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Sample records for conserved wobble uridine

  1. Elongator function in tRNA wobble uridine modification is conserved between yeast and plants

    PubMed Central

    Mehlgarten, Constance; Jablonowski, Daniel; Wrackmeyer, Uta; Tschitschmann, Susan; Sondermann, David; Jäger, Gunilla; Gong, Zhizhong; Byström, Anders S; Schaffrath, Raffael; Breunig, Karin D

    2010-01-01

    Based on studies in yeast and mammalian cells the Elongator complex has been implicated in functions as diverse as histone acetylation, polarized protein trafficking and tRNA modification. Here we show that Arabidopsis mutants lacking the Elongator subunit AtELP3/ELO3 have a defect in tRNA wobble uridine modification. Moreover, we demonstrate that yeast elp3 and elp1 mutants expressing the respective Arabidopsis Elongator homologues AtELP3/ELO3 and AtELP1/ELO2 assemble integer Elongator complexes indicating a high degree of structural conservation. Surprisingly, in vivo complementation studies based on Elongator-dependent tRNA nonsense suppression and zymocin tRNase toxin assays indicated that while AtELP1 rescued defects of a yeast elp1 mutant, the most conserved Elongator gene AtELP3, failed to complement an elp3 mutant. This lack of complementation is due to incompatibility with yeast ELP1 as coexpression of both plant genes in an elp1 elp3 yeast mutant restored Elongator's tRNA modification function in vivo. Similarly, AtELP1, not ScELP1 also supported partial complementation by yeast–plant Elp3 hybrids suggesting that AtElp1 has less stringent sequence requirements for Elp3 than ScElp1. We conclude that yeast and plant Elongator share tRNA modification roles and propose that this function might be conserved in Elongator from all eukaryotic kingdoms of life. PMID:20398216

  2. Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling.

    PubMed

    Scheidt, Viktor; Jüdes, André; Bär, Christian; Klassen, Roland; Schaffrath, Raffael

    2014-11-29

    Previous work in yeast has suggested that modification of tRNAs, in particular uridine bases in the anticodon wobble position (U34), is linked to TOR (target of rapamycin) signaling. Hence, U34 modification mutants were found to be hypersensitive to TOR inhibition by rapamycin. To study whether this involves inappropriate TOR signaling, we examined interaction between mutations in TOR pathway genes (tip41∆, sap190∆, ppm1∆, rrd1∆) and U34 modification defects (elp3∆, kti12∆, urm1∆, ncs2∆) and found the rapamycin hypersensitivity in the latter is epistatic to drug resistance of the former. Epistasis, however, is abolished in tandem with a gln3∆ deletion, which inactivates transcription factor Gln3 required for TOR-sensitive activation of NCR (nitrogen catabolite repression) genes. In line with nuclear import of Gln3 being under control of TOR and dephosphorylation by the Sit4 phosphatase, we identify novel TOR-sensitive sit4 mutations that confer rapamycin resistance and importantly, mislocalise Gln3 when TOR is inhibited. This is similar to gln3∆ cells, which abolish the rapamycin hypersensitivity of U34 modification mutants, and suggests TOR deregulation due to tRNA undermodification operates through Gln3. In line with this, loss of U34 modifications (elp3∆, urm1∆) enhances nuclear import of and NCR gene activation (MEP2, GAP1) by Gln3 when TOR activity is low. Strikingly, this stimulatory effect onto Gln3 is suppressed by overexpression of tRNAs that usually carry the U34 modifications. Collectively, our data suggest that proper TOR signaling requires intact tRNA modifications and that loss of U34 modifications impinges on the TOR-sensitive NCR branch via Gln3 misregulation.

  3. Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling

    PubMed Central

    Scheidt, Viktor; Jüdes, André; Bär, Christian; Klassen, Roland; Schaffrath, Raffael

    2014-01-01

    Previous work in yeast has suggested that modification of tRNAs, in particular uridine bases in the anticodon wobble position (U34), is linked to TOR (target of rapamycin) signaling. Hence, U34 modification mutants were found to be hypersensitive to TOR inhibition by rapamycin. To study whether this involves inappropriate TOR signaling, we examined interaction between mutations in TOR pathway genes (tip41∆, sap190∆, ppm1∆, rrd1∆) and U34 modification defects (elp3∆, kti12∆, urm1∆, ncs2∆) and found the rapamycin hypersensitivity in the latter is epistatic to drug resistance of the former. Epistasis, however, is abolished in tandem with a gln3∆ deletion, which inactivates transcription factor Gln3 required for TOR-sensitive activation of NCR (nitrogen catabolite repression) genes. In line with nuclear import of Gln3 being under control of TOR and dephosphorylation by the Sit4 phosphatase, we identify novel TOR-sensitive sit4 mutations that confer rapamycin resistance and importantly, mislocalise Gln3 when TOR is inhibited. This is similar to gln3∆ cells, which abolish the rapamycin hypersensitivity of U34 modification mutants, and suggests TOR deregulation due to tRNA undermodification operates through Gln3. In line with this, loss of U34 modifications (elp3∆, urm1∆) enhances nuclear import of and NCR gene activation (MEP2, GAP1) by Gln3 when TOR activity is low. Strikingly, this stimulatory effect onto Gln3 is suppressed by overexpression of tRNAs that usually carry the U34 modifications. Collectively, our data suggest that proper TOR signaling requires intact tRNA modifications and that loss of U34 modifications impinges on the TOR-sensitive NCR branch via Gln3 misregulation. PMID:28357221

  4. Loss of anticodon wobble uridine modifications affects tRNA(Lys) function and protein levels in Saccharomyces cerevisiae.

    PubMed

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

    2015-01-01

    In eukaryotes, wobble uridines in the anticodons of tRNA(Lys)UUU, tRNA(Glu)UUC and tRNA(Gln)UUG 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 tRNA(Lys)UUU. 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 tRNA(Lys)UUU hypomodification and malfunction.

  5. SURVEY AND SUMMARY: Roles of 5-substituents of tRNA wobble uridines in the recognition of purine-ending codons

    PubMed Central

    Takai, Kazuyuki; Yokoyama, Shigeyuki

    2003-01-01

    Many tRNA molecules that recognize the purine-ending codons but not the pyrimidine-ending codons have a modified uridine at the wobble position, in which a methylene carbon is attached directly to position 5 of the uracil ring. Although several models have been proposed concerning the mechanism by which the 5-substituents regulate codon-reading properties of the tRNAs, none could explain recent results of the experiments utilizing well-characterized modification-deficient strains of Escherichia coli. Here, we first summarize previous studies on the codon-reading properties of tRNA molecules with a U derivative at the wobble position. Then, we propose a hypothetical mechanism of the reading of the G-ending codons by such tRNA molecules that could explain the experimental results. The hypothesis supposes unconventional base pairs between a protonated form of the modified uridines and the G at the third position of the codon stabilized by two direct hydrogen bonds between the bases. The hypothesis also addresses differences between the prokaryotic and eukaryotic decoding systems. PMID:14602896

  6. Archaeal Tuc1/Ncs6 homolog required for wobble uridine tRNA thiolation is associated with ubiquitin-proteasome, translation, and RNA processing system homologs.

    PubMed

    Chavarria, Nikita E; Hwang, Sungmin; Cao, Shiyun; Fu, Xian; Holman, Mary; Elbanna, Dina; Rodriguez, Suzanne; Arrington, Deanna; Englert, Markus; Uthandi, Sivakumar; Söll, Dieter; Maupin-Furlow, Julie A

    2014-01-01

    While cytoplasmic tRNA 2-thiolation protein 1 (Tuc1/Ncs6) and ubiquitin-related modifier-1 (Urm1) are important in the 2-thiolation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) at wobble uridines of tRNAs in eukaryotes, the biocatalytic roles and properties of Ncs6/Tuc1 and its homologs are poorly understood. Here we present the first report of an Ncs6 homolog of archaea (NcsA of Haloferax volcanii) that is essential for maintaining cellular pools of thiolated tRNA(Lys)UUU and for growth at high temperature. When purified from Hfx. volcanii, NcsA was found to be modified at Lys204 by isopeptide linkage to polymeric chains of the ubiquitin-fold protein SAMP2. The ubiquitin-activating E1 enzyme homolog of archaea (UbaA) was required for this covalent modification. Non-covalent protein partners that specifically associated with NcsA were also identified including UbaA, SAMP2, proteasome activating nucleotidase (PAN)-A/1, translation elongation factor aEF-1α and a β-CASP ribonuclease homolog of the archaeal cleavage and polyadenylation specificity factor 1 family (aCPSF1). Together, our study reveals that NcsA is essential for growth at high temperature, required for formation of thiolated tRNA(Lys)UUU and intimately linked to homologs of ubiquitin-proteasome, translation and RNA processing systems.

  7. Archaeal Tuc1/Ncs6 Homolog Required for Wobble Uridine tRNA Thiolation Is Associated with Ubiquitin-Proteasome, Translation, and RNA Processing System Homologs

    PubMed Central

    Chavarria, Nikita E.; Hwang, Sungmin; Cao, Shiyun; Fu, Xian; Holman, Mary; Elbanna, Dina; Rodriguez, Suzanne; Arrington, Deanna; Englert, Markus; Uthandi, Sivakumar; Söll, Dieter; Maupin-Furlow, Julie A.

    2014-01-01

    While cytoplasmic tRNA 2-thiolation protein 1 (Tuc1/Ncs6) and ubiquitin-related modifier-1 (Urm1) are important in the 2-thiolation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) at wobble uridines of tRNAs in eukaryotes, the biocatalytic roles and properties of Ncs6/Tuc1 and its homologs are poorly understood. Here we present the first report of an Ncs6 homolog of archaea (NcsA of Haloferax volcanii) that is essential for maintaining cellular pools of thiolated tRNALysUUU and for growth at high temperature. When purified from Hfx. volcanii, NcsA was found to be modified at Lys204 by isopeptide linkage to polymeric chains of the ubiquitin-fold protein SAMP2. The ubiquitin-activating E1 enzyme homolog of archaea (UbaA) was required for this covalent modification. Non-covalent protein partners that specifically associated with NcsA were also identified including UbaA, SAMP2, proteasome activating nucleotidase (PAN)-A/1, translation elongation factor aEF-1α and a β-CASP ribonuclease homolog of the archaeal cleavage and polyadenylation specificity factor 1 family (aCPSF1). Together, our study reveals that NcsA is essential for growth at high temperature, required for formation of thiolated tRNALysUUU and intimately linked to homologs of ubiquitin-proteasome, translation and RNA processing systems. PMID:24906001

  8. Elongator Complex Influences Telomeric Gene Silencing and DNA Damage Response by Its Role in Wobble Uridine tRNA Modification

    PubMed Central

    Chen, Changchun; Huang, Bo; Eliasson, Mattias; Rydén, Patrik; Byström, Anders S.

    2011-01-01

    Elongator complex is required for formation of the side chains at position 5 of modified nucleosides 5-carbamoylmethyluridine (ncm5U34), 5-methoxycarbonylmethyluridine (mcm5U34), and 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U34) at wobble position in tRNA. These modified nucleosides are important for efficient decoding during translation. In a recent publication, Elongator complex was implicated to participate in telomeric gene silencing and DNA damage response by interacting with proliferating cell nuclear antigen (PCNA). Here we show that elevated levels of tRNALys s2 UUU, tRNAGln s2 UUG, and tRNAGlu s2 UUC, which in a wild-type background contain the mcm5s2U nucleoside at position 34, suppress the defects in telomeric gene silencing and DNA damage response observed in the Elongator mutants. We also found that the reported differences in telomeric gene silencing and DNA damage response of various elp3 alleles correlated with the levels of modified nucleosides at U34. Defects in telomeric gene silencing and DNA damage response are also observed in strains with the tuc2Δ mutation, which abolish the formation of the 2-thio group of the mcm5s2U nucleoside in tRNALys mcm5s2UUU, tRNAGln mcm5s2UUG, and tRNAGlu mcm5s2UUC. These observations show that Elongator complex does not directly participate in telomeric gene silencing and DNA damage response, but rather that modified nucleosides at U34 are important for efficient expression of gene products involved in these processes. Consistent with this notion, we found that expression of Sir4, a silent information regulator required for assembly of silent chromatin at telomeres, was decreased in the elp3Δ mutants. PMID:21912530

  9. Elongator complex influences telomeric gene silencing and DNA damage response by its role in wobble uridine tRNA modification.

    PubMed

    Chen, Changchun; Huang, Bo; Eliasson, Mattias; Rydén, Patrik; Byström, Anders S

    2011-09-01

    Elongator complex is required for formation of the side chains at position 5 of modified nucleosides 5-carbamoylmethyluridine (ncm⁵U₃₄), 5-methoxycarbonylmethyluridine (mcm⁵U₃₄), and 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U₃₄) at wobble position in tRNA. These modified nucleosides are important for efficient decoding during translation. In a recent publication, Elongator complex was implicated to participate in telomeric gene silencing and DNA damage response by interacting with proliferating cell nuclear antigen (PCNA). Here we show that elevated levels of tRNA(Lys)(s²UUU), tRNA(Gln)(s²UUG), and tRNA(Glu)(s²UUC), which in a wild-type background contain the mcm⁵s²U nucleoside at position 34, suppress the defects in telomeric gene silencing and DNA damage response observed in the Elongator mutants. We also found that the reported differences in telomeric gene silencing and DNA damage response of various elp3 alleles correlated with the levels of modified nucleosides at U₃₄. Defects in telomeric gene silencing and DNA damage response are also observed in strains with the tuc2Δ mutation, which abolish the formation of the 2-thio group of the mcm⁵s²U nucleoside in tRNA(Lys)(mcm⁵s²UUU), tRNA(Gln)(mcm⁵s²UUG), and tRNA(Glu)(mcm⁵s²UUC). These observations show that Elongator complex does not directly participate in telomeric gene silencing and DNA damage response, but rather that modified nucleosides at U₃₄ are important for efficient expression of gene products involved in these processes. Consistent with this notion, we found that expression of Sir4, a silent information regulator required for assembly of silent chromatin at telomeres, was decreased in the elp3Δ mutants.

  10. A conserved modified wobble nucleoside (mcm5s2U) in lysyl-tRNA is required for viability in yeast

    PubMed Central

    Björk, Glenn R.; Huang, Bo; Persson, Olof P.; Byström, Anders S.

    2007-01-01

    Transfer RNAs specific for Gln, Lys, and Glu from all organisms (except Mycoplasma) and organelles have a 2-thiouridine derivative (xm5s2U) as wobble nucleoside. These tRNAs read the A- and G-ending codons in the split codon boxes His/Gln, Asn/Lys, and Asp/Glu. In eukaryotic cytoplasmic tRNAs the conserved constituent (xm5-) in position 5 of uridine is 5-methoxycarbonylmethyl (mcm5). A protein (Tuc1p) from yeast resembling the bacterial protein TtcA, which is required for the synthesis of 2-thiocytidine in position 32 of the tRNA, was shown instead to be required for the synthesis of 2-thiouridine in the wobble position (position 34). Apparently, an ancient member of the TtcA family has evolved to thiolate U34 in tRNAs of organisms from the domains Eukarya and Archaea. Deletion of the TUC1 gene together with a deletion of the ELP3 gene, which results in the lack of the mcm5 side chain, removes all modifications from the wobble uridine derivatives of the cytoplasmic tRNAs specific for Gln, Lys, and Glu, and is lethal to the cell. Since excess of the unmodified form of these three tRNAs rescued the double mutant elp3 tuc1, the primary function of mcm5s2U34 seems to be to improve the efficiency to read the cognate codons rather than to prevent mis-sense errors. Surprisingly, overexpression of the mcm5s2U-lacking tRNALys alone was sufficient to restore viability of the double mutant. PMID:17592039

  11. Evolutionarily conserved proteins MnmE and GidA catalyze the formation of two methyluridine derivatives at tRNA wobble positions

    PubMed Central

    Moukadiri, Ismaïl; Prado, Silvia; Piera, Julio; Velázquez-Campoy, Adrián; Björk, Glenn R.; Armengod, M.-Eugenia

    2009-01-01

    The wobble uridine of certain bacterial and mitochondrial tRNAs is modified, at position 5, through an unknown reaction pathway that utilizes the evolutionarily conserved MnmE and GidA proteins. The resulting modification (a methyluridine derivative) plays a critical role in decoding NNG/A codons and reading frame maintenance during mRNA translation. The lack of this tRNA modification produces a pleiotropic phenotype in bacteria and has been associated with mitochondrial encephalomyopathies in humans. In this work, we use in vitro and in vivo approaches to characterize the enzymatic pathway controlled by the Escherichia coli MnmE•GidA complex. Surprisingly, this complex catalyzes two different GTP- and FAD-dependent reactions, which produce 5-aminomethyluridine and 5-carboxymethylamino-methyluridine using ammonium and glycine, respectively, as substrates. In both reactions, methylene-tetrahydrofolate is the most probable source to form the C5-methylene moiety, whereas NADH is dispensable in vitro unless FAD levels are limiting. Our results allow us to reformulate the bacterial MnmE•GidA dependent pathway and propose a novel mechanism for the modification reactions performed by the MnmE and GidA family proteins. PMID:19767610

  12. C5-substituents of uridines and 2-thiouridines present at the wobble position of tRNA determine the formation of their keto-enol or zwitterionic forms - a factor important for accuracy of reading of guanosine at the 3'-end of the mRNA codons.

    PubMed

    Sochacka, Elzbieta; Lodyga-Chruscinska, Elzbieta; Pawlak, Justyna; Cypryk, Marek; Bartos, Paulina; Ebenryter-Olbinska, Katarzyna; Leszczynska, Grazyna; Nawrot, Barbara

    2017-01-13

    Modified nucleosides present in the wobble position of the tRNA anticodons regulate protein translation through tuning the reading of mRNA codons. Among 40 of such nucleosides, there are modified uridines containing either a sulfur atom at the C2 position and/or a substituent at the C5 position of the nucleobase ring. It is already evidenced that tRNAs with 2-thiouridines at the wobble position preferentially read NNA codons, while the reading mode of the NNG codons by R5U/R5S2U-containing anticodons is still elusive. For a series of 18 modified uridines and 2-thiouridines, we determined the pKa values and demonstrated that both modifying elements alter the electron density of the uracil ring and modulate the acidity of their N3H proton. In aqueous solutions at physiological pH the 2-thiouridines containing aminoalkyl C5-substituents are ionized in ca. 50%. The results, confirmed also by theoretical calculations, indicate that the preferential binding of the modified units bearing non-ionizable 5-substituents to guanosine in the NNG codons may obey the alternative C-G-like (Watson-Crick) mode, while binding of those bearing aminoalkyl C5-substituents (protonated under physiological conditions) and especially those with a sulfur atom at the C2 position, adopt a zwitterionic form and interact with guanosine via a 'new wobble' pattern.

  13. Familial dysautonomia (FD) patients have reduced levels of the modified wobble nucleoside mcm(5)s(2)U in tRNA.

    PubMed

    Karlsborn, Tony; Tükenmez, Hasan; Chen, Changchun; Byström, Anders S

    2014-11-21

    Familial dysautonomia (FD) is a recessive neurodegenerative genetic disease. FD is caused by a mutation in the IKBKAP gene resulting in a splicing defect and reduced levels of full length IKAP protein. IKAP homologues can be found in all eukaryotes and are part of a conserved six subunit protein complex, Elongator complex. Inactivation of any Elongator subunit gene in multicellular organisms cause a wide range of phenotypes, suggesting that Elongator has a pivotal role in several cellular processes. In yeast, there is convincing evidence that the main role of Elongator complex is in formation of modified wobble uridine nucleosides in tRNA and that their absence will influence translational efficiency. To date, no study has explored the possibility that FD patients display defects in formation of modified wobble uridine nucleosides as a consequence of reduced IKAP levels. In this study, we show that brain tissue and fibroblast cell lines from FD patients have reduced levels of the wobble uridine nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U). Our findings indicate that FD could be caused by inefficient translation due to lower levels of wobble uridine nucleosides. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Uridine Triacetate

    MedlinePlus

    ... of your medications or monitor you carefully for side effects.tell your doctor if you have any medical ... Uridine triacetate may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: vomiting nausea diarrhea Uridine triacetate ...

  15. Does Venus wobble

    NASA Technical Reports Server (NTRS)

    Yoder, C. F.; Ward, W. R.

    1979-01-01

    The free wobble damping time for Venus due to solar tides and rotational flexing is found to be approximately 700,000 times Q sub omega years, where Q sub omega is the dissipation function associated with the wobble frequency. The slow spin and expected small (nonhydrostatic) J2 predict a very long wobble period of about 100,000 years. As a result, a simple scaling of the earth's Chandler wobble excitation rate to that of Venus suggests that an appreciable wobble could exist. Detection (or lack thereof) of a free wobble may thus place constraints on the dynamic activity (e.g., mantle convection, Venusquakes, etc.) of the Venus interior.

  16. Divalent metal ion binding to a conserved wobble pair defining the upstream site of cleavage of group I self-splicing introns.

    PubMed Central

    Allain, F H; Varani, G

    1995-01-01

    The upstream site of cleavage of all group I self-splicing introns is identified by an absolutely conserved U.G base pair. Although a wobble C.A pair can substitute the U.G pair, all other combinations of nucleotides at this position abolish splicing, suggesting that it is an unusual RNA structure, rather than sequence, that is recognized by the catalytic intron core. RNA enzymes are metalloenzymes, and divalent metal ion binding may be an important requirement for splice site recognition and catalysis. The paramagnetic broadening of NMR resonances upon manganese binding at specific sites was used to probe the interaction between divalent metal ions and an oligonucleotide model of a group I intron ribozyme substrate. Unlike previous studies in which only imino proton resonances were monitored, we have used isotopically labelled RNA and a set of complete spectral assignments to identify the location of the divalent metal binding site with much greater detail than previously possible. Two independent metal binding sites were identified for this oligonucleotide. A first metal binding site is located in the major groove of the three consecutive G.C base pairs at the end of double helical stem. A second site is found in the major groove of the RNA double helix in the vicinity of the U.G base pair. These results suggest that metal ion coordination (or a metal bridge) and tertiary interactions identified biochemically, may be used by group I intron ribozymes for substrate recognition. Images PMID:7885828

  17. A mini-RNA containing the tetraloop, wobble-pair and loop E motifs of the central conserved region of potato spindle tuber viroid is processed into a minicircle.

    PubMed

    Schrader, O; Baumstark, T; Riesner, D

    2003-02-01

    A Mini-RNA from potato spindle tuber viroid (PSTVd) was constructed specifically for cleavage and ligation to circles in vitro. It contains the C-domain with the so-called central conserved region (CCR) of PSTVd with a 17 nt duplication in the upper strand and hairpin structures at the left and rights ends of the secondary structure. The CCR was previously shown to be essential for processing of in vitro transcripts. When folded under conditions which favor formation of a kinetically controlled conformation and incubated in a potato nuclear extract, the Mini-RNA is cleaved correctly at the 5'- and the 3'-end and ligated to a circle. Thus, the CCR obviously contains all structural and functional requirements for correct processing and therefore may be regarded as 'processing domain' of PSTVd. Using the Mini-RNA as a model substrate, the structural and functional relevance of its conserved non-canonical motifs GAAA tetraloop, loop E and G:U wobble base pair were studied by mutational analysis. It was found that (i) the conserved GAAA tetraloop is essential for processing by favoring the kinetically controlled conformation, (ii) a G:U wobble base pair at the 5'-cleavage site contributes to its correct recognition and (iii) an unpaired nucleotide in loop E, which is different from the corresponding nucleotide in the conserved loop E motif, is essential for ligation of the 5'- with the 3'-end. Hence all three structural motifs are functional elements for processing in a potato nuclear extract.

  18. Transverse Wobbling in 135Pr

    NASA Astrophysics Data System (ADS)

    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.

    2015-02-01

    A pair of transverse wobbling bands is observed in the nucleus 135Pr . The wobbling is characterized by Δ I =1 , E 2 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.

  19. How to Be Wobbly

    ERIC Educational Resources Information Center

    Goldsworthy, Anne

    2007-01-01

    "Primary Science Review's" original "Wobbly Bits" series of articles was born back in 1997, after a conversation about this problem at a meeting of the ASE Primary Committee. The conversation turned to primary science teachers' scientific learning journeys. Each one of them could recount a story where they had completely misunderstood an aspect of…

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

    PubMed

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

    2014-06-01

    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 mcm(5) and ncm(5) 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.

  1. Feynman's wobbling plate

    NASA Astrophysics Data System (ADS)

    Tuleja, Slavomir; Gazovic, Boris; Tomori, Alexander; Hanc, Jozef

    2007-03-01

    In the book Surely You Are Joking, Mr. Feynman! Richard Feynman tells a story of a Cornell cafeteria plate being tossed into the air. As the plate spun, it wobbled. Feynman noticed a relation between the two motions. He solved the motion of the plate by using the Lagrangian approach. This solution didn't satisfy him. He wanted to understand the motion of the plate by analyzing the motion of its individual particles and the forces acting on them. He was successful, but he didn't tell us how he did it. We provide an elementary explanation for the two-to-one ratio of wobble to spin frequencies, based on an analysis of the motion of the particles and the forces acting on them. We also demonstrate the power of numerical simulation and computer animation to provide insight into a physical phenomenon and guidance on how to do the analysis.

  2. Anharmonicity in nuclear wobbling motion

    SciTech Connect

    Oi, M.

    2007-09-15

    An unexpected strong anharmonicity was observed in the wobbling spectrum in {sup 163}Lu. In an attempt to understand what causes the deviation from the original wobbling model by Bohr and Mottelson, an analysis is presented using several different approaches, such as exact diagonalization, a semiclassical model to deal with anharmonic wobbling motion, and a microscopic method based on the self-consistent cranking calculation.

  3. Collective Hamiltonian for wobbling modes

    NASA Astrophysics Data System (ADS)

    Chen, Q. B.; Zhang, S. Q.; Zhao, P. W.; Meng, J.

    2014-10-01

    The simple, longitudinal, and transverse wobblers are systematically studied within the framework of a collective Hamiltonian, where the collective potential and mass parameter included are obtained based on the tilted axis cranking approach. Solving the collective Hamiltonian by diagonalization, the energies and the wave functions of the wobbling states are obtained. The obtained results are compared with those by the harmonic approximation formula and particle rotor model. The wobbling energies calculated by the collective Hamiltonian are closer to the exact solutions by the particle rotor model than the harmonic approximation formula. It is confirmed that the wobbling frequency increases with the rotational frequency in simple and longitudinal wobbling motions while decreases in transverse wobbling motion. These variation trends are related to the stiffness of the collective potential in the collective Hamiltonian.

  4. 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.

  5. The Earth's variable Chandler wobble

    NASA Astrophysics Data System (ADS)

    Bizouard, C.; Remus, F.; Lambert, S. B.; Seoane, L.; Gambis, D.

    2011-02-01

    Aims: We investigated the causes of the Earth's Chandler wobble variability over the past 60 years. Our approach is based on integrating of the atmospheric and oceanic angular momentum computed by global circulation models. We directly compared the result of the integration with the Earth's pole coordinate observed by precise astrometric, space, and geodetic techniques. This approach differs from the traditional approach in which the observed polar motion is transformed into a so-called geodetic excitation function, and compared afterwards with the angular momentum of the external geophysical fluid layers. Methods: In the time domain, we integrated the atmospheric angular momentum time series from the National Center for Environmental Prediction/National Center for Atmospheric Research Reanalysis project and the oceanic angular momentum data from the ECCO consortium. We extracted the Chandler wobble from this modeled polar motion by singular spectrum analysis, and compared it with the Chandler wobble extracted from the observed polar motion given by the International Earth Rotation and Reference Systems Service data. Results: We showed that the combination of the atmosphere and the oceans explains most of the observed Chandler wobble variations, and is consistent with results reported in the literature and obtained with the traditional approach. Our approach allows one to appreciate the separate contributions of the atmosphere and the oceans to the various bumps and valleys observed in the Chandler wobble. Though the atmosphere explains the Chandler wobble amplitude variations between 1949 and 1970, the reexcitation of the Chandler wobble that begins in the 1980s, after a minimum around 1970, and that reaches its maximum in the late 1990s is due to the oceans, while the atmospheric contribution remains stable within the same period.

  6. 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

  7. Spin, Wobble, and Nutation

    NASA Astrophysics Data System (ADS)

    Gross, Richard; Schuh, Harald; Huang, Cheng-li

    2011-01-01

    Observing and Understanding Earth Rotation: A Joint GGOS/IAU Science Workshop; Shanghai, China, 25-28 October 2010 ; The Earth rotates about its axis once a day, but it does not do so uniformly. Instead, the rate of rotation fluctuates by as much as a millisecond a day, the Earth wobbles as it rotates because the Earth's mass is not balanced about its rotation axis, and the Earth's rotation axis precesses and nutates in space. These variations in the Earth's rotation are caused by processes acting within the interior of the Earth such as glacial isostatic adjustment and core-mantle interaction torques, by processes acting at the surface of the Earth such as fluctuations in the transport of mass within the atmosphere and oceans, and by processes acting external to the Earth such as torques due to the gravitational attraction of the Sun, the Moon, and the planets. These and other aspects of the Earth's rotation were discussed at a recent workshop in China that attracted 90 participants from 12 countries. The workshop was jointly organized by the Global Geodetic Observing System (GGOS) of the International Association of Geodesy and Commission 19 (Rotation of the Earth) of the International Astronomical Union (IAU). The objectives of the workshop were to (1) assess our ability to observe the Earth's time-varying rotation, (2) assess our understanding of the causes of the observed variations, (3) assess the consistency of Earth rotation observations with global gravity and shape observations, and (4) explore methods of combining rotation, gravity, and shape observations to gain greater understanding of the processes causing them to change on both the Earth and other planets, like Mars.

  8. High Frequency Chandler Wobble Excitation

    NASA Astrophysics Data System (ADS)

    Seitz, F.; Stuck, J.; Thomas, M.

    2003-04-01

    Variations of Earth rotation on sub-daily to secular timescales are caused by mass redistributions in the Earth system as a consequence of geophysical processes and gravitational influences. Forced oscillations of polar motion are superposed by free oscillations of the Earth, i.e. the Chandler wobble and the free core nutation. In order to study the interactions between externally induced polar motion and the Earth's free oscillations, a non-linear gyroscopic model has been developed. In most of the former investigations on polar motion, the Chandler wobble is introduced as a damped oscillation with predetermined frequency and amplitude. However, as the effect of rotational deformation is a backcoupling mechanism of polar motion on the Earth's rotational dynamics, both period and amplitude of the Chandler wobble are time-dependent when regarding additional excitations from, e.g., atmospheric or oceanic mass redistributions. The gyroscopic model is free of any explicit information concerning amplitude, phase, and period of free oscillations. The characteristics of the Earth's free oscillation is reproduced by the model from rheological and geometrical parameters and rotational deformation is taken into account. This enables to study the time variable Chandler oscillation when the gyro is forced with atmospheric and oceanic angular momentum from the global atmospheric ECHAM3-T21 general circulation model together with the ocean model for circulation and tides OMCT driven by ECHAM including surface pressure. Besides, mass redistributions in the Earth's body due to gravitational and loading deformations are regarded and external torques exerted by Moon and Sun are considered. The numerical results of the gyro are significantly related with the geodetically observed time series of polar motion published by the IERS. It is shown that the consistent excitation is capable to counteract the damping and thus to maintain the Chandler amplitude. Spectral analyses of the ECHAM

  9. Collective Hamiltonian for Chiral and Wobbling Modes

    NASA Astrophysics Data System (ADS)

    Chen, Q. B.; Zhang, S. Q.; Zhao, P. W.; Jolos, R. V.; Meng, J.

    The recent progresses of the collective Hamiltonian for chiral and wobbling modes are briefly introduced. The collective Hamiltonian is constructed from the collective potential and mass parameter obtained in the tilted axis cranking approach. The collective Hamiltonian can reproduce the exact solutions by the particle rotor model very well for both chiral and wobbling modes.

  10. 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.

  11. Multiple inner core wobbles in a simple Earth model with inviscid core

    NASA Astrophysics Data System (ADS)

    Rogister, Yves

    2010-01-01

    The inner core wobble (ICW) is the chandler wobble of the inner core. Its predicted period for the PREM model is about 7.5 years, based upon the resolution of the Liouville equations of conservation of angular momentum. Here, solving the local equation of conservation of linear momentum with a truncated chain that couples the toroidal and spheroidal displacement fields, the ICW is computed for a model made up of three homogeneous layers: an incompressible liquid outer core and rigid mantle and inner core. Contrary to the angular momentum approach, as implemented up to now, that provides a single ICW, the linear momentum approach shows that the dynamics of the neutrally stratified outer core may generate a family of ICWs with periods ranging from a few dozens to thousands of days. The mode with the largest wobble amplitude in the inner core has a period close to that obtained with the angular momentum approach.

  12. Wobbling geometry in a simple triaxial rotor

    NASA Astrophysics Data System (ADS)

    Shi, Wen-Xian; Chen, Qi-Bo

    2015-05-01

    The spectroscopic properties and angular momentum geometry of the wobbling motion of a simple triaxial rotor are investigated within the triaxial rotor model. The obtained exact solutions of energy spectra and reduced quadrupole transition probabilities are compared to the approximate analytic solutions from the harmonic approximation formula and Holstein-Primakoff formula. It is found that the low lying wobbling bands can be well described by the analytic formulae. The evolution of the angular momentum geometry as well as the K-distribution with respect to the rotation and the wobbling phonon excitation are studied in detail. It is demonstrated that with the increase of the wobbling phonon number, the triaxial rotor changes its wobbling motions along the axis with the largest moment of inertia to the axis with the smallest moment of inertia. In this process, a specific evolutionary track that can be used to depict the motion of a triaxial rotating nucleus is proposed. Supported by President's Undergraduate Research Fellowship (PURF), Peking University, Major State 973 Program of China (2013CB834400), National Natural Science Foundation of China (11175002, 11335002, 11375015, 11345004, 11461141002), National Fund for Fostering Talents of Basic Science (NFFTBS) (J1103206) and Research Fund for the Doctoral Program of Higher Education (20110001110087)

  13. 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.

  14. Chandler wobbles and the geomagnetic field

    NASA Astrophysics Data System (ADS)

    Flodmark, Stig; Davstad, K.

    1986-11-01

    Paleomagnetic motion of the magnetic pole is explained by angular momentum balance between the magnetic field, inner core, outer core, and mantle. The Chandler wobbles are explained as a nutation of the mantle and crust, caused by transfer of angular momentum between the core and mantle. Evidence is found for the atmosphere not to be fully responsible for the annual oscillation period of the Chandler wobbles. The main reasons for the principal periods of 12 and 14 months are found to be the flattenings of mantle and core, respectively. The fluid core rotates collectively, as a consequence of globally coworking long-distance electromagnetic coupling. Short-distance forces may locally displace fluid core material without essentially deforming its ellipsoid of inertia. The longitudinal polar drifts of the mantle and outer core are also explained by core-mantle interaction. The core is found to force the Chandler period on the mantle, and it has high wobbling energy in comparison with the mantle.

  15. Uridine Prevents Fenofibrate-Induced Fatty Liver

    PubMed Central

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

    2014-01-01

    Uridine, a pyrimidine nucleoside, can modulate liver lipid metabolism although its specific acting targets have not been identified. Using mice with fenofibrate-induced fatty liver as a model system, the effects of uridine on liver lipid metabolism are examined. At a daily dosage of 400 mg/kg, fenofibrate treatment causes reduction of liver NAD+/NADH ratio, induces hyper-acetylation of peroxisomal bifunctional enzyme (ECHD) and acyl-CoA oxidase 1 (ACOX1), and induces excessive accumulation of long chain fatty acids (LCFA) and very long chain fatty acids (VLCFA). Uridine co-administration at a daily dosage of 400 mg/kg raises NAD+/NADH ratio, inhibits fenofibrate-induced hyper-acetylation of ECHD, ACOX1, and reduces accumulation of LCFA and VLCFA. Our data indicates a therapeutic potential for uridine co-administration to prevent fenofibrate-induced fatty liver. PMID:24475249

  16. 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.

  17. 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.

  18. An adipo-biliary-uridine axis that regulates energy homeostasis.

    PubMed

    Deng, Yingfeng; Wang, Zhao V; Gordillo, Ruth; An, Yu; Zhang, Chen; Liang, Qiren; Yoshino, Jun; Cautivo, Kelly M; De Brabander, Jef; Elmquist, Joel K; Horton, Jay D; Hill, Joseph A; Klein, Samuel; Scherer, Philipp E

    2017-03-17

    Uridine, a pyrimidine nucleoside present at high levels in the plasma of rodents and humans, is critical for RNA synthesis, glycogen deposition, and many other essential cellular processes. It also contributes to systemic metabolism, but the underlying mechanisms remain unclear. We found that plasma uridine levels are regulated by fasting and refeeding in mice, rats, and humans. Fasting increases plasma uridine levels, and this increase relies largely on adipocytes. In contrast, refeeding reduces plasma uridine levels through biliary clearance. Elevation of plasma uridine is required for the drop in body temperature that occurs during fasting. Further, feeding-induced clearance of plasma uridine improves glucose metabolism. We also present findings that implicate leptin signaling in uridine homeostasis and consequent metabolic control and thermoregulation. Our results indicate that plasma uridine governs energy homeostasis and thermoregulation in a mechanism involving adipocyte-dependent uridine biosynthesis and leptin signaling.

  19. On modulations of the Chandler wobble excitation

    NASA Astrophysics Data System (ADS)

    Zotov, L.; Bizouard, C.

    2012-12-01

    We derive the Chandler wobble excitation from the polar motion (PM) observations by using the Panteleev corrective filtering. The latter method is based on inversion of the Euler-Liouville equation, with additional filtering in the Chandler frequency band. The excitation reconstruction reveals amplitude changes different from the one observed in the Chandler wobble itself. Their main feature, well observable over the length of the day (LOD), is the presence of a 18.6-year amplitude modulation synchronous with the lunar orbital precession cycle and tidal effects. The filtering of oceanic and atmospheric excitation in the Chandler frequency band also reveals a coherent 18.6-year oceanic pattern. Most probably the ocean provide a channel for the tidal energy transfer.

  20. 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.

  1. X-ray structures of uridine phosphorylase from Vibrio cholerae in complexes with uridine, thymidine, uracil, thymine, and phosphate anion: Substrate specificity of bacterial uridine phosphorylases

    NASA Astrophysics Data System (ADS)

    Prokofev, I. I.; Lashkov, A. A.; Gabdulkhakov, A. G.; Balaev, V. V.; Seregina, T. A.; Mironov, A. S.; Betzel, C.; Mikhailov, A. M.

    2016-11-01

    In many types of human tumor cells and infectious agents, the demand for pyrimidine nitrogen bases increases during the development of the disease, thus increasing the role of the enzyme uridine phosphorylase in metabolic processes. The rational use of uridine phosphorylase and its ligands in pharmaceutical and biotechnology industries requires knowledge of the structural basis for the substrate specificity of the target enzyme. This paper summarizes the results of the systematic study of the three-dimensional structure of uridine phosphorylase from the pathogenic bacterium Vibrio cholerae in complexes with substrates of enzymatic reactions—uridine, phosphate anion, thymidine, uracil, and thymine. These data, supplemented with the results of molecular modeling, were used to consider in detail the structural basis for the substrate specificity of uridine phosphorylases. It was shown for the first time that the formation of a hydrogen-bond network between the 2'-hydroxy group of uridine and atoms of the active-site residues of uridine phosphorylase leads to conformational changes of the ribose moiety of uridine, resulting in an increase in the reactivity of uridine compared to thymidine. Since the binding of thymidine to residues of uridine phosphorylase causes a smaller local strain of the β-N1-glycosidic bond in this the substrate compared to the uridine molecule, the β-N1-glycosidic bond in thymidine is more stable and less reactive than that in uridine. It was shown for the first time that the phosphate anion, which is the second substrate bound at the active site, interacts simultaneously with the residues of the β5-strand and the β1-strand through hydrogen bonding, thus securing the gate loop in a conformation

  2. 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.

  3. A Xanthomonas uridine 5'-monophosphate transferase inhibits plant immune kinases.

    PubMed

    Feng, Feng; Yang, Fan; Rong, Wei; Wu, Xiaogang; Zhang, Jie; Chen, She; He, Chaozu; Zhou, Jian-Min

    2012-04-15

    Plant innate immunity is activated on the detection of pathogen-associated molecular patterns (PAMPs) at the cell surface, or of pathogen effector proteins inside the plant cell. Together, PAMP-triggered immunity and effector-triggered immunity constitute powerful defences against various phytopathogens. Pathogenic bacteria inject a variety of effector proteins into the host cell to assist infection or propagation. A number of effector proteins have been shown to inhibit plant immunity, but the biochemical basis remains unknown for the vast majority of these effectors. Here we show that the Xanthomonas campestris pathovar campestris type III effector AvrAC enhances virulence and inhibits plant immunity by specifically targeting Arabidopsis BIK1 and RIPK, two receptor-like cytoplasmic kinases known to mediate immune signalling. AvrAC is a uridylyl transferase that adds uridine 5'-monophosphate to and conceals conserved phosphorylation sites in the activation loop of BIK1 and RIPK, reducing their kinase activity and consequently inhibiting downstream signalling.

  4. Signal detection techniques applied to the Chandler wobble

    SciTech Connect

    Gross, R.S.

    1985-10-10

    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. 16 references, 11 figures, 1 table.

  5. 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.

  6. The source of the variable Chandler wobble

    NASA Astrophysics Data System (ADS)

    Bizouard, C.; Lambert, S.; Remus, F.; Seoane, L.; Gambis, D.

    2011-10-01

    In the absence of forcing, the Chandler wobble (CW) would have a period of 430.3 days, and would lose most of its energy after a few decades because of dissipation in the mantle and in the oceans. Observation of the Earth's polar motion, however, reveals a prograde oscillation of which pseudo period can be as far as 20 days from the above value (Vondrák 1988). It gains energy at some epochs (Danjon & Guinot 1954) so that it never disappears. The CW excitation is accounted for, on average, by the atmosphere and oceans (Gross 2000, Brzeziñski & Nastula 2002), but its variability is so far poorly explained. We attempt to interpret it as consequence of the hydro-meteorological forcing, as suggested by Plag (1997), Celaya et al. (1999), and Seitz & Schmidt (2005).

  7. Modified 5-fluorouracil: Uridine phosphorylase inhibitor

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

    5-Fluorouracil (5-FU) is a medication widely used in chemotherapy to treat various types of cancer. Being a substrate for the reverse reaction catalyzed by uridine phosphorylase (UPase), 5-FU serves as a promising prototype molecule (molecular scaffold) for the design of a selective UPase inhibitor that enhances the antitumor activity of 5-FU and exhibits intrinsic cytostatic effects on cancer cells. The chemical formula of the new compound, which binds to the uracil-binding site and, in the presence of a phosphate anion, to the phosphate-binding site of UPase, is proposed and investigated by molecular simulation methods.

  8. Wobbling motion in 135Pr within a collective Hamiltonian

    NASA Astrophysics Data System (ADS)

    Chen, Q. B.; Zhang, S. Q.; Meng, J.

    2016-11-01

    The recently reported wobbling bands in 135Pr are investigated by the collective Hamiltonian, in which the collective parameters, including the collective potential and the mass parameter, are respectively determined from the tilted axis cranking (TAC) model and the harmonic frozen alignment (HFA) formula. It is shown that the experimental energy spectra of both yrast and wobbling bands are well reproduced by the collective Hamiltonian. It is confirmed that the wobbling mode in 135Pr changes from transverse to longitudinal with the rotational frequency. The mechanism of this transition is revealed by analyzing the effective moments of inertia of the three principal axes, and the corresponding variation trend of the wobbling frequency is determined by the softness and shapes of the collective potential.

  9. 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

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

    PubMed

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

    1983-02-11

    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.

  11. Translatory and wobbling micro magnetostrictive actuator

    NASA Astrophysics Data System (ADS)

    Ueno, Toshiyuki; Saito, Chihiro; Imaizumi, Nobuo; Higuchi, Toshiro

    2008-03-01

    We propose a three-DOF magnetostrictive micro actuator using Iron-Gallium alloy (Galfenol). The actuator consists of two parallel beam structure having a Galfenol core, located at either end of a Galfenol rod of 1 mm square cross-section and length 11 mm, with two orthogonal ditches cut down it of width 0.3 mm. Around the resulting prongs are wound, and the prongs are bonded to an iron end cap to close the magnetic circuit. When current is passed through a coil wound round one of the orthogonal parallel beams, the resulting magnetostriction enables the actuator to bend in two directions. In addition, longitudinal displacement with high frequency bandwidth can be generated by excitation of two or of all four coils. Maximum displacements were observed of 8 to 10 μm in bending and 2.2 μm in the longitudinal direction. This actuator is potentially applicable in machining (drilling), positioning, and in a micro-motor using wobbling or translational motion when powered by a small power supply.

  12. Variable forcing of the Chandler wobble

    NASA Astrophysics Data System (ADS)

    Bizouard, Christian

    2010-05-01

    The Chandler wobble (the damped free mode of the rotation axis within the Earth) is strongly irregular, exhibiting amplitude variation up to 100 mas, that is 50% of its mean value. A possible explanation is the variability of the fluid layer excitation at Chandler period (around 433 days). The later is analysed in light of the longest available angular momentum time series of the atmosphere, oceans and land mass water. In contrast with most of the related studies, the geophysical effect on polar motion is computed from the integrated solution of the Euler-Liouville equation. Then the variable effect at the Chandler period is filtered by a sliding window method and compared to the one found in observed polar motion. We show that the Chandler variability mostly originates from the combined atmospheric and oceanic forcing, as estimated from NCEP and ECCO-MIT models respectively. Atmospheric and oceanic processes account for the variable amplitude and phase over years ranging from 1948 to 2008 : decrease of the Chandler amplitude from the 1950's (250 mas) to the 1970's (120 mas), slow increase till mid 1990's (up to 200 mas), and decrease in the first decade of the twenty-first century (present amplitude is 100 mas); the phase variations, less striking, within 40° range, are as well explained. The results we obtained are confirmed by shorter sets of atmospheric and oceanic angular momentum time series.

  13. Black Hole with Wobbling Disk Artist Concept

    NASA Image and Video Library

    2016-07-12

    This artist's impression depicts the accretion disc surrounding a black hole, in which the inner region of the disc precesses. "Precession" means that the orbit of material surrounding the black hole changes orientation around the central object. In these three views, the precessing inner disc shines high-energy radiation that strikes the matter in the surrounding accretion disc. This causes the iron atoms in that disc to emit X-rays, depicted as the glow on the accretion disc to the right (in view a), to the front (in view b) and to the left (in view c) (see Figure 1). In a study published in July 2016, astronomers used data from ESA's XMM-Newton X-ray Observatory and NASA's NuSTAR telescope to measure this "wobble" in X-ray emission from excited iron atoms. Scientists interpreted this as evidence for the Lense-Thirring effect -- a name for the precession phenomenon -- in the strong gravitational field of a black hole. http://photojournal.jpl.nasa.gov/catalog/PIA20697

  14. 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).

  15. Crystal structure of acceptor stem of tRNA(Ala) from Escherichia coli shows unique G.U wobble base pair at 1.16 A resolution.

