcl-2 ARE. Moreover, evidence was provided for the essential, specific and dose-dependent role of the Bcl-2 protein in regulating the decay kinetics of its own mRNA, as ascertained by a luciferase reporter system. Altogether, the data support a model whereby the Bcl-2 protein is the major determinant of its own ARE-dependent transcript half-life in living cells and its effect overcomes the activity of ARE-binding proteins. PMID:19520857

  14. B cell lymphoma (Bcl)-2 protein is the major determinant in bcl-2 adenine-uridine-rich element turnover overcoming HuR activity.

    PubMed

    Ghisolfi, Laura; Calastretti, Angela; Franzi, Sara; Canti, Gianfranco; Donnini, Martino; Capaccioli, Sergio; Nicolin, Angelo; Bevilacqua, Annamaria

    2009-07-31

    In the 3'-untranslated region, the destabilizing adenine-uridine (AU)-rich elements (AREs) control the expression of several transcripts through interactions with ARE-binding proteins (AUBPs) and RNA degradation machinery. Although the fundamental role for AUBPs and associated factors in eliciting ARE-dependent degradation of cognate mRNAs has been recently highlighted, the molecular mechanisms underlying the specific regulation of individual mRNA turnover have not yet been fully elucidated. Here we focused on the post-transcriptional regulation of bcl-2 mRNA in human cell lines under different conditions and genetic backgrounds. In the context of an AUBPs silencing approach, HuR knockdown reduced the expression of endogenous bcl-2, whereas unexpectedly, a bcl-2 ARE-reporter transcript increased significantly, suggesting that HuR expression has opposite effects on endogenous and ectopic bcl-2 ARE. Moreover, evidence was provided for the essential, specific and dose-dependent role of the Bcl-2 protein in regulating the decay kinetics of its own mRNA, as ascertained by a luciferase reporter system. Altogether, the data support a model whereby the Bcl-2 protein is the major determinant of its own ARE-dependent transcript half-life in living cells and its effect overcomes the activity of ARE-binding proteins. PMID:19520857

  15. Stabilization of cellular mRNAs and up-regulation of proteins by oligoribonucleotides homologous to the Bcl2 adenine-uridine rich element motif.

    PubMed

    Bevilacqua, Annamaria; Ghisolfi, Laura; Franzi, Sara; Maresca, Giovanna; Gherzi, Roberto; Capaccioli, Sergio; Nicolin, Angelo; Canti, Gianfranco

    2007-02-01

    Adenine-uridine rich elements (AREs) play an important role in modulating mRNA stability, being the target site of many ARE-binding proteins (AUBPs) that are involved in the decay process. Three 26-mer 2'-O-methyl oligoribonucleotides (ORNs) homologous to the core region of ARE of bcl2 mRNA have been studied for decoy-aptamer activity in UV cross-linking assays. Sense-oriented ORNs competed with the ARE motif for the interaction with both destabilizing and stabilizing AUBPs in cell-free systems and in cell lines. Moreover, ORNs induced mRNA stabilization and up-regulated both Bcl2 mRNA and protein levels in the cells. Bcl2 ORNs stabilized other ARE-containing transcripts and up-regulated their expression. These results indicate that Bcl2 ORNs compete for AUBP-ARE interactions independently of ARE class and suggest that in the cell, the default labile status of ARE-containing mRNAs depends on the combined interaction of such transcripts with destabilizing AUBPs. PMID:17077270

  16. Specific type of interactions in the quaternary system of Cu(II), adenosine 5'-triphosphate, 1,11-diamino-4,8-diazaundecane and uridine.

    PubMed

    Gasowska, Anna; Jastrzab, Renata; Lomozik, Lechoslaw

    2007-10-01

    Complexation reactions in the quaternary system Cu/ATP/3,3,3-tet/Urd have been studied. The stability constants of the complexes of the Cu(ATP)(3,3,3-tet)H(x)(Urd) type have been determined by computer analysis of the potentiometric titration. On the basis of the results of spectroscopic as well as equilibrium studies, the mode of interactions has been proposed. Metal ions coordinate phosphate groups of ATP and nitrogen atoms of polyamine. It has been established that in the conditions of the complex Cu(ATP)(3,3,3-tet) formation, uridine introduced into the Cu(II)/ATP/3,3,3-tet ternary system is involved in hydrogen bonding with the endocyclic nitrogen atoms N(1) and N(7) of the ATP purine ring and formation of the adduct Cu(ATP)(3,3,3-tet)H(Urd) is observed. Introduction of metal ions into the system changes substantially the mode of interactions between complementary base pairs relative to that proposed in the Watson and Crick model. PMID:17606298

  17. Comparative analysis of three-dimensional structures of homodimers of uridine phosphorylase from Salmonella typhimurium in the unligated state and in a complex with potassium ion

    SciTech Connect

    Lashkov, A. A.; Zhukhlistova, N. E.; Gabdulkhakov, A. G.; Mikhailov, A. M.