    PubMed Central

    Mueller, U; Schübel, H; Sprinzl, M; Heinemann, U

    1999-01-01

    The acceptor stem of Escherichia coli tRNA(Ala), rGGGGCUA.rUAGCUCC (ALAwt), contains the main identity element for the correct aminoacylation by the alanyl tRNA synthetase. The presence of a G3.U70 wobble base pair is essential for the specificity of this reaction, but there is a debate whether direct minor-groove contact with the 2-amino group of G3 or a distortion of the acceptor stem induced by the wobble pair is the critical feature recognized by the synthetase. We here report the structure analysis of ALAwt at near-atomic resolution using twinned crystals. The crystal lattice is stabilized by a novel strontium binding motif between two cis-diolic O3'-terminal riboses. The two independent molecules in the asymmetric unit of the crystal show overall A-RNA geometry. A comparison with the crystal structure of the G3-C70 mutant of the acceptor stem (ALA(C70)) determined at 1.4 A exhibits a modulation in ALAwt of helical twist and slide due to the wobble base pair, but no recognizable distortion of the helix fragment distant from the wobble base pair. We suggest that a highly conserved hydration pattern in both grooves around the G3.U70 wobble base pair may be functionally significant. PMID:10334337

  16. 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. © The Author 2015. Published by Oxford University Press on behalf of

  17. Uridine phosphorylase in biomedical, structural, and functional aspects: A review

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

    The activation of xenobiotics often causes malignant tumor cells to resist chemotherapeutic treatment. Uridine phosphorylase is the key enzyme of pyrimidine metabolism and catalyzes the reversible phosphorylation of uridine with the formation of uracil and ribose-1-phosphate. High-selectivity anticancer agents based on uridine phosphorylase inhibitors are promising for treating both oncological and infection diseases. New medicinal preparations can be predicted and rationally developed only on the basis of detailed biomedical, structural, and functional knowledge about the biomacromolecular target enzyme-drug complex.

  18. Analysis of the perturbed Chandler wobble of the Earth pole

    NASA Astrophysics Data System (ADS)

    Markov, Yu. G.; Perepelkin, V. V.; Filippova, A. S.

    2017-06-01

    Based on the model of a viscoelastic rigid body for the deformable Earth, we investigate the behavior of the main component of the perturbed Earth pole oscillation process, the Chandler wobble. An amplitude- frequency analysis of the perturbed Chandler wobble of the Earth pole due to the precessional motion of the lunar orbit is provided. The parameters of the complex dynamical process that describes the mutual orientation of the Earth's instantaneous rotation axis, the axis of its figure, and its angular momentum vector are studied qualitatively. Using a numerical-analytical approach, we consider the possibilities for identifying the Chandler wobble parameters and fitting the developed refined theoretical model to the real trajectory measurements of the Earth pole.

  19. Stochastic modeling of the Chandler wobble and its excitation

    NASA Astrophysics Data System (ADS)

    Brzezinski, A.; Rajner, M.

    2012-12-01

    The Chandler wobble (CW) is the most important rotational eigenmode of the Earth. Its parameters, the frequency F (or, equivalently, the period T) and the quality factor Q should be known as best as possible because 1) they appear in the equation of polar motion, and 2) they are closely related to various geophysical parameters. Here we report an attempt to derive improved estimate of the CW parameters. We apply stochastic models to express the free wobble excitation and the measurements noise. These models are used to derive the state-space formulation which is the base for application of the Kalman filter for analysis of the related observations. The Chandler wobble parameters are derived either from analysis of the polar motion data alone or from simultaneous processing of polar motion and geophysical excitation data. Our estimates of F and Q are finally compared to the earlier results.

  20. Quadrupole moments of wobbling excitations in 163Lu

    SciTech Connect

    Gorgen, A.; Clark, R.M.; Cromaz, M.; Fallon, P.; Hagemann, G.B.; Hubel, H.; Lee, I.Y.; Macchiavelli, A.O.; Sletten, G.; Ward, D.; Bengtsson, R.

    2004-01-01

    Lifetimes of states in the triaxial strongly deformed bands of {sup 163}Lu have been measured in a Gammasphere experiment using the Doppler-shift attenuation method. The bands are interpreted as wobbling-phonon excitations from the characteristic electromagnetic properties of the transitions connecting the bands. Quadrupole moments were extracted for the 0-phonon yrast band and, for the first time, for the 1-phonon wobbling band. The very similar results found for both bands suggest a similar intrinsic structure confirming the wobbling interpretation. While the in-band quadrupole moments for the bands show a decreasing trend towards higher spin, the strength of the inter-band transitions remains constant. Both features can be understood by a small increase in triaxiality towards higher spin. Such a change in triaxiality is also found in cranking calculations, to which the experimental results are compared.

  1. 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.

  2. 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.

  3. [A pharmacological analysis of the anxiolytic activity of uridine].

    PubMed

    Karkishchenko, N N; Khaĭtin, M I; Simkina, Iu N

    1991-01-01

    The effects of prazosin (0.6 and 3 mg/kg), propranolol (5 mg/kg), haloperidol (0.1 and 0.5 mg/kg) and ciproheptaline (0.3 and 0.6 mg/kg) on the anxiolytic (anticonflict) action of a pyrimidine ribonucleoside uridine, a hypothetic endogenic regulator of anxiety states were studied in the experiments on male CBWA mice. It was found that the degree of the anxiolytic effect of uridine decreases at the blockade of alpha 1, beta 2, D2 and H1-receptors and significantly increases at the blockade of 5-HT2-receptors. This suggests the involvement of the mentioned receptors in the processes of realization of uridine anxiolytic activity as well as the presence of the central serotonin-negative component in the mechanisms of action of uridine.

  4. The nucleoside uridine isolated in the gas phase.

    PubMed

    Peña, Isabel; Cabezas, Carlos; Alonso, José L

    2015-03-02

    Herein we present the first experimental observation of the isolated nucleoside uridine, placed in the gas phase by laser ablation and characterized by Fourier transform (FT) microwave techniques. Free from the bulk effects of their native environments, anti/C2'-endo-g+ conformation has been revealed as the most stable form of uridine. Intramolecular hydrogen bonds involving uracil and ribose moieties have been found to play an important role in the stabilization of the nucleoside.

  5. The Nucleoside Uridine Isolated in the Gas Phase**

    PubMed Central

    Peña, Isabel; Cabezas, Carlos; Alonso, José L.

    2016-01-01

    Herein we present the first experimental observation of the isolated nucleoside uridine, placed in the gas phase by laser ablation and characterized by Fourier transform microwave techniques. Free from the bulk effects of their native environments, anti/C2’-endo-g+ conformation has been revealed as the most stable form of uridine. Intramolecular hydrogen bonds involving uracil and ribose moieties have been found to play an important role in the stabilization of the nucleoside. PMID:25683559

  6. 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.

  7. Bistable gaits and wobbling induced by pedestrian-bridge interactions

    NASA Astrophysics Data System (ADS)

    Belykh, Igor V.; Jeter, Russell; Belykh, Vladimir N.

    2016-11-01

    Several modern footbridges around the world have experienced large lateral vibrations during crowd loading events. The onset of large-amplitude bridge wobbling has generally been attributed to crowd synchrony; although, its role in the initiation of wobbling has been challenged. To study the contribution of a single pedestrian into overall, possibly unsynchronized, crowd dynamics, we use a bio-mechanically inspired inverted pendulum model of human balance and analyze its bi-directional interaction with a lively bridge. We first derive analytical estimates on the frequency of pedestrian's lateral gait in the absence of bridge motion. Then, through theory and numerics, we demonstrate that pedestrian-bridge interactions can induce bistable lateral gaits such that switching between the gaits can initiate large-amplitude wobbling. We also analyze the role of stride frequency and the pedestrian's mass in hysteretic transitions between the two types of wobbling. Our results support a claim that the overall foot force of pedestrians walking out of phase can cause significant bridge vibrations.

  8. A cycloidal wobble motor driven by shape memory alloy wires

    NASA Astrophysics Data System (ADS)

    Hwang, Donghyun; Higuchi, Toshiro

    2014-05-01

    A cycloidal wobble motor driven by shape memory alloy (SMA) wires is proposed. In realizing a motor driving mechanism well known as a type of reduction system, a cycloidal gear mechanism is utilized. It facilitates the achievement of bidirectional continuous rotation with high-torque capability, based on its high efficiency and high reduction ratio. The applied driving mechanism consists of a pin/roller based annular gear as a wobbler, a cycloidal disc as a rotor, and crankshafts to guide the eccentric wobbling motion. The wobbling motion of the annular gear is generated by sequential activation of radially phase-symmetrically placed SMA wires. Consequently the cycloidal disc is rotated by rolling contact based cycloidal gearing between the wobbler and the rotor. In designing the proposed motor, thermomechanical characterization of an SMA wire biased by extension springs is experimentally performed. Then, a simplified geometric model for the motor is devised to conduct theoretical assessment of design parametric effects on structural features and working performance. With consideration of the results from parametric analysis, a functional prototype three-phase motor is fabricated to carry out experimental verification of working performance. The observed experimental results including output torque, rotational speed, bidirectional positioning characteristic, etc obviously demonstrate the practical applicability and potentiality of the wobble motor.

  9. 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…

  10. Bistable gaits and wobbling induced by pedestrian-bridge interactions.

    PubMed

    Belykh, Igor V; Jeter, Russell; Belykh, Vladimir N

    2016-11-01

    Several modern footbridges around the world have experienced large lateral vibrations during crowd loading events. The onset of large-amplitude bridge wobbling has generally been attributed to crowd synchrony; although, its role in the initiation of wobbling has been challenged. To study the contribution of a single pedestrian into overall, possibly unsynchronized, crowd dynamics, we use a bio-mechanically inspired inverted pendulum model of human balance and analyze its bi-directional interaction with a lively bridge. We first derive analytical estimates on the frequency of pedestrian's lateral gait in the absence of bridge motion. Then, through theory and numerics, we demonstrate that pedestrian-bridge interactions can induce bistable lateral gaits such that switching between the gaits can initiate large-amplitude wobbling. We also analyze the role of stride frequency and the pedestrian's mass in hysteretic transitions between the two types of wobbling. Our results support a claim that the overall foot force of pedestrians walking out of phase can cause significant bridge vibrations.

  11. 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…

  12. 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.

  13. Uridine-Ribohydrolase Is a Key Regulator in the Uridine Degradation Pathway of Arabidopsis[W

    PubMed Central

    Jung, Benjamin; Flörchinger, Martin; Kunz, Hans-Henning; Traub, Michaela; Wartenberg, Ruth; Jeblick, Wolfgang; Neuhaus, H. Ekkehard; Möhlmann, Torsten

    2009-01-01

    Nucleoside degradation and salvage are important metabolic pathways but hardly understood in plants. Recent work on human pathogenic protozoans like Leishmania and Trypanosoma substantiates an essential function of nucleosidase activity. Plant nucleosidases are related to those from protozoans and connect the pathways of nucleoside degradation and salvage. Here, we describe the cloning of such an enzyme from Arabidopsis thaliana, Uridine-Ribohydrolase 1 (URH1) and the characterization by complementation of a yeast mutant. Furthermore, URH1 was synthesized as a recombinant protein in Escherichia coli. The pure recombinant protein exhibited highest hydrolase activity for uridine, followed by inosine and adenosine, the corresponding Km values were 0.8, 1.4, and 0.7 mM, respectively. In addition, URH1 was able to cleave the cytokinin derivative isopentenyladenine-riboside. Promoter β-glucuronidase fusion studies revealed that URH1 is mainly transcribed in the vascular cells of roots and in root tips, guard cells, and pollen. Mutants expressing the Arabidopsis enzyme or the homolog from rice (Oryza sativa) exhibit resistance toward toxic fluorouridine, fluorouracil, and fluoroorotic acid, providing clear evidence for a pivotal function of URH1 as regulative in pyrimidine degradation. Moreover, mutants with increased and decreased nucleosidase activity are delayed in germination, indicating that this enzyme activity must be well balanced in the early phase of plant development. PMID:19293370

  14. tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding.

    PubMed

    Rezgui, Vanessa Anissa Nathalie; Tyagi, Kshitiz; Ranjan, Namit; Konevega, Andrey L; Mittelstaet, Joerg; Rodnina, Marina V; Peter, Matthias; Pedrioli, Patrick G A

    2013-07-23

    tRNA modifications are crucial to ensure translation efficiency and fidelity. In eukaryotes, the URM1 and ELP pathways increase cellular resistance to various stress conditions, such as nutrient starvation and oxidative agents, by promoting thiolation and methoxycarbonylmethylation, respectively, of the wobble uridine of cytoplasmic (tK(UUU)), (tQ(UUG)), and (tE(UUC)). Although in vitro experiments have implicated these tRNA modifications in modulating wobbling capacity and translation efficiency, their exact in vivo biological roles remain largely unexplored. Using a combination of quantitative proteomics and codon-specific translation reporters, we find that translation of a specific gene subset enriched for AAA, CAA, and GAA codons is impaired in the absence of URM1- and ELP-dependent tRNA modifications. Moreover, in vitro experiments using native tRNAs demonstrate that both modifications enhance binding of tK(UUU) to the ribosomal A-site. Taken together, our data suggest that tRNA thiolation and methoxycarbonylmethylation regulate translation of genes with specific codon content.

  15. Uridine prevents tamoxifen-induced liver lipid droplet accumulation

    PubMed Central

    2014-01-01

    Background Tamoxifen, an agonist of estrogen receptor, is widely prescribed for the prevention and long-term treatment of breast cancer. A side effect of tamoxifen is fatty liver, which increases the risk for non-alcoholic fatty liver disease. Prevention of tamoxifen-induced fatty liver has the potential to improve the safety of long-term tamoxifen usage. Methods Uridine, a pyrimidine nucleoside with reported protective effects against drug-induced fatty liver, was co-administered with tamoxifen in C57BL/6J mice. Liver lipid levels were evaluated with lipid visualization using coherent anti-Stokes Raman scatting (CARS) microscopy, biochemical assay measurement of triacylglyceride (TAG), and liquid chromatography coupled with mass spectrometry (LC-MS) measurement of membrane phospholipid. Blood TAG and cholesterol levels were measured. Mitochondrial respiration of primary hepatocytes in the presence of tamoxifen and/or uridine was evaluated by measuring oxygen consumption rate with an extracellular flux analyzer. Liver protein lysine acetylation profiles were evaluated with 1D and 2D Western blots. In addition, the relationship between endogenous uridine levels, fatty liver, and tamoxifen administration was evaluated in transgenic mice UPase1−/−and UPase1-TG. Results Uridine co-administration prevented tamoxifen-induced liver lipid droplet accumulation in mice. The most prominent effect of uridine co-administration with tamoxifen was the stimulation of liver membrane phospholipid biosynthesis. Uridine had no protective effect against tamoxifen-induced impairment to mitochondrial respiration of primary hepatocytes or liver TAG and cholesterol export. Uridine had no effect on tamoxifen-induced changes to liver protein acetylation profile. Transgenic mice UPase1−/−with increased pyrimidine salvage activity were protected against tamoxifen-induced liver lipid droplet accumulation. In contrast, UPase1-TG mice with increased pyrimidine catabolism activity had

  16. 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.

  17. Sulfur Modifications of the Wobble U34 in tRNAs and their Intracellular Localization in Eukaryotic Cells.

    PubMed

    Nakai, Yumi; Nakai, Masato; Yano, Takato

    2017-02-18

    The wobble uridine (U34) of transfer RNAs (tRNAs) for two-box codon recognition, i.e., tRNA(Lys)UUU, tRNA(Glu)UUC, and tRNA(Gln)UUG, harbor a sulfur- (thio-) and a methyl-derivative structure at the second and fifth positions of U34, respectively. Both modifications are necessary to construct the proper anticodon loop structure and to enable them to exert their functions in translation. Thio-modification of U34 (s²U34) is found in both cytosolic tRNAs (cy-tRNAs) and mitochondrial tRNAs (mt-tRNAs). Although l-cysteine desulfurase is required in both cases, subsequent sulfur transfer pathways to cy-tRNAs and mt-tRNAs are different due to their distinct intracellular locations. The s²U34 formation in cy-tRNAs involves a sulfur delivery system required for the biosynthesis of iron-sulfur (Fe/S) clusters and certain resultant Fe/S proteins. This review addresses presumed sulfur delivery pathways for the s²U34 formation in distinct intracellular locations, especially that for cy-tRNAs in comparison with that for mt-tRNAs.

  18. Sulfur Modifications of the Wobble U34 in tRNAs and their Intracellular Localization in Eukaryotic Cells

    PubMed Central

    Nakai, Yumi; Nakai, Masato; Yano, Takato

    2017-01-01

    The wobble uridine (U34) of transfer RNAs (tRNAs) for two-box codon recognition, i.e., tRNALysUUU, tRNAGluUUC, and tRNAGlnUUG, harbor a sulfur- (thio-) and a methyl-derivative structure at the second and fifth positions of U34, respectively. Both modifications are necessary to construct the proper anticodon loop structure and to enable them to exert their functions in translation. Thio-modification of U34 (s2U34) is found in both cytosolic tRNAs (cy-tRNAs) and mitochondrial tRNAs (mt-tRNAs). Although l-cysteine desulfurase is required in both cases, subsequent sulfur transfer pathways to cy-tRNAs and mt-tRNAs are different due to their distinct intracellular locations. The s2U34 formation in cy-tRNAs involves a sulfur delivery system required for the biosynthesis of iron-sulfur (Fe/S) clusters and certain resultant Fe/S proteins. This review addresses presumed sulfur delivery pathways for the s2U34 formation in distinct intracellular locations, especially that for cy-tRNAs in comparison with that for mt-tRNAs. PMID:28218716

  19. 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.

  20. 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.

  1. 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.

  2. Search for the Exotic Wobbling Mode in Rhenium-171

    DTIC Science & Technology

    2011-05-13

    wobbling mode in 171 Re. High-spin states in 17 1 Re were produced in a reaction at Argonne National Laboratory. Reaction gamma rays were detected...using germanium detectors in the Argonne Gammasphere spectrometer. These gamma -ray data were subsequently analyzed at the Naval Academy. Seven decay...mode was not observed in the neighboring hafnium (Hf) and thulim (Tm) isotopes and was only recently found in an isotope of tantalum (Ta). The

  3. 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.

  4. A chain kinematic model to assess the movement of lower-limb including wobbling masses.

    PubMed

    Thouzé, A; Monnet, T; Bélaise, C; Lacouture, P; Begon, M

    2016-01-01

    Computer simulation models have shown that wobbling mass on the lower limb affects the joint kinetics. Our objective was to propose a non-invasive method to estimate bones and wobbling mass kinematics in the lower limb during hopping. The chain kinematic model has set degrees of freedom at the joints and free wobbling bodies. By comparison to a model without wobbling bodies, the marker residual was reduced by 20% but the joint kinematics remains unchanged. Wobbling bodies' displacements reached 6.9 ± 3.5° and 6.9 ± 2.4 mm relative to the modelled bones. This original method is a first step to assess wobbling mass effect on joint kinetics.

  5. 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

  6. 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.

    2012-12-01

    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.

  7. 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.

  8. 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,…

  9. 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,…

  10. 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

  11. Out of the toolbox: toddlers differentiate wobbly and wooden handrails.

    PubMed

    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, 40 cm) with either a "wobbly" (foam or latex) or a wooden handrail available for assistance. Infants attempted to walk over wider bridges more often than narrow ones, and attempts were more frequent when the sturdy wooden handrail was available. Infants tailored their exploratory behaviors, bridge-crossing strategies, and handrail-use strategies to the material properties of the rail.

  12. 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.

  13. Estimating the Q of the Chandler Wobble in the Absence of Excitation

    NASA Astrophysics Data System (ADS)

    Gross, R. S.

    2015-12-01

    The quality factor Q of the Chandler wobble is a function of various dissipation processes acting in the Earth. Better estimates of the Q of the Chandler wobble can therefore be used to better understand these processes. Because of them, and in the absence of any excitation process, the amplitude of the Chandler wobble will freely decay with a time constant proportional to its Q. If a period of time can be found during which the Chandler wobble is not being excited but is instead freely decaying, then estimating the time constant associated with this free decay yields an estimate of the Q of the Chandler wobble. Observations of the Chandler wobble indicate that it was apparently freely decaying 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 atmospheric and oceanic processes. 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.

  14. Two-dimensional collective Hamiltonian for chiral and wobbling modes

    NASA Astrophysics Data System (ADS)

    Chen, Q. B.; Zhang, S. Q.; Zhao, P. W.; Jolos, R. V.; Meng, J.

    2016-10-01

    A two-dimensional collective Hamiltonian (2DCH) on both azimuth and polar motions in triaxial nuclei is proposed to investigate the chiral and wobbling modes. In the 2DCH, the collective potential and the mass parameters are determined from three-dimensional tilted axis cranking (TAC) calculations. The broken chiral and signature symmetries in the TAC solutions are restored by the 2DCH. The validity of the 2DCH is illustrated with a triaxial rotor (γ =-30∘ ) coupling to one h11 /2 proton particle and one h11 /2 neutron hole. By diagonalizing the 2DCH, the angular momenta and energy spectra are obtained. These results agree with the exact solutions of the particle rotor model (PRM) at high rotational frequencies. However, at low frequencies, the energies given by the 2DCH are larger than those by the PRM due to the underestimation of the mass parameters. In addition, with increasing angular momentum, the transitions from the chiral vibration to chiral rotation and further to longitudinal wobbling motion have been presented in the 2DCH.

  15. Two-Dimensional Collective Hamiltonian for Chiral and Wobbling Modes

    DOE PAGES

    Chen, Q. B.; Zhang, S. Q.; Zhao, P. W.; ...

    2016-10-03

    Here, a two-dimensional collective Hamiltonian (2DCH) on both azimuth and polar motions in triaxial nuclei is proposed to investigate the chiral and wobbling modes. In the 2DCH, the collective potential and the mass parameters are determined from three-dimensional tilted axis cranking (TAC) calculations. The broken chiral and signature symmetries in the TAC solutions are restored by the 2DCH. The validity of the 2DCH is illustrated with a triaxial rotor (γ= -30°) coupling to one h11/2 proton particle and one h11/2 neutron hole. By diagonalizing the 2DCH, the angular momenta and energy spectra are obtained. These results agree with the exactmore » solutions of the particle rotor model (PRM) at high rotational frequencies. However, at low frequencies, the energies given by the 2DCH are larger than those by the PRM due to the underestimation of the mass parameters. In addition, with increasing angular momentum, the transitions from the chiral vibration to chiral rotation and further to longitudinal wobbling motion have been presented in the 2DCH.« less

  16. Two-Dimensional Collective Hamiltonian for Chiral and Wobbling Modes

    SciTech Connect

    Chen, Q. B.; Zhang, S. Q.; Zhao, P. W.; Jolos, R. V.; Meng, J.

    2016-10-03

    Here, a two-dimensional collective Hamiltonian (2DCH) on both azimuth and polar motions in triaxial nuclei is proposed to investigate the chiral and wobbling modes. In the 2DCH, the collective potential and the mass parameters are determined from three-dimensional tilted axis cranking (TAC) calculations. The broken chiral and signature symmetries in the TAC solutions are restored by the 2DCH. The validity of the 2DCH is illustrated with a triaxial rotor (γ= -30°) coupling to one h11/2 proton particle and one h11/2 neutron hole. By diagonalizing the 2DCH, the angular momenta and energy spectra are obtained. These results agree with the exact solutions of the particle rotor model (PRM) at high rotational frequencies. However, at low frequencies, the energies given by the 2DCH are larger than those by the PRM due to the underestimation of the mass parameters. In addition, with increasing angular momentum, the transitions from the chiral vibration to chiral rotation and further to longitudinal wobbling motion have been presented in the 2DCH.

  17. Two-Dimensional Collective Hamiltonian for Chiral and Wobbling Modes

    SciTech Connect

    Chen, Q. B.; Zhang, S. Q.; Zhao, P. W.; Jolos, R. V.; Meng, J.

    2016-10-03

    Here, a two-dimensional collective Hamiltonian (2DCH) on both azimuth and polar motions in triaxial nuclei is proposed to investigate the chiral and wobbling modes. In the 2DCH, the collective potential and the mass parameters are determined from three-dimensional tilted axis cranking (TAC) calculations. The broken chiral and signature symmetries in the TAC solutions are restored by the 2DCH. The validity of the 2DCH is illustrated with a triaxial rotor (γ= -30°) coupling to one h11/2 proton particle and one h11/2 neutron hole. By diagonalizing the 2DCH, the angular momenta and energy spectra are obtained. These results agree with the exact solutions of the particle rotor model (PRM) at high rotational frequencies. However, at low frequencies, the energies given by the 2DCH are larger than those by the PRM due to the underestimation of the mass parameters. In addition, with increasing angular momentum, the transitions from the chiral vibration to chiral rotation and further to longitudinal wobbling motion have been presented in the 2DCH.

  18. CAD mutations and uridine-responsive epileptic encephalopathy.

    PubMed

    Koch, Johannes; Mayr, Johannes A; Alhaddad, Bader; Rauscher, Christian; Bierau, Jörgen; Kovacs-Nagy, Reka; Coene, Karlien L M; Bader, Ingrid; Holzhacker, Monika; Prokisch, Holger; Venselaar, Hanka; Wevers, Ron A; Distelmaier, Felix; Polster, Tilman; Leiz, Steffen; Betzler, Cornelia; Strom, Tim M; Sperl, Wolfgang; Meitinger, Thomas; Wortmann, Saskia B; Haack, Tobias B

    2017-02-01

    Unexplained global developmental delay and epilepsy in childhood pose a major socioeconomic burden. Progress in defining the molecular bases does not often translate into effective treatment. Notable exceptions include certain inborn errors of metabolism amenable to dietary intervention. CAD encodes a multifunctional enzyme involved in de novo pyrimidine biosynthesis. Alternatively, pyrimidines can be recycled from uridine. Exome sequencing in three families identified biallelic CAD mutations in four children with global developmental delay, epileptic encephalopathy, and anaemia with anisopoikilocytosis. Two died aged 4 and 5 years after a neurodegenerative disease course. Supplementation of the two surviving children with oral uridine led to immediate cessation of seizures in both. A 4-year-old female, previously in a minimally conscious state, began to communicate and walk with assistance after 9 weeks of treatment. A 3-year-old female likewise showed developmental progress. Blood smears normalized and anaemia resolved. We establish CAD as a gene confidently implicated in this neurometabolic disorder, characterized by co-occurrence of global developmental delay, dyserythropoietic anaemia and seizures. While the natural disease course can be lethal in early childhood, our findings support the efficacy of uridine supplementation, rendering CAD deficiency a treatable neurometabolic disorder and therefore a potential condition for future (genetic) newborn screening.

  19. 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

  20. 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.

  1. The Ocean De-excites the Chandler Wobble

    NASA Astrophysics Data System (ADS)

    Fang, M.; Hager, B. H.

    2012-12-01

    Numerical simulations have shown that the atmosphere alone is more than adequate to excite the Chandler Wobble; the oceanic excitation in fact de-excites the Chandler Wobble by being out of phase with the atmospheric excitation. This result is consistent with our correlation analysis: the oceanic angular momentum (OAM) tends to be out of phase with the atmospheric angular momentum (AAM) on all time scales. The general physics for this phenomenon lies in the classic fact that a wind swirl does not directly drag the deep ocean circulation. Instead, the wind stress, under the control of the Coriolis force, moves the surface water inward towards or outward from the center of the wind swirl, generating a pressure gradient in the radial direction of the wind swirl. It is this pressure gradient that drives the deep ocean's circulation through geostrophic balance. For harmonic annual and semi-annual variations of basin-scale oceanic gyres, it appears that the phase difference between the OAM and the AAM is primarily due to the delayed adjustment of the depth of the thermocline near the center of the gyres. However, for fast (as compared to the annual variations) and irregular small spatial-scale variations, which are mostly responsible for the Chandler Wobble excitation, the thermally induced adjustments can be ignored. What is the physical mechanism in this situation for the phase difference between the OAM and the AAM? We present a simple model to explore the wind-driven fast and irregular oceanic currents. We find that the time-scale, as compared to the Earth's spin rate, plays a key role in producing the phase difference between the OAM and the AAM. For slow time variation of a wind swirl, the net effect of the Coriolis force is to drive the deep ocean circulation in the same direction as the wind swirl. If variation of a wind swirl (usually on a small spatial scale) is faster than the spin rate, as is the case in real situations, the Coriolis force would act as a

  2. Enzymatic conversion of adenosine to inosine in the wobble position of yeast tRNAAsp: the dependence on the anticodon sequence.

    PubMed Central

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

    1984-01-01

    We have investigated the specificity of the tRNA modifying enzyme that transforms the adenosine at position 34 (wobble position) into inosine in the anticodon of several tRNAs. For this purpose, we have constructed sixteen recombinants of yeast tRNAAsp harboring an AXY anticodon (where X or Y was one of the four nucleotides A, G, C or U). This was done by enzymatic manipulations in vitro of the yeast tRNAAsp, involving specific hydrolysis with S1-nuclease and RNAase A, phosphorylation with T4-polynucleotide kinase and ligation with T4-RNA ligase: it allowed us to replace the normal anticodon GUC by trinucleotides AXY and to introduce simultaneously a 32P-labelled phosphate group between the uridine at position 33 and the newly inserted adenosine at position 34. Each of these 32P-labelled AXY "anticodon-substituted" yeast tRNAAsp were microinjected into the cytoplasm of Xenopus laevis oocytes and assayed for their capacity to act as substrates for the A34 to I34 transforming enzyme. Our results indicate that: 1/ A34 in yeast tRNAAsp harboring the arginine anticodon ACG or an AXY anticodon with a purine at position 35 but with A, G or C but not U at position 36 were efficiently modified into I34; 2/ all yeast tRNAAsp harboring an AXY anticodon with a pyrimidine at position 35 (except ACG) or uridine at position 36 were not modified at all. This demonstrates a strong dependence on the anticodon sequence for the A34 to I34 transformation in yeast tRNAAsp by the putative cytoplasmic adenosine deaminase of Xenopus laevis oocytes. Images PMID:6369251

  3. Enzymatic conversion of adenosine to inosine in the wobble position of yeast tRNAAsp: the dependence on the anticodon sequence.

    PubMed

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

    1984-03-26

    We have investigated the specificity of the tRNA modifying enzyme that transforms the adenosine at position 34 (wobble position) into inosine in the anticodon of several tRNAs. For this purpose, we have constructed sixteen recombinants of yeast tRNAAsp harboring an AXY anticodon (where X or Y was one of the four nucleotides A, G, C or U). This was done by enzymatic manipulations in vitro of the yeast tRNAAsp, involving specific hydrolysis with S1-nuclease and RNAase A, phosphorylation with T4-polynucleotide kinase and ligation with T4-RNA ligase: it allowed us to replace the normal anticodon GUC by trinucleotides AXY and to introduce simultaneously a 32P-labelled phosphate group between the uridine at position 33 and the newly inserted adenosine at position 34. Each of these 32P-labelled AXY "anticodon-substituted" yeast tRNAAsp were microinjected into the cytoplasm of Xenopus laevis oocytes and assayed for their capacity to act as substrates for the A34 to I34 transforming enzyme. Our results indicate that: 1/ A34 in yeast tRNAAsp harboring the arginine anticodon ACG or an AXY anticodon with a purine at position 35 but with A, G or C but not U at position 36 were efficiently modified into I34; 2/ all yeast tRNAAsp harboring an AXY anticodon with a pyrimidine at position 35 (except ACG) or uridine at position 36 were not modified at all. This demonstrates a strong dependence on the anticodon sequence for the A34 to I34 transformation in yeast tRNAAsp by the putative cytoplasmic adenosine deaminase of Xenopus laevis oocytes.

  4. Mutation and Selection on the Wobble Nucleotide in tRNA Anticodons in Marine Bivalve Mitochondrial Genomes

    PubMed Central

    Yu, Hong; Li, Qi

    2011-01-01

    Background Animal mitochondrial genomes typically encode one tRNA for each synonymous codon family, so that each tRNA anticodon essentially has to wobble to recognize two or four synonymous codons. Several factors have been hypothesized to determine the nucleotide at the wobble site of a tRNA anticodon in mitochondrial genomes, such as the codon-anticodon adaptation hypothesis, the wobble versatility hypothesis, the translation initiation and elongation conflict hypothesis, and the wobble cost hypothesis. Principal Findings In this study, we analyzed codon usage and tRNA anticodon wobble sites of 29 marine bivalve mitochondrial genomes to evaluate features of the wobble nucleotides in tRNA anticodons. The strand-specific mutation bias favors G and T on the H strand in all the 29 marine bivalve mitochondrial genomes. A bias favoring G and T is also visible in the third codon positions of protein-coding genes and the wobble sites of anticodons, rejecting that codon usage bias drives the wobble sites of tRNA anticodons or tRNA anticodon bias drives the evolution of codon usage. Almost all codon families (98.9%) from marine bivalve mitogenomes support the wobble versatility hypothesis. There are a few interesting exceptions involving tRNATrp with an anticodon CCA fixed in Pectinoida species, tRNASer with a GCU anticodon fixed in Mytiloida mitogenomes, and the uniform anticodon CAU of tRNAMet translating the AUR codon family. Conclusions/Significance These results demonstrate that most of the nucleotides at the wobble sites of tRNA anticodons in marine bivalve mitogenomes are determined by wobble versatility. Other factors such as the translation initiation and elongation conflict, and the cost of wobble translation may contribute to the determination of the wobble nucleotide in tRNA anticodons. The finding presented here provides valuable insights into the previous hypotheses of the wobble nucleotide in tRNA anticodons by adding some new evidence. PMID:21267462

  5. 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.

  6. tRNA wobble modifications and protein homeostasis

    PubMed Central

    Ranjan, Namit; Rodnina, Marina V.

    2016-01-01

    Abstract tRNA is a central component of the protein synthesis machinery in the cell. In living cells, tRNAs undergo numerous post-transcriptional modifications. In particular, modifications at the anticodon loop play an important role in ensuring efficient protein synthesis, maintaining protein homeostasis, and helping cell adaptation and survival. Hypo-modification of the wobble position of the tRNA anticodon loop is of particular relevance for translation regulation and is implicated in various human diseases. In this review we summarize recent evidence of how methyl and thiol modifications in eukaryotic tRNA at position 34 affect cellular fitness and modulate regulatory circuits at normal conditions and under stress. PMID:27335723

  7. 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.

  8. 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.

  9. Binding affinity of N3-substituted uridine for synaptic membrane and their CNS depressant effects.

    PubMed

    Kimura, T; Miki, M; Watanabe, K; Kondo, S; Ho, I K; Yamamoto, I

    1995-01-01

    The binding affinity for synaptic membrane from bovine thalamus of N3-phenacyl substituted pyrimidine nucleosides having CNS depressant activity was examined by radio receptor assay. N3-Phenacyl derivatives of uridine, thymidine, deoxyuridine, 6-azauridine and arabinofuranosyluracil inhibited specific [3H]uridine binding and exhibited hypnotic activity. However, N3-phenacyl-2',3'-O-isopropylideneuridine, of which structure was different from sugar moiety of N3-phenacyluridine, showed neither the binding affinity nor the hypnotic activity. The results indicated that CNS depressant effect of pyrimidine nucleoside derivatives might relate to uridine binding affinity, so called uridine receptor.

  10. Excitation of the Earth's Chandler wobble by a turbulent oceanic double-gyre

    NASA Astrophysics Data System (ADS)

    Naghibi, S. E.; Jalali, M. A.; Karabasov, S. A.; Alam, M.-R.

    2017-04-01

    We develop a layer-averaged, multiple-scale spectral ocean model and show how an oceanic double-gyre can communicate with the Earth's Chandler wobble. The overall transfers of energy and angular momentum from the double-gyre to the Chandler wobble are used to calibrate the turbulence parameters of the layer-averaged model. Our model is tested against a multilayer quasi-geostrophic ocean model in turbulent regime, and base states used in parameter identification are obtained from mesoscale eddy resolving numerical simulations. The Chandler wobble excitation function obtained from the model predicts a small role of North Atlantic ocean region on the wobble dynamics as compared to all oceans, in agreement with the existing observations.

  11. Excitation of the Earth's Chandler wobble by a turbulent oceanic double-gyre

    NASA Astrophysics Data System (ADS)

    Naghibi, S. E.; Jalali, M. A.; Karabasov, S. A.; Alam, M.-R.

    2017-01-01

    We develop a layer-averaged, multiple-scale spectral ocean model and show how an oceanic double-gyre can communicate with the Earth's Chandler wobble. The overall transfers of energy and angular momentum from the double-gyre to the Chandler wobble are used to calibrate the turbulence parameters of the layer-averaged model. Our model is tested against a multi-layer quasi-geostrophic ocean model in turbulent regime, and base states used in parameter identification are obtained from meso-scale eddy resolving numerical simulations. The Chandler wobble excitation function obtained from the model predicts a small role of North Atlantic ocean region on the wobble dynamics as compared to all oceans, in agreement with the existing observations.

  12. Simulation of the 14-month Chandler wobble in a global climate model

    SciTech Connect

    Hameed, S.; Currie, R.G. )

    1989-03-01

    The agent that generates and maintains the 14-month Chandler wobble of the solid earth about its rotation axis has remained unresolved for a century with first the atmosphere, later earthquakes, and more recently the earth's fluid core proposed as candidates. Here the authors report that surface air pressure calculated in a coupled ocean-atmospheric general circulation model (GCM) displays a 14.7 month signal, whose amplitude is similar to that found by Maksimov (1960) in station data; they identify it as the atmospheric Chandler wobble. This result indicates that changes in atmospheric mass distribution excite and maintain the wobble of the solid earth, and that neither earthquakes nor the fluid core are significant contributors. Another result is that in the GCM, the amplitude of the wobble at high latitudes is a substantial fraction of the annual cycle, and thus is an important factor in climate formation as Maksimov (1960) suggested.

  13. 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

    2016-05-27

    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.

  14. 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

  15. Modification defect at anticodon wobble nucleotide of mitochondrial tRNAs(Leu)(UUR) with pathogenic mutations of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

    PubMed

    Yasukawa, T; Suzuki, T; Ueda, T; Ohta, S; Watanabe, K

    2000-02-11

    The mitochondrial tRNA(Leu)(UUR) (R = A or G) gene possesses several hot spots for pathogenic mutations. A point mutation at nucleotide position 3243 or 3271 is associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes and maternally inherited diabetes with deafness. Detailed studies on two tRNAs(Leu)(UUR) with the 3243 or 3271 mutation revealed some common characteristics in cybrid cells: (i) a decreased life span, resulting in a 70% decrease in the amounts of the tRNAs in the steady state, (ii) a slight decrease in the ratios of aminoacyl-tRNAs(Leu)(UUR) versus uncharged tRNAs(Leu)(UUR), and (iii) accurate aminoacylation with leucine without any misacylation. As a marked result, both of the mutant tRNA molecules were deficient in a modification of uridine that occurs in the normal tRNA(Leu)(UUR) at the first position of the anticodon. The lack of this modification may lead to the mistranslation of leucine into non-cognate phenylalanine codons by mutant tRNAs(Leu)(UUR), according to the mitochondrial wobble rule, and/or a decrease in the rate of mitochondrial protein synthesis. This finding could explain why two different mutations (3243 and 3271) manifest indistinguishable clinical features.

  16. Thio-Modification of tRNA at the Wobble Position as Regulator of the Kinetics of Decoding and Translocation on the Ribosome.

    PubMed

    Ranjan, Namit; Rodnina, Marina V

    2017-04-13

    Uridine 34 (U34) at the wobble position of the tRNA anticodon is post-transcriptionally modified, usually to mcm(5)s(2), mcm(5), or mnm(5). The lack of the mcm(5) or s(2) modification at U34 of tRNA(Lys), tRNA(Glu), and tRNA(Gln) causes ribosome pausing at the respective codons in yeast. The pauses occur during the elongation step, but the mechanism that triggers ribosome pausing is not known. Here, we show how the s(2) modification in yeast tRNA(Lys) affects mRNA decoding and tRNA-mRNA translocation. Using real-time kinetic analysis we show that mcm(5)-modified tRNA(Lys) lacking the s(2) group has a lower affinity of binding to the cognate codon and is more efficiently rejected than the fully modified tRNA(Lys). The lack of the s(2) modification also slows down the rearrangements in the ribosome-EF-Tu-GDP-Pi-Lys-tRNA(Lys) complex following GTP hydrolysis by EF-Tu. Finally, tRNA-mRNA translocation is slower with the s(2)-deficient tRNA(Lys). These observations explain the observed ribosome pausing at AAA codons during translation and demonstrate how the s(2) modification helps to ensure the optimal translation rates that maintain proteome homeostasis of the cell.

  17. Celebrating wobble decoding: Half a century and still much is new.

    PubMed

    Agris, Paul F; Eruysal, Emily R; Narendran, Amithi; Väre, Ville Y P; Vangaveti, Sweta; Ranganathan, Srivathsan V

    2017-08-16

    A simple post-transcriptional modification of tRNA, deamination of adenosine to inosine at the first, or wobble, position of the anticodon, inspired Francis Crick's Wobble Hypothesis 50 years ago. Many more naturally-occurring modifications have been elucidated and continue to be discovered. The post-transcriptional modifications of tRNA's anticodon domain are the most diverse and chemically complex of any RNA modifications. Their contribution with regards to chemistry, structure and dynamics reveal individual and combined effects on tRNA function in recognition of cognate and wobble codons. As forecast by the Modified Wobble Hypothesis 25 years ago, some individual modifications at tRNA's wobble position have evolved to restrict codon recognition whereas others expand the tRNA's ability to read as many as four synonymous codons. Here, we review tRNA wobble codon recognition using specific examples of simple and complex modification chemistries that alter tRNA function. Understanding natural modifications has inspired evolutionary insights and possible innovation in protein synthesis.

  18. Analysis of the wobbling effect in a lens-shaped body rotation

    NASA Astrophysics Data System (ADS)

    Kim, Minho

    2017-03-01

    We discuss the wobbling motion in a lens-shaped body rotation, focusing on the frequencies and the amplitude of nutation by filming the rotational motion and wobbling of the body. The friction coefficient of the surface is altered to examine its influence for two lenses with different curvature radii. MATLAB programs are developed to retrieve the Euler angles, which are graphed according to time. It is shown that the lens with a smaller curvature radius exhibits the wobbling effect in all cases, whereas the lens with a larger curvature radius shows such behaviour in limited circumstances. The study confirms that the friction coefficient has a negative linear correlation with the vertical axis declination amplitude with the R-squared value 0.878, showing that friction gives damping and causes smaller axis declination amplitudes. Negative linear correlation also exists with relation to the number of wobbles before the motion stops, where the R-squared value is 0.938, providing further evidence that friction and wobbling cause higher energy dissipation rates. The frequency of the wobbling motion only has a correlation with the curvature radius of the lens, showing no explicit correlation with the friction coefficient, with its R-squared value being 0.077. No losses of contact were observable in this motion. The overall process does not utilize particularly expensive apparatus and will be applicable for senior undergraduate students to experiment on and analyze the motion of a special situation regarding a rigid body that is both spinning and nutating.

  19. Disruption of uridine homeostasis links liver pyrimidine metabolism to lipid accumulation[S

    PubMed Central

    Le, Thuc T.; Ziemba, Amy; Urasaki, Yasuyo; Hayes, Eugene; Brotman, Steven; Pizzorno, Giuseppe

    2013-01-01

    We report in this study an intrinsic link between pyrimidine metabolism and liver lipid accumulation utilizing a uridine phosphorylase 1 transgenic mouse model UPase1-TG. Hepatic microvesicular steatosis is induced by disruption of uridine homeostasis through transgenic overexpression of UPase1, an enzyme of the pyrimidine catabolism and salvage pathway. Microvesicular steatosis is also induced by the inhibition of dihydroorotate dehydrogenase (DHODH), an enzyme of the de novo pyrimidine biosynthesis pathway. Interestingly, uridine supplementation completely suppresses microvesicular steatosis in both scenarios. The effective concentration (EC50) for uridine to suppress microvesicular steatosis is approximately 20 µM in primary hepatocytes of UPase1-TG mice. We find that uridine does not have any effect on in vitro DHODH enzymatic activity. On the other hand, uridine supplementation alters the liver NAD+/NADH and NADP+/NADPH ratios and the acetylation profile of metabolic, oxidation-reduction, and antioxidation enzymes. Protein acetylation is emerging as a key regulatory mechanism for cellular metabolism. Therefore, we propose that uridine suppresses fatty liver by modulating the liver protein acetylation profile. Our findings reveal a novel link between uridine homeostasis, pyrimidine metabolism, and liver lipid metabolism. PMID:23355744

  20. The uptake and metabolism of uridine by the slime mould Physarum polycephalum.

    PubMed

    Birch, B; Turnock, G

    1976-10-01

    1. Uridine is taken up by microplasmodia of Physarum polycephalum via a saturatable transport system with an apparent Km of 29 muM. An intracellular concentration significantly higher than that in the growth medium is attained, suggesting that the uptake is an active process. Both deoxyribonucleosides and ribonucleosides are competitive inhibitors of the uptake of uridine. 2. In contrast, the rate of entry of uridine into surface plasmodia is a linear function of the concentration of the nucleoside in the growth medium, and the uptake is not inhibited by other nucleosides. 3. As well as serving as a source of pyrimidine nucleotides for the synthesis of nucleic acids, uridine is also catabolised by P. polycephalum. Uracil accumulates in the growth medium and there is also significant conversion of C-2 of the pyrimidine ring to CO2. The proportion of uridine subject to catabolism in surface plasmodia is less than that observed for microplasmodia.

  1. Chandler wobble: two more large phase jumps revealed

    NASA Astrophysics Data System (ADS)

    Malkin, Zinovy; Miller, Natalia

    2010-12-01

    Investigations of the anomalies in the Earth rotation, in particular, the polar motion components, play an important role in our understanding of the processes that drive changes in the Earth's surface, interior, atmosphere, and ocean. This paper is primarily aimed at investigation of the Chandler wobble (CW) at the whole available 163-year interval to search for the major CW amplitude and phase variations. First, the CW signal was extracted from the IERS (International Earth Rotation and Reference Systems Service) Pole coordinates time series using two digital filters: the singular spectrum analysis and Fourier transform. The CW amplitude and phase variations were examined by means of the wavelet transform and Hilbert transform. Results of our analysis have shown that, besides the well-known CW phase jump in the 1920s, two other large phase jumps have been found in the 1850s and 2000s. As in the 1920s, these phase jumps occurred contemporarily with a sharp decrease in the CW amplitude.

  2. WOBBLING AND PRECESSING JETS FROM WARPED DISKS IN BINARY SYSTEMS

    SciTech Connect

    Sheikhnezami, Somayeh; Fendt, Christian E-mail: fendt@mpia.de

    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.

  3. 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.

  4. Prediction of uridine modifications in tRNA sequences.

    PubMed

    Panwar, Bharat; Raghava, Gajendra P S

    2014-10-02

    In past number of methods have been developed for predicting post-translational modifications in proteins. In contrast, limited attempt has been made to understand post-transcriptional modifications. Recently it has been shown that tRNA modifications play direct role in the genome structure and codon usage. This study is an attempt to understand kingdom-wise tRNA modifications particularly uridine modifications (UMs), as majority of modifications are uridine-derived. A three-steps strategy has been applied to develop an efficient method for the prediction of UMs. In the first step, we developed a common prediction model for all the kingdoms using a dataset from MODOMICS-2008. Support Vector Machine (SVM) based prediction models were developed and evaluated by five-fold cross-validation technique. Different approaches were applied and found that a hybrid approach of binary and structural information achieved highest Area under the curve (AUC) of 0.936. In the second step, we used newly added tRNA sequences (as independent dataset) of MODOMICS-2012 for the kingdom-wise prediction performance evaluation of previously developed (in the first step) common model and achieved performances between the AUC of 0.910 to 0.949. In the third and last step, we used different datasets from MODOMICS-2012 for the kingdom-wise individual prediction models development and achieved performances between the AUC of 0.915 to 0.987. The hybrid approach is efficient not only to predict kingdom-wise modifications but also to classify them into two most prominent UMs: Pseudouridine (Y) and Dihydrouridine (D). A webserver called tRNAmod (http://crdd.osdd.net/raghava/trnamod/) has been developed, which predicts UMs from both tRNA sequences and whole genome.

  5. Uridine Nucleoside Thiation: Gas-Phase Structures and Energetics

    NASA Astrophysics Data System (ADS)

    Hamlow, Lucas; Lee, Justin; Rodgers, M. T.; Berden, Giel; Oomens, Jos

    2016-06-01

    The naturally occurring thiated uridine nucleosides, 4-thiouridine (s4Urd) and 2-thiouridine (s2Urd), play important roles in the function and analysis of a variety of RNAs. 2-Thiouridine and its C5 modified analogues are commonly found in tRNAs and are believed to play an important role in codon recognition possibly due to their different structure, which has been shown by NMR to be predominantly C3'-endo. 2-Thiouridine may also play an important role in facilitating nonenzymatic RNA replication and transcription. 4-Thiouridine is a commonly used photoactivatable crosslinker that is often used to study RNA-RNA and RNA-protein cross-linking behavior. Differences in the base pairing between uracil and 4-thiouracil with adenine and guanine are an important factor in their role as a cross linker. The photoactivity of s4Urd may also aid in preventing near-UV lethality in cells. An understanding of their intrinsic structure in the gas-phase may help further elucidate the roles these modified nucleosides play in the regulation of RNAs. In this work, infrared multiple photon dissociation (IRMPD) action spectra of the protonated forms of s2Urd and s4Urd were collected in the IR fingerprint region. Structural information is determined by comparison with theoretical linear IR spectra generated from density functional theory calculations using molecular modeling to generate low-energy candidate structures. Present results are compared with analogous results for the protonated forms of uridine and 2'-deoxyuridine as well as solution phase NMR data and crystal structures.

  6. Functional and Structural Impact of Target Uridine Substitutions on the H/ACA Ribonucleoprotein Particle Pseudouridine Synthase

    SciTech Connect

    Zhou, Jing; Liang, Bo; Li, Hong

    2010-09-17

    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{prime}-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.

  7. Glycal Formation in Crystals of Uridine Phosphorylase †‖‡

    PubMed Central

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

    2010-01-01

    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′-deoxyuridine to 2′-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′-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′. Crystals of bovine uridine phosphorylase treated with 2′-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 motif to the body of information on glycal formation by enzymes catalyzing the cleavage of glycosyl bonds. PMID:20364833

  8. 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.

  9. Synthesis of extended uridine phosphonates derived from an allosteric P2Y2 receptor ligand.

    PubMed

    Song, Lijun; Risseeuw, Martijn D P; Karalic, Izet; Barrett, Matthew O; Brown, Kyle A; Harden, T Kendall; Van Calenbergh, Serge

    2014-04-04

    In this study we report the synthesis of C5/C6-fused uridine phosphonates that are structurally related to earlier reported allosteric P2Y2 receptor ligands. A silyl-Hilbert-Johnson reaction of six quinazoline-2,4-(1H,3H)-dione-like base moieties with a suitable ribofuranosephosphonate afforded the desired analogues after full deprotection. In contrast to the parent 5-(4-fluoropheny)uridine phosphonate, the present extended-base uridine phosphonates essentially failed to modulate the P2Y2 receptor.

  10. Lewis Acid Triggered Regioselective Magnesiation and Zincation of Uracils, Uridines, and Cytidines.

    PubMed

    Klier, Lydia; Aranzamendi, Eider; Ziegler, Dorothée; Nickel, Johannes; Karaghiosoff, Konstantin; Carell, Thomas; Knochel, Paul

    2016-03-04

    The Lewis acid MgCl2 allows control of the metalation regioselectivity of uracils and uridines. In the absence of the Lewis acid, metalation of uracil and uridine derivatives with TMPMgCl·LiCl occurs at the position C(5). In the presence of MgCl2, zincation using TMP2Zn·2LiCl·2MgCl2 occurs at the position C(6). This metalation method provides easy access to functionalized uracils and uridines. Using TMP2Zn·2LiCl·2MgCl2 also allows to functionalize cytidine derivatives at the position C(6).

  11. 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.

  12. Amplitude and phase variations of Earth's Chandler wobble under continual excitation

    NASA Astrophysics Data System (ADS)

    Chao, Benjamin F.; Chung, Wei-Yung

    2012-12-01

    We demonstrate a simple physical explanation for the cause of the well-known but so-far baffling behavior of the Chandler wobble during ˜1925 when it reached a near-zero amplitude and underwent a concurrent large phase jump. We do so by numerical Monte-Carlo simulations, designed based on simple physical reasoning, of the statistical behavior of the Earth's Chandler wobble under continual excitation. Rather than subscribing to the view that something extraordinary or anomalous had occurred to the Earth system sometime during the later half of the 1920s, we assert the scenario that the Chandler wobble excitation during that time happened to oppose and cancel the Chandler motion momentarily before starting anew the motion that became unrelated to its immediate past, hence manifesting as an apparent phase jump in the time series. The seemingly peculiar event was simply fortuitous by chance.

  13. 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.

  14. Crystal structures of the ribonuclease MC1 from bitter gourd seeds, complexed with 2'-UMP or 3'-UMP, reveal structural basis for uridine specificity.

    PubMed

    Suzuki, A; Yao, M; Tanaka, I; Numata, T; Kikukawa, S; Yamasaki, N; Kimura, M

    2000-08-28

    Ribonuclease MC1 (RNase MC1) isolated from seeds of bitter gourd (Momordica charantia) consists of 190 amino acids and is characterized by a preferential cleavage at the 5'-side of uridine. This uridine specificity distinguishes RNase MC1 from other enzymes belonging to the RNase T2 family. The three-dimensional structures of RNase MC1, in a complex with either 2'-UMP or 3'-UMP, were determined at 1.48 and 1.77 A resolutions, respectively. The side chains of Gln9 and Asn71 interact with O4 and N3, respectively, of the uracil base by hydrogen bondings. In addition, the uracil base is sandwiched by the hydrophobic side chains of Leu73 and Phe80. Compared with these amino acid residues and corresponding residues in RNases in the RNase T2 family, Gln9 and Phe80 are highly conserved in the RNases in T2 family, while Asn71 and Leu73 in RNase MC1 are variant in sequences. It is thus likely that interactions of the side chains of Asn71 and Leu73 with the uracil base are responsible for the absolute uridine specificity of RNase MC1. Site-directed mutagenesis experiments showed that replacement of Asn by Thr decreased both the catalytic efficiency and the binding affinity by 2.3- and 7.0-fold, respectively, and substitution of Leu73 for Ala predominantly decreased the binding affinity by 14. 5-fold, compared with findings in case of wild-type RNase MC1. It is thus demonstrated that Asn71 and Leu73 play an essential role in uridine preference for RNase MC1.

  15. 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

  16. 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.

  17. 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

  18. Serum "uracil+uridine" levels in pernicious anaemia.

    PubMed

    Parry, T E; Blackmore, J A

    1976-12-01

    The serum "uracil+uridine" level, expressed as uracil, has been measured in 21 cases of vitamin B12 deficiency, in which the serum folate was normal, and compared with the level in 97 normal subjects. The level in the vitamin B12 deficient group (11.9 mumol/1). was significantly lower than in the controls (15.7 mumol/1., P less than 0.005). Nine of the former were complicated by stystemic illness but the clinical and haematological features in the remaining 12 were consistent with the diagnosis of pernicious anaemia in relapse. The serum uracil level in this group was even lower (10.21 mumol/1., P less than 0.01). This finding is unexpected in view of the generally accepted indirect role of vitamine B12 in the methylation of deoxyuridine monophosphate to deoxythymidine monophosphate. Reasons are given for not accepting these results as reflecting the main biochemical lesion in vitamin B12 deficiency. Although they do not give direct support to an impairment in the methylation of deoxyuridine monophosphate, they do not exclude it as they test only one possible metabolic pathway and moreover they could represent the result of more than one action of vitamin B12 on uracil metabolism. They do show, however, that some aspect of uracil metabolism other than methylation is affected in vitamin B12 deficiency in man.

  19. [Purification and characterization of a uridine phosphorylase from Enterobacter aerogenes EAM-Z1].

    PubMed

    Ruan, Qiping; Zhou, Changlin; Xu, Xudong; Wu, Wutong

    2003-06-01

    A uridine phosphorylase(UPase) was isolation from Enterobacter aerogenes EAM-Z1 and purified by means of ammonium sulfate precipitation, DEAE-cellulose, Phenyl-Sepharose, DEAE-Sepharose, FPLC ion exchange, and Sephacryl S-200 column chromatography. The purified UPase showed homogeneity on the native polacrylamide gel electrophoresis. The UPase is a trimer of 43 kD subunits. Fifteen residues from the amino terminal end of UPase were identified as MRMVDLIATKRDGGE. The isoelectric point was pH 4.46. Michaelis constant for uridine was 0.29 mmol/L. The UPase has a maximal activity at a pH value of 7.8 and 50 degrees C. The UPase could catalyses the phosphorolysis of uridine, thymidine, 5-Fluorouridine, 5-Fluoro-2'-deoxyuridine, uracil-beta-D-arbinofuranoside, and could also catalyse the synthesis of 5-Fluorouridine, a better prodrug form of the anticancer drug 5-fluorouracil, from 5-fluorouracil and uridine, and 47% uridine was converted to 5-Fluoro-uridine.

  20. A reliable Pd-mediated hydrogenolytic deprotection of BOM group of uridine ureido nitrogen.

    PubMed

    Aleiwi, Bilal A; Kurosu, Michio

    2012-07-18

    The benzyloxymethyl (BOM) group has been utilized widely in syntheses of a variety of natural and non-natural products. The BOM group is also one of few choices to protect uridine ureido nitrongen. However, hydrogenolytic cleavage of the BOM group of uridine derivatives has been unrealizably performed via heterogeneous conditions using Pd catalysts. One of the undesirable by-products formed by Pd-mediated hydrogenation conditions is the over-reduced product of which the C5-C6 double bond of the uracil moiety was saturated. To date, we have generated a wide range of uridine-containing antibacterial agents, where the BOM group has been utilized in their syntheses. In screening of deprotection conditions of the BOM group of uridine ureido nitrogen under Pd-mediated hydrogenation conditions, we realized that the addition of water to the (i)PrOH-based hydrogenation conditions can suppress the formation of over-reduced uridine derivatives and the addition of HCO(2)H (0.5%) dramatically improve the reaction rate. An optimized hydrogenation condition described here can be applicable to the BOM-deprotections of a wide range of uridine derivatives.

  1. Estimating the Period and Q of the Chandler Wobble from mass variations.

    NASA Astrophysics Data System (ADS)

    Nastula, Jolanta; Gross, Richard

    2013-04-01

    The free Chandler wobble is the largest component of the observed polar motion. The period of the Chandler wobble and quality factor Q depend on the internal structure and rheology of the Earth. There is quite good agreement in empirical determination and theoretical estimations of the Chandler wobble period but there is still large dispersions of the Q values. One of the methods to assess the value of the period and Q of the Chandler wobble is to determine those values that minimize the power within the Chandler band of the difference between observed and modeled polar motion excitation. Modeling of the polar motion excitation requires information on geophysical fluids distribution. Only recent investigations using atmospheric, oceanic and hydrological excitation computed for the period spanning from 1962 to 2010 shown the value of Q is about 111. Here we estimate the period and Q of the Chandler values on the basis of that method using direct observations of the excitation caused by mass variations as determined from approximately 25 years of SLR data from five geodetic satellites and from GRACE time varying gravitational field. Atmosphere, ocean, and hydrology models are also used to model the excitation caused by both mass and motion variations within these global geophysical fluids.

  2. 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.

  3. A VLBI Search for the Origin of Wobbling in Blazar Jet

    NASA Astrophysics Data System (ADS)

    Agudo, I.

    2009-08-01

    An increasing number of blazars have been reported to show jet wobbling (i.e., non-regular rotations of the structural position angle of their innermost jets in the plane of the sky with amplitudes between 20 deg. and 50 deg., and time scales between 2 yr. and 20 yr.). The physical origin for the observed jet wobbling is still poorly understood, but as this phenomenon is triggered in the innermost regions of the jets, it must be tied to fundamental properties of the inner regions of the accretion system. Thus, jet wobbling may be an interesting potential tool for supermassive black hole, accretion and jet launching studies. As part of a joint theoretical/numerical and observational effort to characterize the observational properties and differences between three possible scenarios we have started a long-term polarimetric phase-reference 43 GHz VLBA monitoring program to observe the jet structure and the absolute motion of the jet core of four of the blazars which have shown some of the clearest evidence of large amplitude jet wobbling: NRAO 150, OJ 287, 3C 273, and 3C 345 . Here we present this project and we argue about its suitability for future VSOP-2 observations.

  4. Actin Dosage Lethality Screening in Yeast Mediated by Selective Ploidy Ablation Reveals Links to Urmylation/Wobble Codon Recognition and Chromosome Stability

    PubMed Central

    Haarer, Brian; Mi-Mi, Lei; Cho, Jessica; Cortese, Matthew; Viggiano, Susan; Burke, Daniel; Amberg, David

    2013-01-01

    The actin cytoskeleton exists in a dynamic equilibrium with monomeric and filamentous states of its subunit protein actin. The spatial and temporal regulation of actin dynamics is critical to the many functions of actin. Actin levels are remarkably constant, suggesting that cells have evolved to function within a narrow range of actin concentrations. Here we report the results of screens in which we have increased actin levels in strains deleted for the ~4800 nonessential yeast genes using a technical advance called selective ploidy ablation. We detected 83 synthetic dosage interactions with actin, 78 resulted in reduced growth, whereas in 5 cases overexpression of actin suppressed the growth defects caused by the deleted genes. The genes were highly enriched in several classes, including transfer RNA wobble uridine modification, chromosome stability and segregation, cell growth, and cell division. We show that actin overexpression sequesters a limited pool of eEF1A, a bifunctional protein involved in aminoacyl-transfer RNA recruitment to the ribosome and actin filament cross-linking. Surprisingly, the largest class of genes is involved in chromosome stability and segregation. We show that actin mutants have chromosome segregation defects, suggesting a possible role in chromosome structure and function. Monomeric actin is a core component of the INO80 and SWR chromatin remodeling complexes and the NuA4 histone modification complex, and our results suggest these complexes may be sensitive to actin stoichiometry. We propose that the resulting effects on chromatin structure can lead to synergistic effects on chromosome stability in strains lacking genes important for chromosome maintenance. PMID:23450344

  5. Intestinal alkaline phosphatase inhibits the proinflammatory nucleotide uridine diphosphate.

    PubMed

    Moss, Angela K; Hamarneh, Sulaiman R; Mohamed, Mussa M Rafat; Ramasamy, Sundaram; Yammine, Halim; Patel, Palak; Kaliannan, Kanakaraju; Alam, Sayeda N; Muhammad, Nur; Moaven, Omeed; Teshager, Abeba; Malo, Nondita S; Narisawa, Sonoko; Millán, José Luis; Warren, H Shaw; Hohmann, Elizabeth; Malo, Madhu S; Hodin, Richard A

    2013-03-15

    Uridine diphosphate (UDP) is a proinflammatory nucleotide implicated in inflammatory bowel disease. Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor capable of inhibiting intestinal inflammation. We used the malachite green assay to show that IAP dephosphorylates UDP. To study the anti-inflammatory effect of IAP, UDP or other proinflammatory ligands (LPS, flagellin, Pam3Cys, or TNF-α) in the presence or absence of IAP were applied to cell cultures, and IL-8 was measured. UDP caused dose-dependent increase in IL-8 release by immune cells and two gut epithelial cell lines, and IAP treatment abrogated IL-8 release. Costimulation with UDP and other inflammatory ligands resulted in a synergistic increase in IL-8 release, which was prevented by IAP treatment. In vivo, UDP in the presence or absence of IAP was instilled into a small intestinal loop model in wild-type and IAP-knockout mice. Luminal contents were applied to cell culture, and cytokine levels were measured in culture supernatant and intestinal tissue. UDP-treated luminal contents induced more inflammation on target cells, with a greater inflammatory response to contents from IAP-KO mice treated with UDP than from WT mice. Additionally, UDP treatment increased TNF-α levels in intestinal tissue of IAP-KO mice, and cotreatment with IAP reduced inflammation to control levels. Taken together, these studies show that IAP prevents inflammation caused by UDP alone and in combination with other ligands, and the anti-inflammatory effect of IAP against UDP persists in mouse small intestine. The benefits of IAP in intestinal disease may be partly due to inhibition of the proinflammatory activity of UDP.

  6. Book Review: Precession, Nutation, and Wobble of the Earth

    NASA Astrophysics Data System (ADS)

    Sterken, Christiaan; Dehant, V.; Mathews, P. M.

    2016-10-01

    This great book describes and explains observational and computational aspects of three apparently tiny changes in the Earth's motion and orientation, viz., precession, nutation, and wobble. The three introductory chapters of this book present fundamental definitions, elementary geodetic theory, and celestial/terrestrial reference systems - including transformations between reference frames. The next chapter on observational techniques describes the principle of accurate measurements of the orientation of the Earth's axis, as obtained from measurements of extra-galactic radio sources using Very Long Baseline Interferometry and GPS observations. Chapter 5 handles precession and nutation of the rigid Earth (i.e., a celestial body that cannot, by definition, deform) and the subsequent chapter takes deformation into consideration, viz., the effect of a centrifugal force caused by a constant-rate rotation that causes the Earth's shape and structure to become ellipsoidal. Deformations caused by external solar-system bodies are discussed in terms of deformability parameters. The next three chapters handle additional complex deviations: non-rigid Earth and more general Earth models, anelastic Earth parameters, and the effects of the fluid layers (i.e., ocean and atmosphere) on Earth rotation. Chapter 10 complements Chapter 7 with refinements that take into account diverse small effects such as the effect of a thermal conductive layer at the top of the core, Core Mantle and Inner Boundary coupling effects on nutation, electromagnetic coupling, and so-called topographic coupling. Chapter 11 covers comparison of observation and theory, and tells us that the present-date precision of the nutation theory is at the level of milliarcseconds in the time domain, and of a tenth of a microsecond in the frequency domain (with some exceptions). This chapter is followed by a 25-page chapter of definitions of equator, equinox, celestial intermediate pole and origin, stellar angle

  7. Synthesis and P2Y2 Receptor Agonist Activities of Uridine 5’-Phosphonate Analogues

    PubMed Central

    Van Poecke, Sara; Barrett, Matthew O.; Kumar, T. Santhosh; Sinnaeve, Davy; Martins, José C.; Jacobson, Kenneth A.; Harden, T. Kendall; Van Calenbergh, Serge

    2012-01-01

    We explored the influence of modifications of uridine 5’-methylenephosphonate on biological activity at the human P2Y2 receptor. Key steps in the synthesis of a series of 5-substituted uridine 5’-methylenephosphonates were the reaction of a suitably protected uridine 5’-aldehyde with [(diethoxyphosphinyl)methylidene]triphenylphosphorane, C-5 bromination and a Suzuki–Miyaura coupling. These analogues behaved as selective agonists at the P2Y2 receptor, with three analogues exhibiting potencies in the submicromolar range. Although maximal activities observed with the phosphonate analogues were much less than observed with UTP, high concentrations of the phosphonates had no effect on the stimulatory effect of UTP. These results suggest that these phosphonates bind to an allosteric site of the P2Y2 receptor. PMID:22386981

  8. [Influence of drying method on content of epigoitrin and uridine in isatidis radix].

    PubMed

    Tan, Ming-Ming; Huang, Yong; Xu, Xiao-Fei; Zhang, Zhuo-Neng; Deng, Qiao-Hua

    2014-04-01

    To study the influence of different drying methods on the content of epigoitrin and uridine in Isatidis Radix. Fresh Isatidis Radix was processed by four drying methods including airing drying and drying in far infrared oven at different temperature,drying in the sun and drying in the shade. The contents of epigoitrin and uridine were determined by HPLC. The contents of epigoitrin as well as uridine in samples valued from 3.847 - 5.204 mg/g and 0.701 - 1.028 mg/g, respectively. The optimal drying method is airing drying at 55 degrees C, which will be serviced in the large-scale processing of Isatidis Radix.

  9. How to detect the Chandler and the annual wobble of the Earth with a large ring laser gyroscope.

    PubMed

    Schreiber, K U; Klügel, T; Wells, J-P R; Hurst, R B; Gebauer, A

    2011-10-21

    We demonstrate a 16 m(2) helium-neon ring laser gyroscope with sufficient sensitivity and stability to directly detect the Chandler wobble of the rotating Earth. The successful detection of both the Chandler and the annual wobble is verified by comparing the time series of the ring laser measurements against the "C04 series" of Earth rotation data from the International Earth Rotation and Reference System Service.

  10. How to Detect the Chandler and the Annual Wobble of the Earth with a Large Ring Laser Gyroscope

    NASA Astrophysics Data System (ADS)

    Schreiber, K. U.; Klügel, T.; Wells, J.-P. R.; Hurst, R. B.; Gebauer, A.

    2011-10-01

    We demonstrate a 16m2 helium-neon ring laser gyroscope with sufficient sensitivity and stability to directly detect the Chandler wobble of the rotating Earth. The successful detection of both the Chandler and the annual wobble is verified by comparing the time series of the ring laser measurements against the “C04 series” of Earth rotation data from the International Earth Rotation and Reference System Service.

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

    PubMed

    Du, Weiliang; Gao, Song

    2011-08-01

    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. 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 sub-pixel 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. 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. 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.

  12. 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.

  13. Analysis of Chandler wobble excitation, reconstructed from observations of the polar motion of the Earth

    NASA Astrophysics Data System (ADS)

    Zotov, L. V.

    2011-10-01

    Chandler excitation was reconstructed since 1846 yr. from EOP C01 by three methods: complex Singular Spectrum Analysis (SSA) with Wilson filter, least squares adjustment (LSA) with Tikhonov regularization, Panteleev smoothing. The aim was to damp annual component and side frequencies and to obtain excitation only for chandler wobble. Results of different methods are in agreement with each other. Modulation of Chandler excitation of ~18.6 yr period, synchronous with Saros tidal effects in the length of the day (LOD) was found. It means that Chandler wobble swings under the influence of Luni-Solar tide. Amplitude and phase evolution in time was analyzed with use of Gabor transform. Phase changes in Chandler excitation found to have ~37 yr period. It explains, why 18.6 yr modulation is not seen in the Chandler component itself, but only in its excitation.

  14. Active-passive biodynamics of the human trunk when seated on a wobble chair.

    PubMed

    Shahvarpour, A; Shirazi-Adl, A; Larivière, C

    2016-04-11

    Unstable sitting on a wobble chair with different balance difficulty levels can be used as an effective tool in exercises as well as evaluation and therapeutic stages of rehabilitation. No data on muscle activity levels and spinal loads are however available to assess its safety compared to other regular daily activities. The goal of this study was to estimate muscle forces and spinal loads in a seated unstable wobble chair task. In vivo 3D kinematics of the trunk and seat collected in an earlier study were used here to drive computational trunk musculoskeletal models of 6 normal and 6 low-back pain subject groups sitting on a wobble chair for a duration of 10s. Results revealed no significant differences between kinematics, muscle forces, spinal loads and force plate reaction forces when comparing these two groups. The estimated muscle forces and spinal loads were moderate though larger than those in a stationary sitting posture. Local spinal forces at the L5-S1 disc varied with time and reached their peaks (1473 N and 1720 N in compression, 691 N and 687 N in posterior-anterior shear and 153 N and 208 N in right-left shear, respectively for healthy and CLBP groups) being much greater relative to those in the stationary sitting posture (means of 12 subjects: 768 N, 284 N and 0 N, respectively). The wobble chair with characteristics considered in this study is found hence safe enough as a therapeutic exercise for both healthy and low-back pain subjects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. An innate twist between Crick's wobble and Watson-Crick base pairs.

    PubMed

    Ananth, Prakash; Goldsmith, Gunaseelan; Yathindra, Narayanarao

    2013-08-01

    Non-Watson-Crick pairs like the G·U wobble are frequent in RNA duplexes. Their geometric dissimilarity (nonisostericity) with the Watson-Crick base pairs and among themselves imparts structural variations decisive for biological functions. Through a novel circular representation of base pairs, a simple and general metric scheme for quantification of base-pair nonisostericity, in terms of residual twist and radial difference that can also envisage its mechanistic effect, is proposed. The scheme is exemplified by G·U and U·G wobble pairs, and their predicable local effects on helical twist angle are validated by MD simulations. New insights into a possible rationale for contextual occurrence of G·U and other non-WC pairs, as well as the influence of a G·U pair on other non-Watson-Crick pair neighborhood and RNA-protein interactions are obtained from analysis of crystal structure data. A few instances of RNA-protein interactions along the major groove are documented in addition to the well-recognized interaction of the G·U pair along the minor groove. The nonisostericity-mediated influence of wobble pairs for facilitating helical packing through long-range interactions in ribosomal RNAs is also reviewed.

  16. New determination of period and quality factor of Chandler wobble, considering geophysical excitations

    NASA Astrophysics Data System (ADS)

    Vondrák, J.; Ron, C.; Chapanov, Ya.

    2017-03-01

    Polar motion consists of both free (Chandler wobble, with approximately 14-month period) and forced components. The latter are caused by different excitations of geophysical origin. Very long-periodic (or secular) part is most probably due to post-glacial rebound, shorter periodic part (with dominant annual period) are caused mainly by motions of the atmosphere and oceans. Recently it was also proposed that impulse-like excitations due to geomagnetic jerks might be responsible for rapid changes of the amplitude and phase of Chandler wobble. In order to precisely determine the parameters of the free part, it is necessary to consider all these influences. We use the IERS combined solution C04 together with ERA atmospheric/oceanic excitations in the interval 1974.0-2014.0, and also additional excitations due to nine geomagnetic jerks, registered during this interval, to determine the period and quality factor of Chandler wobble, free from these geophysical effects. We obtained solutions for three different time intervals: 1974.0-1994.0, 1994.0-2014.0, and 1974.0-2014.0. The estimated values of Q-factor are much smaller if GMJ excitations are used in addition to atmospheric and oceanic ones, and they are determined with higher accuracy. Our preferred values, valid for the whole interval 1974.0-2014.0, are P = 432.86 ± 0.04 days and Q = 35.0 ± 0.3 .

  17. An innate twist between Crick’s wobble and Watson-Crick base pairs

    PubMed Central

    Ananth, Prakash; Goldsmith, Gunaseelan; Yathindra, Narayanarao

    2013-01-01

    Non-Watson-Crick pairs like the G·U wobble are frequent in RNA duplexes. Their geometric dissimilarity (nonisostericity) with the Watson-Crick base pairs and among themselves imparts structural variations decisive for biological functions. Through a novel circular representation of base pairs, a simple and general metric scheme for quantification of base-pair nonisostericity, in terms of residual twist and radial difference that can also envisage its mechanistic effect, is proposed. The scheme is exemplified by G·U and U·G wobble pairs, and their predicable local effects on helical twist angle are validated by MD simulations. New insights into a possible rationale for contextual occurrence of G·U and other non-WC pairs, as well as the influence of a G·U pair on other non-Watson-Crick pair neighborhood and RNA-protein interactions are obtained from analysis of crystal structure data. A few instances of RNA-protein interactions along the major groove are documented in addition to the well-recognized interaction of the G·U pair along the minor groove. The nonisostericity-mediated influence of wobble pairs for facilitating helical packing through long-range interactions in ribosomal RNAs is also reviewed. PMID:23861536

  18. 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

  19. 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

  20. 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.

  1. Truncation Effects in Computing Free Wobble/Nutation Modes Explored Using a Simple Earth Model

    NASA Astrophysics Data System (ADS)

    Seyed-Mahmoud, B.; Rochester, M. G.; Rogers, C. M.

    2016-12-01

    The displacement field accompanying the wobble/nutation of the Earth is conventionally represented by an infinite chain of toroidal and spheroidal vector spherical harmonics, coupled by rotation and ellipticity. Numerical solutions for the eigenperiods require truncation of that chain, and the standard approaches using the linear momentum description (LMD) of deformation during wobble/nutation have truncated it at very low degrees, usually degree 3 or 4, and at most degree 5. The effects of such heavy truncation on the computed eigenperiods have hardly been examined. We here investigate the truncation effects on the periods of the free wobble/nutation modes using a simplified Earth model consisting of a homogeneous incompressible inviscid liquid outer core with a rigid (but not fixed) inner core and mantle. A novel Galerkin method is implemented using a Clairaut coordinate system to solve the classic Poincare problem in the liquid core and, to close the problem, we use the Lagrangean formulation of the Liouville equation for each of the solid parts of the Earth model. We find that, except for the free inner core nutation (FICN), the periods of the free rotational modes converge rather quickly. The period of the tiltover mode (TOM) is found to excellent accuracy. The computed periods of the Chandler wobble (CW) and free core nutation (FCN) are nearly identical to the values cited in the literature for similar Earth models, but that for the inner core wobble (ICW) is slightly different. Truncation at low-degree harmonics causes the FICN period to fluctuate over a range as large as 90 sd, with different values at different truncation levels. For example, truncation at degree 6 gives a period of 752 sd (almost identical with the value cited in the literature for such an Earth model) but truncation at degree 24 is required to obtain convergence, and the resulting period is 746 sd, with no guarantee that its proximity to earlier values is other than fortuitous. We

  2. Truncation effects in computing free wobble/nutation modes explored using a simple Earth model

    NASA Astrophysics Data System (ADS)

    Seyed-Mahmoud, Behnam; Rochester, Michael G.; Rogers, Christopher M.

    2017-03-01

    The displacement field accompanying the wobble/nutation of the Earth is conventionally represented by an infinite chain of toroidal and spheroidal vector spherical harmonics, coupled by rotation and ellipticity. Numerical solutions for the eigenperiods require truncation of that chain, and the standard approaches using the linear momentum description (LMD) of deformation during wobble/nutation have truncated it at very low degrees, usually degree 3 or 4, and at most degree 5. The effects of such heavy truncation on the computed eigenperiods have hardly been examined. We here investigate the truncation effects on the periods of the free wobble/nutation modes using a simplified Earth model consisting of a homogeneous incompressible inviscid liquid outer core with a rigid (but not fixed) inner core and mantle. A novel Galerkin method is implemented using a Clairaut coordinate system to solve the classic Poincaré problem in the liquid core and, to close the problem, we use the Lagrangean formulation of the Liouville equation for each of the solid parts of the Earth model. We find that, except for the free inner core nutation (FICN), the periods of the free rotational modes converge rather quickly. The period of the tiltover mode (TOM) is found to excellent accuracy. The computed periods of the Chandler wobble (CW) and free core nutation (FCN) are nearly identical to the values cited in the literature for similar Earth models, but that for the inner core wobble (ICW) is slightly different. Truncation at low-degree harmonics causes the FICN period to fluctuate over a range as large as 90 sd, with different values at different truncation levels. For example, truncation at degree 6 gives a period of 752 sd (almost identical with the value cited in the literature for such an Earth model) but truncation at degree 24 is required to obtain convergence, and the resulting period is 746 ± 1 sd, as more terms are included, with no guarantee that its proximity to earlier values

  3. Truncation effects in computing free wobble/nutation modes explored using a simple Earth model

    NASA Astrophysics Data System (ADS)

    Seyed-Mahmoud, Behnam; Rochester, Michael G.; Rogers, Christopher M.

    2017-06-01

    The displacement field accompanying the wobble/nutation of the Earth is conventionally represented by an infinite chain of toroidal and spheroidal vector spherical harmonics, coupled by rotation and ellipticity. Numerical solutions for the eigenperiods require truncation of that chain, and the standard approaches using the linear momentum description (LMD) of deformation during wobble/nutation have truncated it at very low degrees, usually degree 3 or 4, and at most degree 5. The effects of such heavy truncation on the computed eigenperiods have hardly been examined. We here investigate the truncation effects on the periods of the free wobble/nutation modes using a simplified Earth model consisting of a homogeneous incompressible inviscid liquid outer core with a rigid (but not fixed) inner core and mantle. A novel Galerkin method is implemented using a Clairaut coordinate system to solve the classic Poincaré problem in the liquid core and, to close the problem, we use the Lagrangean formulation of the Liouville equation for each of the solid parts of the Earth model. We find that, except for the free inner core nutation (FICN), the periods of the free rotational modes converge rather quickly. The period of the tiltover mode is found to excellent accuracy. The computed periods of the Chandler wobble and free core nutation are nearly identical to the values cited in the literature for similar Earth models, but that for the inner core wobble is slightly different. Truncation at low-degree harmonics causes the FICN period to fluctuate over a range as large as 90 sd, with different values at different truncation levels. For example, truncation at degree 6 gives a period of 752 sd (almost identical with the value cited in the literature for such an Earth model) but truncation at degree 24 is required to obtain convergence, and the resulting period is 746 ± 1 sd, as more terms are included, with no guarantee that its proximity to earlier values is other than fortuitous

  4. Uridine supplementation in the treatment of HIV lipoatrophy: Results of ACTG 5229

    PubMed Central

    McComsey, Grace A; Walker, Ulrich A; Budhathoki, Chakra B; Su, Zhaohui; Currier, Judith S; Kosmiski, Lisa; Naini, Linda G; Charles, Stéphannie; Medvik, Kathy; Aberg, Judith A

    2010-01-01

    BACKGROUND Lipoatrophy is prevalent on thymidine NRTIs (tNRTI). A pilot trial showed that uridine (NucleomaxX®) increased limb fat. METHODS A5229 was a multicenter trial in which HIV-infected individuals with lipoatrophy on tNRTI-regimens were randomized to NucleomaxX or placebo. Primary endpoint was change in limb fat from baseline to week-48. The study was powered to detect 400-gram difference between arms at week-48. A stratified Wilcoxon rank-sum test was used to assess between-arm differences. RESULTS The 165 subjects were 91% male, 62% white; median age 49 years, CD4 506 cells/mm3, and limb fat 3037 grams; 81% had HIV-1 RNA ≤50 copies/mL; 76% were on AZT. Baseline characteristics were similar between groups. Only 59% completed 48-weeks of treatment, however only 3 subjects (1 on uridine) discontinued due to toxicity (diarrhea). In intent-to-treat, there was no difference for changes in limb fat between treatments at week-24 or week-48. On as-treated analysis, uridine resulted in an increase in %limb fat vs. placebo (3.4% vs. −0.8%, p=0.01) at week-24 but not at week-48 (1.8% vs.3.8%, p=0.93). Similar results were seen when limiting the analysis to subjects with ≥80% adherence. The results were not related to severity of lipoatrophy or type of tNRTI. No changes were found in facial-anthropometrics, fasting lipids, trunk-fat, CD4, or HIV-RNA. CONCLUSIONS We found a modest transient improvement in limb fat after 24 weeks of uridine. The lack of sustained efficacy at week-48 was not due to changes in adherence or reduction in sample size. Uridine was safe and did not impair virologic control. PMID:20827170

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. Amplitude and phase variations of the chandler wobble from 164-yr polar motion series

    NASA Astrophysics Data System (ADS)

    Malkin, Z. M.; Miller, N. O.

    2011-10-01

    This paper is aimed at investigation of the Chandler wobble (CW) at the 164-year interval to search for the major CW amplitude and phase variations. The CW signal was extracted from the IERS polar motion series using digital filtering. The CW amplitude and phase variations were examined by means of several methods which yield very similar results. Results of our analysis have shown that, besides the well-known CW phase jump in the 1920s, two other large phase jumps have been found in the 1850s and 2000s, all three contemporarily with a sharp decrease in the CW amplitude.

  10. Structure of the homodimer of uridine phosphorylase from Salmonella typhimurium in the native state at 1.9 Å resolution

    NASA Astrophysics Data System (ADS)

    Timofeev, V. I.; Pavlyuk, B. F.; Lashkov, A. A.; Seregina, T. A.; Gabdulkhakov, A. G.; Vaĭnshteĭn, B. K.; Mikhaĭlov, A. M.

    2007-11-01

    Uridine phosphorylase ( UPh) belongs to pyrimidine nucleoside phosphorylases. This enzyme catalyzes cleavage of the C-N glycoside bond in uridine to form uracil and ribose-1’-phosphate. Uridine phosphorylase supplies cells with nucleotide precursors by catalyzing the phosphorolysis of purine and pyrimidine nucleosides. This is an alternative to de novo nucleotide synthesis. The three-dimensional structure of native uridine phosphorylase from Salmonella typhimurium ( StUPh) in a new crystal form was solved and refined at 1.90 Å resolution ( R st = 20.37%; R free = 24.69%; the rmsd of bond lengths and bond angles are 0.009 Å and 1.223°, respectively). A homodimer containing two asynchronously functioning active sites was demonstrated to be the minimum structural unit necessary for function of the hexameric StUPh molecule ( L 33 L 2). Each active site is formed by amino acid residues of both subunits.

  11. Synthesis and preliminary biological assay of uridine glycoconjugate derivatives containing amide and/or 1,2,3-triazole linkers.

    PubMed

    Pastuch-Gawolek, Gabriela; Plesniak, Mateusz; Komor, Roman; Byczek-Wyrostek, Anna; Erfurt, Karol; Szeja, Wieslaw

    2017-06-01

    A series of UDP-sugar analogues was synthesized and their preliminary biological activity was evaluated. Glycoconjugates of uridine 1 and 2 were synthesized by condensation of uridine-5'-carboxylic acid and 1-amino sugars derivatives of d-glucose and d-galactose, glycoconjugates 3 and 4 were synthesized by azide-alkyne 1,3-dipolar cycloaddition (CuAAC) of 1-azido sugars and propargylamide derivatives of uridine while glycoconjugates 5 and 6 were synthesized by CuAAC of propargyl β-O-glycosides and 5'-azido uridine. Evaluation of inhibitory activity of compounds 1-6 against commercially available β-1,4-galactosyltransferase I (β4GalT) show that compound 5 inhibited the enzyme in µmolar range. Additionally, the antitumor activity of the obtained glycoconjugates 1-6 were tested using MTT assay. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Preliminary investigation of the three-dimensional structure of Salmonella typhimurium uridine phosphorylase in the crystalline state.

    PubMed

    Dontsova, Maria V; Gabdoulkhakov, Azat G; Molchan, Olga K; Lashkov, Alexandr A; Garber, Maria B; Mironov, Alexandr S; Zhukhlistova, Nadegda E; Morgunova, Ekaterina Yu; Voelter, Wolfgang; Betzel, Christian; Zhang, Yang; Ealick, Steven E; Mikhailov, Al'bert M

    2005-04-01

    Uridine phosphorylase (UPh) catalyzes the phosphorolytic cleavage of the C-N glycosidic bond of uridine to ribose 1-phosphate and uracil in the pyrimidine-salvage pathway. The crystal structure of the Salmonella typhimurium uridine phosphorylase (StUPh) has been determined at 2.5 A resolution and refined to an R factor of 22.1% and an Rfree of 27.9%. The hexameric StUPh displays 32 point-group symmetry and utilizes both twofold and threefold non-crystallographic axes. A phosphate is bound at the active site and forms hydrogen bonds to Arg91, Arg30, Thr94 and Gly26 of one monomer and Arg48 of an adjacent monomer. The hexameric StUPh model reveals a close structural relationship to Escherichia coli uridine phosphorylase (EcUPh).

  13. Preliminary investigation of the three-dimensional structure of Salmonella typhimurium uridine phosphorylase in the crystalline state

    PubMed Central

    Dontsova, Maria V.; Gabdoulkhakov, Azat G.; Molchan, Olga K.; Lashkov, Alexandr A.; Garber, Maria B.; Mironov, Alexandr S.; Zhukhlistova, Nadegda E.; Morgunova, Ekaterina Yu.; Voelter, Wolfgang; Betzel, Christian; Zhang, Yang; Ealick, Steven E.; Mikhailov, Al’bert M.

    2005-01-01

    Uridine phosphorylase (UPh) catalyzes the phosphorolytic cleavage of the C—­N glycosidic bond of uridine to ribose 1-phosphate and uracil in the pyrimidine-salvage pathway. The crystal structure of the Salmonella typhimurium uridine phosphorylase (StUPh) has been determined at 2.5 Å resolution and refined to an R factor of 22.1% and an R free of 27.9%. The hexameric StUPh displays 32 point-group symmetry and utilizes both twofold and threefold non-crystallographic axes. A phosphate is bound at the active site and forms hydrogen bonds to Arg91, Arg30, Thr94 and Gly26 of one monomer and Arg48 of an adjacent monomer. The hexameric StUPh model reveals a close structural relationship to Escherichia coli uridine phosphorylase (EcUPh). PMID:16511035

  14. The relation between motor activity and [3H]uridine uptake in the mouse brain.

    PubMed

    Pakkenberg, H; Fog, R

    2006-12-01

    Using microautoradiography ex vivo we tested the effect of forced running on a roller drum for 3 h on the nuclear incorporation of [5-(3)H uridine] in mouse brain. Specific neuron types with increased nuclear labelling included primary motor cortex layer 5 nerve cells with nuclei greater than 12 microm (+38%) and large neuron nuclei in putamen (+58%). Mice running for 45 min do not show any change in the labelling of nerve cell nuclei compared with mice moving freely in the cage. The [(3)H]uridine uptake in other cell types, e.g. other neurons in cortical layer 5, neurons in sensory cortex and in the other cell layers in motor cortex, were not different from control mice. We conclude that RNA synthesis is normally low in adult mouse brain, but that physical exercise stimulates RNA synthesis in specific populations of large neurons in the motor system.

  15. Soft tissue contributions to impact forces simulated using a four-segment wobbling mass model of forefoot-heel landings.

    PubMed

    Gittoes, Marianne J R; Brewin, Mark A; Kerwin, David G

    2006-12-01

    The purpose of this investigation was to develop and evaluate a wobbling mass model of a female performing a drop landing and to examine the influence of soft tissue properties on the impact loads experienced. A planar model comprising a foot, shank, thigh and upper body segment was developed. Spring-damper systems coupled the foot to the ground and the wobbling masses to the rigid masses. Unlike traditional wobbling mass models of landing, the model included a foot segment, which allowed replication of forefoot-heel landing techniques and also used subject and movement-specific properties to simulate the landings. Kinematics and force data collected for three drop landings (height 0.46 m) performed by a female were separately used to drive and evaluate the model. The wobbling mass model successfully reproduced the measured force profiles to 9% (RMS differences) of the measured range and replicated the measured peak vertical ground reaction forces to 6%. The accuracies of the wobbling mass model and a corresponding rigid mass model were compared. The inclusion of soft tissue properties in the model contributed up to an 8.6 bodyweights reduction in peak impact loading and produced a 52% more accurate replication of the measured force profiles. The prominent role soft tissues have in load attenuation and the benefits of modelling soft tissue in simulations of landings were therefore highlighted. The success of the wobbling mass model in replicating the kinetics of actual landing performances suggests the model may be used in the future to gain a realistic insight into load attenuation strategies used by females.

  16. 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.

  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. Heterogeneity of uridine incorporation along the rabbit nephron. I. Autoradiographic study

    SciTech Connect

    Vandewalle, A.; Farman, N.; Cluzeaud, F.; Bonvalet, J.P.

    1984-04-01

    An autoradiographic study of uridine labeling in tubular segments microdissected from the rabbit kidney is presented. Kidney pyramids were incubated for 60 min with low (66 nM) and high (66..mu..M) (/sup 3/H)-uridine concentration. At the two concentrations studied the labeling was almost exclusively nuclear in all segments studied. At the low concentration, labeling predominated in the macula densa (MD = 63.88 +/- 6.15 silver grains/100 ..mu..m/sup 2/, n = 11), cortical ascending limb (CAL = 19.65 +/- 1.65, n = 15), and initial distal tubule (DCT/sub a/ = 24.31 +/- 2.70, n = 6). It was minimal in the proximal tubule (PCT/sub 2/ = 9.14 +/- 1.61, n = 16) and in the cortical (CCT = 5.23 +/- 0.75, n = 18) and medullary (MCT = 5.52 +/- 1.10, n = 12) collecting ducts. At a high concentration, the profile of labeling was roughly similar except for a relative increase in labeling much more pronounced in collecting ducts (CCT = +373, MCT = +323%) than in the other structures (MD = -14, CAL = +66, DCT/sub a/ = +49, PCT = +9%). Pulse-chase experiments do not show evidence for differences in turnover or degradation rates of RNA between segments, at least in the PCT and the connecting part of the CCT. Analysis of the results at low and high concentration suggests that the observed heterogeneity in uridine labeling depends on both variable endogenous nucleoside pools and different rates of uridine incorporation into RNA from one segment to another.

  19. High-performance wobbling subreflector for the Millimetre and Infrared Testa Grigia Observatory 2.6-m telescope

    NASA Astrophysics Data System (ADS)

    Mainella, Gianni; de Bernardis, Paolo; de Petris, Marco; Mandiello, Alfonso; Perciballi, Maurizio; Romeo, Gianni

    1996-05-01

    The Millimetre and Infrared Testa Grigia Observatory 2.6-m Cassegrain telescope has been designed to allow high-sensitivity observations in the millimeter spectral range. For this purpose, in order to reduce unwanted contributions from local foregrounds, we adopted a sky-chopping technique, by wobbling the telescope subreflector. We describe the design and performance of the wobbling system, which can endure external forced two and three fields square-wave modulation and includes features such as high frequency, high amplitude, high duty cycle, low microphonics, and high stability. millimeter-wave telescope.

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

    PubMed Central

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

    2015-01-01

    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 tRNATyr 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

  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. 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.

  3. Free and forced polar motion and modern observations of the Chandler wobble

    NASA Astrophysics Data System (ADS)

    Smylie, Doug E.; Zuberi, Midhat

    2009-12-01

    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 particular, we are encouraged that a break in the pole path was found 11 days before the December 26, 2004 Sumatra-Andaman Islands earthquake ( M=9.1).

  4. Determinants of the CmoB carboxymethyl transferase utilized for selective tRNA wobble modification

    PubMed Central

    Kim, Jungwook; Xiao, Hui; Koh, Junseock; Wang, Yikai; Bonanno, Jeffrey B.; Thomas, Keisha; Babbitt, Patricia C.; Brown, Shoshana; Lee, Young-Sam; Almo, Steven C.

    2015-01-01

    Enzyme-mediated modifications at the wobble position of tRNAs are essential for the translation of the genetic code. We report the genetic, biochemical and structural characterization of CmoB, the enzyme that recognizes the unique metabolite carboxy-S-adenosine-L-methionine (Cx-SAM) and catalyzes a carboxymethyl transfer reaction resulting in formation of 5-oxyacetyluridine at the wobble position of tRNAs. CmoB is distinctive in that it is the only known member of the SAM-dependent methyltransferase (SDMT) superfamily that utilizes a naturally occurring SAM analog as the alkyl donor to fulfill a biologically meaningful function. Biochemical and genetic studies define the in vitro and in vivo selectivity for Cx-SAM as alkyl donor over the vastly more abundant SAM. Complementary high-resolution structures of the apo- and Cx-SAM bound CmoB reveal the determinants responsible for this remarkable discrimination. Together, these studies provide mechanistic insight into the enzymatic and non-enzymatic feature of this alkyl transfer reaction which affords the broadened specificity required for tRNAs to recognize multiple synonymous codons. PMID:25855808

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

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

    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↻ and j↻ 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 γ 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° (Rπ) i.e., RπT 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 163Lu.

  6. Variable Chandler and Annual Wobbles in Earth's Polar Motion During 1900-2015

    NASA Astrophysics Data System (ADS)

    Wang, Guocheng; Liu, Lintao; Su, Xiaoqing; Liang, Xinghui; Yan, Haoming; Tu, Yi; Li, Zhonghua; Li, Wenping

    2016-11-01

    The Chandler wobble (CW) and annual wobble (AW) are the two main components of polar motion, which are difficult to separate because of their very close periods. In the light of Fourier dictionary and basis pursuit method, a Fourier basis pursuit (FBP) spectrum is developed, which can reduce spectral smearing and leakage caused by the finite length of the time series. Further, a band-pass filtering method based on FBP spectrum (FBPBPF), which can effectively suppress the edge effect, is proposed in this paper. The simulation test results show that the FBPBPF method can effectively suppress the edge effect caused by spectral smearing and leakage and that its reconstruction accuracy at the boundary is approximately three times higher than the Fourier transform band-pass filtering method, which is based on Hamming windowed FFT spectrum, in extracting quasi-harmonic signals. The FBPBPF method is then applied to Earth's polar motion data during 1900-2015. Through analyzing the amplitude and period variations of CW and AW, and calculating the eccentricity variation of the AW, we found that: (1) the amplitude of the CW is currently at a historic minimum level, and it is even possible to diminish further until a complete stop; and (2) the eccentricity of the AW has a gradually decreased fluctuation during the last 116 years.