    2009-03-15

    The spatial organization of the homodimer of unligated uridine phosphorylase from Salmonella typhimurium (St UPh) was determined with high accuracy. The structure was refined at 1.80 A resolution to R{sub work} = 16.1% and R{sub free} = 20.0%. The rms deviations for the bond lengths, bond angles, and chiral angles are 0.006 A, 1.042{sup o}, and 0.071{sup o}, respectively. The coordinate error estimated by the Luzzati plot is 0.166 A. The coordinate error based on the maximum likelihood is 0.199 A. A comparative analysis of the spatial organization of the homodimer in two independently refined structures and the structure of the homodimer St UPh in the complex with a K{sup +} ion was performed. The substrate-binding sites in the homodimers StUPhs in the unligated state were found to act asynchronously. In the presence of a potassium ion, the three-dimensional structures of the subunits in the homodimer are virtually identical, which is apparently of importance for the synchronous action of both substrate-binding sites. The atomic coordinates of the refined structure of the homodimer and structure factors have been deposited in the Protein Data Bank (PDB ID code 3DPS).

  18. Molecular dynamics and crystallization phenomenon of supercooled and glassy DNA and RNA nucleosides: β-adenosine, β-thymidine, and β-uridine.

    PubMed

    Adrjanowicz, K; Wojnarowska, Z; Grzybowska, K; Hawelek, L; Kaminski, K; Paluch, M; Kasprzycka, A; Walczak, K

    2011-11-01

    Nucleosides are chemical compounds that have an extremely important biological role; they can be found in all types of living organisms. They are crucial components from which DNA and RNA acids are built. In addition, nucleosides are key regulators of many physiological processes. In this paper, the molecular dynamics in the liquid and glassy state of three selected nucleosides, β-adenosine, β-thymidine, and β-uridine, was investigated by means of dielectric spectroscopy. Our results revealed multiple relaxation processes associated with different types of molecular motions. Besides the primary α relaxation, two secondary modes in the glassy states of examined compounds were identified. Crystallization progress monitored by dielectric spectroscopy and x-ray diffraction technique at isostructural relaxation conditions revealed that the examined nucleosides possess completely different tendencies to recrystallize from the liquid as well as the glassy state. We have also made an attempt to predict the time scale of molecular motion below the glass transition temperatures of the respective nucleosides to discuss their potential stability at room temperature over prolonged storage time. Finally, combination of molecular mobility studies with evaluation of thermodynamic parameters from calorimetric measurements allowed us to discuss the fundamental roles of both kinetic and thermodynamic factors in governing the physical stability of the glassy state. PMID:22181422

  19. Molecular dynamics and crystallization phenomenon of supercooled and glassy DNA and RNA nucleosides: β-adenosine, β-thymidine, and β-uridine

    NASA Astrophysics Data System (ADS)

    Adrjanowicz, K.; Wojnarowska, Z.; Grzybowska, K.; Hawelek, L.; Kaminski, K.; Paluch, M.; Kasprzycka, A.; Walczak, K.

    2011-11-01

    Nucleosides are chemical compounds that have an extremely important biological role; they can be found in all types of living organisms. They are crucial components from which DNA and RNA acids are built. In addition, nucleosides are key regulators of many physiological processes. In this paper, the molecular dynamics in the liquid and glassy state of three selected nucleosides, β-adenosine, β-thymidine, and β-uridine, was investigated by means of dielectric spectroscopy. Our results revealed multiple relaxation processes associated with different types of molecular motions. Besides the primary α relaxation, two secondary modes in the glassy states of examined compounds were identified. Crystallization progress monitored by dielectric spectroscopy and x-ray diffraction technique at isostructural relaxation conditions revealed that the examined nucleosides possess completely different tendencies to recrystallize from the liquid as well as the glassy state. We have also made an attempt to predict the time scale of molecular motion below the glass transition temperatures of the respective nucleosides to discuss their potential stability at room temperature over prolonged storage time. Finally, combination of molecular mobility studies with evaluation of thermodynamic parameters from calorimetric measurements allowed us to discuss the fundamental roles of both kinetic and thermodynamic factors in governing the physical stability of the glassy state.