  7. 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.

  8. X-ray structure of Salmonella typhimurium uridine phosphorylase complexed with 5-fluorouracil and molecular modelling of the complex of 5-fluorouracil with uridine phosphorylase from Vibrio cholerae.

    PubMed

    Lashkov, Alexander A; Sotnichenko, Sergey E; Prokofiev, Igor I; Gabdulkhakov, Azat G; Agapov, Igor I; Shtil, Alexander A; Betzel, Christian; Mironov, Alexander S; Mikhailov, Al'bert M

    2012-08-01

    Uridine phosphorylase (UPh), which is a key enzyme in the reutilization pathway of pyrimidine nucleoside metabolism, is a validated target for the treatment of infectious diseases and cancer. A detailed analysis of the interactions of UPh with the therapeutic ligand 5-fluorouracil (5-FUra) is important for the rational design of pharmacological inhibitors of these enzymes in prokaryotes and eukaryotes. Expanding on the preliminary analysis of the spatial organization of the active centre of UPh from the pathogenic bacterium Salmonella typhimurium (StUPh) in complex with 5-FUra [Lashkov et al. (2009), Acta Cryst. F65, 601-603], the X-ray structure of the StUPh-5-FUra complex was analysed at atomic resolution and an in silico model of the complex formed by the drug with UPh from Vibrio cholerae (VchUPh) was generated. These results should be considered in the design of selective inhibitors of UPhs from various species.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  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. Metabolomics profiles delineate uridine deficiency contributes to mitochondria-mediated apoptosis induced by celastrol in human acute promyelocytic leukemia cells

    PubMed Central

    Li, Lei; Huan, Fei; Li, Aiping; Liu, Yanqing; Xia, Yankai; Duan, Jin-ao; Ma, Shiping

    2016-01-01

    Celastrol, extracted from “Thunder of God Vine”, is a promising anti-cancer natural product. However, its effect on acute promyelocytic leukemia (APL) and underlying molecular mechanism are poorly understood. The purpose of this study was to explore its effect on APL and underlying mechanism based on metabolomics. Firstly, multiple assays indicated that celastrol could induce apoptosis of APL cells via p53-activated mitochondrial pathway. Secondly, unbiased metabolomics revealed that uridine was the most notable changed metabolite. Further study verified that uridine could reverse the apoptosis induced by celastrol. The decreased uridine was caused by suppressing the expression of gene encoding Dihydroorotate dehydrogenase, whose inhibitor could also induce apoptosis of APL cells. At last, mouse model confirmed that celastrol inhibited tumor growth through enhanced apoptosis. Celastrol could also decrease uridine and DHODH protein level in tumor tissues. Our in vivo study also indicated that celastrol had no systemic toxicity at pharmacological dose (2 mg/kg, i.p., 21 days). Altogether, our metabolomics study firstly reveals that uridine deficiency contributes to mitochondrial apoptosis induced by celastrol in APL cells. Celastrol shows great potential for the treatment of APL. PMID:27374097

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

    PubMed

    Timofeev, Vladimir I; Lashkov, Alexander A; Gabdoulkhakov, Azat G; Pavlyuk, Bogdan Ph; Kachalova, Galina S; Betzel, Christian; Morgunova, Ekaterina Yu; Zhukhlistova, Nadezhda E; Mikhailov, Al'bert M

    2007-10-01

    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 A. Preliminary analysis of the diffraction data indicates that the crystal belongs to space group P2(1)2(1)2(1), with unit-cell parameters a = 88.52, b = 123.98, c = 133.52 A. The solvent content is 45.51%, assuming the presence of one hexamer molecule per asymmetric unit.

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

    PubMed Central

    Timofeev, Vladimir I.; Lashkov, Alexander A.; Gabdoulkhakov, Azat G.; Pavlyuk, Bogdan Ph.; Kachalova, Galina S.; Betzel, Christian; Morgunova, Ekaterina Yu.; Zhukhlistova, Nadezhda E.; Mikhailov, Al’bert M.

    2007-01-01

    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 P212121, 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. PMID:17909287

  17. Modified nucleoside dependent Watson-Crick and wobble codon binding by tRNALysUUU species.

    PubMed

    Yarian, C; Marszalek, M; Sochacka, E; Malkiewicz, A; Guenther, R; Miskiewicz, A; Agris, P F

    2000-11-07

    Nucleoside modifications are important to the structure of all tRNAs and are critical to the function of some tRNA species. The transcript of human tRNA(Lys3)(UUU) with a UUU anticodon, and the corresponding anticodon stem and loop domain (ASL(Lys3)(UUU)), are unable to bind to poly-A programmed ribosomes. To determine if specific anticodon domain modified nucleosides of tRNA(Lys) species would restore ribosomal binding and also affect thermal stability, we chemically synthesized ASL(Lys) heptadecamers and site-specifically incorporated the anticodon domain modified nucleosides pseudouridine (Psi(39)), 5-methylaminomethyluridine (mnm(5)U(34)) and N6-threonylcarbamoyl-adenosine (t(6)A(37)). Incorporation of t(6)A(37) and mnm(5)U(34) contributed structure to the anticodon loop, apparent by increases in DeltaS, and significantly enhanced the ability of ASL(Lys3)(UUU) to bind poly-A programmed ribosomes. Neither ASL(Lys3)(UUU)-t(6)A(37) nor ASL(Lys3)(UUU)-mnm(5)U(34) bound AAG programmed ribosomes. Only the presence of both t(6)A(37) and mnm(5)U(34) enabled ASL(Lys3)(UUU) to bind AAG programmed ribosomes, as well as increased its affinity for poly-A programmed ribosomes to the level of native Escherichia coli tRNA(Lys). The completely unmodified anticodon stem and loop of human tRNA(Lys1,2)(CUU) with a wobble position-34 C bound AAG, but did not wobble to AAA, even when the ASL was modified with t(6)A(37). The data suggest that tRNA(Lys)(UUU) species require anticodon domain modifications in the loop to impart an ordered structure to the anticodon for ribosomal binding to AAA and require a combination of modified nucleosides to bind AAG.

  18. 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.

  19. 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.

  20. Novel poly-uridine insertion in the 3'UTR and E2 amino acid substitutions in a low virulent classical swine fever virus.

    PubMed

    Coronado, Liani; Liniger, Matthias; Muñoz-González, Sara; Postel, Alexander; Pérez, Lester Josue; Pérez-Simó, Marta; Perera, Carmen Laura; Frías-Lepoureau, Maria Teresa; Rosell, Rosa; Grundhoff, Adam; Indenbirken, Daniela; Alawi, Malik; Fischer, Nicole; Becher, Paul; Ruggli, Nicolas; Ganges, Llilianne

    2017-03-01

    In this study, we compared the virulence in weaner pigs of the Pinar del Rio isolate and the virulent Margarita strain. The latter caused the Cuban classical swine fever (CSF) outbreak of 1993. Our results showed that the Pinar del Rio virus isolated during an endemic phase is clearly of low virulence. We analysed the complete nucleotide sequence of the Pinar del Rio virus isolated after persistence in newborn piglets, as well as the genome sequence of the inoculum. The consensus genome sequence of the Pinar del Rio virus remained completely unchanged after 28days of persistent infection in swine. More importantly, a unique poly-uridine tract was discovered in the 3'UTR of the Pinar del Rio virus, which was not found in the Margarita virus or any other known CSFV sequences. Based on RNA secondary structure prediction, the poly-uridine tract results in a long single-stranded intervening sequence (SS) between the stem-loops I and II of the 3'UTR, without major changes in the stem- loop structures when compared to the Margarita virus. The possible implications of this novel insertion on persistence and attenuation remain to be investigated. In addition, comparison of the amino acid sequence of the viral proteins E(rns), E1, E2 and p7 of the Margarita and Pinar del Rio viruses showed that all non-conservative amino acid substitutions acquired by the Pinar del Rio isolate clustered in E2, with two of them being located within the B/C domain. Immunisation and cross-neutralisation experiments in pigs and rabbits suggest differences between these two viruses, which may be attributable to the amino acid differences observed in E2. Altogether, these data provide fresh insights into viral molecular features which might be associated with the attenuation and adaptation of CSFV for persistence in the field. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Chemoenzymatic Synthesis of 4-Fluoro-N-Acetylhexosamine Uridine Diphosphate Donors: Chain Terminators in Glycosaminoglycan Synthesis.

    PubMed

    Schultz, Victor L; Zhang, Xing; Linkens, Kathryn; Rimel, Jenna; Green, Dixy E; DeAngelis, Paul L; Linhardt, Robert J

    2017-02-17

    Unnatural uridine diphosphate (UDP)-sugar donors, UDP-4-deoxy-4-fluoro-N-acetylglucosamine (4FGlcNAc) and UDP-4-deoxy-4-fluoro-N-acetylgalactosamine (4FGalNAc), were prepared using both chemical and chemoenzymatic syntheses relying on N-acetylglucosamine-1-phosphate uridylyltransferase (GlmU). The resulting unnatural UDP-sugar donors were then tested as substrates in glycosaminoglycan synthesis catalyzed by various synthases. UDP-4FGlcNAc was transferred onto an acceptor by Pastuerella multocida heparosan synthase 1 and subsequently served as a chain terminator.

  2. Biosynthesis of uridine diphosphate N-acetyl-L-fucosamine in a cell-free system from Salmonella arizonae O:59.

    PubMed

    Druzhinina, T N; Kalinchuk, N A; Shibaev, V N

    2005-01-01

    The conversion of uridine diphosphate N-acetyl-D-glucosamine into uridine diphosphate N-acetyl-L-fucosamine was demonstrated with enzymes from cytoplasmic fraction of Salmonella arizonae O:59 cells in the presence of NAD+ (NADP+) and NADPH. The reaction product was identified by ion-pair, reverse-phase HPLC with the use of synthetic nucleoside diphosphate sugar standards under conditions specially developed for separation of uridine diphosphate 2-acetamido-2,6-dideoxyhexoses. L-Fucose dehydrogenase from porcine liver was shown to be applicable for determination of N-acetyl-L-fucosamine, this enzyme being used to confirm L-configuration of the amino sugar residue in the sugar nucleotide formed.

  3. Uptake and Incorporation of Thymine, Thymidine, Uracil, Uridine, and 5-Fluorouracil into the Nucleic Acids of Bacillus subtilis

    PubMed Central

    Bodmer, Walter F.; Grether, Susan

    1965-01-01

    Bodmer, Walter F. (Stanford University School of Medicine, Palo Alto, Calif.), and Susan Grether. Uptake and incorporation of thymine, thymidine, uracil, uridine, and 5-fluorouracil into the nucleic acids of Bacillus subtilis. J. Bacteriol. 89:1011–1014. 1965.—From 55 to 95% of uracil, uridine, or 5-fluorouracil (FU) added to the culture medium is incorporated into the acid-insoluble fraction of cells of Bacillus subtilis strains SB 19 (prototroph) and SB 503 (FU-resistant). Thymine is poorly incorporated (less than 1%); thus, the incorporation of thymidine is limited (less than 12%) by the rapid degradation of the nucleoside to thymine, probably by the enzyme thymidine phosphorylase. Uracil, uridine, and FU were not incorporated into the deoxyribonucleic acid (DNA) of either strain, whereas all the incorporated thymidine was found in the DNA. PMID:14276087

  4. Probing the Watson-Crick, wobble, and sugar-edge hydrogen bond sites of uracil and thymine.

    PubMed

    Müller, Andreas; Frey, Jann A; Leutwyler, Samuel

    2005-06-16

    The nucleobases uracil (U) and thymine (T) offer three hydrogen-bonding sites for double H-bond formation via neighboring N-H and C=O groups, giving rise to the Watson-Crick, wobble and sugar-edge hydrogen bond isomers. We probe the hydrogen bond properties of all three sites by forming hydrogen bonded dimers of U, 1-methyluracil (1MU), 3-methyluracil (3MU), and T with 2-pyridone (2PY). The mass- and isomer-specific S1 <-- S0 vibronic spectra of 2PY.U, 2PY.3MU, 2PY.1MU, and 2PY.T were measured using UV laser resonant two-photon ionization (R2PI). The spectra of the Watson-Crick and wobble isomers of 2PY.1MU were separated using UV-UV spectral hole-burning. We identify the different isomers by combining three different diagnostic tools: (1) Selective methylation of the uracil N3-H group, which allows formation of the sugar-edge isomer only, and methylation of the N1-H group, which leads to formation of the Watson-Crick and wobble isomers. (2) The experimental S1 <-- S0 origins exhibit large spectral blue shifts relative to the 2PY monomer. Ab initio CIS calculations of the spectral shifts of the different hydrogen-bonded dimers show a linear correlation with experiment. This correlation allows us to identify the R2PI spectra of the weakly populated Watson-Crick and wobble isomers of both 2PY.U and 2PY.T. (3) PW91 density functional calculation of the ground-state binding and dissociation energies De and D0 are in agreement with the assignment of the dominant hydrogen bond isomers of 2PY.U, 2PY.3MU and 2PY.T as the sugar-edge form. For 2PY.U, 2PY.T and 2PY.1MU the measured wobble:Watson-Crick:sugar-edge isomer ratios are in good agreement with the calculated ratios, based on the ab initio dissociation energies and gas-phase statistical mechanics. The Watson-Crick and wobble isomers are thereby determined to be several kcal/mol less strongly bound than the sugar-edge isomers. The 36 observed intermolecular frequencies of the nine different H-bonded isomers give

  5. 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

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

    NASA Astrophysics Data System (ADS)

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

    2010-01-01

    The three-dimensional structures of three complexes of Salmonella typhimurium uridine phosphorylase with the inhibitor 2,2'-anhydrouridine, the substrate PO4, and with both the inhibitor 2,2'-anhydrouridine and the substrate PO4 (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 Å 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.

  7. Photoelectron spectroscopy and density functional theory studies on the uridine homodimer radical anions.

    PubMed

    Ko, Yeon Jae; Storoniak, Piotr; Wang, Haopeng; Bowen, Kit H; Rak, Janusz

    2012-11-28

    We report the photoelectron spectrum (PES) of the homogeneous dimer anion radical of uridine, (rU)(2)(●-). It features a broad band consisting of an onset of ∼1.2 eV and a maximum at the electron binding energy (EBE) ranging from 2.0 to 2.5 eV. Calculations performed at the B3LYP∕6-31++G∗∗ level of theory suggest that the PES is dominated by dimeric radical anions in which one uridine nucleoside, hosting the excess charge on the base moiety, forms hydrogen bonds via its O8 atom with hydroxyl of the other neutral nucleoside's ribose. The calculated adiabatic electron affinities (AEAGs) and vertical detachment energies (VDEs) of the most stable homodimers show an excellent agreement with the experimental values. The anionic complexes consisting of two intermolecular uracil-uracil hydrogen bonds appeared to be substantially less stable than the uracil-ribose dimers. Despite the fact that uracil-uracil anionic homodimers are additionally stabilized by barrier-free electron-induced proton transfer, their relative thermodynamic stabilities and the calculated VDEs suggest that they do not contribute to the experimental PES spectrum of (rU)(2)(●-).

  8. Photoelectron spectroscopy and density functional theory studies on the uridine homodimer radical anions

    NASA Astrophysics Data System (ADS)

    Jae Ko, Yeon; Storoniak, Piotr; Wang, Haopeng; Bowen, Kit H.; Rak, Janusz

    2012-11-01

    We report the photoelectron spectrum (PES) of the homogeneous dimer anion radical of uridine, (rU)2•-. It features a broad band consisting of an onset of ˜1.2 eV and a maximum at the electron binding energy (EBE) ranging from 2.0 to 2.5 eV. Calculations performed at the B3LYP/6-31++G** level of theory suggest that the PES is dominated by dimeric radical anions in which one uridine nucleoside, hosting the excess charge on the base moiety, forms hydrogen bonds via its O8 atom with hydroxyl of the other neutral nucleoside's ribose. The calculated adiabatic electron affinities (AEAGs) and vertical detachment energies (VDEs) of the most stable homodimers show an excellent agreement with the experimental values. The anionic complexes consisting of two intermolecular uracil-uracil hydrogen bonds appeared to be substantially less stable than the uracil-ribose dimers. Despite the fact that uracil-uracil anionic homodimers are additionally stabilized by barrier-free electron-induced proton transfer, their relative thermodynamic stabilities and the calculated VDEs suggest that they do not contribute to the experimental PES spectrum of (rU)2•-.

  9. Ab initio calculations of nonlinear optical rotation by several small chiral molecules and by uridine stereoisomers

    NASA Astrophysics Data System (ADS)

    Qu, Weixing; Tabisz, George C.

    2006-05-01

    Expressions for nonlinear optical rotation are presented based on the quantum theory of optical birefringence of Atkins and Barron [Proc. R. Soc. London, Ser. A 304, 303 (1968); 306, 119 (1968)]. As concrete examples, the ordinary and nonlinear optical rotations are calculated with density functional theory (DFT) methodology for some simple single-ring molecules, namely, oxaziridine, diaziridine, and their derivatives, and for two, somewhat more complicated, conformations of uridine. For the single-ring molecules, (1) the angles of the ordinary optical rotation are mostly positive and (2) the contributions of the nonlinear effect to the total optical rotation depend both on the nature of the substituted species and of the host atom located on the ring. For the two conformations of uridine, (1) the signs of nonlinear optical rotation differ even though their ordinary optical rotations have the same sign and (2) whether the molecular structures are geometrically optimized with Hartree-Fock or DFT methodologies has no significant effect on the calculated nonlinear optical rotation when gauge-including atomic orbitals were used, even though the basis sets are small. These studies are expected to be helpful for interpretation of experimental results on nonlinear optical rotation by molecules underway in our research group.

  10. Dinucleosidetetraphosphatase from Ehrlich ascites tumour cells: inhibition by adenosine, guanosine and uridine 5'-tetraphosphates.

    PubMed

    Moreno, A; Lobatón, C D; Sillero, M A; Sillero, A

    1982-01-01

    1. An enzyme has been partially purified from Ehrlich ascites tumour cells which specifically hydrolyses dinucleosidetetraphosphates, with Km values of around 2 microM. The products of the hydrolysis are the corresponding nucleoside tri- and monophosphates. Dinucleoside Tri- and diphosphates were not substrates of the reaction. 2. The enzyme requires Mg2+ or Mn2+, is maximally active at a pH value of approx. 7.5 and has a mol, wt of 19,800 as estimated by filtration on Sephadex G-75. Nucleoside mono-, di- and triphosphates were competitive inhibitors of the reaction with Ki values in the 0.1 mM range. 3. Particularly relevant is the inhibition of this enzyme by adenosine and guanosine 5'tetraphosphates. In the course of this investigation, the presence of uridine 5'-tetraphosphate was detected in a commercial preparation of UTP. Adenosine, guanosine and uridine 5'-tetraphosphates were very strong inhibitors of the reaction with Ki values in the nM range.

  11. The Methanothermobacter thermautotrophicus ExoIII homologue Mth212 is a DNA uridine endonuclease

    PubMed Central

    Georg, Jens; Schomacher, Lars; Chong, James P. J.; Majerník, Alan I.; Raabe, Monika; Urlaub, Henning; Müller, Sabine; Ciirdaeva, Elena; Kramer, Wilfried; Fritz, Hans-Joachim

    2006-01-01

    The genome of Methanothermobacter thermautotrophicus, as a hitherto unique case, is apparently devoid of genes coding for general uracil DNA glycosylases, the universal mediators of base excision repair following hydrolytic deamination of DNA cytosine residues. We have now identified protein Mth212, a member of the ExoIII family of nucleases, as a possible initiator of DNA uracil repair in this organism. This enzyme, in addition to bearing all the enzymological hallmarks of an ExoIII homologue, is a DNA uridine endonuclease (U-endo) that nicks double-stranded DNA at the 5′-side of a 2′-d-uridine residue, irrespective of the nature of the opposing nucleotide. This type of activity has not been described before; it is absent from the ExoIII homologues of Escherichia coli, Homo sapiens and Methanosarcina mazei, all of which are equipped with uracil DNA repair glycosylases. The U-endo activity of Mth212 is served by the same catalytic center as its AP-endo activity. PMID:17012282

  12. 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.

  13. 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.

  14. Design and synthesis of 2'-deoxy-2'-[(1,2,3)triazol-1-yl]uridines using click chemistry approach.

    PubMed

    Kumar, Surender

    2015-01-01

    A series of novel nucleosides bearing a 1,2,3-triazole moiety at the 2'-position of the sugar moiety has been synthesized starting from 2'-azidouridine and using the copper (I)-catalyzed Huisgen-Sharpless-Meldal 1,3-dipolar cycloaddition reaction. The reactions proceeded in overall yield of 52-82% and gave almost exclusively the 1,4-disubstituted 1,2,3-triazoles. The 2'-azidouridine was synthesized from uridine in two steps, and reacted with a variety of differently substituted alkynes to give the desired 2'-triazole-substituted uridine derivatives.

  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.

    PubMed

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

    2016-01-21

    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.

  17. 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.

  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. Improvement of uridine production of Bacillus subtilis by atmospheric and room temperature plasma mutagenesis and high-throughput screening.

    PubMed

    Fan, Xiaoguang; Wu, Heyun; Li, Guoliang; Yuan, Hui; Zhang, Hongchao; Li, Yanjun; Xie, Xixian; Chen, Ning

    2017-01-01

    In the present study, a novel breeding strategy of atmospheric and room temperature plasma (ARTP) mutagenesis was used to improve the uridine production of engineered Bacillus subtilis TD12np. A high-throughput screening method was established using both resistant plates and 96-well microplates to select the ideal mutants with diverse phenotypes. Mutant F126 accumulated 5.7 and 30.3 g/L uridine after 30 h in shake-flask and 48 h in fed-batch fermentation, respectively, which represented a 4.4- and 8.7-fold increase over the parent strain. Sequence analysis of the pyrimidine nucleotide biosynthetic operon in the representative mutants showed that proline 1016 and glutamate 949 in the large subunit of B. subtilis carbamoyl phosphate synthetase were of importance for the allosteric regulation caused by uridine 5'-monophosphate. The proposed mutation method with efficient high-throughput screening assay was proved to be an appropriate strategy to obtain uridine-overproducing strain.

  20. Lack of incorporation of tritiated uridine by nuclei of mature sieve elements in Metasequoia glyptostroboides and Sequoiadendron giganteum.

    PubMed

    Hébant, C

    1975-01-01

    The majority of nuclei which persist in "mature" sieve elements of Metasequoia glyptostroboides Hu and Chen and Sequoiadendron giganteum Buchholz fail to incorporate tritiated uridine (10 μCi/ml; 7 hours incubation of stem fragments). This is interpreted as further evidence for the degenerated condition of these nuclei.

  1. Structure of uridine diphosphate N-acetylglucosamine pyrophosphorylase from Entamoeba histolytica.

    PubMed

    Edwards, Thomas E; Gardberg, Anna S; Phan, Isabelle Q H; Zhang, Yang; Staker, Bart L; Myler, Peter J; Lorimer, Donald D

    2015-05-01

    Uridine diphosphate N-acetylglucosamine pyrophosphorylase (UAP) catalyzes the final step in the synthesis of UDP-GlcNAc, which is involved in cell-wall biogenesis in plants and fungi and in protein glycosylation. Small-molecule inhibitors have been developed against UAP from Trypanosoma brucei that target an allosteric pocket to provide selectivity over the human enzyme. A 1.8 Å resolution crystal structure was determined of UAP from Entamoeba histolytica, an anaerobic parasitic protozoan that causes amoebic dysentery. Although E. histolytica UAP exhibits the same three-domain global architecture as other UAPs, it appears to lack three α-helices at the N-terminus and contains two amino acids in the allosteric pocket that make it appear more like the enzyme from the human host than that from the other parasite T. brucei. Thus, allosteric inhibitors of T. brucei UAP are unlikely to target Entamoeba UAPs.

  2. Purification, crystallization and preliminary X-ray analysis of uridine phosphorylase from Salmonella typhimurium.

    PubMed

    Dontsova, Mariya V; Savochkina, Yulia A; Gabdoulkhakov, Azat G; Baidakov, Sergey N; Lyashenko, Andrey V; Zolotukhina, Maria; Errais Lopes, Liubov; Garber, Mariya B; Morgunova, Ekaterina Yu; Nikonov, Stanislav V; Mironov, Alexandr S; Ealick, Steven E; Mikhailov, Al 'Bert M

    2004-04-01

    The structural udp gene encoding uridine phosphorylase (UPh) was cloned from the Salmonella typhimurium chromosome and overexpressed in Escherichia coli cells. S. typhimurium UPh (StUPh) was purified to apparent homogeneity and crystallized. The primary structure of StUPh has high homology to the UPh from E. coli, but the enzymes differ substantially in substrate specificity and sensitivity to the polarity of the medium. Single crystals of StUPh were grown using hanging-drop vapor diffusion with PEG 8000 as the precipitant. X-ray diffraction data were collected to 2.9 A resolution. Preliminary analysis of the diffraction data indicated that the crystal belonged to space group P6(1(5)), with unit-cell parameters a = 92.3, c = 267.5 A. The solvent content is 37.7% assuming the presence of one StUPh hexamer per asymmetric unit.

  3. 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).

  4. 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.

  5. Search for the 531 day-period wobble signal in the polar motion based on EEMD

    NASA Astrophysics Data System (ADS)

    Ding, H.; Shen, W. B.

    2015-04-01

    In this study, we use a nonlinear and non-stationary time series analysis method, the ensemble empirical mode decomposition method (EEMD), to analyze the polar motion (PM) time series (EOP C04 series from 1962 to 2013) to find a 531 day-period wobble (531 dW) signal. The 531 dW signal has been found in the early PM seires (1962-1977) while cannot be found in the recent PM seires (1978-2013) using conventional analysis approaches. By the virtue of the demodulation feature of EEMD, the 531 dW can be confirmed to be present in PM based on the differences of the amplitudes and phases between different intrinsic mode functions. Results from three sub-series divided from the EOP C04 series show that the period of the 531 dW is subject to variations, in the range of 530.9-524 d, and its amplitude is also time-dependent (about 2-11 mas). Synthetic tests are carried out to explain why the 531 dW can only be observed in recent 30-years PM time series after using EEMD. The 531 dW is also detected in two longest available superconducting gravimeter (SG) records, which further confirms the presence of the 531 dW. The confirmation of 531 dW existence could be significant in establishing a more reasonable Earth rotation model and may effectively contribute to the prediction of the PM and its mechanism interpretation.

  6. 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.

  7. Effects of substituting uridine triphosphate for ATP on the crossbridge cycle of rabbit muscle

    PubMed Central

    Seow, Chun Y; White, Howard D; Ford, Lincoln E

    2001-01-01

    Substituting uridine triphosphate (UTP) for ATP as a substrate for rabbit skeletal myosin and actin at 4°C slowed the dissociation of myosin-S1 from actin by threefold, and hydrolysis of the nucleotide by sevenfold, without a decrease in the rates of phosphate or uridine diphosphate dissociation from actomyosin. The same substitution in skinned rabbit psoas fibres at 2–3°C reduced the maximum shortening velocity by 56% and increased the force asymptote of the force-velocity curve relative to force (α/Po) by 112% without altering the velocity asymptote, β. It also decreased isometric force by 35% and isometric stiffness by 20%, so that the stiffness/force ratio was increased by 23%. Tension transient experiments showed that the stiffness/force increase was associated with a 10% reduction in the amplitude of the rapid, partial (phase 2) recovery relative to the isometric force, and the addition of two new components, one that recovered at a step-size-independent rate of 100 s−1 and another that did not recover following the length change. The increased α/Po with constant β suggests an internal load, as expected of attached crossbridges detained in their movement. An increased stiffness/force ratio suggests a greater fraction of attached bridges in low-force states, as expected of bridges with unhydrolysed UTP detained in low-force states. Decreased phase 2 recovery suggests the detention of high-force bridges, as expected of slowed actomyosin dissociation by nucleotide. These results suggest that the separation of hydrolysed phosphates from nucleotides occurs early in the attached phase of the crossbridge cycle, near and possibly identical to a transition to a firmly attached, low-force state from an initial state where bridges with hydrolysed nucleotides are easily detached by shortening. PMID:11744764

  8. Multi-temperature study of potassium uridine-5'-monophosphate: electron density distribution and anharmonic motion modelling.

    PubMed

    Jarzembska, Katarzyna N; Řlepokura, Katarzyna; Kamiński, Radosław; Gutmann, Matthias J; Dominiak, Paulina M; Woźniak, Krzysztof

    2017-08-01

    Uridine, a nucleoside formed of a uracil fragment attached to a ribose ring via a β-N1-glycosidic bond, is one of the four basic components of ribonucleic acid. Here a new anhydrous structure and experimental charge density distribution analysis of a uridine-5'-monophosphate potassium salt, K(UMPH), is reported. The studied case constitutes the very first structure of a 5'-nucleotide potassium salt according to the Cambridge Structural Database. The excellent crystal quality allowed the collection of charge density data at various temperatures, i.e. 10, 100, 200 and 300 K on one single crystal. Crystal structure and charge density data were analysed thoroughly in the context of related literature-reported examples. Detailed analysis of the charge density distribution revealed elevated anharmonic motion of part of the uracil ring moiety relatively weakly interacting with the neighbouring species. The effect was manifested by alternate positive and negative residual density patterns observed for these atoms, which `disappear' at low temperature. It also occurred that the potassium cation, quite uniformly coordinated by seven O atoms from all molecular fragments of the UMPH(-) anion, including the O atom from the ribofuranose ring, can be treated as spherical in the charge density model which was supported by theoretical calculations. Apart from the predominant electrostatic interactions, four relatively strong hydrogen bond types further support the stability of the crystal structure. This results in a compact and quite uniform structure (in all directions) of the studied crystal, as opposed to similar cases with layered architecture reported in the literature.

  9. 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.

  10. 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.

  11. Chandler wobble in variations of the Pulkovo latitude for 170 years

    NASA Astrophysics Data System (ADS)

    Miller, N. O.

    2011-08-01

    The work studies the Chandler component of polar motion, obtained from variations in the Pulkovo latitude over 170 years (1840-2009). To extend the time series of variations in the Pulkovo latitude back into the past until 1840, we used the first Pulkov observations on the basis of the Reynolds transit instrument in the prime vertical and on the basis of large vertical Ertel circle. We employed different methods of analysis of nonstationary time series, such as wavelet analysis, methods of bandpass filtering, singular spectral analysis, and Fourier and Hilbert transforms. Changes in the Pulkovo latitude from 1904-2006, as inferred from ZTF-135 observations and as calculated from international data, were compared. It was shown that time changes in the amplitude and phase of Chandler polar motion can be studied based on long-term observation time series of latitude at a single observatory, even if these observation records have gaps. We were the first to study the changes in the Chandler wobble for that long time series of variations in the Pulkovo latitude with the help of different methods. The long observation record and the methods of analysis of nonstationary time series had allowed us to identify two similar structures, both well apparent during the periods of 1845-1925 and 1925-2005 in the time variations of phase and amplitude. The presence of this structure indicates that low-frequency regularities may be present in the Chandler polar motion, and one of the manifestations of this may be the well known feature in the region of 1925. The superimposed epoch method was used to estimate the period of variations in the amplitude with a simultaneous change of phase of this oscillation, which was found to be 80 years. In addition, advantages of singular spectral analysis for studying the long-period time series with involved structure are demonstrated.

  12. Search for the 531-day-period wobble signal in the polar motion based on EEMD

    NASA Astrophysics Data System (ADS)

    Ding, H.; Shen, W.

    2015-08-01

    In this study, we use a nonlinear and non-stationary time series analysis method, the ensemble empirical mode decomposition method (EEMD), to analyze the polar motion (PM) time series (EOP C04 series from 1962 to 2013) to find a 531-day-period wobble (531 dW) signal. The 531 dW signal has been found in the early PM series (1962-1977), but cannot be found in the recent PM series (1978-2013) using conventional analysis approaches. By virtue of the demodulation feature of EEMD, the 531 dW can be confirmed to be present in PM based on the differences of the amplitudes and phases between different intrinsic mode functions. Results from three sub-series divided from the EOP C04 series show that the period of the 531 dW is subject to variations, in the range of 530.9-524 days, and its amplitude is also time-dependent (about 2-11 mas). Synthetic tests are carried out to explain why the 531 dW can only be observed in recent 30-year PM time series after using EEMD. The 531 dW is also detected in the two longest available superconducting gravimeter (SG) records, which further confirms the presence of the 531 dW. The confirmation of the 531 dW existence could be significant in establishing a more reasonable Earth rotation model and may effectively contribute to the prediction of the PM and its mechanism interpretation.

  13. Strategies for equilibrium maintenance during single leg standing on a wobble board.

    PubMed

    Silva, Priscila de Brito; Oliveira, Anderson Souza; Mrachacz-Kersting, Natalie; Laessoe, Uffe; Kersting, Uwe Gustav

    2016-02-01

    The aim of this study was to identify and compare movement strategies used to maintain balance while single leg standing on either a firm surface (FS) or on a wobble board (WB). In 17 healthy men, retroreflective markers were positioned on the xiphoid process and nondominant lateral malleolus to calculate trunk and contralateral-leg excursion (EXC) and velocity (VEL), and center of pressure (CoP) EXC and VEL during FS on a force platform. From the WB test, standing time (WBTIME) was determined and the board's angular EXC and VEL were calculated from four markers on the WB as surrogate measures for CoP dynamics. Electromyographic average rectified values (ARV) from eight leg and thigh muscles of the supporting limb were calculated for both tasks. WB ARV amplitudes were normalized with respect to the value of FS ARV and presented significantly higher peroneus longus and biceps femoris activity (p<0.05). WB standing time was correlated to trunk sagittal plane velocity (r=-0.73 at p=0.016) and excursion (r=-0.67 at p=0.03). CoP and WB angular movement measures were weakly and not significantly correlated between tasks. This lack of correlation indicates that WB balance maintenance requires movement beyond the ankle strategy as described for the FS task. WB standing likely demands different biomechanical and neuromuscular control strategies, which has immediate implications for the significance of WB tests in contrast to FS balance tests. Differences in control strategies will also have implications for the understanding of mechanisms for rehabilitation training using such devices.

  14. 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.

  15. Crystallization and preliminary X-ray diffraction analysis of Salmonella typhimurium uridine phosphorylase complexed with 5-fluorouracil.

    PubMed

    Lashkov, A A; Gabdoulkhakov, A G; Shtil, A A; Mikhailov, A M

    2009-06-01

    Uridine phosphorylase (UPh; EC 2.4.2.3) catalyzes the phosphorolytic cleavage of the N-glycosidic bond of uridine to form ribose 1-phosphate and uracil. This enzyme also activates pyrimidine-containing drugs, including 5-fluorouracil (5-FU). In order to better understand the mechanism of the enzyme-drug interaction, the complex of Salmonella typhimurium UPh with 5-FU was cocrystallized using the hanging-drop vapour-diffusion method at 294 K. X-ray diffraction data were collected to 2.2 A resolution. Analysis of these data revealed that the crystal belonged to space group C2, with unit-cell parameters a = 158.26, b = 93.04, c = 149.87 A, alpha = gamma = 90, beta = 90.65 degrees . The solvent content was 45.85% assuming the presence of six hexameric molecules of the complex in the unit cell.

  16. Uridine triphosphate increases proliferation of human cancerous pancreatic duct epithelial cells by activating P2Y2 receptor.

    PubMed

    Choi, Ji Hun; Ji, Young Geon; Lee, Dong Hyeon

    2013-05-01

    The aim of this study was to investigate the effect of uridine triphosphate (UTP) on the proliferation of human cancerous pancreatic duct epithelial cells. Proliferation was measured by immunoassay for bromodeoxyuridine incorporation into the pancreatic cell line PANC-1. Effect of UTP was assayed using selective P2 agonist and antagonist, small interfering RNA, intracellular signal inhibitors, and Western blot. Incubation of PANC-1 cells with UTP or MRS2768, a selective P2Y2 receptor agonist, resulted in a dose- and time-dependent increase of proliferation. The messenger RNA transcript and protein of P2Y2 receptor were expressed in PANC-1 cells. P2 receptor antagonist suramin and small interfering RNA against P2Y2 receptor significantly decreased the proliferative effect of UTP and MRS2768. Activation of P2Y2 receptor by UTP transduced to phospholipase C, inositol 1,4,5-triphosphate (IP3), and protein kinase C. Uridine triphosphate-induced proliferation was mediated by protein kinase D, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, phosphatidylinositol 3-kinase (PI3K), Akt, and phospholipase D. Uridine triphosphate increased phosphorylation of Akt through protein kinase C, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, and PI3K. Uridine triphosphate increases proliferation of human pancreatic duct epithelial cells by activation of P2Y2 receptor and PI3K/Akt pathway. This could be helpful for discovering the long-term roles of P2Y2 receptor in pancreatic cells.

  17. Ultrastructural and cytochemical changes in the respiratory compartment of the lungs in rats after combined treatment with fine silicon dioxide powder and uridine.

    PubMed

    Lebkova, N P; Baranov, V I

    2004-06-01

    Electron microscopy and cytochemical study of alveolar tissue of rat lungs were performed at the early stage after intratracheal treatment with fine silicon dioxide powder. The preparation was administered to animals receiving or not receiving intravenous injection of uridine. Dust particles permeated the cytoplasm, mitochondria, and nuclei of cells in the air-blood barrier of the alveoli. Uridine decreased the severity of dust-induced damage to cells and increased intracellular glycogen content.

  18. Photoelectron and computational studies of the copper-nucleoside anionic complexes, Cu{sup -}(cytidine) and Cu{sup -}(uridine)

    SciTech Connect

    Li Xiang; Ko, Yeon-Jae; Wang Haopeng; Bowen, Kit H.; Guevara-Garcia, Alfredo; Martinez, Ana

    2011-02-07

    The copper-nucleoside anions, Cu{sup -}(cytidine) and Cu{sup -}(uridine), have been generated in the gas phase and studied by both experimental (anion photoelectron spectroscopy) and theoretical (density functional calculations) methods. The photoelectron spectra of both systems are dominated by single, intense, and relatively narrow peaks. These peaks are centered at 2.63 and 2.71 eV for Cu{sup -}(cytidine) and Cu{sup -}(uridine), respectively. According to our calculations, Cu{sup -}(cytidine) and Cu{sup -}(uridine) species with these peak center [vertical detachment energy (VDE)] values correspond to structures in which copper atomic anions are bound to the sugar portions of their corresponding nucleosides largely through electrostatic interactions; the observed species are anion-molecule complexes. The combination of experiment and theory also reveal the presence of a slightly higher energy, anion-molecule complex isomer in the case of the Cu{sup -}(cytidine). Furthermore, our calculations found that chemically bond isomers of these species are much more stable than their anion-molecule complex counterparts, but since their calculated VDE values are larger than the photon energy used in these experiments, they were not observed.

  19. Photoelectron and computational studies of the copper-nucleoside anionic complexes, Cu-(cytidine) and Cu-(uridine)

    NASA Astrophysics Data System (ADS)

    Li, Xiang; Ko, Yeon-Jae; Wang, Haopeng; Bowen, Kit H.; Guevara-García, Alfredo; Martínez, Ana

    2011-02-01

    The copper-nucleoside anions, Cu-(cytidine) and Cu-(uridine), have been generated in the gas phase and studied by both experimental (anion photoelectron spectroscopy) and theoretical (density functional calculations) methods. The photoelectron spectra of both systems are dominated by single, intense, and relatively narrow peaks. These peaks are centered at 2.63 and 2.71 eV for Cu-(cytidine) and Cu-(uridine), respectively. According to our calculations, Cu-(cytidine) and Cu-(uridine) species with these peak center [vertical detachment energy (VDE)] values correspond to structures in which copper atomic anions are bound to the sugar portions of their corresponding nucleosides largely through electrostatic interactions; the observed species are anion-molecule complexes. The combination of experiment and theory also reveal the presence of a slightly higher energy, anion-molecule complex isomer in the case of the Cu-(cytidine). Furthermore, our calculations found that chemically bond isomers of these species are much more stable than their anion-molecule complex counterparts, but since their calculated VDE values are larger than the photon energy used in these experiments, they were not observed.

  20. Uridine-based paramagnetic supramolecular nanoaggregate with high relaxivity capable of detecting primitive liver tumor lesions.

    PubMed

    Bhuniya, Sankarprasad; Moon, Hyeyoung; Lee, Hyunseung; Hong, Kwan Soo; Lee, Sumin; Yu, Dae-Yeul; Kim, Jong Seung

    2011-09-01

    The water soluble uridine-based paramagnetic self-assembled amphiphilic molecules (LGd2-5) with DTTA binding site were synthesized and have been characterized in regard to their T(1) magnetic resonance imaging (MRI) contrast agent (CA) properties. The water proton relaxivities have been measured in phosphate buffered saline (PBS) at 36 °C at 3 different magnetic fields. Among the self-assembled CAs, LGd3 showed unprecedented, high relaxivities of 30.3 and 23.4 mM(-1) s(-1) in PBS solution at 36 °C at 0.47 and 1.41 T, respectively. The non-covalent interactions between the new CAs and human serum albumin (HSA) have been investigated and the relaxivity was further increased by 135-215% depending on alkyl chain lengths. The chemically inertness of these complexes (LGd1, LGd2, LGd3, LGd4) against biologically most abundant metal ion (i.e. Zn(2+)) have shown within the range of commercial DTPA-based CAs. In vivo pharmacokinetics of the complex LGd3 showed highly specific for hepatocytes resulting in increase of contrast noise ratio by ∼240% in T(1)-weighted MR images of mouse liver 2 h after injection of the LGd3. It is capable to detect small hepatocellular carcinoma (HCC) with diameter of 1.5 mm.

  1. Constrictor prostanoids and uridine adenosine tetraphosphate: vascular mediators and therapeutic targets in hypertension and diabetes

    PubMed Central

    Matsumoto, Takayuki; Goulopoulou, Styliani; Taguchi, Kumiko; Tostes, Rita C; Kobayashi, Tsuneo

    2015-01-01

    Vascular dysfunction plays a pivotal role in the development of systemic complications associated with arterial hypertension and diabetes. The endothelium, or more specifically, various factors derived from endothelial cells tightly regulate vascular function, including vascular tone. In physiological conditions, there is a balance between endothelium-derived factors, that is, relaxing factors (endothelium-derived relaxing factors; EDRFs) and contracting factors (endothelium-derived contracting factors; EDCFs), which mediate vascular homeostasis. However, in disease states, such as diabetes and arterial hypertension, there is an imbalance between EDRF and EDCF, with a reduction of EDRF signalling and an increase of EDCF signalling. Among EDCFs, COX-derived vasoconstrictor prostanoids play an important role in the development of vascular dysfunction associated with hypertension and diabetes. Moreover, uridine adenosine tetraphosphate (Up4A), identified as an EDCF in 2005, also modulates vascular function. However, the role of Up4A in hypertension- and diabetes-associated vascular dysfunction is unclear. In the present review, we focused on experimental and clinical evidence that implicate these two EDCFs (vasoconstrictor prostanoids and Up4A) in vascular dysfunction associated with hypertension and diabetes. PMID:26031319

  2. 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

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

    PubMed Central

    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

  4. Abscisic acid uridine diphosphate glucosyltransferases play a crucial role in abscisic acid homeostasis in Arabidopsis.

    PubMed

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

    2014-05-01

    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.

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

    PubMed Central

    Norberg, J; Nilsson, L

    1994-01-01

    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. Images FIGURE 8 FIGURE 10 PMID:7948694

  6. Positional isotope exchange analysis of the uridine-diphosphoglucose pyrophosphorylase reaction

    SciTech Connect

    Hester, L.; Hilscher, L.; Raushel, F.M.

    1986-05-01

    The enzyme uridine-diphosphoglucose pyrophosphorylase catalyzes the reversible formation of pyrophosphate and UDP-glucose from UTP and glc-1P. The positional isotope exchange reaction was measured using oxygen-18 labelled UTP. The synthesis of (..beta..-/sup 18/O/sub 2/, ..beta gamma..-/sup 18/O, ..gamma..-/sup 18/O/sub 3/)UTP was accomplished by the coupled activities of carbamate kinase, nucleoside diphosphate kinase, and nucleoside monophosphate kinase. The exchange of an oxygen-18 from a ..beta..-nonbridge position of the labelled UTP to the ..cap alpha beta..-bridge position was measured with /sup 31/P NMR. The ratio of the rate of net substrate turnover and the positional isotope exchange rate was measured as a function of the initial glc-1P concentration. This ratio was found to increase with an increasing concentration of glc-1P. The intercept at low glc-1P was found to be 1.2 and the slope was 4.5 mM/sup -1/. These results have been interpreted to mean that this enzyme has an ordered addition of substrates. The lower limit for the release of pyrophosphate from E-UDPG-PP/sub i/ relative to V/sub 2/ is 1.2. The rate constant for the release of UTP from E-UTP relative to V/sub 1/ is 9.

  7. Deficiency of uridine monophosphate synthase (DUMPS) and X-chromosome deletion in fetal mummification in cattle.

    PubMed

    Ghanem, Mohamed Elshabrawy; Nakao, Toshihiko; Nishibori, Masahide

    2006-01-01

    Ten mummified fetuses were tested for the deficiency of uridine monophosphate synthase (DUMPS), which is known to contribute to the embryonic and fetal mortality in cattle. Genomic DNAs of the mummified fetuses were extracted from tissue samples collected from the mummies and were amplified by GenomiPhi DNA amplification kit. UMPS gene of the mummies was amplified by polymerase chain reaction (PCR) with DUMPS primers. Out of ten mummies examined, two fetuses were heterozygous (carriers) for DUMPS as indicated by the presences of three bands of 89, 53 and 36 bp. Estimated stage of gestation when the death occurred in the two mummies was 3.5 and 2.5 months, respectively. The other fetuses exhibited only two bands of 53 and 36 bp on the polyacrylamide gel indicated that they were normal. On the other hand, all the mummies were sexed using AMX/Y primers. Specific regions of Y and X chromosomes were amplified by PCR using AMX/Y. The expected 280 bp fragment in the female sample and the 280 and 217 bp in the male sample were observed. Nine mummies had a normal X and Y chromosome bands; however, the other mummified fetus exhibited only Y chromosome band, while the constitutive X chromosome fragment was missing. The estimated stage of gestation when the death occurred in this mummified fetus was 100 days. This might be the first report of DUMPS and X-chromosome deletion at the amelogenin gene in bovine-mummified fetuses in Japan.

  8. Ion-exclusion chromatography determination of organic acid in uridine 5'-monophosphate fermentation broth.

    PubMed

    Niu, Huanqing; Chen, Yong; Xie, Jingjing; Chen, Xiaochun; Bai, Jianxin; Wu, Jinglan; Liu, Dong; Ying, Hanjie

    2012-09-01

    Simultaneous determination of organic acids using ion-exclusion liquid chromatography and ultraviolet detection is described. The chromatographic conditions are optimized when an Aminex HPX-87H column (300 × 7.8 mm) is employed, with a solution of 3 mmol/L sulfuric acid as eluent, a flow rate of 0.4 mL/min and a column temperature of 60°C. Eight organic acids (including orotic acid, α-ketoglutaric acid, citric acid, pyruvic acid, malic acid, succinic acid, lactic acid and acetic acid) and one nucleotide are successfully quantified. The calibration curves for these analytes are linear, with correlation coefficients exceeding 0.999. The average recovery of organic acids is in the range of 97.6% ∼ 103.1%, and the relative standard deviation is in the range of 0.037% ∼ 0.38%. The method is subsequently applied to obtain organic acid profiles of uridine 5'-monophosphate culture broth fermented from orotic acid by Saccharomyces cerevisiae. These data demonstrate the quantitative accuracy for nucleotide fermentation mixtures, and suggest that the method may also be applicable to other biological samples.

  9. 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.

  10. 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

  11. 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. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Uridine Triphosphate Thio Analogues Inhibit Platelet P2Y12 Receptor and Aggregation

    PubMed Central

    Gündüz, Dursun; Tanislav, Christian; Sedding, Daniel; Parahuleva, Mariana; Santoso, Sentot; Troidl, Christian; Hamm, Christian W.; Aslam, Muhammad

    2017-01-01

    Platelet P2Y12 is an important adenosine diphosphate (ADP) receptor that is involved in agonist-induced platelet aggregation and is a valuable target for the development of anti-platelet drugs. Here we characterise the effects of thio analogues of uridine triphosphate (UTP) on ADP-induced platelet aggregation. Using human platelet-rich plasma, we demonstrate that UTP inhibits P2Y12 but not P2Y1 receptors and antagonises 10 µM ADP-induced platelet aggregation in a concentration-dependent manner with an IC50 value of ~250 µM. An eight-fold higher platelet inhibitory activity was observed with a 2-thio analogue of UTP (2S-UTP), with an IC50 of 30 µM. The 4-thio analogue (4S-UTP) with an IC50 of 7.5 µM was 33-fold more effective. A three-fold decrease in inhibitory activity, however, was observed by introducing an isobutyl group at the 4S- position. A complete loss of inhibition was observed with thio-modification of the γ phosphate of the sugar moiety, which yields an enzymatically stable analogue. The interaction of UTP analogues with P2Y12 receptor was verified by P2Y12 receptor binding and cyclic AMP (cAMP) assays. These novel data demonstrate for the first time that 2- and 4-thio analogues of UTP are potent P2Y12 receptor antagonists that may be useful for therapeutic intervention. PMID:28146050

  13. Uridine adenosine tetraphosphate acts as a proangiogenic factor in vitro through purinergic P2Y receptors.

    PubMed

    Zhou, Zhichao; Chrifi, Ihsan; Xu, Yanjuan; Pernow, John; Duncker, Dirk J; Merkus, Daphne; Cheng, Caroline

    2016-07-01

    Uridine adenosine tetraphosphate (Up4A), a dinucleotide, exerts vascular influence via purinergic receptors (PR). We investigated the effects of Up4A on angiogenesis and the putative PR involved. Tubule formation assay was performed in a three-dimensional system, in which human endothelial cells were cocultured with pericytes with various Up4A concentrations for 5 days. Expression of PR subtypes and angiogenic factors was assessed in human endothelial cells with and without P2Y6R antagonist. No difference in initial tubule formation was detected between Up4A stimulation and control conditions at day 2 In contrast, a significant increase in vascular density in response to Up4A was observed at day 5 Up4A at an optimal concentration of 5 μM promoted total tubule length, number of tubules, and number of junctions, all of which were inhibited by the P2Y6R antagonist MRS2578. Higher concentrations of Up4A (10 μM) had no effects on angiogenesis parameters. Up4A increased mRNA level of P2YRs (P2Y2R, P2Y4R, and P2Y6R) but not P2XR (P2X4R and P2X7R) or P1R (A2AR and A2BR), while Up4A upregulated VEGFA and ANGPT1, but not VEGFR2, ANGPT2, Tie1, and Tie2. In addition, Up4A increased VEGFA protein levels. Transcriptional upregulation of P2YRs by Up4A was inhibited by MRS2578. In conclusion, Up4A is functionally capable of promoting tubule formation in an in vitro coculture system, which is likely mediated by pyrimidine-favored P2YRs but not P2XRs or P1Rs, and involves upregulation of angiogenic factors. Copyright © 2016 the American Physiological Society.

  14. Uridine adenosine tetraphosphate is a novel neurogenic P2Y1 receptor activator in the gut

    PubMed Central

    Durnin, Leonie; Hwang, Sung Jin; Kurahashi, Masaaki; Drumm, Bernard T.; Ward, Sean M.; Sasse, Kent C.; Sanders, Kenton M.; Mutafova-Yambolieva, Violeta N.

    2014-01-01

    Enteric purinergic motor neurotransmission, acting through P2Y1 receptors (P2Y1R), mediates inhibitory neural control of the intestines. Recent studies have shown that NAD+ and ADP ribose better meet criteria for enteric inhibitory neurotransmitters in colon than ATP or ADP. Here we report that human and murine colon muscles also release uridine adenosine tetraphosphate (Up4A) spontaneously and upon stimulation of enteric neurons. Release of Up4A was reduced by tetrodotoxin, suggesting that at least a portion of Up4A is of neural origin. Up4A caused relaxation (human and murine colons) and hyperpolarization (murine colon) that was blocked by the P2Y1R antagonist, MRS 2500, and by apamin, an inhibitor of Ca2+-activated small-conductance K+ (SK) channels. Up4A responses were greatly reduced or absent in colons of P2ry1−/− mice. Up4A induced P2Y1R–SK-channel–mediated hyperpolarization in isolated PDGFRα+ cells, which are postjunctional targets for purinergic neurotransmission. Up4A caused MRS 2500-sensitive Ca2+ transients in human 1321N1 astrocytoma cells expressing human P2Y1R. Up4A was more potent than ATP, ADP, NAD+, or ADP ribose in colonic muscles. In murine distal colon Up4A elicited transient P2Y1R-mediated relaxation followed by a suramin-sensitive contraction. HPLC analysis of Up4A degradation suggests that exogenous Up4A first forms UMP and ATP in the human colon and UDP and ADP in the murine colon. Adenosine then is generated by extracellular catabolism of ATP and ADP. However, the relaxation and hyperpolarization responses to Up4A are not mediated by its metabolites. This study shows that Up4A is a potent native agonist for P2Y1R and SK-channel activation in human and mouse colon. PMID:25341729

  15. 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.

  16. 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.

  17. Crystallization of uridine phosphorylase from Shewanella oneidensis MR-1 in the laboratory and under microgravity and preliminary X-ray diffraction analysis.

    PubMed

    Safonova, Tatyana N; Mordkovich, Nadezhda N; Polyakov, Konstantin M; Manuvera, Valentin A; Veiko, Vladimir P; Popov, Vladimir O

    2012-11-01

    Uridine phosphorylase (UDP, EC 2.4.2.3), a key enzyme in the pyrimidine salvage pathway, catalyses the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate. The gene expression of UDP from Shewanella oneidensis MR-1 was performed in the recipient strain Escherichia coli. The UDP protein was crystallized on earth (in the free form and in complex with uridine as the substrate) by the hanging-drop vapour-diffusion method at 296 K and under microgravity conditions (in the free form) aboard the Russian Segment of the International Space Station by the capillary counter-diffusion method. The data sets were collected to a resolution of 1.9 Å from crystals of the free form grown on earth, 1.6 Å from crystals of the complex with uridine and 0.95 Å from crystals of the free form grown under microgravity. All crystals belong to the space group P2(1) and have similar unit-cell parameters. The crystal of uridine phosphorylase grown under microgravity diffracted to ultra-high resolution and gave high-quality X-ray diffraction data.

  18. Uridine uptake inhibition as a cytotoxicity test for a human hepatoma cell line (HepG2 cells): comparison with the neutral red assay.

    PubMed

    Valentin, I; Philippe, M; Lhuguenot, J; Chagnon, M

    2001-02-14

    This study describes a sensitive microassay for measuring cytotoxicity based on the degree of inhibition of RNA synthesis in HepG2 cells. RNA synthesis is measured by the kinetic uptake of radiolabeled uridine. A large number of compounds were tested in a wide range of concentrations. The concentration required to induce 50% inhibition of HepG2 uridine uptake rates (IC(50)) was determined for each compound and used to rank its potency. These IC(50)s were compared with IC(50)s measured with the neutral red assay. 2-acetylaminofluorene, benzo[a]pyrene and methylnitrosourea were not cytotoxic in the neutral red assay. Uridine uptake was always inhibited at lower concentrations than those required in the neutral red assay, suggesting that the uridine uptake assay is a more sensitive indicator of toxic action than the neutral red inclusion. Uridine uptake assay provides a rapid and quantitative method for assessing toxicity in a human cell line. Application of this method to bottled spring waters are described. Due to its high sensitivity and reproducibility, this method provides a suitable tool for screening a great number of samples and will be a helpful test for evaluating food safety and controlling the recycling process of wrapping materials.

  19. Functional and structural variation of uridine diphosphate glycosyltransferase (UGT) gene of Stevia rebaudiana-UGTSr involved in the synthesis of rebaudioside A.

    PubMed

    Madhav, Harish; Bhasker, Salini; Chinnamma, Mohankumar

    2013-02-01

    The sweetness of honey leaf plant Stevia rebaudiana is attributed to steviol glycosides or steviosides, accumulated in the leaves. Steviol glycosides are diterpenoids derived from steviol as the final step of glycosylation by the marker enzyme Uridine diphosphate glycosyltransferase (UGT). Out of the eight different steviol glycosides, rebaudioside A was detected as the sweetest glycoside with reduced bitter aftertaste. The pattern of glycosylation of steviol has a crucial role in maintaining the sweetness as well as the taste perception of stevioside. Within the 12 UGTs of S. rebaudiana so far elucidated, the functional genomics of three UGTs-UGT76G1, UGT74G1 & UGT85C2 in stevioside synthesis were studied. In the present study a UGT gene of S. rebaudiana named UGTSr showing resemblance with UGT76G1 was structurally analyzed and the functional role of the recombinant UGTSr in the synthesis of rebaudioside A was ascertained. The relative expression of UGTSr by qPCR showed a higher level of expression in mature leaves than in tender. Despite the similarity of nucleotide with UGT76G1, the gene UGTSr exhibits 48 SNPs and 39 associated amino acid substitutions with remarkable variation in the secondary and tertiary structure of the protein. The helical changes, the presence of a new amino acid, novel substitutions of amino acids and the hydrogen bond in the conserved histidine and aspartame residues observed in UGTSr support its functional stability and specificity from that of other UGTs of S. rebaudiana. Based on these features UGTSr exhibits a novel status from other UGTs of S. rebaudiana.

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

    PubMed

    Wiegmann, Daniel; Koppermann, Stefan; Wirth, Marius; Niro, Giuliana; Leyerer, Kristin; Ducho, Christian

    2016-01-01

    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.

  1. 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

  2. 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.

  3. 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.

  4. How many tautomerization pathways connect Watson-Crick-like G*·T DNA base mispair and wobble mismatches?

    PubMed

    Brovarets', Ol'ha O; Hovorun, Dmytro M

    2015-01-01

    In this study, we have theoretically demonstrated the intrinsic ability of the wobble G·T(w)/G*·T*(w)/G·T(w1)/G·T(w2) and Watson-Crick-like G*·T(WC) DNA base mispairs to interconvert into each other via the DPT tautomerization. We have established that among all these transitions, only one single G·T(w) ↔ G*·T(WC) pathway is eligible from a biological perspective. It involves short-lived intermediate - the G·T*(WC) base mispair - and is governed by the planar, highly stable, and zwitterionic [Formula: see text] transition state stabilized by the participation of the unique pattern of the five intermolecular O6(+)H⋯O4(-), O6(+)H⋯N3(-), N1(+)H⋯N3(-), N1(+)H⋯O2(-), and N2(+)H⋯O2(-) H-bonds. This non-dissociative G·T(w) ↔ G*·T(WC) tautomerization occurs without opening of the pair: Bases within mispair remain connected by 14 different patterns of the specific intermolecular interactions that successively change each other along the IRC. Novel kinetically controlled mechanism of the thermodynamically non-equilibrium spontaneous point GT/TG incorporation errors has been suggested. The mutagenic effect of the analogues of the nucleotide bases, in particular 5-bromouracil, can be attributed to the decreasing of the barrier of the acquisition by the wobble pair containing these compounds of the enzymatically competent Watson-Crick's geometry via the intrapair mutagenic tautomerization directly in the essentially hydrophobic recognition pocket of the replication DNA-polymerase machinery. Proposed approaches are able to explain experimental data, namely growth of the rate of the spontaneous point incorporation errors during DNA biosynthesis with increasing temperature.

  5. SU-E-T-666: Radionuclides and Activity of the Patient Apertures Used in a Proton Beam of Wobbling System

    SciTech Connect

    Wang, B.Y.; Chen, H.H.; Tsai, H.Y.; Sheu, R.J.

    2015-06-15

    Purpose: To identify the radionuclides and quantify the activity of the patient apertures used in a 190-MeV proton beam of wobbling system. Methods: A proton beam of wobbling system in the first proton center in Taiwan, Chang Gung Memorial Hospital at Linkou, was used to bombard the patient apertures. The patient aperture was composed of 60.5 % copper, 39.4 % Zinc, 0.05 % iron, 0.05 % lead. A protable high-purity germanium (HPGe) coaxial detector was used to measure the spectra of the induced nuclides of patient apertures. The analysis of the spectra and the identification of the radionuclides were preliminarily operated by the Nuclide Navigator III Master Library. On the basis of the results by Nuclide Navigator III Master Library, we manually selected the reliable nuclides by the gamma-ray energies, branching ratio, and half life. In the spectra, we can quantify the activity of radionuclides by the Monte Carlo efficiency transfer method. Results: In this study, the radioisotopes activated in patient apertures by the 190-MeV proton beam were divided into two categories. The first category is long half-life radionuclides, such as Co-56 (half life, 77.3 days). Other radionuclides of Cu-60, Cu-61, Cu-62, Cu-66, and Zn-62 have shorter half life. The radionuclide of Cu-60 had the highest activity. From calculation with the efficiency transfer method, the deviations between the computed results and the measured efficiencies were mostly within 10%. Conclusion: To identify the radionuclides and quantify the activity helps us to estimate proper time intervals for cooling the patient apertures. This study was supported by the grants from the Chang Gung Memorial Hospital (CMRPD1C0682)

  6. Nucleotide Metabolism in Salt-Stressed Zea mays L. Root Tips: I. Adenine and Uridine Nucleotides.

    PubMed

    Peterson, T A; Nieman, R H; Clark, R A

    1987-12-01

    Corn plants (Zea mays L. cv Pioneer 3906) were grown in a glass house on control and saline nutrient solutions, in winter and summer. There were two saline treatments, both with osmotic potential = -0.4 megapascal but with different Ca(2+)/Na(+) ratios: 0.03 and 0.73. Root tips and shoot meristems (culm tissue) of 26 day-old plants were analyzed for nucleotides to ascertain if there were correlations between nucleotide pool size and the reduced growth on saline cultures. Several other cell components also were determined. Plants grown in winter were only half as large as those grown in summer mainly because of the lower light intensity and lower temperature. But the relative yield reduction on salt treatment compared to the control was similar in winter and summer. The two different salt treatments caused similar yield reductions. Neither salt treatment affected nucleotide pools in culm tissue, with the possible exception of UDPG in winter. In the case of root tips, salt treatment had little or no effect on nucleotide pool sizes in winter when many already seemed near a critical minimum, but in summer it reduced several pools including ATP, total adenine nucleotide, UTP, total uridine nucleotide, and UDP-glucose. The reductions were greatest on the salt treatment with low Ca(2+)/Na(+). There was no simple correlation between the effects of salt stress on growth and on nucleotide pool size. The nucleotide pools of culm tissue indicated that in some respects this tissue was effectively insulated from the salt stress. Roots that were in direct contact with the saline solution indicated significant reductions in nucleotide pools only in the summer whereas growth was reduced both summer and winter. It is possible that the nucleotide concentrations of root cells in winter were already near a critical minimum so that nucleotide synthesis and growth were tightly linked. Significant reductions in nucleotide pools that would be expected to affect growth were more evident in

  7. 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.

  8. S-(N-dansylaminoethyl)-6-mercaptoguanosine as a fluorescent probe for the uridine transport system in human erythrocytes.

    PubMed

    Shohami, E; Koren, R

    1979-02-15

    A fluorescent derivative of 6-mercaptoguanosine, S-(N-dansylaminoethyl)-6-mercaptoguanosine, was synthesized, and found to be a strong inhibitor of the uridine transport system of erythrocyte (Ki approximately 0.3 microM). The emission spectrum of this compound has peaks at 400 and 550 nm. The emission at 550, but not that a 400 nm, in environment-sensitive. A method was devised for preparing a suspension of erythrocyte-membrane fragments with sufficiently low light scattering so that a detailed study could be made of the fluorescence of the probe when bound to membranes. Direct binding measurements showed the existence of a tight binding site, with a dissociation constant of the same order of magnitude as the inhibition constant. Binding of probe and substrate are not mutually exclusive, but the fluorescence and affinity of the bound probe are sensitive to the presence of uridine. The emission spectrum suggests that the bound probe penetrates into the bilayer region of the membrane.

  9. A novel procedure for purification of uridine 5'-monophosphate based on adsorption methodology using a hyper-cross-linked resin.

    PubMed

    Wu, Jinglan; Zhu, Hui; Liu, Yanan; Zhou, Jingwei; Zhuang, Wei; Jiao, Pengfei; Ke, Xu; Ying, Hanjie

    2015-05-01

    The conventional ion exchange process used for recovery of uridine 5'-monophosphate (UMP) from the enzymatic hydrolysate of RNA is environmentally harmful and cost intensive. In this work, an innovative benign process, which comprises adsorption technology and use of a hyper-cross-linked resin as a stationary phase is proposed. The adsorption properties of this kind of resin in terms of adsorption equilibrium as well as kinetics were evaluated. The influences of the operating conditions, i.e., initial UMP concentration, feed flow rate, and bed height on the breakthrough curves of UMP in the fixed bed system were investigated. Subsequently, a chromatographic column model was established and validated for the prediction of the experimentally attained breakthrough curves of UMP and the main impurity component (phosphate ion) with a real enzymatic hydrolysate of RNA as a feed mixture. At the end of this paper, the crystallization of UMP was carried out. The purity of the final product (uridine 5'-monophosphate disodium, UMPNa2) of over 99.5 % was obtained.

  10. Cyclic adenosine monophosphate-dependent vascular responses to purinergic agonists adenosine triphosphate and uridine triphosphate in the anesthetized mouse.

    PubMed

    Shah, Mrugeshkumar K; Kadowitz, Philip J

    2002-01-01

    The mechanism by which purinergic agonist adenosine triphosphate (ATP) and uridine triphosphate (UTP) decrease systemic arterial pressure in the anesthetized mouse was investigated. Intravenous injections of adenosine triphosphate (ATP) and uridine triphosphate (UTP) produced dose-dependent decreases in systemic blood pressure in the mouse. The order of potency was ATP > UTP. Vasodilator responses to ATP and UTP were altered by the cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor rolipram. The vascular responses to ATP and UTP were not altered by a nitric oxide synthase inhibitor, a cyclooxygenase inhibitor, a cGMP phosphodiesterase inhibitor, or a particular P2 receptor antagonist. These data suggest that ATP and UTP cause a decrease in systemic arterial pressure in the mouse via a cAMP-dependent pathway via a novel P2 receptor linked to adenylate cyclase and that nitric oxide release, prostaglandin synthesis, cGMP, and P2X1, P2Y1, and P2Y4 receptors play little or no role in the vascular effects of these purinergic agonists in the mouse.

  11. 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.

  12. Amalgamation of nucleosides and amino acids in antibiotic biosynthesis: discovery of an L-threonine:uridine-5'-aldehyde transaldolase.

    PubMed

    Barnard-Britson, Sandra; Chi, Xiuling; Nonaka, Koichi; Spork, Anatol P; Tibrewal, Nidhi; Goswami, Anwesha; Pahari, Pallab; Ducho, Christian; Rohr, Jurgen; Van Lanen, Steven G

    2012-11-14

    The lipopeptidyl nucleoside antibiotics represented by A-90289, caprazamycin, and muraymycin are structurally highlighted by a nucleoside core that contains a nonproteinogenic β-hydroxy-α-amino acid named 5'-C-glycyluridine (GlyU). Bioinformatic analysis of the biosynthetic gene clusters revealed a shared open reading frame encoding a protein with sequence similarity to serine hydroxymethyltransferases, resulting in the proposal that this shared enzyme catalyzes an aldol-type condensation with glycine and uridine-5'-aldehyde to furnish GlyU. Using LipK involved in A-90289 biosynthesis as a model, we now functionally assign and characterize the enzyme responsible for the C-C bond-forming event during GlyU biosynthesis as an l-threonine:uridine-5'-aldehyde transaldolase. Biochemical analysis revealed this transformation is dependent upon pyridoxal-5'-phosphate, the enzyme has no activity with alternative amino acids, such as glycine or serine, as aldol donors, and acetaldehyde is a coproduct. Structural characterization of the enzyme product is consistent with stereochemical assignment as the threo diastereomer (5'S,6'S)-GlyU. Thus this enzyme orchestrates C-C bond breaking and formation with concomitant installation of two stereocenters to make a new l-α-amino acid with a nucleoside side chain.

  13. Gut-brain and brain-gut axis in Parkinson's disease models: Effects of a uridine and fish oil diet.

    PubMed

    Perez-Pardo, Paula; Dodiya, Hemraj B; Broersen, Laus M; Douna, Hidde; van Wijk, Nick; Lopes da Silva, Sofia; Garssen, Johan; Keshavarzian, Ali; Kraneveld, Aletta D

    2017-03-09

    Recent investigations have focused on the potential role of gastrointestinal (GI) abnormalities in the pathogenesis of Parkinson's disease (PD). The 'dual-hit' hypothesis of PD speculates that a putative pathogen enters the brain via two routes: the olfactory system and the GI system. Here, we investigated (1) whether local exposures of the neurotoxin rotenone in the gut or the brain of mice could induce PD-like neurological and GI phenotypes as well as a characteristic neuropathology in accordance with this 'dual-hit hypothesis' and (2) the effects of a diet containing uridine and fish oil providing docosahexaenoic acid (DHA), in both models. Mice were given rotenone either orally or by an injection in the striatum. Dietary interventions were started 1 week before rotenone exposures. We found that (1) both oral and intrastriatal administration of rotenone induced similar PD-like motor deficits, dopaminergic cell loss, delayed intestinal transit, inflammation, and alpha-synuclein accumulation in the colon; (2) the uridine and DHA containing diet prevented rotenone-induced motor and GI dysfunctions in both models. The models suggest possible bidirectional communication between the gut and the brain for the genesis of PD-like phenotype and pathology. The dietary intervention may provide benefits in the prevention of motor and non-motor symptoms in PD.

  14. Crystallization and preliminary X-ray diffraction analysis of Salmonella typhimurium uridine phosphorylase complexed with 5-fluorouracil

    PubMed Central

    Lashkov, A. A.; Gabdoulkhakov, A. G.; Shtil, A. A.; Mikhailov, A. M.

    2009-01-01

    Uridine phosphorylase (UPh; EC 2.4.2.3) catalyzes the phosphorolytic cleavage of the N-glycosidic bond of uridine to form ribose 1-phosphate and uracil. This enzyme also activates pyrimidine-containing drugs, including 5-fluorouracil (5-FU). In order to better understand the mechanism of the enzyme–drug interaction, the complex of Salmonella typhimurium UPh with 5-FU was cocrystallized using the hanging-drop vapour-diffusion method at 294 K. X-ray diffraction data were collected to 2.2 Å resolution. Analysis of these data revealed that the crystal belonged to space group C2, with unit-cell parameters a = 158.26, b = 93.04, c = 149.87 Å, α = γ = 90, β = 90.65°. The solvent content was 45.85% assuming the presence of six hexameric molecules of the complex in the unit cell. PMID:19478441

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

    PubMed

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

    2016-01-19

    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.

  16. Structure and thermodynamics of a conserved U2 snRNA domain from yeast and human.

    PubMed

    Sashital, Dipali G; Venditti, Vincenzo; Angers, Cortney G; Cornilescu, Gabriel; Butcher, Samuel E

    2007-03-01

    The spliceosome is a dynamic ribonucleoprotein complex responsible for the removal of intron sequences from pre-messenger RNA. The highly conserved 5' end of the U2 small nuclear RNA (snRNA) makes key base-pairing interactions with the intron branch point sequence and U6 snRNA. U2 stem I, a stem-loop located in the 5' region of U2, has been implicated in spliceosome assembly and may modulate the folding of the U2 and U6 snRNAs in the spliceosome active site. Here we present the NMR structures of U2 stem I from human and Saccharomyces cerevisiae. These sequences represent the two major classes of U2 stem I, distinguished by the identity of tandem wobble pairs (UU/UU in yeast and CA/GU in human) and the presence of post-transcriptional modifications (four 2'-O-methyl groups and two pseudouracils in human). The structures reveal that the UU/UU and CA/GU tandem wobble pairs are nearly isosteric. The tandem wobble pairs separate two thermodynamically distinct regions of Watson-Crick base pairs, with the modified nucleotides in human stem I conferring a significant increase in stability. We hypothesize that the separate thermodynamic stabilities of U2 stem I exist to allow the structure to transition through different folded conformations during spliceosome assembly and catalysis.

  17. Emergency use of uridine triacetate for the prevention and treatment of life‐threatening 5‐fluorouracil and capecitabine toxicity

    PubMed Central

    Saif, Muhammad Wasif; El‐Rayes, Bassel F.; Fakih, Marwan G.; Cartwright, Thomas H.; Posey, James A.; King, Thomas R.; von Borstel, Reid W.; Bamat, Michael K.

    2016-01-01

    BACKGROUND Increased susceptibility to 5‐fluorouracil (5‐FU)/capecitabine can lead to rapidly occurring toxicity caused by impaired clearance, dihydropyrimidine dehydrogenase deficiency, and other genetic variations in the enzymes that metabolize 5‐FU. Life‐threatening 5‐FU overdoses occur because of infusion pump errors, dosage miscalculations, and accidental or suicidal ingestion of capecitabine. Uridine triacetate (Vistogard) was approved in 2015 for adult and pediatric patients who exhibit early‐onset severe or life‐threatening 5‐FU/capecitabine toxicities or present with an overdose. Uridine triacetate delivers high concentrations of uridine, which competes with toxic 5‐FU metabolites. METHODS In 2 open‐label clinical studies, patients who presented with a 5‐FU/capecitabine overdose or an early onset of severe toxicities were treated. Patients received uridine triacetate as soon as possible (most within the first 96 hours after 5‐FU/capecitabine). Outcomes included survival, resumption of chemotherapy, and safety. Their survival was compared with the survival of a historical cohort of overdose patients who received only supportive care. RESULTS A total of 137 of 142 overdose patients (96%) treated with uridine triacetate survived and had a rapid reversal of severe acute cardiotoxicity and neurotoxicity; in addition, mucositis and leukopenia were prevented, or the patients recovered from them. In the historical cohort, 21 of 25 patients (84%) died. Among the 141 uridine triacetate–treated overdose patients with a diagnosis of cancer (the noncancer patients included 6 intentional or accidental pediatric overdoses), 53 resumed chemotherapy in < 30 days (median time after 5‐FU, 19.6 days), and this indicated a rapid recovery from toxicity. Adverse reactions in patients receiving uridine triacetate included vomiting (8.1%), nausea (4.6%), and diarrhea (3.5%). CONCLUSIONS In these studies, uridine triacetate was a safe and effective

  18. 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.

  19. Low viscosity of the bottom of the Earth's mantle inferred from the decay time of Chandler wobble and tidal deformation

    NASA Astrophysics Data System (ADS)

    Nakada, M.; Karato, S.

    2011-12-01

    Viscosity of the D" layer of the Earth's mantle, the lowermost layer in the Earth's mantle, plays an important role in the dynamics and evolution of the Earth. That is, its rheological properties control a number of important geodynamic processes such as the mantle dynamics and the material exchange between the mantle and core. However, inferring the viscosity of this region is difficult because of the lack of relevant geodynamic observations. Two methods have been used to infer the rheological properties of Earth's mantle. One is to use the observed time-dependent deformation associated with the glacial isostatic adjustment (GIA), and another is to analyze gravity-related observations in terms of the density distributions inside of the mantle. The GIA observations for the relative sea level have little sensitivity to the viscosity of the mantle deeper than ~1200 km. The latter approach can be applied to Earth's deep interior because density variation driving mantle flow can occur in the deep interior of the Earth and resultant gravity signals can be measured at the Earth's surface. However, the gravity signals in terms of heterogeneity in seismic wave velocities suffer from major uncertainties in the velocity-to-density conversion factor, particularly in the deep mantle where the temperature sensitivity of seismic wave velocities decreases due to high pressure. In this paper, we show that the decay time of Chandler wobble and semi-diurnal to 18.6 years tidal deformation combined with the constraints from the GIA observations provide a strong constraint on the viscosity of this layer. In inferring the viscosity structure of the D" layer, we first examine the validity of the Maxwell model based on the microscopic models of rheological properties of Earth materials. That is, we confirm that the Maxwell model is a good approximation at least for the Chandler wobble and 18.6 years tide. The decay time of Chandler wobble (30-300 years) indicates the effective viscosity

  20. Amino acid residues in ribonuclease MC1 from bitter gourd seeds which are essential for uridine specificity.

    PubMed

    Numata, T; Suzuki, A; Yao, M; Tanaka, I; Kimura, M

    2001-01-16

    The ribonuclease MC1 (RNase MC1), isolated from seeds of bitter gourd (Momordica charantia), consists of 190 amino acids and is characterized by specific cleavage at the 5'-side of uridine. Site-directed mutagenesis was used to evaluate the contribution of four amino acids, Asn71, Val72, Leu73, and Arg74, at the alpha4-alpha5 loop between alpha4 and alpha5 helices for recognition of uracil base by RNase MC1. Four mutants, N71T, V72L, L73A, and R74S, in which Asn71, Val72, Leu73, and Arg74 in RNase MC1 were substituted for the corresponding amino acids, Thr, Leu, Ala, and Ser, respectively, in a guanylic acid preferential RNase NW from Nicotiana glutinosa, were prepared and characterized with respect to enzymatic activity. Kinetic analysis with a dinucleoside monophosphate, CpU, showed that the mutant N71T exhibited 7.0-fold increased K(m) and 2.3-fold decreased k(cat), while the mutant L73A had 14.4-fold increased K(m), although it did retain the k(cat) value comparable to that of the wild-type. In contrast, replacements of Val72 and Arg74 by the corresponding amino acids Leu and Ser, respectively, had little effect on the enzymatic activity. This observation is consistent with findings in the crystal structure analysis that Asn71 and Leu73 are responsible for a uridine specificity for RNase MC1. The role of Asn71 in enzymatic reaction of RNase MC1 was further investigated by substituting amino acids Ala, Ser, Gln, and Asp. Our observations suggest that Asn71 has at least two roles: one is base recognition by hydrogen bonding, and the other is to stabilize the conformation of the alpha4-alpha5 loop by hydrogen bonding to the peptide backbone, events which possibly result in an appropriate orientation of the alpha-helix (alpha5) containing active site residues. Mutants N71T and N71S showed a remarkable shift from uracil to guanine specificity, as evaluated by cleavage of CpG, although they did exhibit uridine specificity against yeast RNA and homopolynucleotides.

  1. O⁶-carboxymethylguanine in DNA forms a sequence context-dependent wobble base-pair structure with thymine.

    PubMed

    Zhang, Fang; Tsunoda, Masaru; Kikuchi, Yuji; Wilkinson, Oliver; Millington, Christopher L; Margison, Geoffrey P; Williams, David M; Takénaka, Akio

    2014-06-01

    N-Nitrosation of glycine and its derivatives generates potent alkylating agents that can lead to the formation of O(6)-carboxymethylguanine (O(6)-CMG) in DNA. O(6)-CMG has been identified in DNA derived from human colon tissue and its occurrence has been linked to diets high in red and processed meats, implying an association with the induction of colorectal cancer. By analogy to O(6)-methylguanine, O(6)-CMG is expected to be mutagenic, inducing G-to-A mutations that may be the molecular basis of increased cancer risk. Previously, the crystal structure of the DNA dodecamer d(CGCG[O(6)-CMG]ATTCGCG) has been reported, in which O(6)-CMG forms a Watson-Crick-type pair with thymine similar to the canonical A:T pair. In order to further investigate the versatility of O(6)-CMG in base-pair formation, the structure of the DNA dodecamer d(CGC[O(6)-CMG]AATTTGCG) containing O(6)-CMG at a different position has been determined by X-ray crystallography using four crystal forms obtained under conditions containing different solvent ions (Sr(2+), Ba(2+), Mg(2+), K(+) or Na(+)) with and without Hoechst 33258. The most striking finding is that the pairing modes of O(6)-CMG with T are quite different from those previously reported. In the present dodecamer, the T bases are displaced (wobbled) into the major groove to form a hydrogen bond between the thymine N(3) N-H and the carboxyl group of O(6)-CMG. In addition, a water molecule is bridged through two hydrogen bonds between the thymine O(2) atom and the 2-amino group of O(6)-CMG to stabilize the pairing. These interaction modes commonly occur in the four crystal forms, regardless of the differences in crystallization conditions. The previous and the present results show that O(6)-CMG can form a base pair with T in two alternative modes: the Watson-Crick type and a high-wobble type, the nature of which may depend on the DNA-sequence context.

  2. The absence of A-to-I editing in the anticodon of plant cytoplasmic tRNAArgACG demands a relaxation of the wobble decoding rules

    PubMed Central

    Aldinger, Carolin A.; Leisinger, Anne-Katrin; Gaston, Kirk W.; Limbach, Patrick A.; Igloi, Gabor L.

    2012-01-01

    It is a prevalent concept that, in line with the Wobble Hypothesis, those tRNAs having an adenosine in the first position of the anticodon become modified to an inosine at this position. Sequencing the cDNA derived from the gene coding for cytoplasmic tRNAArgACG from several higher plants as well as mass spectrometric analysis of the isoacceptor has revealed that for this kingdom an unmodified A in the wobble position of the anticodon is the rule rather than the exception. In vitro translation shows that in the plant system the absence of inosine in the wobble position of tRNAArg does not prevent decoding. This isoacceptor belongs to the class of tRNA that is imported from the cytoplasm into the mitochondria of higher plants. Previous studies on the mitochondrial tRNA pool have demonstrated the existence of tRNAArgICG in this organelle. In moss the mitochondrial encoded distinct tRNAArgACG isoacceptor possesses the I34 modification. The implication is that for mitochondrial protein biosynthesis A-to-I editing is necessary and occurs by a mitochondrion-specific deaminase after import of the unmodified nuclear encoded tRNAArgACG. PMID:22922796

  3. The absence of A-to-I editing in the anticodon of plant cytoplasmic tRNA (Arg) ACG demands a relaxation of the wobble decoding rules.

    PubMed

    Aldinger, Carolin A; Leisinger, Anne-Katrin; Gaston, Kirk W; Limbach, Patrick A; Igloi, Gabor L

    2012-10-01

    It is a prevalent concept that, in line with the Wobble Hypothesis, those tRNAs having an adenosine in the first position of the anticodon become modified to an inosine at this position. Sequencing the cDNA derived from the gene coding for cytoplasmic tRNA (Arg) ACG from several higher plants as well as mass spectrometric analysis of the isoacceptor has revealed that for this kingdom an unmodified A in the wobble position of the anticodon is the rule rather than the exception. In vitro translation shows that in the plant system the absence of inosine in the wobble position of tRNA (Arg) does not prevent decoding. This isoacceptor belongs to the class of tRNA that is imported from the cytoplasm into the mitochondria of higher plants. Previous studies on the mitochondrial tRNA pool have demonstrated the existence of tRNA (Arg) ICG in this organelle. In moss the mitochondrial encoded distinct tRNA (Arg) ACG isoacceptor possesses the I34 modification. The implication is that for mitochondrial protein biosynthesis A-to-I editing is necessary and occurs by a mitochondrion-specific deaminase after import of the unmodified nuclear encoded tRNA (Arg) ACG.

  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

    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.

  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

    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.

  6. Short-term administration of uridine increases brain membrane phospholipids precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T

    PubMed Central

    Agarwal, Nivedita; Sung, Young-Hoon; Jensen, J Eric; daCunha, Grace; Harper, David; Olson, David; Renshaw, Perry F

    2010-01-01

    Objectives Altered metabolism of membrane phospholipids has been implicated in bipolar disorder. In humans, uridine is an important precursor of cytidine diphosphate (CDP)-choline, which plays a critical role in phospholipid synthesis and is currently being evaluated as a potential treatment for bipolar depression. Methods A total of 17 healthy males (mean age ± SD: 32.73 ± 7.2 years; range: 21.8- 46.4 years) were enrolled in this study. Subjects underwent a 31-phosphorus magnetic resonance spectroscopy (31P-MRS) acquisition at baseline and then again after seven days of either 2 g of uridine or placebo administration. A two-dimensional chemical shift imaging 31P-MRS acquisition collected spectral data from a 4 × 4 cluster of voxels acquired in the axial plane encompassing the subcortical structures as well as frontaltemporal cortical gray and white matter. The slab thickness was 3 cm and the approximate total volume of brain sampled was 432 cm3. The spectra obtained were analyzed using a fully automated in-house fitting algorithm. A population-averaged generalized estimating equation was used to evaluate changes both in phosphomonoesters (PME) [phosphocholine (PCho) and phosphoethanolamine (PEtn)] and phosphodiesters (PDE) [glycerophosphocholine (GPCho) and glycerophosphethanolamine (GPEtn)]. Metabolite ratios were reported with respect to the total integrated 31P resonance area. Results The uridine group had significantly increased total PME and PEtn levels over the one-week period [6.32% and 7.17% for PME and PEtn, respectively (p < 0.001)]. Other metabolite levels such as PCho, PDE, GPEtn and GPCho showed no significant changes following either uridine or placebo (all p > 0.05). Conclusions This is the first study to report a direct effect of uridine on membrane phospholipid precursors in healthy adults using 31P-MRS. Sustained administration of uridine appears to increase PME in healthy subjects. Further investigation is required to clarify the effects of

  7. Synthesis, photophysical properties and incorporation of a highly emissive and environment-sensitive uridine analogue based on the Lucifer chromophore.

    PubMed

    Tanpure, Arun A; Srivatsan, Seergazhi G

    2014-06-16

    The majority of fluorescent nucleoside analogues used in nucleic acid studies have excitation maxima in the UV region and show very low fluorescence within oligonucleotides (ONs); hence, they cannot be utilised with certain fluorescence methods and for cell-based analysis. Here, we describe the synthesis, photophysical properties and incorporation of a highly emissive and environment-sensitive uridine analogue, derived by attaching a Lucifer chromophore (1,8-naphthalimide core) at the 5-position of uracil. The emissive nucleoside displays excitation and emission maxima in the visible region and exhibits high quantum yield. Importantly, when incorporated into ON duplexes it retains appreciable fluorescence efficiency and is sensitive to the neighbouring base environment. Notably, the nucleoside signals the presence of purine repeats in ON duplexes with an enhancement in fluorescence intensity, a property rarely displayed by other nucleoside analogues. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Syn- and anti-conformations of 5'-deoxy- and 5'-O-methyl-uridine 2',3'-cyclic monophosphate.

    PubMed

    Grabarkiewicz, Tomasz; Hoffmann, Marcin

    2006-01-01

    Two uridine 2',3'-cyclic monophosphate (cUMP) derivatives, 5'-deoxy (DcUMP) and 5'-O-methyl (McUMP), were studied by means of quantum chemical methods. Aqueous solvent effects were estimated based on the isodensity-surface polarized-continuum model (IPCM). Gas phase calculations revealed only slight energy differences between the syn- and anti-conformers of both compounds: the relative energies of the syn-structure are -0.9 and 0.2 kcal mol(-1) for DcUMP and McUMP, respectively. According to the results from the IPCM calculations, however, both syn-conformers become about 14 kcal mol(-1) more stable in aqueous solution than their corresponding anti-structures. Additionally, the effects of a countercation and protonation on DcUMP were studied, revealing that the syn-structure is also favored over the anti-one for these systems.

  9. Theoretical pKa prediction of the α-phosphate moiety of uridine 5‧-diphosphate-GlcNAc

    NASA Astrophysics Data System (ADS)

    Vipperla, Bhavaniprasad; Griffiths, Thomas M.; Wang, Xingyong; Yu, Haibo

    2017-01-01

    The pKa value of the α-phosphate moiety of uridine 5‧-diphosphate-GlcNAc (UDP-GlcNAc) has been successfully calculated using density functional theory methods in conjunction with the Polarizable Continuum Models. Theoretical methods were benchmarked over a dataset comprising of alkyl phosphates. B3LYP/6-31+G(d,p) calculations using SMD solvation model provide excellent agreement with the experimental data. The predicted pKa for UDP-GlcNAc is consistent with most recent NMR studies but much higher than what it has long been thought to be. The importance of this study is evident that the predicted pKa for UDP-GlcNAc supports its potential role as a catalytic base in the substrate-assisted biocatalysis.

  10. Isolation, crystallization in the macrogravitation field, preliminary X-ray investigation of uridine phosphorylase from Escherichia coli K-12.

    PubMed

    Mikhailov, A M; Smirnova, E A; Tsuprun, V L; Tagunova, I V; Vainshtein, B K; Linkova, E V; Komissarov, A A; Siprashvili, Z Z; Mironov, A S

    1992-03-01

    Uridine phosphorylase (UPH) from Escherichia coli K-12 has been purified to near homogeneity from a strain harbouring the udp gene, encoding UPH, on a multicopy plasmid. UPH was purified to electrophoretic homogeneity with the specific activity 230 units/mg with a recovery of 80%, yielding 120 mg of enzyme from 3g cells. Crystals of enzyme suitable for X-ray diffraction analysis were obtained in a preparative ultracentrifuge. The packing of the molecules in the crystals may be described by the space group P2(1)2(1)2(1) with the unit cell constants a = 90.4; b = 128.8; c = 136.8 A. There is one molecule per asymmetric unit, Vm = 2.4. These crystals diffract to at least 2.5-2.7 A resolution. The hexameric structure of UPH was directly demonstrated by electron microscopy study and image processing.

  11. 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

  12. Reparameterization of RNA χ Torsion Parameters for the AMBER Force Field and Comparison to NMR Spectra for Cytidine and Uridine

    PubMed Central

    2010-01-01

    A reparameterization of the torsional parameters for the glycosidic dihedral angle, χ, for the AMBER99 force field in RNA nucleosides is used to provide a modified force field, AMBER99χ. Molecular dynamics simulations of cytidine, uridine, adenosine, and guanosine in aqueous solution using the AMBER99 and AMBER99χ force fields are compared with NMR results. For each nucleoside and force field, 10 individual molecular dynamics simulations of 30 ns each were run. For cytidine with AMBER99χ force field, each molecular dynamics simulation time was extended to 120 ns for convergence purposes. Nuclear magnetic resonance (NMR) spectroscopy, including one-dimensional (1D) 1H, steady-state 1D 1H nuclear Overhauser effect (NOE), and transient 1D 1H NOE, was used to determine the sugar puckering and preferred base orientation with respect to the ribose of cytidine and uridine. The AMBER99 force field overestimates the population of syn conformations of the base orientation and of C2′-endo sugar puckering of the pyrimidines, while the AMBER99χ force field’s predictions are more consistent with NMR results. Moreover, the AMBER99 force field prefers high anti conformations with glycosidic dihedral angles around 310° for the base orientation of purines. The AMBER99χ force field prefers anti conformations around 185°, which is more consistent with the quantum mechanical calculations and known 3D structures of folded ribonucleic acids (RNAs). Evidently, the AMBER99χ force field predicts the structural characteristics of ribonucleosides better than the AMBER99 force field and should improve structural and thermodynamic predictions of RNA structures. PMID:20463845

  13. Zoledronate derivatives as potential inhibitors of uridine diphosphate-galactose ceramide galactosyltransferase 8: A combined molecular docking and dynamic study.

    PubMed

    Pannuzzo, Giovanna; Graziano, Adriana Carol Eleonora; Pannuzzo, Martina; Masman, Marcelo Fabricio; Avola, Rosanna; Cardile, Venera

    2016-11-01

    Krabbe's disease is a neurodegenerative disorder caused by deficiency of galactocerebrosidase activity that affects the myelin sheath of the nervous system, involving dysfunctional metabolism of sphingolipids. It has no cure. Because substrate inhibition therapy has been shown to be effective in some human lysosomal storage diseases, we hypothesize that a substrate inhibition therapeutic approach might be appropriate to allow correction of the imbalance between formation and breakdown of glycosphingolipids and to prevent pathological storage of psychosine. The enzyme responsible for the biosynthesis of galactosylceramide and psychosine is uridine diphosphate-galactose ceramide galactosyltransferase (2-hydroxyacylsphingosine 1-β-galactosyltransferase; UGT8; EC 2.4.1.45), which catalyzes the transferring of galactose from uridine diphosphate-galactose to ceramide or sphingosine, an important step of the biosynthesis of galactosphingolipids. Because some bisphosphonates have been identified as selective galactosyltransferase inhibitors, we verify the binding affinity to a generated model of the enzyme UGT8 and investigate the molecular mechanisms of UGT8-ligand interactions of the bisphosphonate zoledronate by a multistep framework combining homology modeling, molecular docking, and molecular dynamics simulations. From structural information on UGTs' active site stereochemistry, charge density, and access through the hydrophobic environment, the molecular docking procedure allowed us to identify zoledronate as a potential inhibitor of human ceramide galactosyltransferase. More importantly, zoledronate derivates were designed through computational modeling as putative new inhibitors. Experiments in vivo and in vitro have been planned to verify the possibility of using zoledronate and/or the newly identified inhibitors of UGT8 for a substrate inhibition therapy useful for treatment of Krabbe's disease and/or other lysosomal disorders. © 2016 Wiley Periodicals, Inc.

  14. Reparameterization of RNA chi Torsion Parameters for the AMBER Force Field and Comparison to NMR Spectra for Cytidine and Uridine.

    PubMed

    Yildirim, Ilyas; Stern, Harry A; Kennedy, Scott D; Tubbs, Jason D; Turner, Douglas H

    2010-05-11

    A reparameterization of the torsional parameters for the glycosidic dihedral angle, chi, for the AMBER99 force field in RNA nucleosides is used to provide a modified force field, AMBER99chi. Molecular dynamics simulations of cytidine, uridine, adenosine, and guanosine in aqueous solution using the AMBER99 and AMBER99chi force fields are compared with NMR results. For each nucleoside and force field, 10 individual molecular dynamics simulations of 30 ns each were run. For cytidine with AMBER99chi force field, each molecular dynamics simulation time was extended to 120 ns for convergence purposes. Nuclear magnetic resonance (NMR) spectroscopy, including one-dimensional (1D) (1)H, steady-state 1D (1)H nuclear Overhauser effect (NOE), and transient 1D (1)H NOE, was used to determine the sugar puckering and preferred base orientation with respect to the ribose of cytidine and uridine. The AMBER99 force field overestimates the population of syn conformations of the base orientation and of C2'-endo sugar puckering of the pyrimidines, while the AMBER99chi force field's predictions are more consistent with NMR results. Moreover, the AMBER99 force field prefers high anti conformations with glycosidic dihedral angles around 310 degrees for the base orientation of purines. The AMBER99chi force field prefers anti conformations around 185 degrees , which is more consistent with the quantum mechanical calculations and known 3D structures of folded ribonucleic acids (RNAs). Evidently, the AMBER99chi force field predicts the structural characteristics of ribonucleosides better than the AMBER99 force field and should improve structural and thermodynamic predictions of RNA structures.

  15. Peroxisome proliferator-activated receptor gamma coactivator-1alpha enhances antiproliferative activity of 5'-deoxy-5-fluorouridine in cancer cells through induction of uridine phosphorylase.