  20. Improved high-performance liquid chromatographic method for N-acetylgalactosamine-4-sulfate sulfatase (arylsulfatase B) activity determination using uridine diphospho-N-acetylgalactosamine-4-sulfate.

    PubMed

    Leznicki, A J; Bialkowski, K

    1997-08-29

    UDP-N-acetylgalactosamine-4-sulfate (UDP-GalNAc-4-S) was isolated from hen oviduct (isthmus) with a yield of 31 mumol per 100 g of wet tissue and used for arylsulfatase B (ASB) activity determination. Two HPLC methods of separation and quantitation of the reaction product were described: (1) an original gradient elution method which makes it possible to determine the reaction product when only partially purified ASB was used and additional uridine derivatives were formed during incubation; (2) an improved, fast isocratic elution method which may be used in the case of purified ASB preparations, devoid of other nucleotide hydrolysing enzymes. For both methods the detection limit was 0.1 nmol of product with standard error of determination < or = 3%. Using the gradient elution method we have found that UDP-GalNAc-4-S was hydrolysed by bovine arylsulfatase B1 most efficiently at pH 5.0 and concentration 0.5 mM with K(m) = 85 microM. PMID:9323540

  1. Breast milk jaundice: in vitro inhibition of rat liver bilirubin-uridine diphosphate glucuronyltransferase activity and Z protein-bromosulfophthalein binding by human breast milk.

    PubMed

    Foliot, A; Ploussard, J P; Housset, E; Christoforov

    1976-06-01

    Twenty-four samples of breast milk from nine mothers of infants suffering from breast milk jaundice were studied. Eight samples of milk from mothers of nonjaundiced infants, along with five formula milks enriched with polyunsaturated fatty acids, served as controls. Milks from mothers with jaundiced infants had no inhibitory effect when assayed immediately after thawing. However, after these milk samples were stores at 4 degrees, they strongly inhibited bilirubin conjugation (80.3% inhibition of uridine diphosphate glucuronyltransferase (UDPGT) activity) and bromosulfophthalein (BSP) binding to cytoplasmic Z protein (dye binding inhibited 82.1%). There was no effect on BSP binding to Y protein (see Table 1). Heating the milk to 56 degrees modified the results in the following manner; when the milk was heated immediately after thawing, no inhibitory effect was seen, even after storage for 96 hr. On the other hand, when the milk was first stored at 96 hr and then heated, it had the same inhibitory effects as the milks which were stored without heating. The present study shows that pathologic breast milk will inhibit BSP-Z protein binding only when stored under conditions that also cause the appearance of the capacity to inhibit bilirubin conjugation in vitro, as well as causing the liberation of nonesterified fatty acids. Thus, the appearance of this inhibitory capacity in vitro seems linked to the lipolytic activity particular to pathologic milks. PMID:818610

  2. Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine.

    PubMed

    Ritzel, M W; Yao, S Y; Ng, A M; Mackey, J R; Cass, C E; Young, J D

    1998-01-01

    Two Na(+)-dependent nucleoside transporters implicated in adenosine and uridine transport in mammalian cells are distinguished functionally on the basis of substrate specificity: CNT1 is selective for pyrimidine nucleosides but also transports adenosine; CNT2 (also termed SPNT) is selective for purine nucleosides but also transports uridine. Both proteins belong to a gene family that includes the NupC proton/nucleoside symporter of E. coli. cDNAs encoding members of the CNT family have been isolated from rat tissues (jejunum, brain, liver; rCNT1 and rCNT2/SPNT) and, most recently, human kidney (hCNT1 and hSPNT1). Here, the molecular cloning and functional characterization of a CNT2/SPNT-type transporter from human small intestine are described. The encoded 658-residue protein (hCNT2 in the nomenclature) had the same predicted amino acid sequence as human kidney hSPNT1, except for a polymorphism at residue 75 (Arg substituted by Ser), and was 83 and 72% identical to rCNT2 and hCNT1, respectively. Sequence differences between hCNT2 and rCNT2 were greatest at the N-terminus. In Xenopus oocytes, recombinant hCNT2 exhibited the functional characteristics of a Na(+)-dependent nucleoside transporter with selectivity for adenosine, other purine nucleosides and uridine (adenosine and uridine K(m) app values 8 and 40 microM, respectively). hCNT2 transcripts were found in kidney and small intestine but, unlike rCNT2, were not detected in liver. Deoxyadenosine, which undergoes net renal secretion in humans, was less readily transported than adenosine. hCNT2 also mediated small, but significant, fluxes of the antiviral purine nucleoside analogue 2',3'-dideoxyinosine. hCNT2 is, therefore potentially involved in both the intestinal absorption and renal handling of purine nucleosides (including adenosine), uridine and purine nucleoside drugs. The gene encoding hCNT2 was mapped to chromosome 15q15. PMID:10087507