    PubMed

    Kong, Xingxing; Fan, Heng; Liu, Xiaojun; Wang, Rui; Liang, Jichao; Gupta, Nishith; Chen, Yong; Fang, Fude; Chang, Yongsheng

    2009-10-01

    Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is capable of coactivating several nuclear receptors and transcription factors that participate in the regulation of multiple metabolic processes, including gluconeogenesis, mitochondrial biogenesis, and adaptive thermogenesis. Uridine phosphorylase (UPase) catalyzes the reversible conversion of uridine into uracil and contributes to the antineoplastic activity of 5'-deoxy-5-fluorouridine (5'-DFUR) and homeostasis of uridine levels in plasma and tissues. This study demonstrates uridine phosphorylase as a novel target gene of PGC-1alpha, which induces the transcription and enzymatic activity of UPase in various cancer cells and thus augments their susceptibility to 5'-DFUR. PGC-1alpha-induced activation of UPase expression occurs at its transcription level that is mediated by an estrogen-related receptor (ERR) binding site (-1078 to -1070 base pairs) mapped in the promoter region of UPase gene. Our mutational studies using luciferase reporter construct together with electrophoretic mobility shift assays confirm the binding of ERR to PGC-1alpha-responsive element. Moreover, the inhibition of PGC-1alpha/ERRalpha-dependent signaling by 3-[4-(2,4-bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide (XCT790) compromises the ability of PGC-1alpha to induce the transcript of UPase, indicating PGC-1alpha-dependent and ERRalpha-mediated up-regulation of UPase. Finally, the overexpression of PGC-1alpha sensitizes breast and colon cancer cells to growth inhibition by 5'-DFUR presumably by inducing apoptosis in tumor cells and XCT790 can inhibit the process. Taken together, our results corroborate the regulatory function of PGC-1alpha in uridine homeostasis and imply its links with the energy metabolism. The mechanistic elucidation of this association between both cellular pathways should advance the clinical use of 5-fluorouracil

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

    PubMed Central

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

    2016-01-01

    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

  17. Low viscosity of the bottom of the Earth's mantle inferred from the analysis of Chandler wobble and tidal deformation

    NASA Astrophysics Data System (ADS)

    Nakada, Masao; Karato, Shun-ichiro

    2012-02-01

    Viscosity of the D″ layer of the Earth's mantle, the lowermost layer in the Earth's mantle, controls a number of geodynamic processes, but a robust estimate of its viscosity has been hampered by the lack of relevant observations. A commonly used analysis of geophysical signals in terms of heterogeneity in seismic wave velocities suffers from major uncertainties in the velocity-to-density conversion factor, and the glacial rebound observations have little sensitivity to the D″ layer viscosity. We show that the decay of Chandler wobble and semi-diurnal to 18.6 years tidal deformation combined with the constraints from the postglacial isostatic adjustment observations suggest that the effective viscosity in the bottom ˜300 km layer is 1019-1020 Pa s, and also the effective viscosity of the bottom part of the D″ layer (˜100 km thickness) is less than 1018 Pa s. Such a viscosity structure of the D″ layer would be a natural consequence of a steep temperature gradient in the D″ layer, and will facilitate small scale convection and melt segregation in the D″ layer.

  18. DPT tautomerisation of the wobble guanine·thymine DNA base mispair is not mutagenic: QM and QTAIM arguments.

    PubMed

    Brovarets', Ol'ha O; Zhurakivsky, Roman O; Hovorun, Dmytro M

    2015-01-01

    We have shown for the first time, connecting QM methods with QTAIM analysis and using the methodology of the sweeps of the energetical, electron-topological and geometrical parameters, that the tautomerisation of the wobble guanine·thymine (wG·T) DNA base mispair into the wG(*)·T(*) base mispair induced by the double proton transfer (DPT), which undergoes a concerted asynchronous pathway, is not mutagenic. The wG·T → wG(*)·T(*) DPT tautomerisation does not result in the transition of the G base into its mutagenic tautomeric form G(*) able to mispair with the T base within the Watson-Crick base pairing scheme. This observation is explained by the so-called quantum protection of the wG·T DNA base mispair from its mutagenic tautomerisation - the dynamical non-stability of the tautomerised wG(*)·T(*) base mispair and significantly negative value of the Gibbs free energy of activation for the reverse reaction of the wG·T → wG(*)·T(*) DPT tautomerisation.

  19. 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…

  20. 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.

  1. A catalytic metal ion interacts with the cleavage site G•U wobble in the HDV ribozyme†

    PubMed Central

    Chen, Jui-Hui; Gong, Bo; Bevilacqua, Philip C.; Carey, Paul R.; Golden, Barbara L.

    2009-01-01

    The HDV ribozyme self-cleaves by a chemical mechanism involving general acid-base catalysis to generate a 2′,3′-cyclic phosphate and a 5′-hydroxyl termini. Biochemical studies from several laboratories have implicated C75 as the general acid and hydrated magnesium as the general base. We have previously shown that C75 has a pKa shifted > 2 pH units toward neutrality [Gong, B., Chen, J. H., Chase, E., Chadalavada, D. M., Yajima, R., Golden, B. L., Bevilacqua, P. C., and Carey, P. R. (2007) J. Am. Chem. Soc. 129, 13335–13342.], while in crystal structures, it is well-positioned for proton transfer. However no crystallographic evidence for a hydrated magnesium poised to serve as a general base in the reaction has been observed in high-resolution crystal structures of various reaction states and mutants. Herein, we use solution kinetic experiments and parallel Raman crystallographic studies to examine the effects of pH on rate and Mg2+-binding properties of wild-type and 7-deazaguanosine mutants of the HDV ribozyme. These data suggest that a previously-unobserved hydrated magnesium ion interacts with the N7 of the cleavage site G•U wobble base pair. Integrating this metal ion binding site with the available crystal structures provides a new three-dimensional model for the active site of the ribozyme that accommodates all available biochemical data and appears competent for catalysis. The position of this metal is consistent with a role of a magnesium-bound hydroxide as a general base as dictated by biochemical data. PMID:19178151

  2. 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)

  3. The viscosity structure of the D″ layer of the Earth's mantle inferred from the analysis of Chandler wobble and tidal deformation

    NASA Astrophysics Data System (ADS)

    Nakada, Masao; Iriguchi, Chihiro; Karato, Shun-ichiro

    2012-10-01

    The viscosity structure of the D″ layer of the Earth's mantle is inferred from the decay time of the Chandler wobble and semi-diurnal to 18.6 years tidal deformations combined with model viscosity-depth profiles corresponding to a range of temperature-depth models. We use two typical temperature profiles of the D″ layer by considering its dynamic state: (i) bottom thermal boundary layer of the mantle convection (TBL model) and (ii) vigorously small-scale convecting layer (CON model). Three possible models are derived from the comparison between the numerical and observationally inferred decay times of Chandler wobble and tidal deformation. The first and second models are those with a viscosity of ˜1016 Pa s at the core-mantle boundary. The temperature gradient for the first one, TBL model with a thickness of the D″ layer (L) of ˜200 km, is nearly constant within the D″ layer. The second one, TBL and CON models with L ˜ 300 km, requires that the temperature gradient of the lower part (˜100 km thickness) is larger than that of the upper part. The temperature increases within the D″ layer for these two models are larger than ˜1500 K. The third model has a constant low viscosity layer (˜100 km thickness and viscosity smaller than ˜1017 Pa s) at the bottom of the D″ layer in TBL (L ˜ 200 and 300 km) and CON (L ˜ 300 km) models. The temperature increases would be 1000-1600 K depending on the viscosity at the top of the D″ layer (1021-1022 Pa s). The heat flows from the core to the mantle for these three models are estimated to be larger than ˜5 TW. The third model may be preferable after comprehensively taking account of the fitness of the decay time of the Chandler wobble and the tidal deformations for each model.

  4. YibK is the 2'-O-methyltransferase TrmL that modifies the wobble nucleotide in Escherichia coli tRNA(Leu) isoacceptors.

    PubMed

    Benítez-Páez, Alfonso; Villarroya, Magda; Douthwaite, Stephen; Gabaldón, Toni; Armengod, M-Eugenia

    2010-11-01

    Transfer RNAs are the most densely modified nucleic acid molecules in living cells. In Escherichia coli, more than 30 nucleoside modifications have been characterized, ranging from methylations and pseudouridylations to more complex additions that require multiple enzymatic steps. Most of the modifying enzymes have been identified, although a few notable exceptions include the 2'-O-methyltransferase(s) that methylate the ribose at the nucleotide 34 wobble position in the two leucyl isoacceptors tRNA(Leu)(CmAA) and tRNA(Leu)(cmnm5UmAA). Here, we have used a comparative genomics approach to uncover candidate E. coli genes for the missing enzyme(s). Transfer RNAs from null mutants for candidate genes were analyzed by mass spectrometry and revealed that inactivation of yibK leads to loss of 2'-O-methylation at position 34 in both tRNA(Leu)(CmAA) and tRNA(Leu)(cmnm5UmAA). Loss of YibK methylation reduces the efficiency of codon-wobble base interaction, as demonstrated in an amber suppressor supP system. Inactivation of yibK had no detectable effect on steady-state growth rate, although a distinct disadvantage was noted in multiple-round, mixed-population growth experiments, suggesting that the ability to recover from the stationary phase was impaired. Methylation is restored in vivo by complementing with a recombinant copy of yibK. Despite being one of the smallest characterized α/β knot proteins, YibK independently catalyzes the methyl transfer from S-adenosyl-L-methionine to the 2'-OH of the wobble nucleotide; YibK recognition of this target requires a pyridine at position 34 and N⁶-(isopentenyl)-2-methylthioadenosine at position 37. YibK is one of the last remaining E. coli tRNA modification enzymes to be identified and is now renamed TrmL.

  5. Conservation Laws

    NASA Astrophysics Data System (ADS)

    Dewitt, Bryce; Christensen, Steven M.

    In the case of the free particle, we interpreted various components of the energy-momentum-stress density as fluxes of energy and momentum. This interpretation can obviously be extended also to particle ensembles and gases. When we speak of fluxes we usually think of quantities that are conserved. In special relativity, energy and momentum are conserved. In general relativity, they are no longer generally conserved, at least if we do not include the energy and momentum of the gravitational field itself. Nevertheless, their densities and fluxes satisfy a covariant generalization of a true conservation law, which is quite easy to obtain.

  6. Uridine prodrug improves memory in Tg2576 and TAPP mice and reduces pathological factors associated with Alzheimer's disease in related models.

    PubMed

    Saydoff, Joel A; Olariu, Ana; Sheng, Jin; Hu, Zhongyi; Li, Qin; Garcia, Rolando; Pei, Jiong; Sun, Grace Y; von Borstel, Reid

    2013-01-01

    Uridine prodrug PN401 has been shown to have neuroprotective effects in models of Parkinson's disease and Huntington's disease. These age-related neurodegenerative diseases including Alzheimer's disease (AD) are associated with mitochondrial dysfunction, oxidative stress, and inflammation. Attenuation of these pathological factors in AD, in addition to amyloid fibrils and neurofibrillary tangles, is critical to prevent cognitive impairment. The effects of PN401 treatment were tested in the Tg2576 and Tg2576 X P301L (TAPP) mouse models of AD. Treatment with PN401 reduced impairments in the Tg2576 mice in contextual fear conditioning and novel object recognition. In the TAPP mice, PN401 reduced the impairments in novel object recognition and social transmission of food preference. PN401 also improved motor behavior and reduced anxiety-like behavior in the TAPP mice. TAPP mouse hippocampal tau phosphorylation and lipid peroxidation were reduced by PN401 treatment. Increased tau phosphorylation was significantly correlated with worsening novel object recognition memory. PN401 did not affect amyloid plaque area in the AD mice. In other AD-related animal studies, PN401 treatment reduced blood-brain barrier damage due to intracortical LPS, elevation of serum TNFα due to systemic LPS, and hippocampal CA1 neuronal loss in the gerbil stroke model. Uridine dose-dependently protected cells from chemical hypoxia and ceramide, and decreased formation of reactive oxygen species and mitochondrial DNA damage due to hydrogen peroxide. These protective effects were achieved by raising uridine levels to at least 25-50 μM and serum uridine levels in this range in humans were obtained with oral PN401.

  7. Toward analogues of MraY natural inhibitors: synthesis of 5'-triazole-substituted-aminoribosyl uridines through a Cu-catalyzed azide-alkyne cycloaddition.

    PubMed

    Fer, Mickaël J; Olatunji, Samir; Bouhss, Ahmed; Calvet-Vitale, Sandrine; Gravier-Pelletier, Christine

    2013-10-18

    A straightforward strategy for the synthesis of triazole-containing MraY inhibitors has been developed. It involves the sequential introduction of a terminal alkyne at the 5' position of an uridine derivative and O-glycosylation with a protected aminoribose leading to an elaborated alkyne scaffold. An efficient Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) allowed the introduction of chemical diversity toward a small library of inhibitors.

  8. The effect of chemical modification of 3-(3-amino-3-carboxypropyl)uridine on tRNA function.

    PubMed

    Friedman, S

    1979-08-10

    The minor base 3-(3-amino-3-carboxypropyl)uridine (acp3U) in Escherichia coli tRNAPhe was acylated with the N-hydroxysuccinimide esters of acetic, phenoxy-acetic, and naphthoxyacetic acid, as well as the ester of 5-dimethylaminonaphthalene-1-sulfonyl (dansyl)-glycine. The derivatives of tRNAPhe formed were all capable of accepting phenylalanine. There were only minor effects on the kinetic parameters of these derivatives for E. coli phenylalanyl-tRNA synthetase. There was no effect on the ability of tRNAPhe to participate in poly(U)- or poly(ACU)-directed polypeptide synthesis or in the poly(U)-stimulated binding to E. coli ribosomes. The rate of photodynamic cross-linking of 4-Srd 8 to Cyd 13 was decreased in tRNAs containing the acetyl and dansyl-glycyl derivatives of acp3U, indicating that acylation of this base may perturb the tertiary structure of the tRNA. This base in tRNAPhe does not appear to play any role in the known biological functions of tRNAPhe.

  9. Selective Nucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2) Inhibitors: Nucleotide Mimetics Derived from Uridine-5′-carboxamide†

    PubMed Central

    Brunschweiger, Andreas; Iqbal, Jamshed; Umbach, Frank; Scheiff, Anja B.; Munkonda, Mercedes N.; Sévigny, Jean; Knowles, Aileen F.; Müller, Christa E

    2016-01-01

    Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases, subtypes 1, 2, 3, 8 of NTPDases) dephosphorylate nucleoside tri- and diphosphates to the corresponding di- and monophosphates. In the present study we synthesized adenine and uracil nucleotide mimetics, in which the phosphate residues were replaced by phosphonic acid esters attached to the nucleoside at the 5′-position by amide linkers. Among the synthesized uridine derivatives, we identified the first potent and selective inhibitors of human NTPDase2. The most potent compound was 19a (PSB-6426), which was a competitive inhibitor of NTPDase2 exhibiting a Ki value of 8.2 μM and selectivity versus other NTPDases. It was inactive toward uracil nucleotide-activated P2Y2, P2Y4, and P2Y6 receptor subtypes. Compound 19a was chemically and metabolically highly stable. In contrast to the few known (unselective) NTPDase inhibitors, 19a is an uncharged molecule and may be perorally bioavailable. NTPDase2 inhibitors have potential as novel cardioprotective drugs for the treatment of stroke and for cancer therapy. PMID:18630897

  10. 5'-Methylene-triazole-substituted-aminoribosyl uridines as MraY inhibitors: synthesis, biological evaluation and molecular modeling.

    PubMed

    Fer, Mickaël J; Bouhss, Ahmed; Patrão, Mariana; Le Corre, Laurent; Pietrancosta, Nicolas; Amoroso, Ana; Joris, Bernard; Mengin-Lecreulx, Dominique; Calvet-Vitale, Sandrine; Gravier-Pelletier, Christine

    2015-07-14

    The straightforward synthesis of 5'-methylene-[1,4]-triazole-substituted aminoribosyl uridines is described. Two families of compounds were synthesized from a unique epoxide which was regioselectively opened by acetylide ions (for compounds II) or azide ions (for compounds III). Sequential diastereoselective glycosylation with a ribosyl fluoride derivative, Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) with various complementary azide and alkyne partners afforded the targeted compounds after final deprotection. The biological activity of the 16 resulting compounds together with that of 14 previously reported compounds I, lacking the 5' methylene group, was evaluated on the MraY transferase activity. Out of the 30 tested compounds, 18 compounds revealed MraY inhibition with IC50 ranging from 15 to 150 μM. A molecular modeling study was performed to rationalize the observed structure-activity relationships (SAR), which allowed us to correlate the activity of the most potent compounds with an interaction involving Leu191 of MraYAA. The antibacterial activity was also evaluated and seven compounds exhibited a good activity against Gram-positive bacterial pathogens with MIC ranging from 8 to 32 μg mL(-1), including the methicillin resistant Staphylococcus aureus (MRSA).

  11. Kinetic Isotope Effects and Stereochemical Studies on a Ribonuclease Model: Hydrolysis Reactions of Uridine 3'-Nitrophenyl Phosphate.

    PubMed

    Hengge; Bruzik; Tobin; Cleland; Tsai

    2000-06-01

    The reactions of a ribonuclease model substrate, the compound uridine-3'-p-nitrophenyl phosphate, have been examined using heavy-atom isotope effects and stereochemical analysis. The cyclization of this compound is subject to catalysis by general base (by imidazole buffer), specific base (by carbonate buffer), and by acid. All three reactions proceed by the same mechanistic sequence, via cyclization to cUMP, which is stable under basic conditions but which is rapidly hydrolyzed to a mixture of 2'- and 3'-UMP under acid conditions. The isotope effects indicate that the specific base-catalyzed reaction exhibits an earlier transition state with respect to bond cleavage to the leaving group compared to the general base-catalyzed reaction. Stereochemical analysis indicates that both of the base-catalyzed reactions proceed with the same stereochemical outcome. It is concluded that the difference in the nucleophile in the two base-catalyzed reactions results in a difference in the transition state structure but both reactions are most likely concerted, with no phosphorane intermediate. The (15)N isotope effects were also measured for the reaction of the substrate with ribonuclease A. The results indicate that considerably less negative charge develops on the leaving group in the transition state than for the general base-catalyzed reaction in solution. Copyright 2000 Academic Press.

  12. Separation and purification of uridine diphosphate-glucuronosyltransferases by chromatofocusing on a high-performance liquid chromatograph.

    PubMed

    Takanashi, H; Homma, H; Matsui, M

    1989-06-01

    A rapid method for the separation and purification of uridine diphosphate-glucuronosyltransferases (GT) was developed with the use of chromatofocusing on a high-performance liquid chromatograph. GT isoenzymes solubilized from hepatic microsomes of Wistar rats were separated on a Mono P column, a pre-packed column for chromatofocusing. Using 4-nitrophenol, testosterone and androsterone as substrates, four fractions with different GT activities were separated in a pH gradient from 9.5 to 7.0. Two isoenzymes, testosterone GT and androsterone GT were purified to apparent homogeneity. They were eluted at pH 8.9 and 8.0 and had subunit molecular weight values of 50000 and 52000, respectively. Approximately 10 mg of solubilized microsomal proteins was applied and the elution was completed within 2 h. Addition of N-nitrodiethylamine, an in vitro activator of GT activity, enhanced the GT activity toward 4-nitrophenol in the three fractions. This chromatographic analysis confirmed the absence of androsterone GT isoenzyme in LA Wistar rats, a mutant strain in terms of androsterone glucuronidation.

  13. 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. © 2014 The Royal Entomological Society.

  14. Gender-dependent differences in uridine 5'-diphospho-glucuronosyltransferase have implications in metabolism and clearance of xenobiotics.

    PubMed

    Liu, Wei; Kulkarni, Kaustubh; Hu, Ming

    2013-12-01

    Gender differences have a significant impact on absorption, disposition and overall systemic bioavailability of various xenobiotics in rodents as well as humans. Over the past few years, significant research has explored and investigated the effects of gender differences on the expression profiles of uridine 5'-diphospho-glucuronosyltransferases (or UGTs) in rodents but no data is available that could effectively help predict the metabolic clearance or systemic bioavailability of xenobiotics predominantly metabolized by UGT enzymes in vivo. This review highlights and explains the unique features of the metabolic clearance reactions catalyzed by UGTs (metabolite formation) and its intricate interactions with the efflux transporters that will transport hydrophilic glucuronides out of cell in vivo. In addition, the article reviews the gender differences in hepatic and extrahepatic UGT isoforms and efflux transporter expression profiles in rodents. Furthermore, the article highlights the implications of sex hormone differences on metabolic clearance and thereby oral bioavailability of xenobiotics that are predominantly metabolized by UGTs in vivo. Finally, the article reviews the impact of plasma sex hormone level differences on UGT enzyme and efflux transporter expression profiles using in situ and in vivo models. The authors believe that the article demonstrates that gender, and perhaps more importantly the differences in plasma sex hormone levels in female species, will drive the gender-dependent differences in expression profiles of UGT enzymes and efflux transporters. These differences significantly affect the metabolic clearance and the systemic bioavailability of compounds eliminated via this disposition pathway.

  15. Conservation Tillage

    NASA Astrophysics Data System (ADS)

    Gebhardt, Maurice R.; Daniel, Tommy C.; Schweizer, Edward E.; Allmaras, Raymond R.

    1985-11-01

    Conservation production systems combine tillage and planting practices to reduce soil erosion and loss of water from farmland. Successful conservation tillage practices depend on the ability of farm managers to integrate sound crop production practices with effective pest management systems. More scientific information is needed to determine the relations between tillage practices and physical, chemical, and biological soil factors that affect plant and pest ecology. There is a need to devise improved pest management strategies for conservation tillage and to better understand the impact of conservation tillage on water quality, especially as it is related to use of agricultural chemicals. While savings in fuel, labor, and soil have induced many farmers to adopt conservation tillage, improved methods and equipment should increase adoption even more.

  16. 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

  17. Enzymatic 2'-O-methylation of the wobble nucleoside of eukaryotic tRNAPhe: specificity depends on structural elements outside the anticodon loop.

    PubMed Central

    Droogmans, L; Haumont, E; de Henau, S; Grosjean, H

    1986-01-01

    We have investigated the specificity of the enzyme tRNA (wobble guanosine 2'-O-)methyltransferase which catalyses the maturation of guanosine-34 of eukaryotic tRNAPhe to the 2'-O-methyl derivative Gm-34. This study was done by micro-injection into Xenopus laevis oocytes of restructured yeast tRNAPhe in which the anticodon GmAA and the 3' adjacent nucleotide 'Y' were substituted by various tetranucleotides. The results indicate that the enzyme is cytoplasmic; the chemical nature of the bases of the anticodon and its 3' adjacent nucleotide is not critical for the methylation of G-34; the size of the anticodon loop is however important; structural features beyond the anticodon loop are involved in the specific recognition of the tRNA by the enzyme since Escherichia coli tRNAPhe and four chimeric yeast tRNAs carrying the GAA anticodon are not substrates; unexpectedly, the 2'-O-methylation is not restricted to G-34 since C-34, U-34 and A-34 in restructured yeast tRNAPhe also became methylated. It seems probable that the tRNA (wobble guanosine 2'-O-)methyltransferase is not specific for the type of nucleotide-34 in eukaryotic tRNAPhe; however the existence in the oocyte of several methylation enzymes specific for each nucleotide-34 has not yet been ruled out. Images Fig. 2. PMID:3522221

  18. Enzymatic 2'-O-methylation of the wobble nucleoside of eukaryotic tRNAPhe: specificity depends on structural elements outside the anticodon loop.

    PubMed

    Droogmans, L; Haumont, E; de Henau, S; Grosjean, H

    1986-05-01

    We have investigated the specificity of the enzyme tRNA (wobble guanosine 2'-O-)methyltransferase which catalyses the maturation of guanosine-34 of eukaryotic tRNAPhe to the 2'-O-methyl derivative Gm-34. This study was done by micro-injection into Xenopus laevis oocytes of restructured yeast tRNAPhe in which the anticodon GmAA and the 3' adjacent nucleotide 'Y' were substituted by various tetranucleotides. The results indicate that the enzyme is cytoplasmic; the chemical nature of the bases of the anticodon and its 3' adjacent nucleotide is not critical for the methylation of G-34; the size of the anticodon loop is however important; structural features beyond the anticodon loop are involved in the specific recognition of the tRNA by the enzyme since Escherichia coli tRNAPhe and four chimeric yeast tRNAs carrying the GAA anticodon are not substrates; unexpectedly, the 2'-O-methylation is not restricted to G-34 since C-34, U-34 and A-34 in restructured yeast tRNAPhe also became methylated. It seems probable that the tRNA (wobble guanosine 2'-O-)methyltransferase is not specific for the type of nucleotide-34 in eukaryotic tRNAPhe; however the existence in the oocyte of several methylation enzymes specific for each nucleotide-34 has not yet been ruled out.

  19. 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

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

    1991-01-15

    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.

  20. Conserved glutamate residues are critically involved in Na+/nucleoside cotransport by human concentrative nucleoside transporter 1 (hCNT1).

    PubMed

    Yao, Sylvia Y M; Ng, Amy M L; Slugoski, Melissa D; Smith, Kyla M; Mulinta, Ras; Karpinski, Edward; Cass, Carol E; Baldwin, Stephen A; Young, James D

    2007-10-19

    Human concentrative nucleoside transporter 1 (hCNT1), the first discovered of three human members of the SLC28 (CNT) protein family, is a Na+/nucleoside cotransporter with 650 amino acids. The potential functional roles of 10 conserved aspartate and glutamate residues in hCNT1 were investigated by site-directed mutagenesis and heterologous expression in Xenopus oocytes. Initially, each of the 10 residues was replaced by the corresponding neutral amino acid (asparagine or glutamine). Five of the resulting mutants showed unchanged Na+-dependent uridine transport activity (D172N, E338Q, E389Q, E413Q, and D565N) and were not investigated further. Three were retained in intracellular membranes (D482N, E498Q, and E532Q) and thus could not be assessed functionally. The remaining two (E308Q and E322Q) were present in normal quantities at cell surfaces but exhibited low intrinsic transport activities. Charge replacement with the alternate acidic amino acid enabled correct processing of D482E and E498D, but not of E532D, to cell surfaces and also yielded partially functional E308D and E322D. Relative to wild-type hCNT1, only D482E exhibited normal transport kinetics, whereas E308D, E308Q, E322D, E322Q, and E498D displayed increased K50(Na+) and/or Km(uridine) values and diminished Vmax(Na+) and Vmax(uridine) values. E322Q additionally exhibited uridine-gated uncoupled Na+ transport. Together, these findings demonstrate roles for Glu-308, Glu-322, and Glu-498 in Na+/nucleoside cotransport and suggest locations within a common cation/nucleoside translocation pore. Glu-322, the residue having the greatest influence on hCNT1 transport function, exhibited uridine-protected inhibition by p-chloromercuriphenyl sulfonate and 2-aminoethyl methanethiosulfonate when converted to cysteine.

  1. 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)

  2. Energy Conservation

    ERIC Educational Resources Information Center

    Abelson, Philip H.

    1972-01-01

    Comments on The Potential for Energy Conservation,'' a study by the Office of Emergency Preparedness, emphasizing the coming dependence on foreign oil, and presses for government influence to encourage development of more efficient cars. (AL)

  3. Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density.

    PubMed

    Haakensen, Vilde D; Biong, Margarethe; Lingjærde, Ole Christian; Holmen, Marit Muri; Frantzen, Jan Ole; Chen, Ying; Navjord, Dina; Romundstad, Linda; Lüders, Torben; Bukholm, Ida K; Solvang, Hiroko K; Kristensen, Vessela N; Ursin, Giske; Børresen-Dale, Anne-Lise; Helland, Aslaug

    2010-01-01

    Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD. SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is

  4. 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](+).

  5. AM-2201 Inhibits Multiple Cytochrome P450 and Uridine 5'-Diphospho-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes.

    PubMed

    Kim, Ju-Hyun; Kwon, Soon-Sang; Kong, Tae Yeon; Cheong, Jae Chul; Kim, Hee Seung; In, Moon Kyo; Lee, Hye Suk

    2017-03-10

    AM-2201 is a synthetic cannabinoid that acts as a potent agonist at cannabinoid receptors and its abuse has increased. However, there are no reports of the inhibitory effect of AM-2201 on human cytochrome P450 (CYP) or uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes. We evaluated the inhibitory effect of AM-2201 on the activities of eight major human CYPs (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4) and six major human UGTs (1A1, 1A3, 1A4, 1A6, 1A9, and 2B7) enzymes in pooled human liver microsomes using liquid chromatography-tandem mass spectrometry to investigate drug interaction potentials of AM-2201. AM-2201 potently inhibited CYP2C9-catalyzed diclofenac 4'-hydroxylation, CYP3A4-catalyzed midazolam 1'-hydroxylation, UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-glucuronidation, and UGT2B7-catalyzed naloxone 3-glucuronidation with IC50 values of 3.9, 4.0, 4.3, and 10.0 μM, respectively, and showed mechanism-based inhibition of CYP2C8-catalyzed amodiaquine N-deethylation with a Ki value of 2.1 μM. It negligibly inhibited CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, UGT1A1, UGT1A4, UGT1A6, and UGT1A9 activities at 50 μM in human liver microsomes. These in vitro results indicate that AM-2201 needs to be examined for potential pharmacokinetic drug interactions in vivo due to its potent inhibition of CYP2C8, CYP2C9, CYP3A4, UGT1A3, and UGT2B7 enzyme activities.

  6. Association of Uridine Diphosphate-Glucuronosyltransferase 2B Gene Variants with Serum Glucuronide Levels and Prostate Cancer Risk

    PubMed Central

    Hoyo, Cathrine; Oliver, Shannon D.; Gerber, Leah; Shuler, Katie; Calloway, Elizabeth; Gaines, Alexis R.; McPhail, Megan; Livingston, Jonathan N.; Richardson, Ricardo M.; Schildkraut, Joellen M.; Freedland, Stephen J.

    2013-01-01

    Aims: Uridine diphosphate-glucuronosyltransferase 2B (UGT2B) enzymes conjugate testosterone metabolites to enable their excretion in humans. The functional significance of the UGT2B genetic variants has never been described in humans. We evaluated UGT2B variants in relation to plasma androstane-3α,17β-diol-glucuronide (AAG) levels and the prostate cancer risk. Results: AAG levels were measured in sera from 150 controls and compared to the polymorphisms of UGT2B17, UGT2B15, and UGT2B7. Genomic DNA from controls (301) and cases (148) was genotyped for the polymorphisms, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analyses. Having two copies of UGT2B17 was associated with higher AAG levels in controls among Whites (p=0.02), but not Blacks (p=0.82). Logistic regression models adjusting for age and race revealed that homozygosity for the G allele of the UGT2B15D85Y polymorphism was directly associated with the prostate cancer risk (OR=2.70, 95% CI=1.28, 5.55). Conclusions: While the small sample size limits inference, our findings suggest that an association between the UGT2B17 copy number variant (CNV) and serum AAG levels in Whites, but unexpectedly not in Blacks. This novel observation suggests that genetic determinants of AAG levels in Blacks are unrelated to the UGT2B17 CNV. This study replicates the results that show an association of UGT215D85Y with an increased prostate cancer risk. PMID:23098242

  7. Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density

    PubMed Central

    2010-01-01

    Introduction Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Methods Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD. Results SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Conclusions Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes

  8. Expression, purification, crystallization and preliminary X-ray structure analysis of Vibrio cholerae uridine phosphorylase in complex with thymidine

    PubMed Central

    Lashkov, Alexander A.; Gabdulkhakov, Azat G.; Prokofev, Igor I.; Seregina, Tatyana A.; Sotnichenko, Sergey E.; Lyashenko, Andrey V.; Shtil, Alexander A.; Mironov, Alexander S.; Betzel, Christian; Mikhailov, Al’bert M.

    2012-01-01

    A high-resolution structure of the complex of Vibrio cholerae uridine phosphorylase (VchUPh) with its physiological ligand thymidine is important in order to determine the mechanism of the substrate specificity of the enzyme and for the rational design of pharmacological modulators. Here, the expression and purification of VchUPh and the crystallization of its complex with thymidine are reported. Conditions for crystallization were determined with an automated Cartesian Dispensing System using The Classics, MbClass and MbClass II Suites crystallization kits. Crystals of the VchUPh–thymidine complex (of dimensions ∼200–350 µm) were grown by the sitting-drop vapour-diffusion method in ∼7 d at 291 K. The crystallization solution consisted of 1.5 µl VchUPh (15 mg ml−1), 1 µl 0.1 M thymidine and 1.5 µl reservoir solution [15%(w/v) PEG 4000, 0.2 M MgCl2.6H2O in 0.1 M Tris–HCl pH 8.5]. The crystals diffracted to 2.12 Å resolution and belonged to space group P21 (No. 4), with unit-cell parameters a = 91.80, b = 95.91, c = 91.89 Å, β = 119.96°. The Matthews coefficient was calculated as 2.18 Å3 Da−1; the corresponding solvent content was 43.74%. PMID:23143257

  9. Tilting a wobbly chair

    NASA Astrophysics Data System (ADS)

    Cross, Rod

    2017-03-01

    If a small object is placed under the front leg of a chair, the chair tilts backwards. If the object is placed under a rear leg, the chair tilts sideways. The effect is surprising but can be analysed in terms of elementary physics.

  10. 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…

  11. Tilting a Wobbly Chair

    ERIC Educational Resources Information Center

    Cross, Rod

    2017-01-01

    If a small object is placed under the front leg of a chair, the chair tilts backwards. If the object is placed under a rear leg, the chair tilts sideways. The effect is surprising but can be analysed in terms of elementary physics.

  12. 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…

  13. Conservation endocrinology

    USGS Publications Warehouse

    McCormick, Stephen; Romero, L. Michael

    2017-01-01

    Endocrinologists can make significant contributions to conservation biology by helping to understand the mechanisms by which organisms cope with changing environments. Field endocrine techniques have advanced rapidly in recent years and can provide substantial information on the growth, stress, and reproductive status of individual animals, thereby providing insight into current and future responses of populations to changes in the environment. Environmental stressors and reproductive status can be detected nonlethally by measuring a number of endocrine-related endpoints, including steroids in plasma, living and nonliving tissue, urine, and feces. Information on the environmental or endocrine requirements of individual species for normal growth, development, and reproduction will provide critical information for species and ecosystem conservation. For many taxa, basic information on endocrinology is lacking, and advances in conservation endocrinology will require approaches that are both “basic” and “applied” and include integration of laboratory and field approaches.

  14. Structure of human uridine-cytidine kinase 2 determined by SIRAS using a rotating-anode X-ray generator and a single samarium derivative.

    PubMed

    Appleby, Todd C; Larson, Gary; Cheney, I Wayne; Walker, Heli; Wu, Jim Z; Zhong, Weidong; Hong, Zhi; Yao, Nanhua

    2005-03-01

    Uridine-cytidine nucleoside kinase 2 (UCK2) is the rate-limiting enzyme in the pyrimidine-nucleotide salvage pathway. UCK2 catalyzes the phosphorylation of the natural ribonucleosides cytidine and uridine to cytidine 5'-monophosphate (CMP) and uridine 5'-monophosphate (UMP), respectively, and activates several important frontline antimetabolite drugs. The present contribution reports the rapid crystal structure determination of human UCK2 complexed with a magnesium ion and the reaction products adenosine 5'-diphosphate (ADP) and CMP. Diffraction data were collected on a copper rotating-anode X-ray generator from one native UCK2 crystal and a single samarium-derivative crystal. Utilizing the relatively high anomalous signal from the samarium derivative at the Cu Kalpha wavelength, the structure was determined by single isomorphous replacement and single anomalous signal (SIRAS) phasing techniques. Two of the four major samarium sites are located in the active sites of the two UCK2 molecules that form the asymmetric unit and appear to displace the magnesium ions present in the native crystals. The crystal structures of UCK2 alone and in complex with various ligands have recently been determined using traditional multiple isomorphous replacement (MIR) phasing techniques and data from three heavy-atom derivatives. The reported structures validate our independently determined structure. Of more than 1000 kinase crystal structure entries in the Protein Data Bank, less than 1% of them have been determined by SIRAS. For the published kinase crystal structures determined by SIRAS, all data were reportedly collected at various synchrotron-radiation facilities. This study demonstrates that diffraction data collected from a single samarium derivative using Cu Kalpha radiation provides sufficient phasing power to determine a novel macromolecular crystal structure.

  15. The mechanisms of citrate on regulating the distribution of carbon flux in the biosynthesis of uridine 5'-monophosphate by Saccharomyces cerevisiae.

    PubMed

    Chen, Yong; Li, Shuya; Xiong, Jian; Li, Zhenjiang; Bai, Jianxin; Zhang, Lei; Ye, Qi; Ouyang, Pingkai; Ying, Hanjie

    2010-03-01

    A whole cell biocatalytic process for uridine 5'-monophosphate (UMP) production from orotic acid by Saccharomyces cerevisiae was developed. The concentration of UMP was increased by 23% when 1 g l(-1) sodium citrate was fed into the broth. Effects of citrate addition on UMP production were investigated. Glucose-6-phosphate pool was elevated by onefold, while FBP and pyruvate were decreased by 42% and 40%, respectively. Organic acid pools such as acetate and succinate were averagely decreased by 30% and 49%. The results demonstrated that manipulation of citrate levels could be used as a novel tool to regulate the metabolic fluxes distribution among glycolysis, pentose phosphate pathway, and TCA cycle.

  16. 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

  17. On the Observation of Discrete Fluorine NMR Spectra for Uridine 5′-β,γ-Fluoromethylenetriphosphate Diastereomers at Basic pH

    PubMed Central

    2015-01-01

    Jakeman et al. recently reported the inability to distinguish the diastereomers of uridine 5′-β,γ-fluoromethylenetriphosphate (β,γ-CHF-UTP, 1) by 19F NMR under conditions we previously prescribed for the resolution of the corresponding β,γ-CHF-dGTP spectra, stating further that 1 decomposed under these basic conditions. Here we show that the 19F NMR spectra of 1 (∼1:1 diastereomer mixture prepared by coupling of UMP-morpholidate with fluoromethylenebis(phosphonic acid)) in D2O at pH 10 are indeed readily distinguishable. 1 in this solution was stable for 24 h at rt. PMID:24819695

  18. Protection by uridine diphosphoglucuronic acid and DT-diaphorase against the cytotoxicity of polycyclic aromatic hydrocarbons isolated from a complex coal gasification condensate.

    PubMed

    Swanson, M S; Haugen, D A; Reilly, C A; Stamoudis, V C

    1986-06-30

    The cytotoxicities of polycyclic aromatic hydrocarbon (PAH) subclasses isolated from a complex organic mixture (coal gasification condensate) were studied in vitro in Chinese hamster ovary cells, in the presence of rat liver microsomes from animals pretreated with Aroclor. Toxicity was enhanced by microsomal metabolism and was inversely related to aromatic ring number. Rat liver cytosol, semipurified DT-diaphorase, and uridine diphosphoglucuronic acid decreased the cytotoxicity of a variety of PAH mixtures and representative PAH, as well as individual PAH metabolites. The results indicate that the in vitro toxicity of complex PAH mixtures is caused primarily by hydroxy-PAH and quinone metabolites of the predominant, nonmutagenic two- and three-ring PAHs.

  19. [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…

  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. 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)

  2. Lighting Conservation

    ERIC Educational Resources Information Center

    Arnold, Frank D.

    1975-01-01

    With the energy crisis has come an awareness of wasteful consumption practices. One area where research is being done is in lighting conservation. Information in this article is concerned with finding more effective and efficient lighting designs which include daylight utilization, task-oriented lighting, and lighting controls. (MA)

  3. Energy Conservation.

    ERIC Educational Resources Information Center

    Land, Amy A.

    This selection of class activities involves a sequence of 10 class sessions. The goal of the collection is to aid students in learning the concepts of energy conservation and to put this knowledge into practice. Attention is also given to the development of alternate energy sources. Each lesson includes an activity title, motivational hints,…

  4. 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…

  5. 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…

  6. A genome-wide screen identifies genes required for formation of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces cerevisiae

    PubMed Central

    Huang, Bo; Lu, Jian; Byström, Anders S.

    2008-01-01

    We recently showed that the γ-subunit of Kluyveromyces lactis killer toxin (γ-toxin) is a tRNA endonuclease that cleaves , , and 3′ of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U). The 5-methoxycarbonylmethyl (mcm5) side chain was important for efficient cleavage by γ-toxin, and defects in mcm5 side-chain synthesis correlated with resistance to γ-toxin. Based on this correlation, a genome-wide screen was performed to identify gene products involved in the formation of the mcm5 side chain. From a collection of 4826 homozygous diploid Saccharomyces cerevisiae strains, each with one nonessential gene deleted, 63 mutants resistant to Kluyveromyces lactis killer toxin were identified. Among these, eight were earlier identified to have a defect in formation of the mcm5 side chain. Analysis of the remaining mutants and other known γ-toxin resistant mutants revealed that sit4, kti14, and KTI5 mutants also have a defect in the formation of mcm5. A mutant lacking two of the Sit4-associated proteins, Sap185 and Sap190, displays the same modification defect as a sit4-null mutant. Interestingly, several mutants were found to be defective in the synthesis of the 2-thio (s2) group of the mcm5s2U nucleoside. In addition to earlier described mutants, formation of the s2 group was also abolished in urm1, uba4, and ncs2 mutants and decreased in the yor251c mutant. Like the absence of the mcm5 side chain, the lack of the s2 group renders less sensitive to γ-toxin, reinforcing the importance of the wobble nucleoside mcm5s2U for tRNA cleavage by γ-toxin. PMID:18755837

  7. 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.

  8. Adenosine-uridine-rich element is one of the required cis-elements for epimastigote form stage-specific gene expression of the congolense epimastigote specific protein.

    PubMed

    Suganuma, Keisuke; Mochabo, Kennedy Miyoro; Hakimi, Hassan; Yamasaki, Shino; Yamagishi, Junya; Asada, Masahito; Kawazu, Shin-Ichiro; Inoue, Noboru

    2013-09-01

    It is known that gene expression in kinetoplastida is regulated post-transcriptionally. Several previous studies have shown that stage-specific gene expression in trypanosomes is regulated by cis-elements located in the 3' untranslated region (UTR) of each mRNA and also by RNA binding proteins. Our previous study revealed that gene expression of congolense epimastigote specific protein (cesp) was regulated by cis-elements located in the 3'UTR. In the present study, we identified the adenosine and uridine rich region in the cesp 3'UTR. Using transgenic trypanosome cell lines with different egfp expression cassettes, we showed that this adenosine and uridine rich region is one of the regulatory elements for epimastigote form (EMF) stage-specific gene expression via the regulatory cis-element of the eukaryotic AU rich element (ARE). Therefore this required element within the cesp 3'UTR was designated as T. congolense ARE. This required cis-element might selectively stabilize mRNA in the EMF stage and destabilize mRNA in other stages. By RNA electro mobility shift assay, unknown stage-specific RNA binding proteins (RBPs) whose sequences specifically interacted with the required cis-element were found. These results indicate that EMF stage specific cis-element and RBP complexes might specifically stabilize cesp mRNA in EMF. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Energy conservation

    SciTech Connect

    Not Available

    1990-05-01

    Under the Warner Amendment, oil overcharge funds are designated for states' use in certain authorized energy conservation and assistance programs. During FY 1982-87 Warner funds accounted for $200 million of the $3.3 billion states received from the oil overcharge escrow account. The $3.3 billion was in addition to the $13.3 billion that the Congress appropriated for the conservation and assistance programs. More than 4 years after their distribution, states had not used all the Warner funds. This report provides the status of all oil overcharge funds; the use of Warner funds and the time it is taking to spend the funds in Arizona, California, and Illinois.

  10. Heron conservation

    USGS Publications Warehouse

    Kushlan, J.A.; Hafner, H.

    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.

  11. Energy Conservation

    SciTech Connect

    Simpson, P.

    1995-06-01

    There are two fundamental reasons or motivations for energy conservation: (1) economics; and (2) consideration of energy - its sources and availability. Economics speaks for itself and needs little explanation: a project is undertaken, the cost is recovered in a given period of time (we hope) and our company realizes cost savings thereafter. We study and propose a project; we estimate the payback. If approved, we implement the project. Then, we eagerly watch for its effectiveness - for the proposed payback. The second consideration in regard to energy conservation might - in the foreseeable future - become by far the most important - that of availability. Very knowledgeable persons have stated that this - in reality - is the most serious problem facing our nation today. Readily available, reasonably priced energy has given to the US the high form of living experienced today. An interruption in this flow could catapult our nation in an awesome catastrophe. The energy shortage of the late 70`s might be a forerunner of such an experience.

  12. Human tRNA(Lys3)(UUU) is pre-structured by natural modifications for cognate and wobble codon binding through keto-enol tautomerism.

    PubMed

    Vendeix, Franck A P; Murphy, Frank V; Cantara, William A; Leszczyńska, Grażyna; Gustilo, Estella M; Sproat, Brian; Malkiewicz, Andrzej; Agris, Paul F

    2012-03-02

    Human tRNA(Lys3)(UUU) (htRNA(Lys3)(UUU)) decodes the lysine codons AAA and AAG during translation and also plays a crucial role as the primer for HIV-1 (human immunodeficiency virus type 1) reverse transcription. The posttranscriptional modifications 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U(34)), 2-methylthio-N(6)-threonylcarbamoyladenosine (ms(2)t(6)A(37)), and pseudouridine (Ψ(39)) in the tRNA's anticodon domain are critical for ribosomal binding and HIV-1 reverse transcription. To understand the importance of modified nucleoside contributions, we determined the structure and function of this tRNA's anticodon stem and loop (ASL) domain with these modifications at positions 34, 37, and 39, respectively (hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39)). Ribosome binding assays in vitro revealed that the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39) bound AAA and AAG codons, whereas binding of the unmodified ASL(Lys3)(UUU) was barely detectable. The UV hyperchromicity, the circular dichroism, and the structural analyses indicated that Ψ(39) enhanced the thermodynamic stability of the ASL through base stacking while ms(2)t(6)A(37) restrained the anticodon to adopt an open loop conformation that is required for ribosomal binding. The NMR-restrained molecular-dynamics-derived solution structure revealed that the modifications provided an open, ordered loop for codon binding. The crystal structures of the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39) bound to the 30S ribosomal subunit with each codon in the A site showed that the modified nucleotides mcm(5)s(2)U(34) and ms(2)t(6)A(37) participate in the stability of the anticodon-codon interaction. Importantly, the mcm(5)s(2)U(34)·G(3) wobble base pair is in the Watson-Crick geometry, requiring unusual hydrogen bonding to G in which mcm(5)s(2)U(34) must shift from the keto to the enol form. The results unambiguously demonstrate that modifications pre-structure the anticodon as a key

  13. A QM/QTAIM detailed look at the Watson-Crick↔wobble tautomeric transformations of the 2-aminopurine·pyrimidine mispairs.

    PubMed

    Brovarets', Ol'ha O; Voiteshenko, Ivan S; Pérez-Sánchez, Horacio; Hovorun, Dmytro M

    2017-07-28

    This work is devoted to the careful QM/QTAIM analysis of the evolution of the basic physico-chemical parameters along the intrinsic reaction coordinate (IRC) of the biologically important 2AP·T(WC)↔2AP·T*(w) and 2AP·C*(WC)↔2AP·C(w) Watson-Crick(WC)↔wobble(w) tautomeric transformations obtained at each point of the IRC using original authors' methodology. Established profiles reflect the high similarity between the courses of these processes. Basing on the scrupulous analysis of the profiles of their geometric and electron-topological parameters, it was established that the dipole-active WC↔w tautomerizations of the Watson-Crick-like 2AP·T(WC)/2AP·C*(WC) mispairs, stabilized by the two classical N3H⋯N1, N2H⋯O2 and one weak C6H⋯O4/N4 H-bonds, into the wobble 2AP·T*(w)/2AP·C(w) base pairs, respectively, joined by the two classical N2H⋯N3 and O4/N4H⋯N1 H-bonds, proceed via the concerted stepwise mechanism through the sequential intrapair proton transfer and subsequent large-scale shifting of the bases relative each other, through the planar, highly stable, zwitterionic transition states stabilized by the participation of the four H-bonds - N1(+)H⋯O4(-)/N4(-), N1(+)H⋯N3(-), N2(+)H⋯N3(-), and N2(+)H⋯O2(-). Moreover, it was found out that the 2AP·T(WC)↔2AP·T*(w)/2AP·C*(WC)↔2AP·C(w) tautomerization reactions occur non-dissociatively and are accompanied by the consequent replacement of the 10 unique patterns of the specific intermolecular interactions along the IRC. Obtained data are of paramount importance in view of their possible application for the control and management of the proton transfer, e.g. by external electric or laser fields.

  14. Glycan structure and site of glycosylation in the ER-resident glycoprotein, uridine 5'-diphosphate-glucose: glycoprotein glucosyltransferases 1 from rat, porcine, bovine, and human.

    PubMed

    Daikoku, Shusaku; Seko, Akira; Ito, Yukishige; Kanie, Osamu

    2014-08-29

    Here we report glycan structures and their position of attachment to a carrier protein, uridine 5'-diphosphate-glucose: glycoprotein glucosyltransferase (UGGT1), as detected using tandem mass spectrometry. UGGT1 acts as a folding sensor of newly synthesized glycosylated polypeptides in the endoplasmic reticulum, and the transferase itself is known to be glycosylated. The structure of glycan attached to UGGT1, however, has not been investigated. In this study, we reveal the site of glycosylation (N269) and the glycan structures (Hex5-8HexNAc2) in UGGT1 obtained from rat (Rattus norvegicus), pig (Sus scrofa), cow (Bos taurus), and human (Homo sapiens). Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Efficient heterologous expression and one-step purification of fully active c-terminal histidine-tagged uridine monophosphate kinase from Mycobacterium tuberculosis.

    PubMed

    Penpassakarn, Praweenuch; Chaiyen, Pimchai; Palittapongarnpim, Prasit

    2011-11-01

    Tuberculosis has long been recognized as one of the most significant public health problems. Finding novel antituberculous drugs is always a necessary approach for controlling the disease. Mycobacterium tuberculosis pyrH gene (Rv2883c) encodes for uridine monophosphate kinase (UMK), which is a key enzyme in the uridine nucleotide interconversion pathway. The enzyme is essential for M. tuberculosis to sustain growth and hence is a potential drug target. In this study, we have developed a rapid protocol for production and purification of M. tuberculosis UMK by cloning pyrH (Rv2883c) of M. tuberculosis H37Rv with the addition of 6-histidine residues to the C-terminus of the protein, and expressing in E. coli BL21-CodonPlus (DE3)-RIPL using an auto-induction medium. The enzyme was efficiently purified by a single-step TALON cobalt affinity chromatography with about 8 fold increase in specific activity, which was determined by a coupled assay with the pyruvate kinase and lactate dehydrogenase. The molecular mass of monomeric UMK was 28.2 kDa and that of the native enzyme was 217 kDa. The enzyme uses UMP as a substrate but not CMP and TMP and activity was enhanced by GTP. Measurements of enzyme kinetics revealed the kcat value of 7.6 +/- 0.4 U mg(-1) or 0.127 +/- 0.006 sec(-1).The protocol reported here can be used for expression of M. tuberculosis UMK in large quantity for formulating a high throughput target-based assay for screening anti-tuberculosis UMK compounds.

  16. Nitrogen-15 labeled 5S RNA. Identification of uridine base pairs in Escherichia coli 5S RNA by sup 1 H- sup 15 N multiple quantum NMR

    SciTech Connect

    Davis, D.R.; Yamaizumi, Z.; Nishimura, S.; Poulter, C.D. )

    1989-05-02

    Escherichia coli 5S RNA labeled with {sup 15}N at N3 of the uridines was isolated from the S{phi}-187 uracil auxotroph grown on a minimal medium supplemented with (3-{sup 15}N)uracil. {sup 1}H-{sup 15}N multiple quantum filtered and 2D chemical shift correlated spectra gave resonances for the uridine imino {sup 1}H-{sup 15}N units whose protons were exchanging slowly with solvent. Peaks with {sup 1}H/{sup 15}N shifts at 11.6/154.8, 11.7/155.0, 11.8/155.5, 12.1/155.0, and 12.2/155.0 ppm were assigned to GU interactions. Two labile high-field AU resonances at 12.6/156.8 and 12.8/157.3 ppm typical of Au pairs in a shielded environment at the end of a helix were seen. Intense AU signals were also found at 13.4/158.5 and 13.6/159.2 ppm where {sup 1}H-{sup 15}N units in normal Watson-Crick pairs resonate. {sup 1}H resonances at 10.6 and 13.8 ppm were too weak, presumably because of exchange with water, to give peaks in chemical shift correlated spectra. {sup 1}H chemical shifts suggest that the resonance at 13.8 ppm represents a labile AU pair, while the resonance at 10.6 ppm is typical of a tertiary interaction between U and a tightly bound water or a phosphate residue. The NMR data are consistent with proposed secondary structures for 5S RNA.

  17. 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).

  18. 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).

  19. S-Geranyl-2-thiouridine wobble nucleosides of bacterial tRNAs; chemical and enzymatic synthesis of S-geranylated-RNAs and their physicochemical characterization

    PubMed Central

    Sierant, Malgorzata; Leszczynska, Grazyna; Sadowska, Klaudia; Dziergowska, Agnieszka; Rozanski, Michal; Sochacka, Elzbieta; Nawrot, Barbara

    2016-01-01

    Recently, highly lipophilic S-geranylated derivatives of 5-methylaminomethyl-2-thiouridine (mnm5geS2U) and 5-carboxymethylaminomethyl-2-thiouridine (cmnm5geS2U) were found at the first (wobble) anticodon position in bacterial tRNAs specific for Lys, Glu and Gln. The function and cellular biogenesis of these unique tRNAs remain poorly understood. Here, we present one direct and two post-synthetic chemical routes for preparing model geS2U-RNAs. Our experimental data demonstrate that geS2U-RNAs are more lipophilic than their parent S2U-RNAs as well as non-modified U-RNAs. Thermodynamic studies revealed that the S-geranyl-2-thiouridine-containing RNA has higher affinity toward complementary RNA strand with G opposite the modified unit than with A. Recombinant tRNA selenouridine synthase (SelU) exhibits sulfur-specific geranylation activity toward model S2U-RNA, which is composed of the anticodon-stem-loop (ASL) from the human tRNALys3 sequence. In addition, the presence of magnesium ions is required to achieve appreciable geranylation efficiencies. PMID:27566149

  20. Tautomeric transition between wobble A·C DNA base mispair and Watson-Crick-like A·C* mismatch: microstructural mechanism and biological significance.

    PubMed

    Brovarets', Ol'ha O; Hovorun, Dmytro M

    2015-06-21

    Here, we use MP2/DFT quantum-chemical methods combined with Quantum Theory of Atoms in Molecules to study the tautomeric transition between wobble A·C(w) mismatch and Watson-Crick-like A·C*(WC) base mispair, proceeding non-dissociatively via sequential proton transfer between bases through the planar, highly stable and zwitterionic TS(A∙C-)(A∙C(W)<-->A∙C&(WC)) transition state joined by the participation of (A)N6(+)H∙∙∙N4(-)(C), (A)N1(+)H∙∙∙N4(-)(C) and (A)C2(+)H∙∙∙N3(-)(C) H-bonds. Notably, the A·C(w) ↔ A·C*(WC) tautomerization reaction is accompanied by 10 unique patterns of the specific intermolecular interactions that consistently replace each other. Our data suggest that biologically significant A·C(w) → A·C*(WC) tautomerization is a kinetically controlled pathway for formation of the enzymatically competent Watson-Crick-like A·C*(WC) DNA base mispair in the essentially hydrophobic recognition pocket of the high-fidelity DNA-polymerase, responsible for the occurrence of spontaneous point AC/CA incorporation errors during DNA biosynthesis.

  1. Arabidopsis tRNA Adenosine Deaminase Arginine Edits the Wobble Nucleotide of Chloroplast tRNAArg(ACG) and Is Essential for Efficient Chloroplast Translation[W

    PubMed Central

    Delannoy, Etienne; Le Ret, Monique; Faivre-Nitschke, Emmanuelle; Estavillo, Gonzalo M.; Bergdoll, Marc; Taylor, Nicolas L.; Pogson, Barry J.; Small, Ian; Imbault, Patrice; Gualberto, José M.

    2009-01-01

    RNA editing changes the coding/decoding information relayed by transcripts via nucleotide insertion, deletion, or conversion. Editing of tRNA anticodons by deamination of adenine to inosine is used both by eukaryotes and prokaryotes to expand the decoding capacity of individual tRNAs. This limits the number of tRNA species required for codon-anticodon recognition. We have identified the Arabidopsis thaliana gene that codes for tRNA adenosine deaminase arginine (TADA), a chloroplast tRNA editing protein specifically required for deamination of chloroplast (cp)-tRNAArg(ACG) to cp-tRNAArg(ICG). Land plant TADAs have a C-terminal domain similar in sequence and predicted structure to prokaryotic tRNA deaminases and also have very long N-terminal extensions of unknown origin and function. Biochemical and mutant complementation studies showed that the C-terminal domain is sufficient for cognate tRNA deamination both in vitro and in planta. Disruption of TADA has profound effects on chloroplast translation efficiency, leading to reduced yields of chloroplast-encoded proteins and impaired photosynthetic function. By contrast, chloroplast transcripts accumulate to levels significantly above those of wild-type plants. Nevertheless, absence of cp-tRNAArg(ICG) is compatible with plant survival, implying that two out of three CGN codon recognition occurs in chloroplasts, though this mechanism is less efficient than wobble pairing. PMID:19602623

  2. Effect of BrU on the transition between wobble Gua-Thy and tautomeric Gua-Thy base-pairs: ab initio molecular orbital calculations

    NASA Astrophysics Data System (ADS)

    Nomura, Kazuya; Hoshino, Ryota; Hoshiba, Yasuhiro; Danilov, Victor I.; Kurita, Noriyuki

    2013-04-01

    We investigated transition states (TS) between wobble Guanine-Thymine (wG-T) and tautomeric G-T base-pair as well as Br-containing base-pairs by MP2 and density functional theory (DFT) calculations. The obtained TS between wG-T and G*-T (asterisk is an enol-form of base) is different from TS got by the previous DFT calculation. The activation energy (17.9 kcal/mol) evaluated by our calculation is significantly smaller than that (39.21 kcal/mol) obtained by the previous calculation, indicating that our TS is more preferable. In contrast, the obtained TS and activation energy between wG-T and G-T* are similar to those obtained by the previous DFT calculation. We furthermore found that the activation energy between wG-BrU and tautomeric G-BrU is smaller than that between wG-T and tautomeric G-T. This result elucidates that the replacement of CH3 group of T by Br increases the probability of the transition reaction producing the enol-form G* and T* bases. Because G* prefers to bind to T rather than to C, and T* to G not A, our calculated results reveal that the spontaneous mutation from C to T or from A to G base is accelerated by the introduction of wG-BrU base-pair.

  3. Electrostatics Explains the Position-Dependent Effect of G⋅U Wobble Base Pairs on the Affinity of RNA Kissing Complexes.

    PubMed

    Abi-Ghanem, Josephine; Rabin, Clémence; Porrini, Massimiliano; Dausse, Eric; Toulmé, Jean-Jacques; Gabelica, Valérie

    2017-07-31

    In the RNA realm, non-Watson-Crick base pairs are abundant and can affect both the RNA 3D structure and its function. Here, we investigated the formation of RNA kissing complexes in which the loop-loop interaction is modulated by non-Watson-Crick pairs. Mass spectrometry, surface plasmon resonance, and UV-melting experiments show that the G⋅U wobble base pair favors kissing complex formation only when placed at specific positions. We tried to rationalize this effect by molecular modeling, including molecular mechanics Poisson-Boltzmann surface area (MMPBSA) thermodynamics calculations and PBSA calculations of the electrostatic potential surfaces. Modeling reveals that the G⋅U stabilization is due to a specific electrostatic environment defined by the base pairs of the entire loop-loop region. The loop is not symmetric, and therefore the identity and position of each base pair matters. Predicting and visualizing the electrostatic environment created by a given sequence can help to design specific kissing complexes with high affinity, for potential therapeutic, nanotechnology or analytical applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. S-Geranyl-2-thiouridine wobble nucleosides of bacterial tRNAs; chemical and enzymatic synthesis of S-geranylated-RNAs and their physicochemical characterization.

    PubMed

    Sierant, Malgorzata; Leszczynska, Grazyna; Sadowska, Klaudia; Dziergowska, Agnieszka; Rozanski, Michal; Sochacka, Elzbieta; Nawrot, Barbara

    2016-12-15

    Recently, highly lipophilic S-geranylated derivatives of 5-methylaminomethyl-2-thiouridine (mnm5geS2U) and 5-carboxymethylaminomethyl-2-thiouridine (cmnm5geS2U) were found at the first (wobble) anticodon position in bacterial tRNAs specific for Lys, Glu and Gln. The function and cellular biogenesis of these unique tRNAs remain poorly understood. Here, we present one direct and two post-synthetic chemical routes for preparing model geS2U-RNAs. Our experimental data demonstrate that geS2U-RNAs are more lipophilic than their parent S2U-RNAs as well as non-modified U-RNAs. Thermodynamic studies revealed that the S-geranyl-2-thiouridine-containing RNA has higher affinity toward complementary RNA strand with G opposite the modified unit than with A. Recombinant tRNA selenouridine synthase (SelU) exhibits sulfur-specific geranylation activity toward model S2U-RNA, which is composed of the anticodon-stem-loop (ASL) from the human tRNA(Lys3) sequence. In addition, the presence of magnesium ions is required to achieve appreciable geranylation efficiencies.

  5. 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

  6. Variable frequency of plastid RNA editing among ferns and repeated loss of uridine-to-cytidine editing from vascular plants.

    PubMed

    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.

  7. SU-E-T-263: Development of Dose Monitor Unit Calculation Using Clarkson Integration for Proton Beam Therapy Using Beam-Wobbling System

    SciTech Connect

    Nagata, Y; Takada, Y; Yamaguchi, H; Kohno, R; Hotta, K; Akimoto, T

    2015-06-15

    Purpose: The purpose of the present study is to develop a calculation method of dose-calibration-factor using Clarkson integration for proton therapy employing the wobbling system and to evaluate accuracy of the calculation by comparison between calculations and measurements. Methods: CF and CALF stand for a dose-calibration-factor and a dose per monitor unit (MU), respectively. A measured dose-calibration-factor CFmeas is defined as a ratio of the measured dose per monitor unit in a patient-specific condition CALFpat to the measured dose per MU in a reference beam condition CALFref. The CFcalc is a product of three factors: CF1, CF2 and CF3. The CF1 and CF2 are a factor reflecting the effect of common beam delivery devices and that of patient specific devices and parameter (an aperture collimator, a range compensator and an air gap), respectively. The CF1 was obtained by interpolation using measured data. The CF2 was calculated using the Simplified Monte Carlo (SMC) method. The SMC method calculates a dose distribution by tracing individual protons and by using a measured Bragg curve in water. The CF3 representing the correction factor of field size effect was obtained by using the Clarkson integration. We compared the calculated and measured CF values for 20 prostate cases. Results: Field size correction was found to be important. The calculations reproduce the measurement results within an error of ±2.0%, except for a few cases. The error was about –3.1% for the small field area of less than19 square centimeters. Conclusion: We have developed a calculation method of dose-calibration-factor. Calculations agreed with measurements within ±2.0% for 90% of 20 prostate cases. Except for a small field size cases, the calculation method can be applied to determine the dose-calibration–factor for majority cases of prostate cancer.

  8. Influence of 5-HALOGENATION on the Structure of Protonated Uridine: Irmpd Action Spectroscopy and Theoretical Studies of the Protonated 5-HALOURIDINES

    NASA Astrophysics Data System (ADS)

    Roy, Harrison; Hamlow, Lucas; Lee, Justin; Rodgers, M. T.; Berden, Giel; Oomens, Jos

    2016-06-01

    The chemical and structural diversity and the extent of post-transcriptional modification of RNA is remarkable! Presently, there are 142 different naturally-occurring and many more synthetically modified nucleosides known. Uridine (Urd) is the most commonly modified nucleoside among those that occur naturally, but has also been an important target for synthesis and development of modified nucleosides for pharmaceutical applications. Indeed, modified nucleosides are of pharmaceutical interest due to their bioactivities. In particular, 5-bromouridine (br5Urd) has been shown to exhibit antiviral activity to human immunodeficiency virus and has been used in RNA labeling studies. Halogenation is a common modification employed in pharmaceutical studies that enables systematic variation is the electronic properties of the molecule of interest due to the availability of halogen substituents that vary in size, dipole moment, polarizability, and electron withdrawing properties. In order to elucidate the influence of 5-halogenation on the intrinsic gas-phase structure and stability on the protonated form of Urd, synergistic spectroscopic and theoretical studies of the protonated forms of the 5-halouridines are performed here, where x5Urd = 5-fluorouridine (f5Urd), 5-chlorouridine (cl5Urd), br5Urd, and 5-iodouridine (i5Urd). Infrared multiple photon dissociation (IRMPD) action spectra of the protonated forms of the 5-halouridines, [x5Urd+H]+, are measured over the IR fingerprint region using the FELIX free electron laser and the hydrogen stretching region using an OPO/OPA laser from 3300-3800 wn. Complementary electronic structure calculations are performed to determine the stable low-energy conformations available to these species and to predict their IR spectra. Comparative analyses of the measured IRMPD spectra and predicted IR spectra are performed to elucidate the preferred sites of protonation, and the low-energy tautomeric conformations that are populated by

  9. 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

    NASA Astrophysics Data System (ADS)

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

    2009-03-01

    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 Å resolution to R work = 16.1% and R free = 20.0%. The rms deviations for the bond lengths, bond angles, and chiral angles are 0.006 Å, 1.042°, and 0.071°, respectively. The coordinate error estimated by the Luzzati plot is 0.166 Å. The coordinate error based on the maximum likelihood is 0.199 Å. 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+ 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).

  10. Investigation of the recognition of an important uridine in an internal loop of a hairpin ribozyme prepared using post-synthetically modified oligonucleotides.

    PubMed Central

    Komatsu, Y; Kumagai, I; Ohtsuka, E

    1999-01-01

    We introduced 4-thio- ((4S)U), 2-thio- ((2S)U), 4- O -methyluridine ((4Me)U) and cytidine substitutions for U+2, which is an important base for cleavage in a substrate RNA. Oligonucleotides containing 4-thio- and 4- O -methyluridine were prepared by a new convenient post-synthetic modification method using a 4- O - p -nitrophenyl-uridine derivative. A hairpin ribozyme cleaved the substrate RNA with either C+2, (4S)U+2 or (4Me)U+2 at approximately 14-, 6- and 4-fold lower rates, respectively, than that of the natural substrate. In contrast, the substrate with a (2S)U+2 was cleaved with the same activity as the natural substrate. These results suggest that the O4 of U+2 is involved in hydrogen bonding at loop A, but the O2 of U+2 is not recognized by the active residues. Circular dichroism data of the ribozymes containing (4S)U+2 and (2S)U+2, as well as the susceptibility of the thiocarbonyl group to hydrogen peroxide, suggest that a conformational change of U+2 occurs during the domain docking in the cleavage reaction. We propose here the conformational change of U+2 from the ground state to the active molecule during the reaction. PMID:10536137

  11. 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).

  12. Uridine diphosphate-glucuronosyltransferase 2B15 D85Y gene polymorphism is associated with lower prostate cancer risk: a systematic review and meta-analysis.

    PubMed

    Zhong, Xiao; Feng, Jiayu; Xiao, Ya; Wang, Pingxian; Fan, Qiming; Wu, Ronghua; Hu, Wengang; Huang, Chibing

    2017-08-08

    UGT2B15 (uridine diphosphate-glucuronosyltransferase 2B15) catalyzes the conversion of lipophilic C19 steroid androgens such as dihydrotestosterone (DHT) into water-soluble metabolites that can be excreted. Studies of the association between the UGT2B15 gene D85Y polymorphism and prostate cancer have yielded contradictory results. We therefore systematically searched in the PubMed, EMBASE, Science Direct/Elsevier, CNKI, and Cochrane Library databases, and identified six relevant studies with which to perform a meta-analysis of the relation between UGT2B15 D85Y polymorphism and prostate cancer risk. Our meta-analysis revealed a significant association between UGT2B15 D85Y gene polymorphism and prostate cancer in all genetic models (P<0.05). The combined odds ratios and 95% confidence intervals were as follows: additive model, 0.53 and 0.32-0.88; dominant model, 0.51 and 0.33-0.79; recessive model, 0.76 and 0.60-0.96; co-dominant model, 0.55 and 0.35-0.86; and allele model, 0.70 and 0.55-0.89. These results are consistent with the idea that the UGT2B15 D85Y enzyme variant reduces the risk of prostate cancer by efficiently metabolizing dihydrotestosterone (DHT), which is associated with prostate cancer progression.

  13. A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

    PubMed Central

    Walter, Heidi-Kristin; Olshausen, Bettina; Schepers, Ute

    2017-01-01

    The arabino-configured analog of uridine with a propargyl group at the 2’-position was synthesized and incorporated into DNA by solid-phase chemistry. The fluorescence quantum yields of DNA strands that were postsynthetically modified by blue and green emitting cyanine-styryl dyes were improved due to the arabino-configured anchor. These oligonucleotides were used as energy transfer donors in hybrids with oligonucleotides modified with acceptor dyes that emit in the yellow-red range. These combinations give energy transfer pairs with blue–yellow, blue–red and green–red emission color changes. All combinations of arabino- and ribo-configured donor strands with arabino- and ribo-configured acceptor strands were evaluated. This array of doubly modified hybrids was screened by their emission color contrast and fluorescence quantum yield. Especially mixed combinations, that means donor dyes with arabino-configured anchor with acceptor dyes with ribo-configured anchor, and vice versa, showed significantly improved fluorescence properties. Those were successfully applied for fluorescent imaging of DNA after transport into living cells. PMID:28228854

  14. 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.

  15. 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.

  16. Conservation potential of agricultural water conservation subsidies

    NASA Astrophysics Data System (ADS)

    Huffaker, Ray

    2008-07-01

    A current policy subsidizes farmers to invest in improved on-farm irrigation efficiency, expecting water to be conserved off farm. Contrary to expectation, water has been increasingly depleted in some regions after such improvements. This paper investigates the policy's failure to conserve water consistently by (1) formulating an economic model of irrigated crop production to determine a profit-maximizing irrigator's range of responses to a subsidy and (2) embedding these responses into hypothetical streamflow diagrams to ascertain their potential to conserve water under various hydrologic regimes. Testable hypotheses are developed to predict the conservation potential of a subsidy in real-world application.

  17. Conservation Education Today & Tomorrow: Resource Conservation.

    ERIC Educational Resources Information Center

    Illinois State Dept. of Conservation, Springfield.

    This kit was developed by the Illinois Department of Conservation's Education Program with assistance from the State Board of Education, as a teaching tool which can be used to promote conservation awareness of young people. It is designed to enable educators to help students in grades 7-10 learn about Illinois' renewable natural resources through…

  18. 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

  19. Two Leptinotarsa uridine diphosphate N-acetylglucosamine pyrophosphorylases are specialized for chitin synthesis in larval epidermal cuticle and midgut peritrophic matrix.

    PubMed

    Shi, Ji-Feng; Fu, Jia; Mu, Li-Li; Guo, Wen-Chao; Li, Guo-Qing

    2016-01-01

    Uridine diphosphate-N-acetylglucosamine-pyrophosphorylase (UAP) is involved in the biosynthesis of chitin, an essential component of the epidermal cuticle and midgut peritrophic matrix (PM) in insects. In the present paper, two putative LdUAP genes were cloned in Leptinotarsa decemlineata. In vivo bioassay revealed that 20-hydroxyecdysone (20E) and an ecdysteroid agonist halofenozide activated the expression of the two LdUAPs, whereas a decrease in 20E by RNA interference (RNAi) of an ecdysteroidogenesis gene LdSHD and a 20E signaling gene LdFTZ-F1 repressed the expression. Juvenile hormone (JH), a JH analog pyriproxyfen and an increase in JH by RNAi of an allatostatin gene LdAS-C downregulated LdUAP1 but upregulated LdUAP2, whereas a decrease in JH by silencing of a JH biosynthesis gene LdJHAMT had converse effects. Thus, expression of LdUAPs responded to both 20E and JH. Moreover, knockdown of LdUAP1 reduced chitin contents in whole larvae and integument samples, thinned tracheal taenidia, impaired larval-larval molt, larval-pupal ecdysis and adult emergence. In contrast, silencing of LdUAP2 significantly reduced foliage consumption, decreased chitin content in midgut samples, damaged PM, and retarded larval growth. The resulting larvae had lighter fresh weights, smaller body sizes and depleted fat body. As a result, the development was arrested. Combined knockdown of LdUAP1 and LdUAP2 caused an additive negative effect. Our data suggest that LdUAP1 and LdUAP2 have specialized functions in biosynthesizing chitin in the epidermal cuticle and PM respectively in L. decemlineata.

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

    PubMed

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

    2016-08-01

    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. 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. 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. 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.

  1. Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer.

    PubMed

    Yun, Fan; Lulu, Miao; Zhiyu, Huang; Lei, Gong; Haifeng, Yu; Tao, Lei; Haiyan, Yang; Conghua, Xie

    2014-11-01

    The aim was to investigate the association between uridine diphosphate glucuronide transferase 1A1 (UGT1A1) gene promoter region polymorphism and irinotecan-related adverse effects and efficacy on recurrent and refractory small cell lung cancer (SCLC). A total of 31 patients with recurrent and refractory SCLC were enrolled in this study from June 2012 to August 2013 and received at least two cycles of single-agent irinotecan chemotherapy. The efficacy and adverse effects of irinotecan were evaluated. DNA was extracted from peripheral blood and direct sequencing method was employed to test UGT1A1FNx0128 polymorphism, thus analyzing the correlation between UGT1A1FNx0128 polymorphism and irinotecan-related side-effects and efficacy. A total of 25 cases (80.6%) were UGT1A1FNx0128 wild-type (TA) 6 /(TA) 6 ; 6 cases (19.4%) were heterozygous mutant (TA) 6 /(TA) 7 , no homozygous mutant genotype (TA) 7 /(TA) 7 was found. The incidences of grade 3/4 neutropenia, diarrhea and thrombocytopenia were 35.5%, 25.8% and 22.6% in all the patients, respectively. The incidence of 3/4 adverse effects in patients with genotype (TA) 6 /(TA) 6 and heterozygous (TA) 6 /(TA) 7 had no statistical difference (P > 0.05 for all). The overall response rate (ORR) was 32.3%. Median progression free survival (PFS) and overall survival (OS) were 4 months and 7.5 months in all patients, respectively. There was no statistical difference in ORR, PFS and OS between genotype (TA) 6 /(TA) 6 patients and heterozygous (TA) 6 /(TA) 7 patients. Irinotecan showed efficacy in patients with recurrent and refractory SCLC; UGT1A1 FNx01 28 polymorphism failed to predict the incidence of serious adverse effects and efficacy of irinotecan.

  2. 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

  3. 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

    2014-01-03

    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.

  4. Uridine stimulate laxative effect in the loperamide-induced constipation of SD rats through regulation of the mAChRs signaling pathway and mucin secretion.

    PubMed

    Kim, Ji Eun; Go, Jun; Sung, Ji Eun; Lee, Hyun Ah; Yun, Woo Bin; Hong, Jin Tae; Hwang, Dae Youn

    2017-01-26

    Uridine (Urd), which has been reported as a major component of RNA, plays an important role in various biological process including neuroprotection, biochemical modulation and glycolysis, although its role in constipation has yet to be established. Therefore, in this study, we investigated the laxative effects of Urd on chronic constipation. The constipation phenotypes and their related mechanisms were investigated in the transverse colons of SD rats with loperamide (Lop)-induced constipation after treatment with 100 mg/kg of Urd. The number, weight and water contents of stools were significantly higher in the Lop + Urd treated group than the Lop + Vehicle treated group, while food intake and water consumption of the same group were maintained at a constant level. The thickness of the mucosa layer, muscle and flat luminal surface, as well as the number of goblet cells, paneth cells and lipid droplets were enhanced in the Lop + Urd treated group. Furthermore, the expression of the muscarinic acetylcholine receptors M2 and M3 (mAChR M2 and M3) at the transcriptional and translational level was recovered in the Lop + Urd treated group, while some markers such as Gα and inositol triphosphate (IP3) in their downstream signaling pathway were completely recovered by Urd treatment. Moreover, the ability for mucin secretion and the expression of membrane water channel (aquaporine 8, AQP8) were increased significantly in the Lop + Urd treated group compared with Lop + Vehicle treated group. Finally, the activity of Urd was confirmed in primary smooth muscle of rat intestine cells (pRISMC) based on Gα expression and IP3 concentration. The results of the present study provide the first strong evidence that Urd can be considered an important candidate for improving chronic constipation induced by Lop treatment in animal models.

  5. The effect of uridine diphosphate glucuronosyltransferase (UGT)1A6 genetic polymorphism on valproic acid pharmacokinetics in Indian patients with epilepsy: a pharmacogenetic approach.

    PubMed

    Munisamy, Murali; Tripathi, Manjari; Behari, Madhuri; Raghavan, S; Jain, D C; Ramanujam, Barghavi; Arumugam, Karthik; Rajakannan, Thiyagu; Mallayasamy, Surulivel Rajan; Subbiah, Vivekanandhan

    2013-10-01

    Sodium valproate is a widely prescribed broad-spectrum antiepileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range. We evaluated the effects of polymorphic uridine diphosphate glucuronosyltransferase (UGT)1A6 (541A>G, 552A>C) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy. Genotype analysis of the patients was made with polymerase chain-restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration-time data were analyzed by using a non-compartmental approach. The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT1A6 (541A>G) or UGT1A6 (552A>C) polymorphic enzymes. The elimination half-life (t ½ = 40.2 h) of valproic acid was longer and the clearance rate (CL = 917 ml/h) was lower in the poor metabolizers group of UGT1A6 (552A>C) polymorphism who showed toxicity than in the intermediate metabolizers group (t ½ = 35.5 h, CL = 1,022 ml/h) or the extensive metabolizers group (t ½ = 25.4 h, CL = 1,404 ml/h). Our findings suggest that the UGT1A6 (552A>C) genetic polymorphism plays a significant role in the steady state concentration of valproic acid, and it thereby has an impact on the toxicity of the valproic acid used in the patients with epilepsy.

  6. Building robust conservation plans.

    PubMed

    Visconti, Piero; Joppa, Lucas

    2015-04-01

    Systematic conservation planning optimizes trade-offs between biodiversity conservation and human activities by accounting for socioeconomic costs while aiming to achieve prescribed conservation objectives. However, the most cost-efficient conservation plan can be very dissimilar to any other plan achieving the set of conservation objectives. This is problematic under conditions of implementation uncertainty (e.g., if all or part of the plan becomes unattainable). We determined through simulations of parallel implementation of conservation plans and habitat loss the conditions under which optimal plans have limited chances of implementation and where implementation attempts would fail to meet objectives. We then devised a new, flexible method for identifying conservation priorities and scheduling conservation actions. This method entails generating a number of alternative plans, calculating the similarity in site composition among all plans, and selecting the plan with the highest density of neighboring plans in similarity space. We compared our method with the classic method that maximizes cost efficiency with synthetic and real data sets. When implementation was uncertain--a common reality--our method provided higher likelihood of achieving conservation targets. We found that χ, a measure of the shortfall in objectives achieved by a conservation plan if the plan could not be implemented entirely, was the main factor determining the relative performance of a flexibility enhanced approach to conservation prioritization. Our findings should help planning authorities prioritize conservation efforts in the face of uncertainty about future condition and availability of sites. © 2014 Society for Conservation Biology.

  7. Wobbly Planet Orbital Schematic Illustration

    NASA Image and Video Library

    2014-02-04

    This illustration shows the unusual orbit of planet Kepler-413b around a close pair of orange and red dwarf stars. The planet 66-day orbit is tilted 2.5 degrees with respect to the plane of the binary stars orbit.

  8. The wobbling Christmas tree toy

    NASA Astrophysics Data System (ADS)

    Prigo, R. B.

    1984-04-01

    A common but fascinating little toy is analyzed for its unusual oscillatory behavior. A simplified model of the toy lends itself nicely to a Lagrangian-effective potential solution. Some results are obtained. Others are left to the interested classical mechanics student at the intermediate level.

  9. From conservation genetics to conservation genomics.

    PubMed

    Primmer, Craig R

    2009-04-01

    Although the application of population and evolutionary genetic theory and methods to address issues of conservation relevance has a long history, the formalization of conservation genetics as a research field is still relatively recent. One of the periodic catalysts for increased research effort in the field has been advances in molecular technologies, leading to an increasingly wider variety of molecular markers for application in conservation genetic studies. To date, genetic methods have been applied in conservation biology primarily as selectively neutral molecular tools for resolving questions of conservation relevance. However, there has been renewed interest in complementing the analysis of neutral markers with the assessment of loci that may be directly involved in responses to processes such as environmental change, with a view to identifying the genes involved in them. These kinds of studies are now possible due to the increase in availability of genomic resources for nonmodel organisms, and there will likely be an even more rapid increase in the near future due to the advent of new ultrahigh throughput-sequencing technologies. This review considers the implications of the most recent developments in genomic technologies and their potential for contributing to the conservation of populations and species. Three "conservation genomics" case studies are presented (Atlantic salmon, Salmo sala; the butterfly, Melitaea cinxia; and the California condor, Gymnogyps californianus) in order to demonstrate the diversity of applications now possible. While it is clear that genomics approaches in conservation will not replace other tried-and-true methods, these recent developments open up an exciting new range of possibilities that will enable further diversification of the application of genomics in conservation biology.

  10. Meeting global conservation challenges

    NASA Astrophysics Data System (ADS)

    2016-10-01

    Hot on the heels of last year's Sustainable Development Goals and the Paris Agreement, representatives from the global conservation community met to set the conservation agenda that will help to implement these targets.

  11. Conservation and Reading Readiness

    ERIC Educational Resources Information Center

    Brekke, Beverly W.; And Others

    1973-01-01

    Conservation is positively correlated with reading readiness and intelligence. Suggests that conservation is worthy of attention by primary teachers as a predictor of the child's readiness for learning to read. (ST)

  12. 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…

  13. 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)

  14. Identity, Compensation, and Conservation.

    ERIC Educational Resources Information Center

    Acredolo, Curt; Acredolo, Linda P.

    1979-01-01

    Tests Piaget's assertions regarding compensation, identity, and conservation using a modified replication of Piaget and Taponier's classic study of liquid conservation. A total of 96 children in kindergarten and first grade were presented with a sequence of anticipation-of-liquid-conservation, anticipation-of-water-levels, and standard…

  15. 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…

  16. 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)

  17. Conservation genetics in transition to conservation genomics.

    PubMed

    Ouborg, N Joop; Pertoldi, Cino; Loeschcke, Volker; Bijlsma, R Kuke; Hedrick, Phil W

    2010-04-01

    Over the past twenty years conservation genetics has progressed from being mainly a theory-based field of population biology to a full-grown empirical discipline. Technological developments in molecular genetics have led to extensive use of neutral molecular markers such as microsatellites in conservation biology. This has allowed assessment of the impact of genetic drift on genetic variation, of the level of inbreeding within populations, and of the amount of gene flow between or within populations. Recent developments in genomic techniques, including next generation sequencing, whole genome scans and gene-expression pattern analysis, have made it possible to step up from a limited number of neutral markers to genome-wide estimates of functional genetic variation. Here, we focus on how the transition of conservation genetics to conservation genomics leads to insights into the dynamics of selectively important variation and its interaction with environmental conditions, and into the mechanisms behind this interaction. Copyright 2010 Elsevier Ltd. All rights reserved.

  18. 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.

  19. 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.

  20. 7 CFR 12.23 - Conservation plans and conservation systems.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 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...

  1. 7 CFR 12.23 - Conservation plans and conservation systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 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...

  2. 7 CFR 12.23 - Conservation plans and conservation systems.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 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...

  3. 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.

  4. 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.

  5. The bacterial ribonuclease P holoenzyme requires specific, conserved residues for efficient catalysis and substrate positioning.

    PubMed

    Reiter, Nicholas J; Osterman, Amy K; Mondragón, Alfonso

    2012-11-01

    RNase P is an RNA-based enzyme primarily responsible for 5'-end pre-tRNA processing. A structure of the bacterial RNase P holoenzyme in complex with tRNAPhe revealed the structural basis for substrate recognition, identified the active site location, and showed how the protein component increases functionality. The active site includes at least two metal ions, a universal uridine (U52), and P RNA backbone moieties, but it is unclear whether an adjacent, bacterially conserved protein loop (residues 52-57) participates in catalysis. Here, mutagenesis combined with single-turnover reaction kinetics demonstrate that point mutations in this loop have either no or modest effects on catalytic efficiency. Similarly, amino acid changes in the 'RNR' region, which represent the most conserved region of bacterial RNase P proteins, exhibit negligible changes in catalytic efficiency. However, U52 and two bacterially conserved protein residues (F17 and R89) are essential for efficient Thermotoga maritima RNase P activity. The U52 nucleotide binds a metal ion at the active site, whereas F17 and R89 are positioned >20 Å from the cleavage site, probably making contacts with N(-4) and N(-5) nucleotides of the pre-tRNA 5'-leader. This suggests a synergistic coupling between transition state formation and substrate positioning via interactions with the leader.

  6. Physiology, behavior, and conservation.

    PubMed

    Cooke, Steven J; Blumstein, Daniel T; Buchholz, Richard; Caro, Tim; Fernández-Juricic, Esteban; Franklin, Craig E; Metcalfe, Julian; O'Connor, Constance M; St Clair, Colleen Cassady; Sutherland, William J; Wikelski, Martin

    2014-01-01

    Many animal populations are in decline as a result of human activity. Conservation practitioners are attempting to prevent further declines and loss of biodiversity as well as to facilitate recovery of endangered species, and they often rely on interdisciplinary approaches to generate conservation solutions. Two recent interfaces in conservation science involve animal behavior (i.e., conservation behavior) and physiology (i.e., conservation physiology). To date, these interfaces have been considered separate entities, but from both pragmatic and biological perspectives, there is merit in better integrating behavior and physiology to address applied conservation problems and to inform resource management. Although there are some institutional, conceptual, methodological, and communication-oriented challenges to integrating behavior and physiology to inform conservation actions, most of these barriers can be overcome. Through outlining several successful examples that integrate these disciplines, we conclude that physiology and behavior can together generate meaningful data to support animal conservation and management actions. Tangentially, applied conservation and management problems can, in turn, also help advance and reinvigorate the fundamental disciplines of animal physiology and behavior by providing advanced natural experiments that challenge traditional frameworks.

  7. Conservation and behavioral neuroendocrinology.

    PubMed

    Cockrem, J F

    2005-11-01

    The total number of threatened species of vertebrates is likely to be more than 10,000, with approximately one quarter of the world's mammal species, one eighth of the birds and one third of the amphibians threatened with extinction. The rate of loss of animal species and hence of biodiversity is increasing and may become even greater as ecosystems become affected by climate change due to global warming. Behavioral neuroendocrinology, which considers interactions between behavior and neuroendocrine function in animals from all vertebrate taxa, can contribute to animal conservation. Research with laboratory animals can address questions in basic biology relevant to conservation and develop methods for use with threatened animals. Field work with free-living animals considers the basic biology of new species and the use of endocrine tools to assess the susceptibility of species to threats. Non-invasive measurements of hormone concentrations, especially fecal steroids, are extensively used to assess reproductive function and the stress status of animals in captive breeding programs and in the wild. Biodiversity and natural selection both depend on individual variation, and conservation programs often work with animals on an individual basis. The consideration of data from individuals is essential in conservation endocrinology. Direct contributions to conservation programs are challenging as study situations are determined by practical conservation concerns. Indirect contributions such as the provision of scientific input to conservation plans and participation in public education programs offer significant benefits for conservation programs. Directly and indirectly, there are many opportunities for behavioral neuroendocrinologists to contribute to conservation.

  8. Pharmacology of INS37217 [P(1)-(uridine 5')-P(4)- (2'-deoxycytidine 5')tetraphosphate, tetrasodium salt], a next-generation P2Y(2) receptor agonist for the treatment of cystic fibrosis.

    PubMed

    Yerxa, B R; Sabater, J R; Davis, C W; Stutts, M J; Lang-Furr, M; Picher, M; Jones, A C; Cowlen, M; Dougherty, R; Boyer, J; Abraham, W M; Boucher, R C

    2002-09-01

    INS37217 [P(1)-(uridine 5')-P(4)-(2'-deoxycytidine 5')tetraphosphate, tetrasodium salt] is a deoxycytidine-uridine dinucleotide with agonist activity at the P2Y(2) receptor. In primate lung tissues, the P2Y(2) receptor mRNA was located by in situ hybridization predominantly in epithelial cells and not in smooth muscle or stromal tissue. The pharmacologic profile of INS37217 parallels that of UTP, leading to increased chloride and water secretion, increased cilia beat frequency, and increased mucin release. The combined effect of these actions was confirmed in an animal model of tracheal mucus velocity that showed that a single administration of INS37217 significantly enhanced mucus transport for at least 8 h after dosing. This extended duration of action is consistent with the ability of INS37217 to resist metabolism by airway cells and sputum enzymes. The enhanced metabolic stability and resultant increased duration of improved mucociliary clearance may confer significant advantages to INS37217 over other P2Y(2) agonists in the treatment of diseases such as cystic fibrosis.

  9. Biodiversity Conservation and Conservation Biotechnology Tools

    USDA-ARS?s Scientific Manuscript database

    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...

  10. Paradigms for parasite conservation.

    PubMed

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  11. Analysis of the binding of the N-terminal conserved domain of yeast Cbf5p to a box H/ACA snoRNA.

    PubMed

    Normand, Christophe; Capeyrou, Regine; Quevillon-Cheruel, Sophie; Mougin, Annie; Henry, Yves; Caizergues-Ferrer, Michele

    2006-10-01

    During ribosome biogenesis, the RNA precursor to mature rRNAs undergoes numerous post-transcriptional chemical modifications of bases, including conversions of uridines to pseudouridines. In archaea and eukaryotes, these conversions are performed by box H/ACA small ribonucleoprotein particles (box H/ACA RNPs), which contain a small guide RNA responsible for the selection of substrate uridines and four proteins, including the pseudouridine synthase, Cbf5p. So far, no in vitro reconstitution of eukaryotic box H/ACA RNPs from purified components has been achieved, principally due to difficulties in purifying recombinant eukaryotic Cbf5p. In this study, we present the purification of a truncated derivative of yeast Cbf5p (Cbf5(Delta)p) that retains the highly conserved TRUB and PUA domains. We have used band retardation assays to show that Cbf5(Delta)p on its own binds to box H/ACA small nucleolar (sno)RNAs. We demonstrate that the conserved H and ACA boxes enhance the affinity of the protein for the snoRNA. Furthermore, like its archaeal homologs, Cbf5(Delta)p can bind to a single stem-loop-box ACA RNA. Finally, we report the first enzymatic footprinting analysis of a Cbf5-RNA complex. Our results are compatible with the view that two molecules of Cbf5p interact with a binding platform constituted by the 5' end of the RNA, the single-stranded hinge domain containing the conserved H box, and the 3' end of the molecule, including the conserved ACA box.

  12. 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…

  13. 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…

  14. Fixism and conservation science.

    PubMed

    Robert, Alexandre; Fontaine, Colin; Veron, Simon; Monnet, Anne-Christine; Legrand, Marine; Clavel, Joanne; Chantepie, Stéphane; Couvet, Denis; Ducarme, Frédéric; Fontaine, Benoît; Jiguet, Frédéric; le Viol, Isabelle; Rolland, Jonathan; Sarrazin, François; Teplitsky, Céline; Mouchet, Maud

    2017-08-01

    The field of biodiversity conservation has recently been criticized as relying on a fixist view of the living world in which existing species constitute at the same time targets of conservation efforts and static states of reference, which is in apparent disagreement with evolutionary dynamics. We reviewed the prominent role of species as conservation units and the common benchmark approach to conservation that aims to use past biodiversity as a reference to conserve current biodiversity. We found that the species approach is justified by the discrepancy between the time scales of macroevolution and human influence and that biodiversity benchmarks are based on reference processes rather than fixed reference states. Overall, we argue that the ethical and theoretical frameworks underlying conservation research are based on macroevolutionary processes, such as extinction dynamics. Current species, phylogenetic, community, and functional conservation approaches constitute short-term responses to short-term human effects on these reference processes, and these approaches are consistent with evolutionary principles. © 2016 Society for Conservation Biology.

  15. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 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)

  17. 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)…

  18. Setting conservation priorities.

    PubMed

    Wilson, Kerrie A; Carwardine, Josie; Possingham, Hugh P

    2009-04-01

    A generic framework for setting conservation priorities based on the principles of classic decision theory is provided. This framework encapsulates the key elements of any problem, including the objective, the constraints, and knowledge of the system. Within the context of this framework the broad array of approaches for setting conservation priorities are reviewed. While some approaches prioritize assets or locations for conservation investment, it is concluded here that prioritization is incomplete without consideration of the conservation actions required to conserve the assets at particular locations. The challenges associated with prioritizing investments through time in the face of threats (and also spatially and temporally heterogeneous costs) can be aided by proper problem definition. Using the authors' general framework for setting conservation priorities, multiple criteria can be rationally integrated and where, how, and when to invest conservation resources can be scheduled. Trade-offs are unavoidable in priority setting when there are multiple considerations, and budgets are almost always finite. The authors discuss how trade-offs, risks, uncertainty, feedbacks, and learning can be explicitly evaluated within their generic framework for setting conservation priorities. Finally, they suggest ways that current priority-setting approaches may be improved.

  19. Youth Conservation Corps Guidance.

    ERIC Educational Resources Information Center

    Fish and Wildlife Service (Dept. of Interior), Washington, DC.

    This document provides guidelines for operating Youth Conservation Corps programs under both the Fish and Wildlife Service and the National Park Service. The guide contains 11 units that cover the following topics: (1) enrollees; (2) enrollee payroll; (3) enrollee problems; (4) Youth Conservation Corps staff; (5) accounting; (6) operations; (7)…

  20. 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…

  1. Teaching Teachers Conservation.

    ERIC Educational Resources Information Center

    Meyers, N. L.; And Others

    1987-01-01

    Describes a two-week summer course for elementary and secondary teachers on soil and water conservation taught in Wisconsin. Discusses the efforts to recruit teachers for the course, the course content, the field trips, and the evaluation procedures. Stresses the cooperation between educators and conservation agencies in developing the course. (TW)

  2. 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…

  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. 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)…

  5. Nature Conservation in Bophuthatswana.

    ERIC Educational Resources Information Center

    Motaung, Maria

    1992-01-01

    This presentation to the International Girl Guides Jamboree, July 1991, addressed the issue of nature conservation and the role of the National Parks and Wildlife Management Board of Bophuthatswana in creating parks and conserving wildlife. Describes three national parks and the boards' achievements in preserving wildlife. (MDH)

  6. 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…

  7. Nature Conservation in Bophuthatswana.

    ERIC Educational Resources Information Center

    Motaung, Maria

    1992-01-01

    This presentation to the International Girl Guides Jamboree, July 1991, addressed the issue of nature conservation and the role of the National Parks and Wildlife Management Board of Bophuthatswana in creating parks and conserving wildlife. Describes three national parks and the boards' achievements in preserving wildlife. (MDH)

  8. 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)

  9. 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…

  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)

  11. 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…

  12. 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.

  13. Wilderness and biodiversity conservation

    NASA Astrophysics Data System (ADS)

    Mittermeier, R. A.; Mittermeier, C. G.; Brooks, T. M.; Pilgrim, J. D.; Konstant, W. R.; da Fonseca, G. A. B.; Kormos, C.

    2003-09-01

    Human pressure threatens many species and ecosystems, so conservation efforts necessarily prioritize saving them. However, conservation should clearly be proactive wherever possible. In this article, we assess the biodiversity conservation value, and specifically the irreplaceability in terms of species endemism, of those of the planet's ecosystems that remain intact. We find that 24 wilderness areas, all > 1 million hectares, are > 70% intact and have human densities of less than or equal to five people per km2. This wilderness covers 44% of all land but is inhabited by only 3% of people. Given this sparse population, wilderness conservation is cost-effective, especially if ecosystem service value is incorporated. Soberingly, however, most wilderness is not speciose: only 18% of plants and 10% of terrestrial vertebrates are endemic to individual wildernesses, the majority restricted to Amazonia, Congo, New Guinea, the Miombo-Mopane woodlands, and the North American deserts. Global conservation strategy must target these five wildernesses while continuing to prioritize threatened biodiversity hotspots.