  3. Do Cyclosporine A, an IL-1 Receptor Antagonist, Uridine Triphosphate, Rebamipide, and/or Bimatoprost Regulate Human Meibomian Gland Epithelial Cells?

    PubMed Central

    Kam, Wendy R.; Liu, Yang; Ding, Juan; Sullivan, David A.

    2016-01-01

    Purpose Researchers have hypothesized that treatment with cyclosporine A (CyA), interleukin-1 receptor antagonists (IL-1RA; e.g., anakinra), P2Y2 receptor agonists (e.g., uridine triphosphate; UTP), and rebamipide may alleviate human meibomian gland dysfunction (MGD) and/or dry eye disease. Investigators have also proposed that prostaglandin analogues (e.g., bimatoprost) may induce MGD. Our goal was to determine whether these compounds directly influence human meibomian gland epithelial cell (HMGEC) function. Methods Multiple concentrations of each compound were tested for effects on immortalized (I) HMGEC morphology and survival. Nontoxic dosages were used for our studies. Immortalized HMGEC were cultured in the presence of vehicle, CyA, IL-1RA, UTP, rebamipide, or bimatoprost for up to 6 days in various media. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract), differentiation (azithromycin), and signaling pathway activation (insulin-like growth factor 1). Cells were analyzed for neutral lipid staining, lysosome accumulation, lipid composition, and phosphatidylinositol-3-kinase/Akt (AKT), phosphorylation. Results Our findings demonstrate that CyA, IL-1RA, UTP, rebamipide, and bimatoprost had no effect on the proliferation; neutral lipid content; lysosome number; or levels of free cholesterol, triglycerides, or phospholipids in IHMGECs. Cylosporine A, IL-1RA, rebamipide, and bimatoprost significantly reduced the phosphorylation of AKT, as compared to control. Of interest, tested doses of CyA above 8 nM killed the IHMGECs. Conclusions Our results show that CyA, IL-1RA, UTP, rebamipide, and bimatoprost do not influence the proliferation or differentiation of IHMGEC. However, with the exception of UTP, these compounds do decrease the activity of the AKT signaling pathway, which is known to promote cell survival. PMID:27552406

  4. Optimized methods for targeted peptide-based quantification of human uridine 5'-diphosphate-glucuronosyltransferases in biological specimens using liquid chromatography-tandem mass spectrometry.

    PubMed

    Sato, Yuichiro; Nagata, Masanori; Tetsuka, Kazuhiro; Tamura, Kouichi; Miyashita, Aiji; Kawamura, Akio; Usui, Takashi

    2014-05-01

    The aim of this study was to optimize methods for quantifying 13 uridine 5'-diphosphate-glucuronosyltransferase (UGT) isoforms (UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B15, and 2B17) in human liver, intestinal, and kidney microsomes, and in recombinant human UGT-expressing insect cell membranes (rhUGTs) by targeted peptide-based quantification using liquid chromatography-tandem mass spectrometry. Production of targeted peptides was compared by combining three denaturing agents (urea, sodium deoxycholate, and octyl glucoside) and three denaturing temperatures (37°C, 60°C, and 95°C) followed by tryptic digestion for 2-20 hours. Denaturing conditions and digestion times yielding high production efficiency varied markedly among isoforms and specimens, indicating the importance of specific optimization. Each UGT isoform was quantified using the methods found to be optimal. The expression of 10 (1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B10, 2B15, and 2B17), 6 (1A1, 1A3, 1A4, 1A10, 2B7, and 2B17), and 3 (1A6, 1A9, and 2B7) isoforms was detected in human liver, intestinal, and kidney microsomes, respectively, and levels were reproducible using multiple protocols. All isoforms were quantified in rhUGTs. Determining the levels of UGTs in human tissue specimens and those in rhUGTs is important for estimating the contribution of glucuronidation to body clearance based on in vitro-in vivo extrapolation. PMID:24595681

  5. Enzymatic synthesis of 2'-deoxyuridine by whole cell catalyst co-expressing uridine phosphorylase and thymidine phosphorylase through auto-induction system.