  14. Conservative mastectomies: an overview

    PubMed Central

    Nava, Maurizio Bruno; Catanuto, Giuseppe

    2015-01-01

    Conservative mastectomies provide removal of the entire breast parenchyma, saving the outer covering of the mammary gland with the possibility of performing an immediate reconstruction preserving women body image. We rationalised and systematically organized our reconstructive algorythms giving a new different light to mastectomies, the so-called “conservative mastectomies”, an oxymoron indicating skin-sparing mastectomies (SSM), nipple-areola complex-sparing mastectomies (NSM) and skin-reducing mastectomies (SRM). Eventhough randomized controlled trials comparing conservative mastectomies with traditional mastectomy and breast conserving surgery would be auspicable in order to achieve higher levels of evidence, we could confidently conclude that conservative mastectomies offer the psychological advantages of good cosmesis and maintenance of woman body image without compromising the oncological safety of mastectomy. PMID:26645000

  15. Urban Water Conservation

    NASA Astrophysics Data System (ADS)

    Moomaw, Ronald L.

    According to its abstract, this book attempts ‘an assessment of various water conservation measures aimed at reducing residential water usage.’ Its intent is to develop a research program whose ‘ultimate goal is to engender a conservation ethic among water users and managers and develop a predictable array of conservation methodologies. …’ Professor Flack indeed has presented an excellent assessment of conservation methodologies, but I believe that the proposed research program is too limited.Following a brief introductory chapter, chapter II presents an extensive review of the water conservation literature published in the 1970's and earlier. It and chapter III, which describes Flack's systematic comparison of the technical, economic, and political aspects of each conservation methodology, are the heart of the book. Chapter IV is a brief discussion and analysis of conservation programs (with examples) that a water utility might adopt. Chapter V is essentially a pilot study of methods of assessing political and social feasibility. Finally, a set of recommendations is presented in chapter VI. All in all, this book is a nice blend of literature review and original research that deals with an important issue.

  16. Commitment and energy conservation

    SciTech Connect

    Pallak, M.S.; Cook, D.A.; Sullivan, J.J.

    1980-01-01

    The authors discuss the process of becoming committed to energy conservation research, then describe practical issues of field research and several data sets on household energy conservation. Their results show that taking a stand affected behavior in reducing the levels of natural gas and electricity usage, with the effect continuing even after the study ended. Although based on the assumption that homeowners were initially favorable toward energy conservation, the studies suggest that energy-related behavior is malleable and amenable to approaches familiar to psychologists. The study indicates that feedback on energy use during peak seasons could help to avoid power shortages. 16 references, 6 tables.

  17. Policy: Palatable forest conservation

    NASA Astrophysics Data System (ADS)

    Tacconi, Luca

    2011-06-01

    Current policies to reduce emissions from forest loss could mean that rising demand for food is not met. A new approach to forest conservation that reduces emissions while meeting demand for agricultural products may be feasible, but more expensive.

  18. Monitoring for conservation

    USGS Publications Warehouse

    Nichols, J.D.; Williams, B.K.

    2006-01-01

    Human-mediated environmental changes have resulted in appropriate concern for the conservation of ecological systems and have led to the development of many ecological monitoring programs worldwide. Many programs that are identified with the purpose of `surveillance? represent an inefficient use of conservation funds and effort. Here, we revisit the 1964 paper by Platt and argue that his recommendations about the conduct of science are equally relevant to the conduct of ecological monitoring programs. In particular, we argue that monitoring should not be viewed as a stand-alone activity, but instead as a component of a larger process of either conservation-oriented science or management. Corresponding changes in monitoring focus and design would lead to substantial increases in the efficiency and usefulness of monitoring results in conservation.

  19. Conservation among Elderly Women.

    ERIC Educational Resources Information Center

    Hughston, George A.; Protinsky, Howard O.

    1979-01-01

    The majority of 63 elderly women were able to pass tests in the conservation of mass (98 percent), volume (100 percent), and surface area (65 percent). These results conflict with previous research about Piagetian abilities of elderly people. (RL)

  20. Potential conservation laws

    SciTech Connect

    Kunzinger, Michael; Popovych, Roman O.

    2008-10-15

    We prove that potential conservation laws have characteristics depending only on local variables if and only if they are induced by local conservation laws. Therefore, characteristics of pure potential conservation laws have to essentially depend on potential variables. This statement provides a significant generalization of results of the recent paper by Bluman et al. [J. Math. Phys. 47, 113505 (2006)]. Moreover, we present extensions to gauged potential systems, Abelian and general coverings, and general foliated systems of differential equations. An example illustrating possible applications of these results is given. A special version of the Hadamard lemma for fiber bundles and the notions of weighted jet spaces are proposed as new tools for the investigation of potential conservation laws.

  1. The Librarian as Conservator

    ERIC Educational Resources Information Center

    Henderson, James W.; Krupp, Robert G.

    1970-01-01

    Guideposts for the librarian who seeks to establish a total conservation program: organizing the program and management in selection, screening, maintenance, treatment, personnel, costs, and cooperation. (Author/JS)

  2. Energy: Conservation, Energy Briefs

    ERIC Educational Resources Information Center

    Nation's Schools and Colleges, 1975

    1975-01-01

    A comprehensive energy conservation program at College of the Holy Cross has saved nearly one-third of the fuel oil and one-fifth of the electricity used at the college; briefs on boilers, lights, design. (Author/MLF)

  3. Energy: Conservation, Energy Briefs

    ERIC Educational Resources Information Center

    Nation's Schools and Colleges, 1975

    1975-01-01

    A comprehensive energy conservation program at College of the Holy Cross has saved nearly one-third of the fuel oil and one-fifth of the electricity used at the college; briefs on boilers, lights, design. (Author/MLF)

  4. Conservation among Elderly Women.

    ERIC Educational Resources Information Center

    Hughston, George A.; Protinsky, Howard O.

    1979-01-01

    The majority of 63 elderly women were able to pass tests in the conservation of mass (98 percent), volume (100 percent), and surface area (65 percent). These results conflict with previous research about Piagetian abilities of elderly people. (RL)

  5. IUCN Conservation Programs

    ERIC Educational Resources Information Center

    Budowski, Gerardo

    1972-01-01

    Brief, but comprehensive, description of the International Union for Conservation of Nature and Natural Resources (IUCN), a non-governmental organization located in Morges, Switzerland. Presents its objectives, broad purpose and describes the specific activities of the organization. (LK)

  6. Conservation of wading birds

    USGS Publications Warehouse

    Kushlan, J.A.

    1996-01-01

    The conservation and management of wading birds has received considerable attention over the past twenty years, through research, population monitoring, habitat protection, and through activities of specialist groups devoted to all three groups, the herons, ibises and allies, and flamingos. While populations are best known in North America, greatest advances in knowledge may have come in Australasia. The status of most species and many populations is now sufficiently known to allow assessment of risk. Conservation and management techniques allow creation of global and regional action plans for conservation of many species. Global action plans are being developed, but few regional plans have been undertaken. Management of nesting sites is now particularly well appreciated. Although known in broad stroke, much remains to be learned about managing feeding habitat. Problems related to disturbance, conflict with humans, habitat loss, contaminants and other environmental stresses remain for some species and many populations. New challenges lie in creating conservation action that account for genetic stocks.

  7. Energy conservation in infants.

    PubMed

    Blass, Elliott

    2015-08-01

    Energy acquisition through suckling has been widely studied in rat and human infants. Processes mediating energy conservation, however, have not received the attention that they deserve. This essay, in honor of Professor Jerry Hogan, discusses parallel behaviors used by rat and human mothers to minimize energy loss in their offspring. Parallel mechanisms underlying energy preservation have been identified in rats and humans, suggesting phylogenetic conservation and possibly continuity. This article is part of a Special Issue entitled: In Honor of Jerry Hogan.

  8. Study of [18F]FLT and [123I]IaraU for cellular imaging in HSV1 tk-transfected murine fibrosarcoma cells: evaluation of the tracer uptake using 5-fluoro, 5-iodo and 5-iodovinyl arabinosyl uridines as competitive probes.

    PubMed

    Huang, Ho-Lien; Chiang, Li-Wu; Chen, Jia-Rong; Yang, Wen K; Jeng, Kee-Ching; Chen, Jenn-Tzong; Duh, Ting-Shien; Lin, Wuu-Jyh; Farn, Shiou-Shiow; Chiang, Chi-Shiun; Huang, Chia-Wen; Lin, Kun-I; Yu, Chung-Shan

    2012-04-01

    As one of the most intensively studied probes for imaging of the cellular proliferation, [(18)F]FLT was investigated whether the targeting specificity of thymidine kinase 1 (TK1) dependency could be enhanced through a synergistic effect mediated by herpes simplex type 1 virus (HSV1) tk gene in terms of the TK1 or TK2 expression. 5-[(123)I]Iodo arabinosyl uridine ([(123)I]IaraU) was prepared in a radiochemical yield of 8% and specific activity of 21 GBq/μmol, respectively. Inhibition of the cellular uptake of these two tracers was compared by using the arabinosyl uridine analogs such as 5-iodo, 5-fluoro and 5-(E)-iodovinyl arabinosyl uridine along with 2'-fluoro-5-iodo arabinosyl uridine (FIAU). Due to potential instability of the iodo group, accumulation index of 1.6 for [(123)I]IaraU by HSV1-TK vs. control cells could virtually be achieved at 1.5 h, but dropped to 0.2 compared to 2.0 for [(18)F]FLT at 5 h. The results from competitive inhibition by these nucleosides against the accumulation of [(18)F]FLT implied that FLT exerted a mixed TK1- and TK2-dependent inhibition with HSV1-tk gene transfection because of the shifting of thymidine kinase status. Taken together, the combination of [(18)F]FLT and HSV1-TK provides a synergistic imaging potency. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Conservation ethics and anaesthesia.

    PubMed

    Houghton, I T

    2003-10-01

    The current attitude of conservators towards restoration is to preserve objects and materials in the condition as they are but without attempting to restore them 'as new'. Museum objects have generally ceased to serve their original utilitarian function but have become objects for study, information and inspiration. Conservation and restoration are discussed in relation to anaesthetic exhibits. Conservation is the prevention, detection, containment, control and recovery but risk avoidance and monitoring hopefully will lessen the need for conservation. Some objects such as rubber and plastic items are, by their very nature, prone to ageing, accident and mistreatment. Cleaning and maintenance may lead to loss of original detail and is 'an act of critical interpretation'. Reshaping of distorted objects and repair of broken pieces can sometimes be justified but, in other work, the actual restoration may become part of the object's history that should not be lost in trying to restore something to a presumed earlier state. The mind interprets images by reference to earlier patterns and so imperfections, if not disguised, may be unduly distracting. Museums exist for information, evidence, enlightenment and even entertainment. Conservation must serve these purposes and is not an end in its own right. The professional actions of the conservator must be governed by a total respect for physical, historic, and aesthetic integrity but this must be interpreted widely.

  10. Conservation Kickstart- Catalyzing Conservation Initiatives Worldwide

    NASA Astrophysics Data System (ADS)

    Treinish, G.

    2014-12-01

    Adventurers and Scientists for Conservation (ASC) is a nonprofit organization that collects environmental data to catalyze conservation initiatives worldwide. Adventure athletes have the skills and motivation to reach the most remote corners of the world. ASC utilizes those skills to provide the scientific community with data while providing the outdoor community with purpose beyond the personal high of reaching a summit or rowing across an ocean. We carefully select projects, choosing partnerships that will maximize the impact of ASC volunteers. Each project must have a clear path to a tangible conservation outcome and demonstrate a clear need for our brand of volunteers. We partner with government agencies, universities, and independant reseachers to kickstart data collection efforts around the world. Last year, through a partnership with the Olympic National Forest, 20 volunteers from the Seattle area set up and monitored camera traps in an effort to survey for costal Pacific marten. Our work led to the species' listing as "critically imperiled" with NatureServe. A partnership with the inaugural Great Pacific Race, engaging trans-Pacific rowing teams, searched for microplastics in the Pacific Ocean as part of our ongoing microplastics campaign. In a multi-year partnership with the American Prairie Reserve (APR), ASC volunteer crews live and work on the Reserve collecting wildlife data year round. The data we obtain directly informs the Reserve's wildlife management decisions. On this project, our crews have safely and effectively navigated temperature extremes from -30 degrees to 100+ degrees while traveling in a remote location. We are currently scouting projects in the Okavango Delta of Botswana and the rainforest of Suriname where we will be able to cover large amounts of area in a short periord of time. ASC is at the crossroads of the adventure and coservation science communities. Our approach of answering specific questions by using highly skilled and

  11. Resource Management and Conservation Education

    ERIC Educational Resources Information Center

    Arey, David G.; Baumann, Duane D.

    1972-01-01

    The definition of conservation, the future of resource availability, the status of conservation education today are topics examined and suggestions are made on improving the content and emphasis of conservation courses. (Author)

  12. Effects of co-treatment with sulforaphane and autophagy modulators on uridine 5′-diphospho-glucuronosyltransferase 1A isoforms and cytochrome P450 3A4 expression in Caco-2 human colon cancer cells

    PubMed Central

    WANG, MIN; ZHU, JING-YU; CHEN, SHUO; QING, YING; WU, DONG; LIN, YING-MIN; LUO, JI-ZHUANG; HAN, WEI; LI, YAN-QING

    2014-01-01

    Sulforaphane (SFN), which is highly enriched in cruciferous vegetables, has been investigated for its cancer chemopreventive properties and ability to induce autophagy. Uridine 5′-diphospho (UDP)-glucuronosyltransferase (UGT)1A induction is one of the mechanisms that is responsible for the cancer chemopreventive activity of SFN. The current study demonstrates that rapamycin may enhance the chemopreventive effects of SFN on Caco-2 cells; this may be partially attributed to nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2)- and human pregnane X receptor (hPXR)-mediated UGT1A1, UGT1A8 and UGT1A10 induction. These results indicate that targeting autophagy modulation may be a promising strategy for increasing the chemopreventive effects of SFN in cases of colon cancer. PMID:25364403

  13. Photoelectron spectroscopic study of the hydrated nucleoside anions: Uridine(-)(H(2)O)(n=0-2), cytidine(-)(H(2)O)(n=0-2), and thymidine(-)(H(2)O)(n=0,1).

    PubMed

    Li, Xiang; Wang, Haopeng; Bowen, Kit H

    2010-10-14

    The hydrated nucleoside anions, uridine(-)(H(2)O)(n=0-2), cytidine(-)(H(2)O)(n=0-2), and thymidine(-)(H(2)O)(n=0,1), have been prepared in beams and studied by anion photoelectron spectroscopy in order to investigate the effects of a microhydrated environment on parent nucleoside anions. Vertical detachment energies (VDEs) were measured for all eight anions, and from these, estimates were made for five sequential anion hydration energies. Excellent agreement was found between our measured VDE value for thymidine(-)(H(2)O)(1) and its calculated value in the companion article by S. Kim and H. F. Schaefer III.

  14. Photoelectron spectroscopic study of the hydrated nucleoside anions: Uridine-(H2O)n=0-2, cytidine-(H2O)n=0-2, and thymidine-(H2O)n=0,1

    NASA Astrophysics Data System (ADS)

    Li, Xiang; Wang, Haopeng; Bowen, Kit H.

    2010-10-01

    The hydrated nucleoside anions, uridine-(H2O)n=0-2, cytidine-(H2O)n=0-2, and thymidine-(H2O)n=0,1, have been prepared in beams and studied by anion photoelectron spectroscopy in order to investigate the effects of a microhydrated environment on parent nucleoside anions. Vertical detachment energies (VDEs) were measured for all eight anions, and from these, estimates were made for five sequential anion hydration energies. Excellent agreement was found between our measured VDE value for thymidine-(H2O)1 and its calculated value in the companion article by S. Kim and H. F. Schaefer III.

  15. A double-blind, randomized, comparative study of the use of a combination of uridine triphosphate trisodium, cytidine monophosphate disodium, and hydroxocobalamin, versus isolated treatment with hydroxocobalamin, in patients presenting with compressive neuralgias

    PubMed Central

    Goldberg, Henrique; Mibielli, Marco Antonio; Nunes, Carlos Pereira; Goldberg, Stephanie Wrobel; Buchman, Luiz; Mezitis, Spyros GE; Rzetelna, Helio; Oliveira, Lisa; Geller, Mauro; Wajnsztajn, Fernanda

    2017-01-01

    Context This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (uridine triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B12. Objectives To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B12. Methods A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B12, and Group B (n=200) receiving vitamin B12 alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. Results The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B12, with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. Conclusion The combination of uridine, cytidine, and vitamin B12 was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma. PMID:28243144

  16. Physiology in conservation translocations

    PubMed Central

    Tarszisz, Esther; Dickman, Christopher R.; Munn, Adam J.

    2014-01-01

    Conservation translocations aim to restore species to their indigenous ranges, protect populations from threats and/or reinstate ecosystem functions. They are particularly important for the conservation and management of rare and threatened species. Despite tremendous efforts and advancement in recent years, animal conservation translocations generally have variable success, and the reasons for this are often uncertain. We suggest that when little is known about the physiology and wellbeing of individuals either before or after release, it will be difficult to determine their likelihood of survival, and this could limit advancements in the science of translocations for conservation. In this regard, we argue that physiology offers novel approaches that could substantially improve translocations and associated practices. As a discipline, it is apparent that physiology may be undervalued, perhaps because of the invasive nature of some physiological measurement techniques (e.g. sampling body fluids, surgical implantation). We examined 232 publications that dealt with translocations of terrestrial vertebrates and aquatic mammals and, defining ‘success’ as high or low, determined how many of these studies explicitly incorporated physiological aspects into their protocols and monitoring. From this review, it is apparent that physiological evaluation before and after animal releases could progress and improve translocation/reintroduction successes. We propose a suite of physiological measures, in addition to animal health indices, for assisting conservation translocations over the short term and also for longer term post-release monitoring. Perhaps most importantly, we argue that the incorporation of physiological assessments of animals at all stages of translocation can have important welfare implications by helping to reduce the total number of animals used. Physiological indicators can also help to refine conservation translocation methods. These approaches fall

  17. Hydrology and Conservation Ecology

    NASA Astrophysics Data System (ADS)

    Narayanan, M.

    2006-12-01

    Responses to change in the behavior of ecological systems are largely governed by interactions at different levels. Research is essential and is to be necessarily designed to gain insights into various interactions at the community level. Sustainable resource management is only possible if conservation of biodiversity can be accomplished by properly using the knowledge discovered. It is well known that the United States Department of Agriculture provides technical information, resources, and data necessary to assist the researchers in addressing their conservation needs. Conservation aims to protect, preserve and conserve the earth's natural resources. These include, but not limited to the conservation of soil, water, minerals, air, plants and all living beings. The United States Department of Agriculture also encourages farmers and ranchers to voluntarily address threats to soil and water. Protection of wetlands and wildlife habitat has been on the radar screen of conservation experts for a very long time. The main objective has always been to help farmers and landowners conform and comply with federal and state environmental laws. During the implementation phase, farmers should be encouraged to make beneficial, cost-effective changes to methods of irrigation systems. In some cases, the hydrologic regime of the project area can be thought of as principally an issue of river flow regimes for floodplain forests. In this presentation, the author tries to focus on the impact of hydrology and conservation ecology on global warming. He also discusses the impact of hydrology and conservation ecology global air concerns such as greenhouse gas concentrations in the atmosphere. References: Chow, V. T, D. R. Maidment, and L. W. Mays. 1988. Applied Hydrology. McGraw-Hill, Inc. U.S. Soil Conservation Service. Technical Release 55: Urban Hydrology for Small Watersheds. USDA (U.S. Department of Agriculture). June 1986. Lehner, B. and P. Döll (2004). Development and validation

  18. Creative Conservation Communication

    NASA Astrophysics Data System (ADS)

    Houston, Jason

    2015-04-01

    I am a fellow with the International League of Conservation photographers (iLCP) and have been focused on photographing conservation dynamics at the intersection of social and environmental issues for a decade. Subjects have included traditional concerns such as deforestation, water conservation, endangered species, and fisheries. However, I rarely make photographs of the traditional nature, wildlife, landscapes, or environmental atrocities that most people think of when they think about environmentalism. Instead, I photograph people and how they live on the planet, as I believe passionately that without also considering social and cultural concerns, we will not be able to effectively and sustainably do conservation work or achieve positive environmental change. My presentation will share recent photography projects on forest conservation in Indonesian Borneo and fisheries management in Central America where I used a 'stakeholder profile-based' process to broadly survey the complexity of the issues while also making personal connections for these projects' diverse audiences. Through these case studies I will explore the opportunities and challenges of combining the authenticity, accuracy, and scientific validity of journalistic and documentary work with the emotional impact of the conventions of art and storytelling.

  19. Wilderness and biodiversity conservation.

    PubMed

    Mittermeier, R A; Mittermeier, C G; Brooks, T M; Pilgrim, J D; Konstant, W R; da Fonseca, G A B; Kormos, C

    2003-09-02

    Human pressure threatens many species and ecosystems, so conservation efforts necessarily prioritize saving them. However, conservation should clearly be proactive wherever possible. In this article, we assess the biodiversity conservation value, and specifically the irreplaceability in terms of species endemism, of those of the planet's ecosystems that remain intact. We find that 24 wilderness areas, all > or = 1 million hectares, are > or = 70% intact and have human densities of less than or equal to five people per km2. This wilderness covers 44% of all land but is inhabited by only 3% of people. Given this sparse population, wilderness conservation is cost-effective, especially if ecosystem service value is incorporated. Soberingly, however, most wilderness is not speciose: only 18% of plants and 10% of terrestrial vertebrates are endemic to individual wildernesses, the majority restricted to Amazonia, Congo, New Guinea, the Miombo-Mopane woodlands, and the North American deserts. Global conservation strategy must target these five wildernesses while continuing to prioritize threatened biodiversity hotspots.

  20. Energy conservation in distillation

    NASA Astrophysics Data System (ADS)

    Mix, T. W.; Dweck, J. S.; Weinberg, M.; Armstrong, R. C.

    1981-07-01

    An audit of major industrial and processes and key colums in each major process indicated that approximately twoquads of energy were consumed for distillation in the US in 1976. Energy usage by industry is included: petroleum refineries, 66% chemical (including petrochemical) industry, 29% natural gas liquids processing, 5%. Techniques and current practices for conserving distillation energy are reviewed, and guidelines indicating those process conditons which favor the use of each energy conserving technique are enumerated. Expressions for payout time for tray and control retrofit options are developed based on energy savings and increased throughput. Calculations for industrial colums suggested that both types of retrofits would frequently have short (,6 months) payout times based on either criterion. Extractive distillation is also discussed, and criteria enabling the estimation of the energy which may be conserved using this technique are developed. Good housekeeping practices and field techniques for checking the energy efficiency of industrial distillations are also discussed.

  1. Energy Conservation Simplified

    NASA Astrophysics Data System (ADS)

    Hecht, Eugene

    2008-02-01

    The standard formulation of energy conservation involves the subsidiary ideas of kinetic energy (KE), work (W), thermal energy, internal energy, and a half-dozen different kinds of potential energy (PE): elastic, chemical, nuclear, gravitational, and so forth. These quantities came to be recognized during the centuries over which the principle developed. The final conservation law, although rich in specificity, is fairly involved. More significantly, it obscures a fundamental underlying simplicity, which could only be appreciated post-relativity (1905). Energy is the scalar measure of physical change. Using the special theory it will be shown that there are only two all-encompassing classifications of energy—energy of rest and energy of motion—and that we can apply the idea of conservation of energy to all physical processes using only these two energy types as quantified by mass and KE.

  2. Conservation reaches new heights.

    PubMed

    Pepall, J; Khanal, P

    1992-10-01

    The conservation program with the management assistance of the Woodlands Mountain Institute in 2 contiguous parks, the Mount Everest National Park in Nepal and the Qomolangma Nature Reserve in China, in 2 countries is described. The focus is on conservation of the complex ecosystem with sustainable development by showing local people how to benefit from the park without environmental damage. Cultural diversity is as important as biological diversity. The area has been designated by UNESCO as a World Heritage Site with the "last pure ecological seed" of the Himalayas. The regional geography and culture are presented. Population growth has impacted natural resources through overgrazing, cultivation of marginal land, and deforestation; future plans to build a dam and road bordering the nature reserve pose other threats. Proposed management plans for the Makalu-Barun Nature Park (established in November 1991) and Conservation Area include a division of the park into nature reserve areas free of human activity, protected areas which permit traditional land use, and special sites and trail for tourists and religious pilgrims. The conservation area will act as a buffer for the park and provide economic opportunities; further subdivisions include land use for biodiversity protection, community forest and pasture, agroforestry, and agriculture and settlement. Efforts will be made to increase the welfare of women and local people; proposed projects include the introduction of higher milk-producing animals for stall feeding. Also proposed is a cultural and natural history museum. 70% of the project's resources will be directed to local community participation in consultation and park maintenance. The project is a model of how conservation and protection of natural resources can coexist with local economic development and participation; an integration of preservation of biological diversity, mountain wisdom, and the value of local people as resources for conservation.

  3. Conservation of tidal marshes

    SciTech Connect

    Daiber, F.C.

    1986-01-01

    This book is the first attempt to examine collectively the various uses and the consequences of marsh conservation efforts. Author Franklin Daiber emphasizes tidal marsh conservation from a holistic perspective rather than from the perspective of a single purpose or special economic interest. He addresses a topic receiving increasing attention, namely the concept of open marsh management as a means of controlling mosquito production without harmful effects on other marsh organisms. Topics considered include: water management; dikes, impoundments, ponds and ditches; reclaimed land and impoundments; ditching and ponding for mosquito control; sewage disposal and waste treatment; dredge material for wetland restoration; insecticides; oil pollution; and petroleum hydrocarbon interactions.

  4. Two Centuries of Soil Conservation.

    ERIC Educational Resources Information Center

    Helms, Douglas

    1991-01-01

    Narrates U.S. soil conservation history since the late eighteenth century. Discusses early practices such as contour plowing. Profiles individuals who promoted soil conservation and were largely responsible for the creation of the Soil Conservation Service. Explains the causes of erosion and how soil conservation districts help farmers prevent…

  5. Two Centuries of Soil Conservation.

    ERIC Educational Resources Information Center

    Helms, Douglas

    1991-01-01

    Narrates U.S. soil conservation history since the late eighteenth century. Discusses early practices such as contour plowing. Profiles individuals who promoted soil conservation and were largely responsible for the creation of the Soil Conservation Service. Explains the causes of erosion and how soil conservation districts help farmers prevent…

  6. Soil: Conservation practices

    USDA-ARS?s Scientific Manuscript database

    The primary source to meet global food and fiber demands is production agriculture, but accelerated soil erosion threatens its sustainability. Soil erosion is an important contributor to the normal soil formation process, but erosion becomes problematic when it is accelerated. Soil conservation prac...

  7. Speyeria (Lepidoptera: Nymphalidae) Conservation

    PubMed Central

    Sims, Steven R.

    2017-01-01

    Speyeria (Nymphalidae) are a conspicuous component of the North American butterfly fauna. There are approximately 16 species and >100 associated subspecies (or geographical variants). Speyeria are univoltine, occupy a wide range of habitats, overwinter as first instar larvae, and feed only on native violets. Speyeria species have become a model group for studies of evolution, speciation, and conservation. Several species and subspecies are threatened or endangered. The reasons for this vary with the taxa involved, but always involve the degradation or loss of quality habitat for larvae and adults. The impacts of climate change must be considered among the causes for habitat degradation and in the establishment of conservation measures. In addition to increasing the available habitat, conservation efforts should consider maintaining habitat in a seral “disturbed” successional stage that selectively favors the growth of violets and preferred adult nectar sources. A major future challenge will be determining the most effective allocation of conservation resources to those species and subspecies that have the greatest potential to respond favorably to these efforts. PMID:28441319

  8. Conservation Awareness Guide.

    ERIC Educational Resources Information Center

    Santa Rosa County Board of Public Instruction, Milton, FL.

    Recommendations for incorporating conservation education into the K-5 curriculum comprise this teacher's guide. Examined are eight natural resources: air, energy, forests and plant life, human resources, minerals, soil, water, and wildlife. Each of these topics is considered in two ways: (1) a chart depicts concepts basic to understanding the…

  9. Energy Conservation Simplified

    ERIC Educational Resources Information Center

    Hecht, Eugene

    2008-01-01

    The standard formulation of energy conservation involves the subsidiary ideas of kinetic energy ("KE"), work ("W"), thermal energy, internal energy, and a half-dozen different kinds of potential energy ("PE"): elastic, chemical, nuclear, gravitational, and so forth. These quantities came to be recognized during the centuries over which the…

  10. Conservation Commissions in Massachusetts.

    ERIC Educational Resources Information Center

    Scheffey, Andrew J. W.

    The Conservation Foundation reported on the experience of a resource development specialist in the state of Massachusetts on the public's growing concern for environmental quality. After tracing the origins of the Massachusetts movement, the report draws upon a variety of specific state experiences to illustrate the commission's growing pains and…

  11. Energy conservation resource directory

    SciTech Connect

    Silver, D.; Paddock, D.; Doyle, L.

    1982-05-01

    Listed are energy conservation contacts among governments, local entities, and utilities serving the state of Washington. Statewide organizations and contacts are given, followed by lists for each county, including energy contacts for cities, community action agencies, the council of government, the county, Indian tribes, and utilities serving that county. Whenever possible, program staff people are identified rather than the executive staff. (LEW)

  12. Hearing Conservation Medical Program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background on hearing impairment is presented including causes and criteria for safe noise levels. The purpose of the Hearing Conservation Program at LeRC is outlined, and the specifics of the Medical Surveillance Program for Hearing Impairment at LeRC are discussed.

  13. Designing for Energy Conservation.

    ERIC Educational Resources Information Center

    Estes, R. C.

    1979-01-01

    Alief Independent School District, Texas, has been successful in obtaining energy efficient designs for its new schools by developing energy goals prior to the selection of architects and engineers. Features of four projects designed to conserve energy are described. (Author/MLF)

  14. Conservative Public Interest Litigation

    ERIC Educational Resources Information Center

    Pell, Terence J.

    2007-01-01

    The idea that lawsuits can move a public as well as a legal agenda is not new. In recent years, conservatives have brought high profile lawsuits designed both to vindicate the rights of an individual plaintiff and to educate the public about an important issue. For example, lawsuits filed nearly 10 years ago against the University of Michigan's…

  15. Science Experience Unit: Conservation.

    ERIC Educational Resources Information Center

    Ferguson-Florissant School District, Ferguson, MO.

    GRADES OR AGES: Intermediate grades. SUBJECT MATTER: Conservation. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into 24 experiments. It is mimeographed and staple-bound with a paper cover. OBJECTIVES AND ACTIVITIES: A specific skill or knowledge objective is stated at the beginning of each experiment. Detailed procedures are listed…

  16. Foundry energy conservation workbook

    SciTech Connect

    1990-10-01

    This report discusses methods for promoting energy conservation in foundries. Use of electric power, natural gas, and coke are evaluated. Waste heat recovery systems are considered. Energy consumption in the specific processes of electric melting, natural gas melting, heat treatments, ladle melting, and coke fuel melting is described. An example energy analysis is included. (GHH)

  17. Foundry energy conservation workbook

    SciTech Connect

    Not Available

    1990-12-31

    This report discusses methods for promoting energy conservation in foundries. Use of electric power, natural gas, and coke are evaluated. Waste heat recovery systems are considered. Energy consumption in the specific processes of electric melting, natural gas melting, heat treatments, ladle melting, and coke fuel melting is described. An example energy analysis is included. (GHH)

  18. Communities, Cameras, and Conservation

    ERIC Educational Resources Information Center

    Patterson, Barbara

    2012-01-01

    Communities, Cameras, and Conservation (CCC) is the most exciting and valuable program the author has seen in her 30 years of teaching field science courses. In this citizen science project, students and community volunteers collect data on mountain lions ("Puma concolor") at four natural areas and public parks along the Front Range of Colorado.…

  19. Conservation of fern spores

    USDA-ARS?s Scientific Manuscript database

    Ferns are a diverse and important group of plants, but diversity of species and populations are at risk from increasing social pressures, loss of habitat and climate change. Ex situ conservation is a useful strategy to limit decline in genetic diversity and requires technologies to preserve fern ger...

  20. "Conservative" views of abortion.

    PubMed

    Devine, P E

    1997-01-01

    The introduction to this essay, which presents and defends the "conservative" position on abortion, explains that this position holds that 1) abortion is wrong because it destroys the fetus; 2) the fetus has full personhood from conception (or very near conception); 3) abortion is only justified under special circumstances, such as when the pregnancy poses a threat to the woman's life; and 4) these conclusions should be reflected in law and public policy. Part 2 sets forth the moral foundations for this position. The third part considers the status of the fetus and reviews the various arguments that have been forwarded to resolve the question, such as the species principle, the potentiality principle, the sentience principle, and the conventionalist principle. Part 4 applies the conservative position to problems posed by hard cases, determines that abortion is a form of homicide from two weeks after fertilization (at the latest), reviews circumstances in which various legal definitions of homicide are applicable, argues for the denial of abortion funding by the state, and notes that violent militancy is not the appropriate response to a belief that abortion should be illegal. Section 5 refutes objections to the conservative position based on the fact that some opponents of abortion also oppose contraception, based on feminist ideals, and based on calls for religious freedom in a pluralistic society. In conclusion, the labels applied to the abortion debate are examined, and it is suggested that "communitarian" is the best term for the conservative position.

  1. [Lateral epicondylitis: conservative - operative].

    PubMed

    Altintas, Burak; Greiner, Stefan

    2016-10-01

    Lateral epicondylitis is a common disease of the common extensor origin at the lateral humerus. Despite its common self-limitation it can lead to chronic therapy-resistant pain with remarkable functional disability of the affected arm. Different conservative and operative treatment options of lateral epicondylitis are described and compared regarding benefits and risks. Additionally, recent surgical techniques and their complications are mentioned. Based on the current literature, it is shown which treatment option can be recommended. This review was based on the literature analysis in PubMed regarding "conservative and operative therapy of lateral epicondylitis" as well as the clinical experience of the authors. Conservative treatment is the primary choice for the treatment of lateral epicondylitis if concomitant pathologies such as instability among others can be excluded. It should include strengthening against resistance with eccentric stretching of the extensor group. In persistent cases, operative treatment is warranted. Resection of the pathologic tissue at the extensor origin with debridement and refixation of the healthy tendinous tissue yields good results. Most patients with lateral epicondylitis can be treated conservatively with success. Radiological evaluation should be performed in therapy-resistant cases. In the case of partial or complete rupture of the extensor origin, operative therapy is indicated.

  2. Conserved herpesvirus protein kinases

    PubMed Central

    Gershburg, Edward; Pagano, Joseph S.

    2008-01-01

    Conserved herpesviral protein kinases (CHPKs) are a group of enzymes conserved throughout all subfamilies of Herpesviridae. Members of this group are serine/threonine protein kinases that are likely to play a conserved role in viral infection by interacting with common host cellular and viral factors; however along with a conserved role, individual kinases may have unique functions in the context of viral infection in such a way that they are only partially replaceable even by close homologues. Recent studies demonstrated that CHPKs are crucial for viral infection and suggested their involvement in regulation of numerous processes at various infection steps (primary infection, nuclear egress, tegumentation), although the mechanisms of this regulation remain unknown. Notwithstanding, recent advances in discovery of new CHPK targets, and studies of CHPK knockout phenotypes have raised their attractiveness as targets for antiviral therapy. A number of compounds have been shown to inhibit the activity of human cytomegalovirus (HCMV)-encoded UL97 protein kinase and exhibit a pronounced antiviral effect, although the same compounds are inactive against Epstein-Barr Virus (EBV)-encoded protein kinase BGLF4, illustrating the fact that low homology between the members of this group complicates development of compounds targeting the whole group, and suggesting that individualized, structure-based inhibitor design will be more effective. Determination of CHPK structures will greatly facilitate this task. PMID:17881303

  3. Biological science in conservation

    Treesearch

    David M. Johns

    2000-01-01

    Large-scale wildlands reserve systems offer one of the best hopes for slowing, if not reversing, the loss of biodiversity and wilderness. Establishing such reserves requires both sound biology and effective advocacy. Attempts by The Wildlands Project and its cooperators to meld science and advocacy in the service of conservation is working, but is not without some...

  4. Energy Conservation Simplified

    ERIC Educational Resources Information Center

    Hecht, Eugene

    2008-01-01

    The standard formulation of energy conservation involves the subsidiary ideas of kinetic energy ("KE"), work ("W"), thermal energy, internal energy, and a half-dozen different kinds of potential energy ("PE"): elastic, chemical, nuclear, gravitational, and so forth. These quantities came to be recognized during the centuries over which the…

  5. [Conservative Therapy of Osteoarthritis].

    PubMed

    Krasselt, Marco; Baerwald, Christoph

    2015-12-01

    The therapy of osteoarthritis is based on conservative therapeutic approaches, depending on the disease's severity. In this context, physical therapy and the use of sufficient analgesic regimes are of decisive importance. This article will discuss the current evidence based therapeutic concepts as well as promising new therapeutic approaches.

  6. Conservation Awareness Guide.

    ERIC Educational Resources Information Center

    Santa Rosa County Board of Public Instruction, Milton, FL.

    Recommendations for incorporating conservation education into the K-5 curriculum comprise this teacher's guide. Examined are eight natural resources: air, energy, forests and plant life, human resources, minerals, soil, water, and wildlife. Each of these topics is considered in two ways: (1) a chart depicts concepts basic to understanding the…

  7. Conservation, Preservation, and Digitization.

    ERIC Educational Resources Information Center

    Lynch, Clifford A.; Brownrigg, Edwin B.

    1986-01-01

    Digital technologies should be considered a method of preservation for library materials. Current conservation strategies of restoration, deacidification, and microfilming are expensive, and they limit access. Digitization offers improved access while preserving materials and reflects a change in the library role from depository of printed…

  8. Communities, Cameras, and Conservation

    ERIC Educational Resources Information Center

    Patterson, Barbara

    2012-01-01

    Communities, Cameras, and Conservation (CCC) is the most exciting and valuable program the author has seen in her 30 years of teaching field science courses. In this citizen science project, students and community volunteers collect data on mountain lions ("Puma concolor") at four natural areas and public parks along the Front Range of Colorado.…

  9. The Conservation Fund

    DTIC Science & Technology

    2004-08-01

    Create Walkable Neighborhoods 3. Encourage Community and Stakeholder Collaboration 4. Foster Distinctive, Attractive Communities with a Strong Sense of...Network www.smartgrowth.org Smart Growth America www.smartgrowthamerica.net The International City /County Management Assn. www.icma.org The Conservation

  10. Scale in conservation planning

    USDA-ARS?s Scientific Manuscript database

    Conservation planning has been widely embraced as a method to efficiently allocate limited resources to those aspects of biodiversity most in need of protection or management. However, in order to create successful strategies for long-term biodiversity protection and sustainability, explicit conside...

  11. Conservation and gene banking

    USDA-ARS?s Scientific Manuscript database

    Plant conservation has several objectives the main ones include safeguarding our food supply, preserving crop wild relatives for breeding and selection of new cultivars, providing material for industrial and pharmaceutical uses and preserving the beauty and diversity of our flora for generations to ...

  12. Supply curves of conserved energy

    NASA Astrophysics Data System (ADS)

    Meier, A. K.

    1982-05-01

    Supply curves of conserved energy provide an accounting framework that expresses the potential for energy conservation. The economic worthiness of a conservation measure is expressed in terms of the cost of conserved energy, and a measure is considered economical when the cost of conserved energy is less than the price of the energy it replaces. A supply curve of conserved energy is independent of energy prices; however, the economical reserves of conserved energy will depend on energy prices. Double-counting of energy savings and error propagation are common problems when estimating conservation potentials, but supply curves minimize these difficulties and make their consequences predictable. The sensitivity of the cost of conserved energy is examined, as are variations in the optimal investment strategy in response to changes in inputs. Guidelines are presented for predicting the consequences of such changes.

  13. Energy-conservation indicators

    SciTech Connect

    Belzer, D.B.

    1982-06-01

    A series of Energy Conservation Indicators were developed for the Department of Energy to assist in the evaluation of current and proposed conservation strategies. As descriptive statistics that signify current conditions and trends related to efficiency of energy use, indicators provide a way of measuring, monitoring, or inferring actual responses by consumers in markets for energy services. Related sets of indicators are presented in some 30 one-page indicator summaries. Indicators are shown graphically, followed by several paragraphs that explain their derivation and highlight key findings. Indicators are classified according to broad end-use sectors: Aggregate (economy), Residential, Commercial, Industrial, and transportation. In most cases annual time series information is presented covering the period 1960 through 1981.

  14. Three strategies for conservation

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The three strategies considered as energy conservation oriented were given: national energy conservation, electrification, and diversification. The first one applies to the near term period (now-1985), the second one to the mid term (1985-2000), and the third one to the far term (2000- ). The rest of this section was focussed on the near term period. The following proposed actions were considered: (1) roll back the price of newly discovered oil, (2) force conversion of many power plants from gas and oil to coal, (3) freeze gasoline production for three years at 1972 levels, (4) mandate automobile mileage requirements, (5) require industry to improve energy efficiency, and (6) require manufacture of household appliances with greater efficiency. Each of these six actions was described and discussed in more detail.

  15. Energy Conservation in GTR

    NASA Astrophysics Data System (ADS)

    Hoefer, Carl

    The topics of gravitational field energy and energy-momentum conservation in General Relativity theory have been unjustly neglected by philosophers. If the gravitational field in space free of ordinary matter, as represented by the metric g ab itself, can be said to carry genuine energy and momentum, this is a powerful argument for adopting the substantivalist view of spacetime. This paper explores the standard textbook account of gravitational field energy and argues that (a) so-called stress-energy of the gravitational field is well-defined neither locally nor globally; and (b) there is no general principle of energy-momentum conservation to be found in General Relativity. I discuss the nature and justification of the zero-divergence law for ordinary stress-energy, and its possible connection with the failure of General Relativity to realise Mach's principle.

  16. Laser conservation paleontology

    NASA Astrophysics Data System (ADS)

    Asmus, John F.

    2001-10-01

    Just as lasers have found countless applications in science, industry, medicine, and entertainment, an array of real and potential uses for lasers in art-conservation analytes and practice have been investigated over the past thirty years. These include holographic recording, holographic recording, holographic nondestructive testing, laser-induced ultrasonic imaging, laser-scattering surface characterization, atomic and molecular analyses, photoacoustic spectroscopy, surface modification, as well as surface divestment and cleaning. The initial endeavors in exploring and assessing the utility of these tools for art conservation are recounted for investigations involving ruby, glass, ion, YAG, carbon dioxide, dye, and excimer lasers as well as high-intensity nonlaser light generators such as xenon flashlamps and argon pinchlamps. Initially, laser divestment/cleaning was, by general consensus, the least plausible laser application in art conservation. In the past ten years it has emerged to dominate all the other applications noted above. Today, at least a dozen firms supply user-friendly laser systems optimized for a range of art-conservation divestment applications. The first-generation laser-cleaning tools are essentially a laser, a beam-delivery device, and a debris- collection accessory. Advanced developmental work has turned in large measure to ancillary subsystems for more sophisticated process control. Of particular importance are acoustic, optical, spectral, EMP, and electronic-vision process control. Beam direction may be via manual, translational-scanner, or robotic beam positioning implemented by means of fiber optics, minors, or prisms and computer control. Substrate thermal alteration and debris redeposition may be minimized or avoided through the incorporation of a gas jet, fluid or fluid jet, or dry-ice blast.

  17. Motor Energy Conservation Measures

    SciTech Connect

    Ian Metzger, Jesse Dean

    2010-12-31

    This software requires inputs of simple motor inventory information and calculates the energy and cost benefits of various retrofit opportunities. This tool includes energy conservation measures for: High Efficiency Motor retrofit and Cogged V-belts retrofit. This tool calculates energy savings, demand reduction, cost savings, and building life cycle costs including: simple payback, discounted payback, net-present value, and savings to investment ratio. In addition this tool also displays the environmental benefits of a project.

  18. Landscapes, tourism, and conservation

    PubMed

    Burger

    2000-04-17

    One key aspect of global change is a decrease in ecological integrity as more and more landscapes are developed, leaving a mosaic of intact refuges and degraded patches that may not be sufficient for conserving biodiversity. While increases in human population and shifts in the distribution of people affect land use, the temporary movement of people can have major implications for conservation and biodiversity. Three examples are presented where recreation/tourism can enhance the conservation of land on a landscape scale, leading to habitat protection and biodiversity preservation: (1) Shorebirds often require a matrix of different habitat types during migratory stopovers, and ecotourism can serve as a catalyst for landscape scale protection of habitat. (2) Riparian habitats can serve as corridors to link diverse habitat patches, as well as serving as biodiversity hotspots. (3) Remediation and rehabilitation of contaminated lands, such as those of the US Department of Energy, aimed at developing recreational activities on the uncontaminated portions, can be the most economical form of re-development with no increase in human or ecological risk. Since large areas on many DOE sites have been undisturbed since the Second World War, when they were acquired, they contain unique or valuable ecosystems that serve an important role within their regional landscapes. In all three cases the judicious development of recreational/tourist interests can encourage both the conservation of habitats and the wise management of habitats on a landscape scale. While some species or habitats are too fragile for sustained tourism, many can be managed so that species, ecosystems and ecotourists flourish. By contributing to the economic base of regions, ecotourists/recreationists can influence the protection of land and biodiversity on a landscape scale, contributing to ecosystem management. The human dimensions of land preservation and biodiversity protection are key to long

  19. The conservation attitude

    USGS Publications Warehouse

    Leopold, Luna Bergere

    1960-01-01

    Forsaking his inheritance and its assurance of a comfortable existence, Guatama Buddha adopted the life of a pauper to seek the intellectual joys of pure contemplation. Under a mulberry tree, it is said, he propounded a 12-point program of ethical conduct stressing the development of a disinterested outlook in each individual. Temples, ritual, and idols he considered distractions from the basic need. He felt that there was a basic need for the development of an attitude.The Brahmins as well as the lower castes recognized the merits of the system suggested by Buddha, but they molded his teachings into an accessory to existing rituals and dogma. They soon forgot that Guatama wanted no idols and no temples. They forgot his admonition that an attitude was the thing that really counted. Despite his expressed wish, today Buddha in stone, in bronze, and in gold ponders these things in thousands of temples and hears the prayers of millions who still seek the truths of an ethical life.Today, conservation has its temples. The temples of conservation include hundreds of irrigation reservoirs; it has prayer-sticks in miles of contour plow furrows, and the Buddha of a drop-inlet structure looks down on a conservation pool in myriad detention dams.Conservation is well established today in the minds of the American public. It seems appropriate to analyze at this time just what it is that is established in the public mind. In what ways have we, too, substituted the temples, the ritual, and the idols for an attitude?

  20. Human tRNALys3UUU Is Pre-Structured by Natural Modifications for Cognate and Wobble Codon Binding through Keto-Enol Tautomerism

    SciTech Connect

    Vendeix, Franck A.P.; Murphy, IV, Frank V.; Cantara, William A.; Leszczy,; #324; ska, Gra; #380; yna,; Gustilo, Estella M.; Sproat, Brian; Malkiewicz, Andrzej; Agris, Paul F.

    2013-09-27

    nucleotides mcm5s2U34 and ms2t6A37 participate in the stability of the anticodon–codon interaction. Importantly, the mcm5s2U34·G3 wobble base pair is in the Watson–Crick geometry, requiring unusual hydrogen bonding to G in which mcm5s2U34 must shift from the keto to the enol form. The results unambiguously demonstrate that modifications pre-structure the anticodon as a key prerequisite for efficient and accurate recognition of cognate and wobble codons.