    PubMed

    Xiong, Shuli; Wang, Yingbin; Wang, Xi; Wang, Jie; Li, Jie; Zhang, Guiyou; Zhang, Rongqing; Xie, Liping; Wang, Hongzhong

    2014-12-01

    Genes encoding uridine phosphorylase (UP) and thymidine phosphorylase (TP) from Escherichia coli K12 were cloned and recombined respectively into plasmids pET-21a(+) and pET-28a(+). The recombinant plasmids BL21/pET21a-UP and BL21/pET28a-TP were co-transformed into E. coli BL21(DE3) to construct highly effective BTU strain (BL21/pET28a-TP, pET21a-UP) overexpressing both of UP and TP. BTU was cultivated in ZYM-Fe-5052 medium for 10 h and used as catalyst to synthesize 2'-deoxyuridine (dUR). It was found to increase the productivity of dUR by 8-9 fold when compared to wild E. coli K12 and E. coli BL21(DE3) strains. A series of experiments were carried out to find out the optimal conditions for synthesis of dUR. At 50°C, with 0.25‰ dry wt./v to catalyze the reaction of 2:1 β-thymidine: uracil (60 mM β-thymidine, 30 mM uracil), the conversion rate of dUR would reach 61.6% at 1 h, which was much higher than the rates obtained by BTU strain cultured in LB medium and induced by IPTG. This result proved co-expression and auto-induction were efficient methods in enhancing the expression quantity and activity of nucleoside phosphorylases, and they also had significant implications for large-scale industrial production of dUR and synthesis of other nucleoside derivatives. PMID:24910260

  6. Hepatic Conversion of Bilirubin Monoglucuronide to Diglucuronide in Uridine Diphosphate-Glucuronyl Transferase-Deficient Man and Rat by Bilirubin Glucuronoside Glucuronosyltransferase

    PubMed Central

    Chowdhury, J. Roy; Jansen, P. L. M.; Fischberg, E. B.; Daniller, A.; Arias, I. M.

    1978-01-01

    The microsomal enzyme uridine diphosphate (UDP) glucuronate glucuronyltransferase (E.C. 2.4.1.17) catalyzes formation of bilirubin mono-glucuronide from bilirubin and UDPglucuronic acid. Bilirubin glucuronoside glucuronosyltransferase (E.C. 2.4.1.95), an enzyme concentrated in plasma membrane-enriched fractions of rat liver, converts bilirubin monoglucuronide to bilirubin diglucuronide. Bilirubin glucuronoside glucuronosyltransferase activity was studied in homogenates of liver biopsy specimens obtained from patients with the Crigler-Najjar syndrome (Type I) and in subcellular liver fractions of rats homozygous for UDP glucuronate glucuronyltransferase deficiency (Gunn strain). In patients with the Crigler-Najjar syndrome (Type I) and in Gunn rats, hepatic UDPglucuronate glucuronyltransferase activity was not measurable; however, bilirubin glucuronoside glucuronosyltransferase activity was similar to that in normal controls. The subcellular distribution of bilirubin glucuronoside glucuronosyltransferase activity in Gunn rat liver was similar to the distribution observed in normal Wistar rat liver. When bilirubin monoglucuronide was infused intravenously into Gunn rats, 29±5% of the conjugated bilirubin excreted in bile was bilirubin diglucuronide. After transplantation of normal Wistar rat kidney, which contained UDPglucuronate glucuronyltransferase activity, in Gunn rats, the serum bilirubin concentration decreased by 80% in 4 days. The major route of bilirubin removal was biliary excretion of conjugated bilirubin, approximately 70% of which was bilirubin diglucuronide. Although patients with the Crigler-Najjar syndrome (Type I) and Gunn rats lack UDP glucuronate glucuronyltransferase, their livers enzymatically convert bilirubin monoglucuronide to diglucuronide in vitro. Conversion in bilirubin monoglucuronide to diglucuronide was demonstrated in Gunn rats in vivo. PMID:96142

  7. Screening for bovine leukocyte adhesion deficiency, deficiency of uridine monophosphate synthase, complex vertebral malformation, bovine citrullinaemia, and factor XI deficiency in Holstein cows reared in Turkey

    PubMed Central

    2010-01-01

    Background Bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), complex vertebral malformation (CVM), bovine citrullinaemia (BC) and factor XI deficiency (FXID) are autosomal recessive hereditary disorders, which have had significant economic impact on dairy cattle breeding worldwide. In this study, 350 Holstein cows reared in Turkey were screened for BLAD, DUMPS, CVM, BC and FXID genotypes to obtain an indication on the importance of these defects in Turkish Holsteins. Methods Genomic DNA was obtained from blood and the amplicons of BLAD, DUMPS, CVM, BC and FXID were obtained by using PCR. PCR products were digested with TaqI, AvaI and AvaII restriction enzymes for BLAD, DUMPS, and BC, respectively. These digested products and PCR product of FXID were analyzed by agarose gel electrophoresis stained with ethidium bromide. CVM genotypes were detected by DNA sequencing. Additionally, all genotypes were confirmed by DNA sequencing to determine whether there was a mutant allele or not. Results Fourteen BLAD, twelve CVM and four FXID carriers were found among the 350 Holstein cows examined, while carriers of DUMPS and BC were not detected. The mutant allele frequencies were calculated as 0.02, 0.017, and 0.006 for BLAD, CVM and FXID, respectively with corresponding carrier prevalence of 4.0% (BLAD), 3.4% (CVM) and 1.2% (FXID). Conclusion This study demonstrates that carriers of BLAD, CVM and FXID are present in the Turkish Holstein population, although at a low frequency. The actual number of clinical cases is unknown, but sporadic cases may appear. As artificial insemination is widely used in dairy cattle breeding, carriers of BLAD, CVM and FXID are likely present within the population of breeding sires. It is recommended to screen breeding sires for these defective genes in order to avoid an unwanted spread within the population. PMID:20929557

  8. Borate-aided anion exchange high-performance liquid chromatography of uridine diphosphate-sugars in brain, heart, adipose and liver tissues.

    PubMed

    Oikari, Sanna; Venäläinen, Tuula; Tammi, Markku

    2014-01-01

    In this paper we describe a method optimized for the purification of uridine diphosphate (UDP)-sugars from liver, adipose tissue, brain, and heart, with highly reproducible up to 85% recoveries. Rapid tissue homogenization in cold ethanol, lipid removal by butanol extraction, and purification with a graphitized carbon column resulted in isolation of picomolar quantities of the UDP-sugars from 10 to 30mg of tissue. The UDP-sugars were baseline separated from each other, and from all major nucleotides using a CarboPac PA1 anion exchange column eluted with a gradient of acetate and borate buffers. The extraction and purification protocol produced samples with few unidentified peaks. UDP-N-acetylglucosamine was a dominant UDP-sugar in all the rat tissues studied. However, brain and adipose tissue showed high UDP-glucose levels, equal to that of UDP-N-acetylglucosamine. The UDP-N-acetylglucosamine showed 2.3-2.7 times higher levels than UDP-N-acetylgalactosamine in all tissues, and about the same ratio was found between UDP-glucose and UDP-galactose in adipose tissue and brain (2.6 and 2.8, respectively). Interestingly, the UDP-glucose/UDP-galactose ratio was markedly lower in liver (1.1) and heart (1.7). The UDP-N-acetylglucosamine/UDP-glucuronic acid ratio was also constant, between 9.7 and 7.7, except in liver with the ratio as low as 1.8. The distinct UDP-glucose/galactose ratio, and the abundance of UDP-glucuronic acid may reflect the specific role of liver in glycogen synthesis, and metabolism of hormones and xenobiotics, respectively, using these UDP-sugars as substrates. PMID:24309714

  9. Selectivity and affinity of DNA triplex forming oligonucleotides containing the nucleoside analogues 2'-O-methyl-5-(3-amino-1-propynyl)uridine and 2'-O-methyl-5-propynyluridine.

    PubMed

    Li, Hong; Miller, Paul S; Seidman, Michael M

    2008-11-21

    Triplex forming oligonucleotides (TFOs) containing the nucleoside analogues 2'-O-methyl-5-propynyluridine (1) and 2'-O-methyl-5-(3-amino-1-propynyl)uridine (2) were synthesized. The affinity and selectivity of triplex formation by these TFOs were studied by gel shift analysis, T(m) value measurement, and association rate assays. The results show that the introduction of 1 and 2 into TFOs can improve the stability of the triplexes under physiological conditions. Optimized distribution of 1 or 2 in the TFOs combined with a cluster of contiguous nucleosides with 2'-aminoethoxy sugars resulted in formation of triplexes with further enhanced stability and improved selectivity. PMID:18972052

  10. Culture and conservation

    SciTech Connect

    McNeely, J.A.; Pitt, D.

    1985-01-01

    The threat posed by human activity in the natural environment is one of the major global problems of the present time. Much has been done throughout the world to promote conservation, but one theme that has generally been neglected is the contribution that local culture can make to conservation. Many people pass on from one generation to the next traditional lore and customs which amount to effective conservation policies. This book identifies such traditional conservation measures, examines their extent, and judges their effectiveness.

  11. Conservation Action Handbook.

    ERIC Educational Resources Information Center

    National Rifle Association, Washington, DC.

    Conservation problems are identified, with some suggestions for action. General areas covered are: Wildlife Conservation, Soil Conservation, Clean Water, Air Pollution Action, and Outdoor Recreation Action. Appendices list private organizations or agencies concerned with natural resource use and/or management, congressional committees considering…

  12. Conservation in Physics.

    ERIC Educational Resources Information Center

    Finkel, Edward

    1991-01-01

    Discussed is the physical concept of conservation as it is framed within the laws of conservation of mass, of momentum, and of energy. The derivation of Ohm's Law as a generalization of the relationship between the observed measurements of voltage and current serves as the exemplar of how conservation theories are formed. (JJK)

  13. Exactly conservative integrators

    SciTech Connect

    Shadwick, B.A.; Bowman, J.C.; Morrison, P.J.

    1995-07-19

    Traditional numerical discretizations of conservative systems generically yield an artificial secular drift of any nonlinear invariants. In this work we present an explicit nontraditional algorithm that exactly conserves invariants. We illustrate the general method by applying it to the Three-Wave truncation of the Euler equations, the Volterra-Lotka predator-prey model, and the Kepler problem. We discuss our method in the context of symplectic (phase space conserving) integration methods as well as nonsymplectic conservative methods. We comment on the application of our method to general conservative systems.

  14. Conservation: Toward firmer ground

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The following aspects of energy conservation were reviewed in order to place the problems in proper perspective: history and goals, conservation accounting-criteria, and a method to overcome obstacles. The effect of changing prices and available supplies of energy sources and their causes on consumption levels during the last few decades were described. Some examples of attainable conservation goals were listed and justified. A number of specific criteria applicable to conservation accounting were given. Finally, a discussion was presented to relate together the following aspects of energy conservation: widespread impact, involvement of government, industry, politics, moral and ethical aspects, urgency and time element.

  15. 7 CFR 12.23 - Conservation plans and conservation systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Conservation plans and conservation systems. 12.23 Section 12.23 Agriculture Office of the Secretary of Agriculture HIGHLY ERODIBLE LAND AND WETLAND CONSERVATION Highly Erodible Land Conservation § 12.23 Conservation plans and conservation systems. (a) Use of field office technical guide. A...

  16. Conservation: Toward firmer ground

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The following aspects of energy conservation were discussed: conservation history and goals, conservation modes, conservation accounting-criteria, and a method to overcome obstacles. The conservation modes tested fall into one of the following categories: reduced energy consumption, increased efficiency of energy utilization, or substitution of one or more forms of energy for another which is in shorter supply or in some sense thought to be of more value. The conservation accounting criteria include net energy reduction, economic, and technical criteria. A method to overcome obstacles includes (approaches such as: direct personal impact (life style, income, security, aspiration), an element of crisis, large scale involvement of environmental, safety, and health issues, connections to big government, big business, big politics, involvement of known and speculative science and technology, appeal to moral and ethical standards, the transient nature of opportunities to correct the system.

  17. Biodiversity Conservation and Conservation Biotechnology Tools

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This special issue is dedicated to the in vitro tools and methods used to conserve the genetic diversity of rare and threatened species from around the world. Species that are on the brink of extinction, due to the rapid loss of genetic diversity and habitat, come mainly from resource poor areas the...

  18. Introducing Conservation of Momentum

    ERIC Educational Resources Information Center

    Brunt, Marjorie; Brunt, Geoff

    2013-01-01

    The teaching of the principle of conservation of linear momentum is considered (ages 15 + ). From the principle, the momenta of two masses in an isolated system are considered. Sketch graphs of the momenta make Newton's laws appear obvious. Examples using different collision conditions are considered. Conservation of momentum is considered…

  19. Conservation in perspective

    SciTech Connect

    Warren, A.; Goldsmith, F.B.; Goldsmith, B.

    1984-01-01

    This book reflects the changes that have taken place in the nature conservation movement over the last decade. It includes essays on issues of nature conservation itself, rather than on environmental issues. Habitats, elements of the ecosystem, and some of the political and organizational activity currently of interest are covered.

  20. Resource Conservation Glossary.

    ERIC Educational Resources Information Center

    Soil Conservation Society of America, Ankeny, IA.

    This glossary is a composite of terms selected from 13 technologies, and is the expanded revision of the original 1952 edition of "The Soil and Water Conservation Glossary." The terms were selected from these areas: agronomy, biology, conservation, ecology, economics, engineering, forestry, geology, hydrology, range, recreation, soils, and…

  1. The Syntax of Conservation.

    ERIC Educational Resources Information Center

    Hargis, Charles H.

    This paper outlines the syntactic structures which represent a stage in the cognitive development of children, and focusses on an aspect of cognitive development known as conservation. The cognitive components of conservation are presented as the primordial base for the set of syntactic structures which map or mirror them. Piaget proposed four…

  2. Conservation and Reading Comprehension.

    ERIC Educational Resources Information Center

    Backus, Mary Giafagleone

    In this study it was hypothesized that those students classified as conservers would score significantly higher on cloze passages related to the concepts of number, quantity, and volume than would those students classified as non-conservers. The subjects consisted of a group of 42 sixth grade urban public school students judged to be of low socio…

  3. Conservation Science Fair Projects.

    ERIC Educational Resources Information Center

    Soil Conservation Society of America, Ankeny, IA.

    Included are ideas, suggestions, and examples for selecting and designing conservation science projects. Over 70 possible conservation subject areas are presented with suggested projects. References are cited with each of these subject areas, and a separate list of annotated references is included. The references pertain to general subject…

  4. Creative Soil Conservation

    ERIC Educational Resources Information Center

    Smith, Martha

    2010-01-01

    Take plant lessons outdoors with this engaging and inquiry-based activity in which third-grade students learn how to apply soil conservation methods to growing plants. They also collect data and draw conclusions about the effectiveness of their method of soil conservation. An added benefit to this activity is that the third-grade students played…

  5. On exactly conservative integrators

    SciTech Connect

    Bowman, J.C.; Shadwick, B.A.; Morrison, P.J.

    1997-06-01

    Traditional explicit numerical discretizations of conservative systems generically predict artificial secular drifts of nonlinear invariants. These algorithms are based on polynomial functions of the time step. The authors discuss a general approach for developing explicit algorithms that conserve such invariants exactly. They illustrate the method by applying it to the truncated two-dimensional Euler equations.

  6. Home Energy Conservation Primer.

    ERIC Educational Resources Information Center

    DeLuca, V. William; And Others

    This guide was prepared to support a program of training for community specialists in contemporary and practical techniques of home energy conservation. It is designed to assist professionals in efficient operation of energy conservation programs and to provide ideas for expanding education operations. Eight major sections are presented: (1)…

  7. Conservation: Threatened by Luxury.

    PubMed

    Webb, Thomas J

    2016-06-20

    When animals are traded in lucrative international luxury markets, individuals really do matter to conservation. Identifying the intrinsic and extrinsic factors that make some species especially vulnerable to this kind of threat helps set guidelines for more effective conservation. PMID:27326710

  8. Conservation--Selected Bibliography.

    ERIC Educational Resources Information Center

    Australian Conservation Foundation, Parkville, Victoria.

    Developed by the Australian Conservation Foundation to meet the need for a general conservation bibliography, this booklet offers resources for a wide spectrum of possible users. Material selected is that which is relevant and helpful for conservationists in their various fields of activity and what is likely to be in print and obtainable without…

  9. Conservation in transportation

    SciTech Connect

    1980-05-30

    A nationwide examination was made of grassroots energy conservation programs related to transportation. Information compiled from civic groups, trade associations, and corporations is included on driver awareness/mass transit; travel; and ride sharing. It is concluded that a willingness by the public to cooperate in transportation energy conservation exists and should be exploited. (LCL)

  10. Water Conservation Resource List.

    ERIC Educational Resources Information Center

    NJEA Review, 1981

    1981-01-01

    Alarmed by the growing water shortage, the New Jersey State Office of Dissemination has prepared this annotated list of free or inexpensive instructional materials for teaching about water conservation, K-l2. A tipsheet for home water conservation is appended. (Editor/SJL)